Mutabon

Italy
Brand name Mutabon
Form tablets, film-coated
Active substance / Dosage
PERPHENAZINE
AMITRIPTYLINE
Prescription type Prescription only
ATC code
N06CA01
Registration number 021460
Manufacturer NEOPHARMED GENTILI S.P.A.
Mutabon tablets, film-coated

Table of Contents

Package leaflet: Information for the patient

Mutabon Ansiolitico 4 mg + 10 mg film-coated tablets

Perphenazine + Amitriptyline hydrochloride
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

  1. What Mutabon Ansiolitico is and what it is used for
  2. What you need to know before taking Mutabon Ansiolitico
  3. How to take Mutabon Ansiolitico
  4. Possible side effects
  5. How to store Mutabon Ansiolitico
  6. Contents of the pack and other information

1. What Mutabon Ansiolitico is and what it is used for

Mutabon Ansiolitico contains two active substances: perphenazine and amitriptyline hydrochloride.
Perphenazine belongs to a group of medicines called phenothiazines, which acts on the central nervous system, reducing anxiety states (anxiolytic property) and exerting therapeutic effects on psychotic symptoms (delusions and hallucinations).
Amitriptyline hydrochloride belongs to a group of medicines known as "tricyclic antidepressants", used in the treatment of depression.
Mutabon Ansiolitico is therefore an antidepressant combined with a neuroleptic, used for the treatment of certain mental disorders, which may have genetic causes (endogenous), or may be triggered by an unpleasant life event (reactive disorders), characterized by the coexistence of anxiety, tension and agitation, together with a depressive state.
Mutabon Ansiolitico is useful for the treatment of the following disorders:

  • simple anxiety associated with relatively mild or slight depressive symptoms;
  • severe insomnia associated with anxiety and depression.

2. What you should know before taking Mutabon Anxiolytic

Do not take Mutabon Anxiolytic if:

  • you are allergic to the active substances (perphenazine and amitriptyline hydrochloride), or to other similar medicines, or to any of the other ingredients of this medicine (listed in section 6);
  • you are taking or have taken within the last two weeks medicines for depression known as monoamine oxidase inhibitors (MAOIs) (see section “Other medicines and Mutabon Anxiolytic”);
  • you have increased pressure inside the eye;
  • you suffer from an eye disease due to increased intraocular pressure (glaucoma);
  • you have urogenital system disorders such as prostate enlargement (prostatic hypertrophy) or suspected or confirmed difficulty in bladder emptying (urinary retention);
  • you have a muscle disease characterized by loss of tone and strength (myasthenia gravis);
  • you have a blood disorder characterized by changes in blood composition (haematological dyscrasia);
  • you have impaired bone marrow function that fails to produce sufficient numbers of blood cells (bone marrow depression);
  • you have disorders in blood cell production (haematopoietic disturbances); therefore, administration of medicines that may cause a reduction in white blood cells (leukopenic drugs) must be avoided;
  • you have liver disease;
  • you are taking other medicines that reduce central nervous system activity (such as barbiturates, ethyl alcohol, narcotics, analgesics, antihistamines); see section “Other medicines and Mutabon Anxiolytic”);
  • you are in a state of reduced level of consciousness (severe obtundation) or coma;
  • you suffer from severe depression;
  • you have suspected or confirmed brain damage (subcortical brain damage), as you may experience an increase in body temperature up to over 40°C, sometimes occurring 14 or 16 hours after taking the medicine;
  • you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”);
  • you have recently had a heart attack (myocardial infarction).

Warnings and precautions
Talk to your doctor or pharmacist before taking Mutabon Anxiolytic.
Inform your doctor if:

  • you have or have had episodes of epilepsy or seizures (involuntary muscle contractions) or are being treated with medicines used to control seizures. Your doctor will assess whether it is necessary to increase the dose of such medicines when taken together with Mutabon Anxiolytic;
  • you are taking other medicines with similar action (neuroleptics);
  • you have a tumour of the adrenal glands (pheochromocytoma) or a dysfunction of the heart's mitral valve (mitral insufficiency). In such cases, you will require closer monitoring during perphenazine administration due to the risk of low blood pressure (hypotension). If you have pheochromocytoma, you may experience high blood pressure after stopping treatment with Mutabon Anxiolytic (rebound hypertension);
  • you have a breast tumour. In this case, perphenazine will be administered with particular caution, as it increases the concentration of a hormone (prolactin) that may worsen your condition;
  • you are scheduled for surgery. Your doctor will advise you whether treatment with Mutabon Anxiolytic should be discontinued several days before the procedure;
  • you are in the post-operative phase, as vomiting and aspiration may occur;
  • you have recently undergone surgery and are taking high doses of this medicine. In such cases, your doctor will monitor you closely due to the risk of low blood pressure (hypotension). Additionally, it may be necessary to reduce the dosage of anaesthetics or sedatives you are taking;
  • you are generally exposed to extremely high or low temperatures, as perphenazine in Mutabon Anxiolytic may impair the body's temperature regulation mechanisms;
  • you have reduced kidney function or severe kidney disease;
  • you are predisposed to or already affected by Parkinson’s disease or Parkinson-like conditions, or other motor disorders, as perphenazine may increase muscle rigidity;
  • you have previously experienced difficulty in bladder emptying (urinary retention);
  • you have or have had difficulty in stomach emptying (pyloric stenosis) or suffer from intestinal blockage (intestinal obstruction);
  • you suffer from thyroid diseases (hyperthyroidism) or are taking thyroid hormone medications. Your doctor will keep you under close surveillance;
  • you have respiratory system diseases caused by lung infections or chronic respiratory disorders such as severe asthma or emphysema;
  • you consume alcohol, as it may enhance the effects of the medicine and significantly lower blood pressure (hypotension). If you abuse alcohol, your risk of suicide or overdose may increase (see section “Mutabon Anxiolytic with alcohol”);
  • you are experiencing alcohol withdrawal;
  • you suddenly develop sore throat or other signs of infection, as Mutabon Anxiolytic may cause disturbances in blood cell production. Your doctor will perform blood tests, particularly between the fourth and tenth week of treatment. If tests show a significant decrease in white blood cells, your doctor will instruct you to stop treatment; however, a slight decrease in white blood cells is not in itself a reason to discontinue treatment;
  • you have cognitive impairment (dementia), as treatment with Mutabon Anxiolytic may increase the risk of cerebrovascular events (cerebrovascular problems);
  • you suffer from heart and blood vessel diseases (cardiovascular diseases), especially if you are elderly, have a family history of heart rhythm conduction abnormalities (QT prolongation), or have risk factors for stroke (pathological cerebrovascular event), because antidepressant medicines, particularly when administered at high doses, may cause heart rhythm disturbances (arrhythmias, sinus tachycardia, and conduction time prolongation) or more serious events such as myocardial infarction and stroke;
  • you have had diseases associated with blood clot formation or have a family history of such diseases;
  • you have hardening, thickening, and loss of elasticity of the arterial wall in the brain (cerebral arteriosclerosis);
  • you suffer from mental disorders such as manic-depressive psychosis or a personality disorder characterized by a persistent tendency to interpret others' behaviour with distrust and suspicion (paranoid disorder), as tricyclic antidepressants like amitriptyline may exacerbate symptoms of these conditions. However, the calming effect of Mutabon Anxiolytic reduces the risk of such effects;
  • you are scheduled for electroconvulsive therapy, as risks associated with this procedure may increase when combined with amitriptyline; in such cases, your doctor will limit the use of Mutabon Anxiolytic to situations where treatment is absolutely essential;
  • you are taking medicines containing buprenorphine. Using these medicines together with Mutabon Anxiolytic may lead to serotonin syndrome, a condition that can be fatal (see “Other medicines and Mutabon Anxiolytic”).

Suicide/Suicidal thoughts
Depression is associated with an increased risk of suicidal thoughts, self-harm (self-injury), and suicide. The risk of experiencing such thoughts may increase in the early stages of improvement and may persist until your symptoms significantly improve. Since improvement may not occur during the first few weeks of treatment or immediately thereafter, you will be closely monitored by your doctor until improvement occurs.
Other mental disorders for which Mutabon Anxiolytic is prescribed may increase the risk of suicidal behaviour and major depressive disorder (a depressive disorder characterised by alternating periods of well-being and depressive phases). If you suffer from major depressive disorder, your doctor will follow the same precautions as during treatment of patients with other psychiatric disorders.
You are more likely to experience suicidal thoughts if:

  • you have previously considered suicide;
  • you are a young person under 25 years of age being treated with antidepressants. Your doctor will closely monitor you throughout the treatment period, especially during the initial stages and after any dose adjustments, and if you are considered at high risk for suicidal thoughts. Contact your doctor immediately if you experience worsening symptoms, the onset of suicidal behaviour or thoughts, or behavioural changes.

It is possible that during treatment with Mutabon Anxiolytic the following may occur:

  • development of involuntary muscle movements (tardive dyskinesia), especially if you are elderly. Both the risk of developing dyskinesia and the likelihood that it becomes irreversible increase with the duration of treatment and total amount of medicine taken. Discontinuation of treatment may lead to partial or complete resolution of this condition. If you notice the onset of these symptoms, inform your doctor, who will evaluate the possibility of adjusting the dose or discontinuing treatment;
  • increased or decreased blood sugar levels;
  • development of skin sensitivity to light (photosensitivity). Therefore, avoid excessive exposure to sunlight during treatment with Mutabon Anxiolytic.

Cardiac problems, known as "QT interval prolongation" (seen on electrocardiogram, ECG) and heart rhythm disorders (accelerated or irregular heartbeat), have been reported in association with the use of Mutabon Anxiolytic. Contact your doctor if:

  • you have a slow heart rate,
  • you have or have had a condition in which your heart was unable to pump blood properly through your body (a condition called heart failure),
  • you are taking other medicines that may cause heart problems, or
  • you have a condition causing abnormally low levels of potassium or magnesium or abnormally high levels of potassium in the blood.

Stop treatment with Mutabon Anxiolytic and contact your doctor if you experience:
a significant increase in body temperature not attributable to a specific cause. This temperature rise may suggest hypersensitivity to perphenazine, and your doctor will instruct you to discontinue treatment.
a potentially fatal group of symptoms called neuroleptic malignant syndrome, characterised by: elevated body temperature, muscle rigidity, reduced or loss of ability to perform movements (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), heart rhythm disturbances (arrhythmias)), and altered mental status, which may progress to partial loss of consciousness (stupor) and coma. Your doctor will instruct you to stop treatment and initiate therapy to manage these symptoms.
abnormal blood urea levels.
During treatment with Mutabon Anxiolytic, you will need to undergo periodic checks to evaluate red blood cell counts and liver and kidney function. If abnormalities occur, your doctor will discontinue treatment.
The use of Mutabon Anxiolytic may mask signs of overdose of other medicines or make diagnosis of diseases such as intestinal obstruction, Reye's syndrome (an acute, potentially fatal illness generally seen in patients under 18 years of age, characterised by symptoms primarily affecting the brain and liver), brain tumours, or other diseases altering the structure and/or function of the brain (encephalopathies) more difficult.

Children and adolescents
The use of Mutabon Anxiolytic is not recommended in children under 12 years of age due to lack of data on safety and efficacy.

Other medicines and Mutabon Anxiolytic
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not take Mutabon Anxiolytic together with the following medicines:

  • monoamine oxidase inhibitors (MAOIs). Do not take Mutabon Anxiolytic simultaneously or within two weeks after stopping treatment with monoamine oxidase inhibitors, as severe reactions may occur, including marked increase in body temperature (hyperpyrexic crisis), seizures, coma, and death (see section “Do not take Mutabon Anxiolytic if”). After this period, your doctor will cautiously initiate treatment with Mutabon Anxiolytic, gradually increasing the dose until a satisfactory response is achieved.
  • opioids, barbiturates, or other sedatives, antihistamines, anaesthetics, tranquillisers, and meperidine (and other opioid analgesics). Concomitant administration with Mutabon Anxiolytic may enhance the central nervous system depressant effects of these medicines, including respiratory depression. Conversely, these medicines may enhance the effects of Mutabon Anxiolytic. Therefore, you must not take Mutabon Anxiolytic together with these medicines (see section “Do not take Mutabon Anxiolytic if”).

Contact your doctor or pharmacist if you are taking:

  • medicines that may cause a reduction in white blood cells (leukopenic drugs), as Mutabon Anxiolytic may cause disturbances in blood cell production (see section “Do not take Mutabon Anxiolytic if” and “Warnings and precautions”);
  • other psychotropic medicines, medicines with anticholinergic action (inhibition of acetylcholine, a substance acting in the nervous system), or medicines acting on the autonomic nervous system (sympathomimetics), due to the possible occurrence of adverse effects from interaction with Mutabon Anxiolytic;
  • medicines with anticholinergic action, such as atropine, or antihistamines, as this may enhance effects on the cholinergic system, leading to risk of intestinal blockages (paralytic ileus), blurred vision, and possible changes in eye pressure in the presence of glaucoma;
  • medicines acting on the autonomic nervous system (sympathomimetic amines) such as epinephrine combined with local anaesthetics, as this may increase the activity of such medicines or of Mutabon Anxiolytic. Your doctor will closely monitor you and adjust the dose to prevent adverse effects on blood pressure and cardiac function, which may sometimes be fatal;
  • reserpine, methyldopa, other medicines for high blood pressure (hypertension) such as guanethidine (concomitant use requires dose adjustment by the doctor), beta-blockers that block adrenergic receptors such as propranolol or similar medicines, as this may cause low blood pressure (hypotension). Concomitant use of Mutabon Anxiolytic and such medicines is therefore not recommended. Your doctor may require blood pressure checks before starting treatment with Mutabon Anxiolytic and weekly checks during the first month of treatment;
  • medicines for seizure control (see section “Warnings and precautions”);
  • phenytoin, a medicine used to treat epilepsy, as Mutabon Anxiolytic may alter its effectiveness;
  • antipsychotic medicines;
  • sedative medicines such as diazepam;
  • high doses of ethchlorvynol (a sedative and hypnotic medicine), as transient delirium has been reported with this combination. The combination with Mutabon Anxiolytic should be used with caution;
  • medicines for stomach hyperacidity containing aluminium salts, as they may reduce absorption of Mutabon Anxiolytic;
  • medicines that prolong the QT interval, as this increases the risk of heart rhythm disturbances (cardiac arrhythmias);
  • medicines that cause electrolyte imbalances in the blood;
  • medicines containing cimetidine, as they may increase amitriptyline blood concentrations and its effects, possibly leading to severe adverse effects;
  • medicines that inhibit cytochrome P450 2D6 (an enzyme in the body involved in drug metabolism), such as quinidine, cimetidine, many other antidepressants, phenothiazines, propafenone, flecainide, and all medicines known as selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, and paroxetine, and serotonin-noradrenaline reuptake inhibitors (duloxetine). In such cases, your doctor may prescribe lower than recommended doses for both these medicines and Mutabon Anxiolytic;
  • levodopa and phenylbutazone, as the anticholinergic effects of tricyclic antidepressants may slow gastrointestinal motility, interfering with the absorption of these medicines;
  • valproic acid;
  • medicines containing buprenorphine. These medicines may interact with Mutabon Anxiolytic and cause symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, and fever above 38°C. Contact your doctor if you experience such symptoms.

Mutabon Anxiolytic may interfere with the absorption of various other drugs.
Inform your doctor if you are exposed to organophosphorus insecticides.

Mutabon Anxiolytic and laboratory tests
Taking Mutabon Anxiolytic may darken the urine and cause alterations in the results of certain laboratory tests:

  • false positives (positive results not truly present) in the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens, and 5-hydroxy-indoleacetic acid;
  • electrocardiogram changes such as QT interval prolongation;
  • abnormalities in electroencephalogram;
  • alteration (increase) in levels of iodine bound to blood proteins;
  • changes in hypothalamic-pituitary function tests, as the medicine may cause a decrease in certain hormone levels;
  • false positives and false negatives in urine pregnancy tests;
  • possible increases and decreases in blood sugar levels.

Mutabon Anxiolytic and alcohol
Mutabon Anxiolytic must not be taken together with alcohol (ethanol) due to the possible enhancement of the medicine's effects, including a reduction in blood pressure (hypotension). In addition, this combination may increase the risk of suicide and the danger of overdose.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Mutabon Anxiolytic must not be used during pregnancy, confirmed or suspected, due to the risk of adverse effects in the newborn (see section “Do not take Mutabon Anxiolytic if” and section 4 “Undesirable effects in children”).

Breastfeeding
You must not use Mutabon Anxiolytic if you are breastfeeding (see section “Do not take Mutabon Anxiolytic if”), as Mutabon Anxiolytic passes into breast milk and may cause adverse effects in the newborn.

Driving and using machines
Mutabon Anxiolytic affects the ability to drive and use machinery, as it may alter reaction time (the interval between perceiving a danger and initiating a response to avoid it). Therefore, exercise appropriate caution when driving or operating machinery.

Mutabon Anxiolytic contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Mutabon Anxiolytic contains Sunset Yellow colouring (E-110), which may cause allergic reactions.

3. How to take Mutabon Ansiolitico

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The optimal dose of Mutabon Ansiolitico must be determined by your doctor, depending on the specific condition being treated, the duration and severity of the illness, and your individual response to therapy.
The recommended dose is 1 tablet, 3–4 times daily. It generally takes several days to achieve a noticeable effect from Mutabon Ansiolitico.
Please note that the tranquilizing effect appears more rapidly (after 2 or 3 days) than the antidepressant effect (after 1 week or longer); therefore, symptoms of tension and anxiety disappear much earlier than depressive symptoms.
If you suffer from persistent insomnia, it is advisable—especially during the first days of treatment—to take 1 or 2 tablets in the evening, half an hour before going to bed. The remaining tablets prescribed by your doctor can be taken throughout the day.
To achieve full benefit, you must continue treatment for several weeks, as advised by your doctor. Once symptom control has been achieved, your doctor will gradually reduce your dose until establishing the most suitable maintenance dose for you.
Your doctor will periodically assess whether you still require continued treatment with Mutabon Ansiolitico.

Use in children and adolescents
Mutabon Ansiolitico is not recommended for children under 12 years of age (see section “Children and adolescents”).

Use in the elderly
The dose and frequency of administration of Mutabon Ansiolitico in elderly patients must be carefully determined by the doctor, who may consider reducing the above-mentioned dose based on individual needs.

If you take more Mutabon Ansiolitico than you should
In case of accidental or intentional overdose, contact your doctor or pharmacist immediately or go to the nearest hospital.
Symptoms of overdose appear rapidly, so immediate hospital monitoring is required.
Overdose with Mutabon Ansiolitico, as with other medicines in the same class, may result in death.
Symptoms of overdose may correspond to any of the adverse effects listed for the two active substances, perfenazine or amitriptyline hydrochloride (see section “Possible side effects”).

Symptoms of perfenazine overdose include motor system disturbances (extrapyramidal symptoms), such as involuntary muscle movements (dyskinesia) and abnormal muscle contractions (dystonia). However, these may be masked by the anticholinergic effects of amitriptyline. Other symptoms may include partial loss of consciousness (stupor) or coma; children may experience epileptic seizures.

Symptoms of amitriptyline overdose include irregular heartbeat (cardiac arrhythmias), severe drop in blood pressure (severe hypotension), involuntary muscle contractions (convulsions), and reduced activity of the central nervous system (central nervous system depression), including coma.
Electrocardiogram (ECG) abnormalities affecting heart conduction have also been reported.

Other symptoms of overdose include: confusion, difficulty concentrating, temporary visual hallucinations, dilated pupils, agitation, hyperactive reflexes, drowsiness, muscle rigidity, vomiting, decreased body temperature (hypothermia), fever, or any of the side effects listed.

Overdose with amitriptyline in children may lead to serious consequences. Children are particularly susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low blood sodium levels, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.

Treatment in case of overdose with Mutabon Ansiolitico
There is no specific antidote to counteract the effects of Mutabon Ansiolitico overdose. In case of accidental or intentional overdose, contact your doctor or pharmacist immediately or go to the nearest hospital.
You will be given appropriate emergency treatment, such as gastric lavage and electrocardiographic (ECG) monitoring, and will be closely observed for possible central nervous system effects, breathing difficulties, low blood pressure, heart rhythm abnormalities and/or conduction blocks, and epileptic seizures.
Your doctor may decide to contact the local poison control center.

If you forget to take Mutabon Ansiolitico
Do not take a double dose to make up for the missed tablet. Continue your treatment as prescribed.

If you stop taking Mutabon Ansiolitico
Do not stop taking Mutabon Ansiolitico without first consulting your doctor.
Phenothiazines (perfenazine) generally do not cause psychological dependence. However, sudden discontinuation of high-dose treatment may lead to symptoms such as gastritis, nausea, vomiting, dizziness, tremors, and motor hyperactivity. If you experience these symptoms, consult your doctor, who will prescribe appropriate treatment.

Sudden discontinuation of high-dose tricyclic antidepressant therapy (amitriptyline hydrochloride) may cause symptoms such as malaise, chills, cold-like symptoms, muscle pain, headache, nausea, vomiting, anxiety, instability, dizziness, and a constant urge to move (akathisia). These symptoms are not indicative of addiction.

If you suddenly stop high-dose treatment with Mutabon Ansiolitico, inform your doctor and pay attention to any symptoms you may experience.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, Mutabon Anxiolytic may cause adverse effects, although not everyone experiences them.
The adverse effects of Mutabon Anxiolytic are the same as those associated with the two active substances (perphenazine and amitriptyline) when taken individually. No adverse effects due solely to their combination in Mutabon Anxiolytic have been reported.
In very rare cases, patients hypersensitive to phenothiazines (perphenazine) have developed excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse, and death.
Occasionally, treatment with phenothiazines may cause intestinal muscle paralysis leading to cessation of intestinal content progression (adynamic ileus), which, if severe, may result in complications and death.
Stop treatment with Mutabon Anxiolytic and contact your doctor immediately if you experience:

  • Neuroleptic Malignant Syndrome (NMS), a potentially fatal condition characterized by symptoms such as elevated body temperature, muscle rigidity, reduced movement (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), cardiac rhythm abnormalities (arrhythmias)), altered mental status that may progress to stupor and coma (see “Stop treatment with Mutabon Anxiolytic and inform your doctor if you experience” in section 2);
  • persistent abnormalities in muscle contractions and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia) (see “Stop treatment with Mutabon Anxiolytic and inform your doctor if” in section 2);
  • swelling of the hands, feet, ankles, or even the face, lips, tongue, and/or throat, causing difficulty swallowing or breathing (angioedema);
  • increased body temperature (hyperpyrexia);
  • allergic reactions with skin eruptions (urticaria), irritation and appearance of red spots on the skin (erythema), itchy inflammatory skin reactions (eczema), skin inflammation with lesion formation and shedding of the superficial layer (exfoliative dermatitis), itching, skin sensitivity to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoid), swelling due to fluid accumulation in the upper airways (laryngeal edema), contact dermatitis.
  • formation of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the legs), which may travel through blood vessels to the lungs causing chest pain and difficulty breathing (the frequency of this adverse effect cannot be determined from available data);
  • worsening of depressive state, including, rarely, suicidal thoughts or behavior (see section “Warnings and precautions”).

Adverse effects related to perphenazine
The most common symptoms reported during treatment with perphenazine, as with all medicines belonging to the same pharmacological class as perphenazine, are motor system disturbances and abnormalities (extrapyramidal reactions), such as:

  • abnormal posture characterized by hyperextension of the neck, rigidity, and severe arching of the back (opisthotonus), abnormal contraction of jaw muscles with difficulty opening the mouth (trismus), limited mobility or blockage of the neck accompanied by cervical pain and contraction of lateral neck muscles (torticollis), torticollis associated with a deviated head posture and sudden muscle spasms causing abrupt head rotation (spastic torticollis), pain and tingling in the limbs, agitation with excessive motor activity (motor restlessness), eye deviation in one direction (oculogyric crisis), hyper-reflexivity characterized by abnormal muscle contractions (hyperreflexia), movement disorder involving involuntary muscle contractions (dystonia), including abnormalities of the tongue (color changes, pain, protrusion or rolling), sudden involuntary contractions of masticatory muscles, throat tightness, difficulty in speech and swallowing (dysphagia), inability to sit still, a group of symptoms including tremor, muscle rigidity, slowed movement execution, and postural abnormalities (parkinsonism), and loss of muscle coordination (ataxia).
    The frequency and severity of these symptoms generally increase with increasing doses of Mutabon Anxiolytic.
    Additionally, the following may occur:

  • abnormalities in the protein composition of cerebrospinal fluid, headache (cephalalgia), drowsiness;

  • worsening of psychotic symptoms such as thought disturbances, delusions and hallucinations, motor, emotional and behavioral abnormalities (catatonic-like states), thought patterns detached from reality (paranoid reactions), deep sleep state (lethargy), excitement, restlessness and hyperactivity, nocturnal confusion, bizarre dreams, sleep disturbances (insomnia);

  • abnormal milk secretion from the breasts (galactorrhea), breast enlargement in women and men (gynaecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), sexual desire alterations, ejaculation inhibition, false positive pregnancy tests, increased and decreased blood sugar levels (hyperglycemia and hypoglycemia), presence of sugar in urine (glycosuria), excessive release of an antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH);

  • drop in blood pressure upon standing from a sitting or lying position (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, fainting and dizziness;

  • decreased white blood cells (agranulocytosis, leukopenia), increased levels of a specific type of white blood cells (eosinophilia), reduced number of red blood cells (hemolytic anemia), abnormal destruction of platelets (thrombocytopenic purpura), reduced number of all blood cells (pancytopenia);

  • inflammation and obstruction of bile ducts (biliary stasis);

  • yellowing of the skin and whites of the eyes (jaundice).

Less frequent adverse effects:

  • sedation, blood disorders (hematological dyscrasia), involuntary muscle contractions (seizures).

Occasionally observed:

  • dry mouth and hypersalivation, nausea, vomiting and diarrhea, gastric retention, anorexia, constipation (stipsis), persistent constipation and formation of a hard mass of dehydrated feces in the intestine (fecaloma), difficulty emptying the bladder (urinary retention), frequent need to urinate and involuntary urine leakage (incontinence), loss of bladder function (bladder paralysis), increased urine output (polyuria);

  • nasal congestion (nasal congestion);

  • pallor, increased (mydriasis) and decreased (miosis) pupil size, blurred vision, eye disease characterized by increased pressure inside the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), decreased blood pressure (hypotension), altered pulse rate;

Rarely observed:

  • abnormalities in cardiac conduction (QT prolongation), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest;
  • swelling of the salivary glands (parotid swelling).

Adverse effects associated with long-term therapy:

  • liver damage;
  • skin discoloration (cutaneous pigmentation), visual disturbances due to deposition of fine particulate material in the cornea and lens, which in severe cases may lead to stellate lens opacities, corneal inflammation (epithelial keratopathies), retinal abnormalities, retinal destruction leading to vision loss (pigmentary retinopathy);
  • persistent abnormalities in muscle contractions and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia), which may also develop after discontinuation of treatment.

Other adverse effects:

  • fluid accumulation in the lower limbs (peripheral edema), sedative state (epinephrine reversal effect), altered levels of proteins binding iodine (increased PBI not attributable to increased thyroxine), lupus erythematosus-like syndrome (an inflammatory autoimmune disease affecting multiple organs and tissues), increased appetite and weight, abnormally increased food consumption (polyphagia), excessive light sensitivity (photophobia), muscle weakness.

Sudden death has been occasionally reported in patients treated with phenothiazines.
In some patients, the cause of death could not be determined, nor could it be established whether death was attributable to phenothiazine.
In elderly patients with dementia, a slight increase in mortality has been reported in those taking antipsychotics compared to those not taking them.

Adverse effects related to amitriptyline hydrochloride
Treatment with antidepressant medicines, including amitriptyline hydrochloride, may trigger the onset of latent schizophrenia, which in some cases may be prevented by the antipsychotic effect of perphenazine contained in Mutabon Anxiolytic.
In patients with chronic schizophrenia, epileptic seizures (epileptiform convulsions) have been observed during treatment with amitriptyline hydrochloride.
Moreover, amitriptyline hydrochloride may cause, in addition to some of the adverse effects reported for perphenazine, the following:

  • increased risk of bone fractures;
  • skin rash;
  • pupil abnormalities (accommodation disturbances), difficulty emptying the bladder (urinary retention and urinary tract dilation);
  • awareness of heartbeats (palpitations), heart attack and stroke, heart rhythm disturbances (arrhythmias), impaired conduction of electrical impulses in the heart that may lead to complete or partial heart stoppage (cardiac block);
  • confusion, concentration difficulties, disorientation, fixations and hallucinations, excitement, nervousness, anxiety and agitation, insomnia and nightmares, hearing loss, tingling and altered sensation in the limbs (paresthesia), dysfunction of the peripheral nervous system (peripheral neuropathy), tremors and seizures, abnormalities in electroencephalogram, hearing disturbances (tinnitus);
  • increased testicle size;
  • gastrointestinal disorders (epigastric discomfort and heartburn), inflammation of the oral cavity (stomatitis), altered taste, dark discoloration of the tongue;
  • rarely, liver inflammation (hepatitis) has occurred;
  • bone marrow depression (when the bone marrow fails to produce sufficient blood cells), decreased white blood cells (agranulocytosis, leukopenia), rupture of capillaries beneath the skin surface (purpura), increased levels of a specific type of white blood cells (eosinophilia), reduced platelet count (thrombocytopenia);
  • a heart condition called "QT interval prolongation" (seen on electrocardiogram, ECG) (common frequency);
  • dizziness, weakness and fatigue, weight gain or loss, hair loss (alopecia);
  • dry eyes (frequency "not known").

Abrupt discontinuation of long-term treatment may cause:

  • nausea, headache (cephalalgia), malaise.

Adverse effects in children
The following symptoms have been observed in newborns of mothers who took antipsychotics, including Mutabon Anxiolytic, during the last three months of pregnancy: agitation, muscle rigidity and/or weakness, hyperactive reflexes, tremor, motor system disturbances and abnormalities (extrapyramidal symptoms), drowsiness, breathing difficulties, feeding problems, and neonatal withdrawal syndrome.
If your baby shows any of these symptoms, contact your doctor immediately.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, please consult your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Mutabon Ansiolitico

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Exp”.
The expiry date refers to the last day of that month.
The stated expiry date applies to the product in its original, undamaged packaging, stored correctly.
This medicine does not require any special storage temperature conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mutabon Ansiolitico contains

  • The active substances are perphenazine and amitriptyline hydrochloride. Each film-coated tablet contains 4 mg of perphenazine and 10 mg of amitriptyline hydrochloride.
  • The other ingredients are rice starch, lactose, magnesium stearate, povidone, Opadry® orange (Hypromellose E-464, Macrogol, Titanium dioxide E-171, Hydroxypropylcellulose E-463, Erythrosine E-127 aluminium lake, Quinoline Yellow E-104 aluminium lake, Sunset Yellow E-110 aluminium lake).

Description of the appearance of Mutabon Ansiolitico and package contents
Mutabon Ansiolitico is available in packs of 30 film-coated tablets, contained in a blister.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan
Manufacturers
Vamfarma S.r.l.
Via Kennedy, 5
26833 Comazzo (LO)
SPECIAL PRODUCT’S LINE S.P.A.
Via Fratta Rotonda Vado Largo, 1
Anagni (Frosinone) – Italy
Patient Information Leaflet: Information for the patient

Mutabon Antidepressant 2 mg + 25 mg Film-coated Tablets

Perphenazine + Amitriptyline hydrochloride
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, consult your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

  1. What Mutabon Antidepressant is and what it is used for
  2. What you need to know before taking Mutabon Antidepressant
  3. How to take Mutabon Antidepressant
  4. Possible side effects
  5. How to store Mutabon Antidepressant
  6. Package contents and other information

2. What Mutabon Antidepressant is and what it is used for

Mutabon Antidepressant contains two active substances: perfenazine and amitriptyline hydrochloride.
Perfenazine belongs to a group of medicines called phenothiazines which act on the central nervous system, reducing anxiety states (anxiolytic property) and exerting therapeutic effects against psychotic symptoms (delusions and hallucinations).
Amitriptyline hydrochloride belongs to a group of medicines known as "tricyclic antidepressants", used in the treatment of depression.
Therefore, Mutabon Antidepressant is an antidepressant combined with a neuroleptic, used for the treatment of certain mental disorders, which may have genetic causes (endogenous), or may be triggered by an unpleasant life event (reactive disorders), characterized by the coexistence of anxiety, tension, and agitation together with a depressive state.
Mutabon Antidepressant is useful for the treatment of the following disorders:

  • emotional disorders characterized by depression and anxiety that are caused or associated with other diseases;
  • psychosomatic disorders, characterized by physical symptoms induced by mental disorders;
  • depressive symptoms accompanied by a state of tension, even if this is not evident or may be masked;
  • severe insomnia associated with anxiety and depression.

5. What you need to know before taking Mutabon Antidepressive

Do not take Mutabon Antidepressive if:

  • you are allergic to the active substances (perphenazine and amitriptyline hydrochloride) or to other similar medicines, or to any of the other ingredients of this medicine (listed in section 6);
  • you are taking or have taken within the last two weeks medicines for the treatment of depression known as monoamine oxidase inhibitors (MAOIs) (see section “Other medicines and Mutabon Antidepressive”);
  • you have increased pressure inside the eye;
  • you suffer from an eye disease due to increased intraocular pressure (glaucoma);
  • you have diseases affecting the urogenital system such as enlarged prostate (prostatic hypertrophy) or suspected or confirmed difficulty in emptying the bladder (urinary retention);
  • you have a muscle disease characterized by loss of tone and strength (myasthenia gravis);
  • you have a blood disorder characterized by changes in blood composition (blood dyscrasia);
  • you have impaired bone marrow function that fails to produce sufficient numbers of blood cells (bone marrow depression);
  • you suffer from disorders in blood cell production (hematopoietic disturbances); therefore, administration of medicines that may cause a reduction in white blood cells (leukopenic drugs) must be avoided;
  • you have liver disease;
  • you are taking other medicines that reduce the activity of the central nervous system (such as barbiturates, ethyl alcohol, narcotics, analgesics, antihistamines; see section “Other medicines and Mutabon Antidepressive”);
  • you are in a state of reduced level of consciousness (severe obtundation) or coma;
  • you suffer from severe depression;
  • you have suspected or confirmed brain damage (subcortical cerebral damage), as you may experience an increase in body temperature up to over 40°C, sometimes 14 or 16 hours after taking the medicine;
  • you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”);
  • you have recently had a heart attack (myocardial infarction).

Warnings and precautions
Talk to your doctor or pharmacist before taking Mutabon Antidepressive.
Inform your doctor if:

  • you have or have had episodes of epilepsy or seizures (involuntary muscle contractions) or are being treated with medicines used to suppress seizures. Your doctor will assess whether it is necessary to increase the dose of these medicines when taken together with Mutabon Antidepressive;
  • you are taking other medicines with similar action (neuroleptics);
  • you have a tumor of the adrenal glands (pheochromocytoma) or a heart valve disorder (mitral insufficiency). In such cases, you will be monitored more closely during perphenazine administration due to risks related to low blood pressure (hypotension). If you have pheochromocytoma, you may experience high blood pressure after stopping treatment with Mutabon Antidepressive (rebound hypertension);
  • you have a breast tumor. In this case, perphenazine will be administered with particular caution, as it causes an increase in the concentration of a hormone (prolactin) that may worsen your condition;
  • you are scheduled for surgery. Your doctor will advise you whether it is necessary to stop treatment with Mutabon Antidepressive several days before the procedure;
  • you are in the post-operative phase, as aspiration of vomit may occur;
  • you have undergone surgery and are taking high doses of this medicine. In this case, your doctor will monitor you closely due to the risk of low blood pressure (hypotension). Additionally, it may be necessary to reduce the amount of anesthetics or sedatives you are taking;
  • you are generally exposed to extremely high or low temperatures, as perphenazine contained in Mutabon Antidepressive may impair the body's temperature regulation mechanisms;
  • you have severe kidney disease or reduced kidney function;
  • you are predisposed to or already affected by Parkinson’s disease or Parkinson-like conditions, or other motor disorders, as perphenazine may increase muscle rigidity;
  • you have previously had problems with bladder emptying (urinary retention);
  • you have or have had difficulty in stomach emptying (pyloric stenosis) or suffer from intestinal blockage (intestinal obstruction);
  • you have thyroid diseases (hyperthyroidism) or are taking medicines containing thyroid hormones. Your doctor will monitor you closely;
  • you have respiratory diseases caused by lung infections or chronic respiratory disorders such as severe asthma or emphysema;
  • you consume alcohol, as it may enhance the effects of the medicine and significantly lower blood pressure (hypotension). If you abuse alcohol, your risk of suicide or overdose may increase (see section “Mutabon Antidepressive with alcohol”);
  • you are experiencing alcohol withdrawal;
  • you experience sudden onset of sore throat or other signs of infection, as Mutabon Antidepressive may cause disturbances in blood cell production. Your doctor will order blood tests, particularly between the fourth and tenth week of therapy. If tests show a significant decrease in white blood cells, your doctor will instruct you to stop treatment; however, a slight decrease in white blood cells is not in itself an indication to discontinue treatment;
  • you have cognitive impairment (dementia), as treatment with Mutabon Antidepressive may increase the risk of cerebrovascular problems (cerebrovascular events);
  • you suffer from heart and blood vessel diseases (cardiovascular diseases), especially if you are elderly, or have a family history of cardiac conduction abnormalities (QT prolongation), or risk factors for stroke (pathological vascular event in the brain), because antidepressant medicines, when administered at high doses, may cause disturbances in heart rhythm (arrhythmias, sinus tachycardia, and prolonged conduction times) or more serious events such as myocardial infarction and stroke;
  • you have had diseases associated with blood clot formation or have a family history of such diseases;
  • you have hardening, thickening, and loss of elasticity of the arterial wall in the brain (cerebral arteriosclerosis);
  • you suffer from mental disorders such as manic-depressive psychosis (a disorder characterized by cyclical mood changes from excessive excitement to depression), or a personality disorder characterized by a persistent tendency to interpret others' behaviors with distrust and suspicion (paranoid disorder), as tricyclic antidepressants like amitriptyline may exacerbate symptoms of these disorders; however, the calming effect of Mutabon Antidepressive reduces the risk of such effects;
  • you are scheduled for electroconvulsive therapy, as risks associated with this procedure may increase when combined with amitriptyline; in such cases, your doctor will limit the use of Mutabon Antidepressive to cases where treatment is absolutely essential;
  • you are taking medicines containing buprenorphine. Using these medicines together with Mutabon Antidepressive may result in serotonin syndrome, a condition that can be fatal (see “Other medicines and Mutabon Antidepressive”).

Suicide/Thoughts of suicide
Depression is associated with an increased risk of suicidal thoughts, self-harm (intentional physical harm to oneself), and suicide. The risk that you experience such thoughts may increase in the early stages of improvement and persist until you show significant symptom improvement. Since improvement may not occur during the first weeks of treatment or immediately thereafter, you will be closely monitored by your doctor until improvement occurs.
Other mental disorders for which Mutabon Antidepressive is prescribed may also increase the risk of suicidal behavior and a depressive disorder characterized by alternating periods of well-being and depression (major depressive disorder). If you suffer from major depressive disorder, your doctor will follow the same precautions as in treating patients with other psychiatric conditions.
You are more likely to experience suicidal thoughts if:

  • you have previously considered taking your own life;
  • you are a young person under 25 years of age being treated with antidepressants. Your doctor will monitor you closely, especially during the initial stages of treatment, after any dose adjustments, and if you are at high risk of developing suicidal thoughts. Contact your doctor immediately if you experience worsening of symptoms, emergence of suicidal behavior or thoughts, or behavioral changes.

It is possible that during treatment with Mutabon Antidepressive the following may occur:

  • onset of involuntary muscle movements (tardive dyskinesia), especially if you are elderly. Both the risk of developing dyskinesia and the possibility that it becomes irreversible increase with the duration of treatment and total dose taken, although less frequently it may also occur after short treatment periods and at low doses. Discontinuation of treatment may resolve this condition. If you notice the onset of these symptoms, inform your doctor, who will evaluate the possibility of adjusting the dose or stopping treatment;
  • increase or decrease in blood sugar levels;
  • onset of skin sensitivity reactions to light (photosensitivity). Therefore, avoid excessive exposure to sunlight during treatment with Mutabon Antidepressive.

Cases of a heart condition called "QT interval prolongation" (seen on electrocardiogram, ECG) and cardiac rhythm disorders (accelerated or irregular heartbeat) have been reported in connection with the use of Mutabon Antidepressive. Contact your doctor if:

  • you have a slow heart rate,
  • you have or have had a condition in which your heart was unable to pump blood properly through your body (a condition called heart failure),
  • you are taking other medicines that can cause heart problems,
  • you have a condition causing abnormally low levels of potassium or magnesium or abnormally high levels of potassium in the blood.

Stop treatment with Mutabon Antidepressive and inform your doctor if you experience:

  • a significant increase in body temperature not attributable to a specific cause. Such temperature increase may suggest hypersensitivity to perphenazine, and in this case your doctor will instruct you to stop therapy.
  • a potentially fatal group of symptoms known as neuroleptic malignant syndrome, characterized by: elevated body temperature, muscle rigidity, reduced or loss of ability to perform spontaneous movements (akinesia), autonomic disturbances (pulse and blood pressure irregularities, sweating, increased heart rate (tachycardia), cardiac rhythm disturbances (arrhythmias)), altered mental status that may progress to partial loss of consciousness (stupor) and coma. Your doctor will instruct you to stop therapy and initiate treatment for these symptoms.
  • abnormal blood urea values.

During treatment with Mutabon Antidepressive, you will need periodic check-ups to monitor red blood cell counts and liver and kidney function. If abnormalities occur in test results, your doctor will discontinue therapy.
The use of Mutabon Antidepressive may mask signs of overdose of other medicines or make diagnosis of diseases such as intestinal obstruction, Reye's syndrome (an acute illness generally found in patients under 18 years of age, potentially fatal, characterized by symptoms mainly affecting the brain and liver), brain tumors, or other diseases altering brain structure and/or function (encephalopathies) more difficult.

Children and adolescents
The use of Mutabon Antidepressive is not recommended in children under 12 years of age due to lack of data on safety and efficacy.

Other medicines and Mutabon Antidepressive
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not take Mutabon Antidepressive with the following medicines:

  • monoamine oxidase inhibitors (MAOIs). Do not take Mutabon Antidepressive simultaneously or within two weeks after stopping treatment with monoamine oxidase inhibitors, as severe reactions may occur, including marked increase in body temperature (hyperpyretic crisis), seizures, coma, and death (see section “Do not take Mutabon Antidepressive if”). After this period has passed, your doctor will cautiously start treatment with Mutabon Antidepressive, gradually increasing the dose until a satisfactory response is achieved.
  • opioids, barbiturates, or other sedatives, antihistamines, anesthetics, tranquilizers, and meperidine (and other opioid analgesics). Concomitant administration with Mutabon Antidepressive may enhance the central nervous system depressant effects of these medicines, including respiratory depression. Conversely, these medicines may enhance the effects of Mutabon Antidepressive. Therefore, you must not take Mutabon Antidepressive together with these medicines (see section “Do not take Mutabon Antidepressive if”).

Talk to your doctor or pharmacist if you are taking:

  • other psychotropic medicines, medicines with anticholinergic action (inhibition of acetylcholine, a substance acting in the nervous system), or medicines acting on the autonomic nervous system (sympathomimetics), due to the possible occurrence of adverse effects due to their interaction with Mutabon Antidepressive;
  • medicines with anticholinergic action, such as atropine or similar medicines, or antihistamines, as potentiation of effects on the cholinergic system may occur, leading to risk of intestinal blockages (paralytic ileus), blurred vision, and possible alteration of eye pressure in the presence of glaucoma;
  • medicines acting on the autonomic nervous system (sympathomimetic amines) such as epinephrine combined with local anesthetics, as increased activity of these medicines or of Mutabon Antidepressive may occur. Your doctor will closely monitor you and adjust the dose to avoid adverse effects on blood pressure and cardiac function, which may sometimes be fatal;
  • reserpine, methyldopa, other medicines for the treatment of high blood pressure (hypertension) such as guanethidine (concomitant use requires dose adjustment by the doctor), beta-blockers blocking adrenergic receptors such as propranolol or similar medicines, as low blood pressure (hypotension) may occur; therefore, concomitant use of Mutabon Antidepressive and these medicines is not recommended. Your doctor may require you to have blood pressure checked before starting treatment with Mutabon Antidepressive and weekly checks during the first month of treatment;
  • medicines for the treatment of seizures (see section “Warnings and precautions”);
  • phenytoin, a medicine used to treat epilepsy, as Mutabon Antidepressive may alter its effectiveness;
  • antipsychotic medicines;
  • sedative medicines such as diazepam;
  • high doses of ethchlorvynol (a sedative and hypnotic medicine), as transient delirium has been reported with this combination. The combination with Mutabon Antidepressive should be used with caution;
  • medicines for the treatment of stomach hyperacidity containing aluminum salts, as they may reduce the absorption of Mutabon Antidepressive;
  • medicines that prolong the QT interval, as this increases the risk of developing cardiac rhythm disturbances (cardiac arrhythmias);
  • medicines that cause electrolyte imbalances in the blood;
  • medicines containing cimetidine, as they may increase amitriptyline blood concentrations and its related effects, possibly leading to serious adverse effects;
  • medicines that may inhibit cytochrome P450 2D6 (an enzyme in the body involved in drug metabolism), such as quinidine, cimetidine, many other antidepressants, phenothiazines, propafenone, flecainide, and all medicines known as

selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, and
paroxetine, or serotonin-noradrenaline reuptake inhibitors (duloxetine). In such
cases, your doctor may prescribe lower than recommended doses, both for these
medicines and for Mutabon Antidepressive. Your doctor will monitor you closely also when switching from one medicine to another, especially when switching from
fluoxetine to Mutabon Antidepressive.

  • levodopa and phenylbutazone, as Mutabon Antidepressive may interfere with the absorption of these medicines;
  • valproic acid;
  • medicines containing buprenorphine. These medicines may interact with Mutabon Antidepressive and symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movements, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, fever above 38°C may occur. Contact your doctor if you experience such symptoms.

Mutabon Antidepressive may interfere with the absorption of various other drugs.
Inform your doctor if you are exposed to organophosphorus insecticides.

Mutabon Antidepressive and laboratory tests
Taking Mutabon Antidepressive may cause darkening of the urine and alterations in the results of certain laboratory tests:

  • false positives (positive results that are not real) in the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens, and 5-hydroxyindoleacetic acid;
  • alterations in electrocardiogram such as QT interval prolongation;
  • abnormalities in electroencephalogram;
  • alteration (increase) in levels of iodine bound to blood proteins;
  • alterations in hypothalamic-pituitary function tests, as the medicine may cause a decrease in certain hormones;
  • false positives and false negatives in urine pregnancy tests;
  • possible increases and decreases in blood sugar levels.

Mutabon Antidepressive with alcohol
Mutabon Antidepressive must not be taken together with alcohol (ethanol) due to a possible increase in the medicine’s effects, including a reduction in blood pressure (hypotension). In addition, this combination may increase the risk of suicide and the danger of overdose.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Mutabon Antidepressive must not be used during pregnancy, confirmed or suspected, due to the risk of adverse effects in the newborn (see section “Do not take Mutabon Antidepressive if” and section 4 “Adverse effects in children”).
Breastfeeding
You must not use Mutabon Antidepressive if you are breastfeeding (see section “Do not take Mutabon Antidepressive if”), as Mutabon Antidepressive passes into breast milk and may cause adverse effects in the newborn.

Driving and using machines
Mutabon Antidepressive affects the ability to drive vehicles and use machinery, as it may alter reaction time (the interval between perceiving a danger and starting to react to avoid it). Therefore, exercise appropriate caution when driving or operating machinery.

Mutabon Antidepressive contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

6. How to take Mutabon Antidepressant

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The optimal dose of Mutabon Antidepressant must be determined by your doctor, depending on the specific disorder being treated, the duration and severity of the illness, and your response to therapy.
The recommended dose is 1 tablet, taken 3–4 times daily. Several days are generally required before a noticeable effect of Mutabon Antidepressant is achieved.
Please note that the tranquilizing effect appears more rapidly (after 2 or 3 days) than the antidepressant effect (after 1 week or more); therefore, symptoms of tension and anxiety disappear much earlier than depressive symptoms.
If you suffer from persistent insomnia, it is advisable, especially during the first days of treatment, to take 1 or 2 tablets in the evening, half an hour before going to bed; the remaining tablets prescribed by your doctor can be taken during the day.
To achieve full benefit, you must continue treatment for several weeks, as advised by your doctor. Once symptom control has been achieved, your doctor will gradually reduce your dose until establishing the most suitable maintenance dose for you.
Your doctor will periodically assess the need to continue treatment with Mutabon Antidepressant.

Use in children and adolescents
Mutabon Antidepressant is not recommended for children and adolescents under 12 years of age (see section “Children and adolescents”).

Use in the elderly
The dose and frequency of administration of Mutabon Antidepressant in elderly patients must be carefully determined by the doctor, who will consider reducing the above-mentioned dose based on individual needs.

If you take more Mutabon Antidepressant than you should
In case of accidental or intentional overdose of Mutabon Antidepressant, contact your doctor or pharmacist immediately, or go to the nearest hospital.
Signs and symptoms of overdose appear rapidly, so hospital monitoring is required as soon as possible.
Overdose with Mutabon Antidepressant, as with other medicines in the same class, may result in death.
Symptoms of overdose may correspond to any of the adverse effects listed for the two active substances, perphenazine or amitriptyline hydrochloride (see section “Possible side effects”).
Symptoms of perphenazine overdose include motor system abnormalities (extrapyramidal symptoms), such as involuntary muscle movements (dyskinesia) and abnormal muscle contractions (dystonia); however, these may be masked by the anticholinergic effects of amitriptyline. Other symptoms may include partial loss of consciousness (stupor) or coma; children may experience epileptic seizures.
Symptoms of amitriptyline overdose include irregular heartbeat (cardiac arrhythmias), severe drop in blood pressure (severe hypotension), involuntary muscle contractions (convulsions), and reduced activity of the nervous system (central nervous system depression), including coma.
Electrocardiogram (ECG) abnormalities in cardiac conduction have also been reported.
Other overdose symptoms include: confusion, difficulty concentrating, temporary visual hallucinations, dilated pupils, agitation, hyperactive reflexes, drowsiness, muscle rigidity, vomiting, lowered body temperature (hypothermia), fever, or any of the side effects listed.
Overdose of amitriptyline in children may lead to serious consequences. Children are particularly susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low blood sodium levels, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.

Management in case of overdose with Mutabon Antidepressant
There is no specific antidote available to counteract the effects of Mutabon Antidepressant overdose. In case of accidental or intentional overdose, contact your doctor or pharmacist immediately or go to the nearest hospital. Your doctor will initiate appropriate emergency treatment, such as gastric lavage and electrocardiographic monitoring (ECG), and will closely observe you for any signs of central nervous system involvement, breathing difficulties, low blood pressure, abnormal heart rhythm and/or heart conduction block, and epileptic seizures.
Your doctor may decide to contact the local poison control center.

If you forget to take Mutabon Antidepressant
Do not take a double dose to make up for a missed tablet. Continue your treatment as prescribed.

If you stop taking Mutabon Antidepressant
Do not stop taking Mutabon Antidepressant without first consulting your doctor.
Generally, phenothiazines (perphenazine) do not cause psychological dependence. However, sudden discontinuation of high-dose treatment may lead to symptoms such as gastritis, nausea, vomiting, dizziness, tremors, and motor hyperactivity. If you experience such symptoms, consult your doctor, who will prescribe appropriate treatment.
Sudden discontinuation of high-dose tricyclic antidepressants (amitriptyline hydrochloride) may cause symptoms such as: malaise, chills, cold-like symptoms, muscle pain, headache, nausea, vomiting, anxiety, instability, dizziness, and a constant urge to move (akathisia). These symptoms are not indicative of addiction.
If you abruptly stop high-dose treatment with Mutabon Antidepressant, inform your doctor and pay attention to any symptoms you may experience.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

7. Possible side effects

Like all medicines, Mutabon Antidepressive may cause side effects, although not everybody experiences them.
The side effects of Mutabon Antidepressive are the same as those reported for the two active substances (perphenazine and amitriptyline) when taken individually. No side effects specifically due to their combination in Mutabon Antidepressive have been reported.
In very rare cases, patients with hypersensitivity to phenothiazines (perphenazine) have developed excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse, and death.
Occasionally, treatment with phenothiazines may cause intestinal muscle paralysis leading to cessation of intestinal content progression (adynamic ileus), which, if severe, may result in complications and death.
Stop treatment with Mutabon Antidepressive and contact your doctor immediately if you experience:

  • Neuroleptic Malignant Syndrome (NMS), a potentially fatal condition characterized by symptoms such as elevated body temperature, muscle rigidity, reduced movement (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), cardiac rhythm abnormalities (arrhythmias)), altered mental status that may progress to stupor and coma (see “Stop treatment with Mutabon Antidepressive and inform your doctor if you experience” in section 2);
  • persistent abnormalities in muscle contractions and movements, including abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia) (see “Stop treatment with Mutabon Antidepressive and inform your doctor if you experience” in section 2);
  • swelling of the hands, feet, ankles, or face, lips, tongue, and/or throat, causing difficulty in swallowing or breathing (angioedema);
  • increased body temperature (hyperpyrexia);
  • allergic reactions with skin rashes (urticaria), irritation and appearance of red spots on the skin (erythema), itchy inflammatory skin reactions (eczema), skin inflammation with lesion formation and shedding of the superficial layer (exfoliative dermatitis), itching, skin sensitivity to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoid reactions), swelling due to fluid accumulation in the upper airways (laryngeal edema), contact dermatitis, formation of blood clots in veins, especially in the legs (symptoms include leg swelling, pain, and redness), which may travel through blood vessels to the lungs causing chest pain and breathing difficulties (the frequency of this adverse effect cannot be determined based on available data);
  • worsening of depressive state, including, rarely, suicidal thoughts or behavior (see section “Warnings and precautions”).

Side effects related to perphenazine
The most common symptoms reported during treatment with perphenazine, as with all medicines belonging to the same pharmacological class as perphenazine, are disturbances and abnormalities of the motor system (extrapyramidal reactions), such as:

  • abnormal posture characterized by hyperextension of the neck, rigidity, and severe arching of the back (opisthotonus), abnormal contraction of jaw muscles with difficulty opening the mouth (trismus), limited mobility or blockage of the neck accompanied by neck pain and contraction of lateral neck muscles (torticollis), torticollis associated with a deviated head posture and sudden muscle spasms causing abrupt head rotations (spastic torticollis), pain and tingling in limbs, restlessness with excessive motor activity (motor restlessness), eye deviation in one direction (oculogyric crisis), hyper-reflexia characterized by abnormal muscle contractions, movement disorder involving involuntary muscle contractions (dystonia), including abnormalities affecting the tongue (color, pain, protrusion, or rolling), sudden involuntary contractions of masticatory muscles, throat tightness, difficulty in articulating words and swallowing (dysphagia), inability to sit still, a group of symptoms including tremor, muscle rigidity, slowed movement speed, and postural abnormalities (parkinsonism), and loss of muscular coordination (ataxia). The frequency and severity of these symptoms generally increase with increasing doses of Mutabon Antidepressive.

Additionally, the following may occur:

  • abnormalities in the protein composition of cerebrospinal fluid, headache (cephalalgia), drowsiness;
  • worsening of psychotic symptoms such as thought disorders, delusions and hallucinations, motor, emotional and behavioral abnormalities (catatonic-like states), thought patterns detached from reality (paranoid reactions), deep sleep state (lethargy), paradoxical excitement, restlessness and hyperactivity, nocturnal confusion, bizarre dreams, sleep disturbances (insomnia);
  • abnormal milk secretion from the breasts (galactorrhea), breast enlargement in women and men (gynecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), sexual desire disturbances, ejaculation inhibition, false positive pregnancy tests, increased or decreased blood sugar levels (hyperglycemia and hypoglycemia), presence of sugar in urine (glucosuria), excessive release of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH);
  • drop in blood pressure upon standing from sitting or lying down (postural hypotension), increased or decreased heart rate (tachycardia and bradycardia), cardiac arrest, fainting and dizziness;
  • decreased white blood cells (agranulocytosis, leukopenia), increased levels of a specific type of white blood cells (eosinophilia), decreased red blood cells (hemolytic anemia), abnormal destruction of platelets (thrombocytopenic purpura), reduced number of all blood cells (pancytopenia);
  • inflammation and obstruction of bile ducts (biliary stasis);
  • yellowing of the skin and whites of the eyes (jaundice).

Less frequent side effects:

  • sedation, blood disorders (hematological dyscrasia), involuntary muscle contractions (seizures).

Occasionally observed:

  • dry mouth and hypersalivation, nausea, vomiting and diarrhea, gastric retention, anorexia, constipation (stipsis), persistent constipation and formation of a hard mass of dehydrated feces in the intestine (fecaloma), difficulty emptying the bladder (urinary retention), frequent need to urinate and involuntary urine leakage (incontinence), loss of bladder function (bladder paralysis), increased urine output (polyuria);
  • nasal congestion;
  • pallor, increased (mydriasis) or decreased (miosis) pupil size, blurred vision, eye disease characterized by increased intraocular pressure (glaucoma), excessive sweating, increased blood pressure (hypertension), decreased blood pressure (hypotension), altered pulse rate.

Rarely observed:

  • disturbances in cardiac conduction (QT prolongation), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest;
  • swelling of the salivary glands (parotid swelling).

Side effects associated with long-term therapy:

  • liver damage;
  • skin discoloration (cutaneous pigmentation), visual disturbances due to deposition of fine particulate material in the cornea and lens, which in severe cases may lead to star-shaped lens opacities, corneal inflammation (epithelial keratopathies), retinal abnormalities, retinal destruction leading to vision loss (pigmentary retinopathy);
  • persistent abnormalities in muscle contractions and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia), which may occur even after discontinuation of treatment.

Other side effects:

  • fluid accumulation in the lower limbs (peripheral edema), sedative state (epinephrine reversal effect), changes in levels of proteins binding iodine (increased PBI not attributable to increased thyroxine), lupus erythematosus-like syndrome (an inflammatory autoimmune disease affecting multiple organs and tissues), increased appetite and weight gain, abnormally increased food intake (polyphagia), excessive sensitivity to light (photophobia), muscle weakness.

Sudden death has been occasionally reported in patients treated with phenothiazines.
In some patients, the cause of death could not be determined, nor could it be established whether death was attributable to phenothiazine.
In elderly patients with dementia, a slight increase in mortality has been reported in patients taking antipsychotics compared to those not taking them.

Side effects related to amitriptyline hydrochloride
Treatment with antidepressant medicines, including amitriptyline hydrochloride, may trigger the onset of latent schizophrenia, which in some cases may be prevented by the antipsychotic effect of perphenazine contained in Mutabon Antidepressive.
In patients with chronic schizophrenia, epileptic seizures (epileptiform convulsions) have been reported during treatment with amitriptyline hydrochloride.
In addition, amitriptyline hydrochloride may cause, besides some of the side effects listed for perphenazine, the following adverse effects:

  • increased risk of bone fractures;
  • skin rash;
  • pupil abnormalities (accommodation disturbances), difficulty emptying the bladder (urinary retention and urinary tract dilation);
  • awareness of heartbeats (palpitations), heart attack and stroke, heart rhythm disturbances (arrhythmias), disturbances in electrical conduction of the heart that may lead to complete or partial cardiac arrest (cardiac block);
  • confusion, concentration disturbances, disorientation, fixations and hallucinations, excitement, nervousness, anxiety and agitation, insomnia and nightmares, hearing loss, tingling and altered sensation in limbs (paresthesia), dysfunction of the peripheral nervous system (peripheral neuropathy), tremors and seizures, changes in electroencephalogram, hearing disturbances (tinnitus);
  • increased testicle size;
  • gastrointestinal disorders (epigastric discomfort and heartburn), inflammation of the oral cavity (stomatitis), altered taste, dark discoloration of the tongue;
  • rarely, liver inflammation (hepatitis) has occurred;
  • bone marrow suppression (when bone marrow fails to produce sufficient blood cells), decreased white blood cells (agranulocytosis, leukopenia), capillary rupture under the skin (purpura), increased levels of a specific type of white blood cells (eosinophilia), reduced platelet count (thrombocytopenia);
  • a heart condition called "QT interval prolongation" (seen on electrocardiogram, ECG) (common frequency);
  • dizziness, weakness and fatigue, weight gain or loss, hair loss (alopecia);
  • dry eyes (frequency "not known").

Abrupt discontinuation of long-term treatment may cause:

  • nausea, headache (cephalalgia), malaise.

Side effects in children
The following symptoms have been observed in newborns of mothers who took antipsychotics, including Mutabon Antidepressive, during the last three months of pregnancy: agitation, muscle rigidity and/or weakness, hyperactive reflexes, tremor, motor system disturbances and abnormalities (extrapyramidal symptoms), drowsiness, breathing problems, feeding difficulties, and neonatal withdrawal syndrome.
If your baby shows any of these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

7. How to store Mutabon Antidepressant

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp".
The expiry date refers to the last day of that month.
The stated expiry date applies to the product in its original packaging, stored correctly.
This medicine does not require any special storage temperature.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

8. Contents of the pack and other information

What Mutabon Antidepressant contains

  • The active substances are perphenazine and amitriptyline hydrochloride.

Each film-coated tablet contains 2 mg of perphenazine and 25 mg of amitriptyline
hydrochloride.

  • The other components are rice starch, lactose, magnesium stearate, povidone, Opadry pink (hypromellose E-464, polyethylene glycol, titanium dioxide E-171, hydroxypropylcellulose E-463, erythrosine E-127, aluminium lake).

Description of the appearance of Mutabon Antidepressant and pack contents
Mutabon Antidepressant is available in packs of 30 film-coated tablets, contained in a blister.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan
Manufacturers
Vamfarma S.r.l.
Via Kennedy, 5
26833 Comazzo (LO)
SPECIAL PRODUCT’S LINE S.P.A.
Via Fratta Rotonda Vado Largo, 1
Anagni (Frosinone) – Italy
Package leaflet: information for the patient

Mutabon Forte 4 mg + 25 mg film-coated tablets

Perphenazine + Amitriptyline hydrochloride
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

  1. What Mutabon Forte is and what it is used for
  2. What you need to know before taking Mutabon Forte
  3. How to take Mutabon Forte
  4. Possible side effects
  5. How to store Mutabon Forte
  6. Package contents and other information

3. What Mutabon Forte is and what it is used for

Mutabon Forte contains two active substances: perphenazine and amitriptyline hydrochloride.
Perphenazine belongs to a group of medicines called phenothiazines, which act on the central
nervous system, reducing anxiety states (anxiolytic property) and exerting therapeutic effects
on psychotic symptoms (delusions and hallucinations).
Amitriptyline hydrochloride belongs to a group of medicines known as "tricyclic antidepressants",
used in the treatment of depression.
Mutabon Forte is therefore an antidepressant combined with a psycholeptic agent, used for the
treatment of certain mental disorders, which may have genetic causes (endogenous) or may be
triggered by an unpleasant life event (reactive disorders), characterized by the coexistence of
anxiety, tension, and agitation, together with a depressive state.
Mutabon Forte is useful for the treatment of the following disorders:

  • Neurotic disorders and psychosomatic disorders. The latter are physical symptoms caused by mental disorders;
  • Menopausal syndrome (a combination of emotional, physical, and psychological changes attributable to hormonal deficiency);
  • Depression and anxiety associated with other diseases;
  • Intoxication caused by excessive consumption of alcoholic beverages (acute alcoholism) and alcohol dependence (chronic alcoholism);
  • Depressive and manic-depressive syndromes (the latter characterized by cyclical mood changes, alternating between excessive excitement and depression);
  • Schizophrenia, a mental disorder manifesting with various symptoms including hallucinations, delusions, tendency to social withdrawal, and difficulty in organizing thoughts;
  • Psychotic disorders associated with aging (involutional psychoses);
  • Sexual behaviour disorders;
  • Behavioural problems associated with diseases of the central nervous system (mental deficiency);
  • Severe insomnia associated with anxiety and depressive states.

8. What you need to know before taking Mutabon Forte

Do not take Mutabon Forte if:

  • you are allergic to the active substances (perphenazine and amitriptyline hydrochloride), or to other similar medicines, or to any of the other ingredients of this medicine (listed in section 6);
  • you are taking or have taken within the last two weeks medicines for depression known as monoamine oxidase inhibitors (MAOIs) (see section "Other medicines and Mutabon Forte");
  • you have increased pressure inside the eye;
  • you suffer from an eye disease due to increased intraocular pressure (glaucoma);
  • you have urogenital disorders such as prostate enlargement (prostatic hypertrophy) or suspected or confirmed difficulty in bladder emptying (urinary retention);
  • you have a muscle disease characterized by loss of tone and strength (myasthenia gravis);
  • you have a blood disorder characterized by changes in blood composition (blood dyscrasia);
  • you have impaired bone marrow function that fails to produce sufficient blood cells (bone marrow depression);
  • you suffer from disorders in blood cell production (haematopoietic disturbances). The administration of medicines that may cause a reduction in white blood cells (leukopenic drugs) should therefore be avoided;
  • you have liver disease;
  • you are taking other medicines that reduce central nervous system activity (such as barbiturates, ethanol, narcotics, analgesics, antihistamines; see section "Other medicines and Mutabon Forte");
  • you are in a state of reduced consciousness (severe obtundation) or coma;
  • you suffer from severe depression;
  • you have suspected or confirmed brain damage (subcortical brain damage), as you may experience an increase in body temperature up to over 40°C, sometimes 14 or 16 hours after taking the medicine;
  • you are pregnant or breastfeeding (see section "Pregnancy and breastfeeding");
  • you have recently had a heart attack (myocardial infarction).

Warnings and precautions
Talk to your doctor or pharmacist before taking Mutabon Forte.
Inform your doctor if:

  • you have or have had episodes of epilepsy or seizures (involuntary muscle contractions) or are being treated with medicines used to control seizures. Your doctor will assess whether the dose of these medicines needs to be increased when taken together with Mutabon Forte;
  • you are taking other medicines with similar action (neuroleptics);
  • you have a tumour of the adrenal glands (pheochromocytoma) or a dysfunction of the heart's mitral valve (mitral insufficiency). In such cases, you will require closer monitoring during perphenazine administration due to risks related to low blood pressure (hypotension). If you have pheochromocytoma, you may experience high blood pressure after stopping treatment with Mutabon Forte (rebound hypertension);
  • you have a breast tumour. In this case, perphenazine will be administered with particular caution, as it causes an increase in the concentration of a hormone (prolactin) that may worsen your condition;
  • you are scheduled for surgery. Your doctor will advise you whether you need to stop taking Mutabon Forte several days before the procedure;
  • you are in the post-operative phase, as vomiting and aspiration may occur;
  • you have recently undergone surgery and are taking high doses of this medicine. In such cases, your doctor will monitor you closely due to the risk of low blood pressure (hypotension). Additionally, it may be necessary to reduce the amount of anaesthetics or sedatives you are taking;
  • you are generally exposed to extremely high or low temperatures, as perphenazine in Mutabon Forte may impair the body's temperature regulation mechanisms;
  • you have reduced kidney function or severe kidney disease;
  • you are predisposed to or already suffer from Parkinson's disease or Parkinson-like disorders, or other motor disorders, as perphenazine may increase muscle rigidity;
  • you have previously experienced bladder emptying problems (urinary retention);
  • you have or have had difficulty in stomach emptying (pyloric stenosis) or suffer from intestinal blockage (intestinal obstruction);
  • you suffer from thyroid diseases (hyperthyroidism) or are taking thyroid hormone medicines. Your doctor will monitor you closely;
  • you have respiratory diseases caused by lung infections or chronic respiratory disorders such as severe asthma or emphysema;
  • you consume alcohol, as it may enhance the medicine's effects, including a significant drop in blood pressure (hypotension). If you abuse alcohol, your risk of suicide or overdose may increase (see section "Mutabon Forte with alcohol");
  • you are experiencing alcohol withdrawal;
  • you suddenly develop sore throat or other signs of infection, as Mutabon Forte may cause disturbances in blood cell production. Your doctor will perform blood tests, particularly between the fourth and tenth week of treatment. If tests show a significant decrease in white blood cells, your doctor will advise you to stop treatment; a slight decrease in white blood cells is not in itself a reason to discontinue treatment;
  • you have cognitive impairment (dementia), as treatment with Mutabon Forte may increase the risk of cerebrovascular events (cerebrovascular problems);
  • you suffer from heart and blood vessel diseases (cardiovascular diseases), especially if you are elderly, have a family history of heart rhythm conduction abnormalities (QT prolongation), or risk factors for stroke (pathological brain vascular events), because antidepressant medicines, particularly when given at high doses, may cause heart rhythm disturbances (arrhythmias, sinus tachycardia, and conduction delays) or more serious events such as myocardial infarction and stroke;
  • you have had diseases associated with blood clot formation or have a family history of such diseases;
  • you have hardening, thickening, and loss of elasticity of the arterial wall in the brain (cerebral arteriosclerosis);
  • you suffer from mental disorders such as manic-depressive psychosis or a personality disorder characterized by a persistent tendency to interpret others' behaviour with suspicion and distrust (paranoid disorder), as tricyclic antidepressants like amitriptyline may worsen symptoms of these conditions. However, the calming effect of Mutabon Forte reduces the risk of such effects;
  • you are scheduled for electroconvulsive therapy, as risks associated with this procedure may increase when combined with amitriptyline. In such cases, your doctor will limit the use of Mutabon Forte to situations where treatment is absolutely essential;
  • you are taking medicines containing buprenorphine. Using these medicines together with Mutabon Forte may cause serotonin syndrome, a potentially fatal condition (see "Other medicines and Mutabon Forte").

Suicide/ Suicidal thoughts
Depression is associated with an increased risk of suicidal thoughts, self-harm (self-injury), and suicide. The risk of experiencing such thoughts may increase in the early stages of improvement and persist until your symptoms significantly improve. Since improvement may not occur during the first few weeks of treatment or immediately thereafter, you will be closely monitored by your doctor until improvement occurs.
Other mental disorders for which Mutabon Forte is prescribed may also increase the risk of suicidal behaviour and major depressive disorder (a depressive disorder characterized by alternating periods of well-being and depression). If you suffer from major depressive disorder, your doctor will follow the same precautions as in the treatment of patients with other psychiatric disorders.
You are more likely to experience suicidal thoughts if:

  • you have previously considered suicide;
  • you are a young person under 25 years of age being treated with antidepressants. Your doctor will monitor you closely throughout the treatment period, especially during the initial phase and after dose changes, and if you are at high risk of suicidal thoughts. Contact your doctor immediately if you experience worsening symptoms, the onset of suicidal thoughts or behaviour, or behavioural changes.

It is possible that during treatment with Mutabon Forte the following may occur:

  • development of involuntary muscle movements (tardive dyskinesia), especially if you are elderly. The risk of developing dyskinesia and the likelihood that it becomes irreversible increase with the duration of treatment and total amount of medicine taken, although it may less frequently occur after short treatment periods and at low doses. Stopping treatment may lead to partial or complete resolution of this condition. If you notice the onset of these symptoms, inform your doctor, who will assess whether to adjust the dose or discontinue treatment;
  • increased or decreased blood sugar levels;
  • development of skin sensitivity to light (photosensitivity). For this reason, avoid excessive exposure to sunlight during treatment with Mutabon Forte.

Cardiac problems, known as "QT interval prolongation" (seen on electrocardiogram, ECG), and heart rhythm disorders (accelerated or irregular heartbeat) have been reported with the use of Mutabon Forte. Contact your doctor if:

  • you have a slow heart rate,
  • you have or have had a condition in which your heart is unable to pump blood properly through your body (a condition called heart failure),
  • you are taking other medicines that may cause heart problems, or
  • you have a condition causing low levels of potassium or magnesium or high levels of potassium in the blood.

Stop taking Mutabon Forte and inform your doctor if you experience:

  • a significant increase in body temperature not attributable to a specific cause. This temperature rise may suggest hypersensitivity to perphenazine, and your doctor will advise you to stop treatment;
  • a potentially fatal group of symptoms known as neuroleptic malignant syndrome, characterized by: increased body temperature, muscle rigidity, reduced or loss of ability to perform spontaneous movements (akinesia), autonomic disturbances (pulse and blood pressure irregularities, sweating, increased heart rate (tachycardia), heart rhythm disturbances (arrhythmias)), and altered mental status, which may progress to partial loss of consciousness (stupor) and coma. Your doctor will instruct you to stop treatment and initiate therapy to manage these symptoms;
  • abnormal blood urea levels.

During treatment with Mutabon Forte, you will need to undergo periodic tests to monitor red blood cell levels and liver and kidney function. If abnormalities occur, your doctor will discontinue treatment.
Taking Mutabon Forte may mask signs of overdose from other medicines or make it more difficult to diagnose conditions such as intestinal obstruction, Reye's syndrome (an acute illness generally seen in patients under 18 years of age, potentially fatal, characterized by symptoms primarily affecting the brain and liver), brain tumours, or other diseases that alter the structure and/or function of the brain (encephalopathies).
Children and adolescents
The use of Mutabon Forte is not recommended in children under 12 years of age due to lack of safety and efficacy data.
Other medicines and Mutabon Forte
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not take Mutabon Forte with the following medicines:

  • monoamine oxidase inhibitors (MAOIs). Do not take Mutabon Forte simultaneously or within two weeks after stopping treatment with monoamine oxidase inhibitors, as this may cause severe reactions, including high fever (hyperpyrexic crisis), seizures, coma, and death (see section "Do not take Mutabon Forte if").
    After this period has passed, your doctor will cautiously start treatment with Mutabon Forte, gradually increasing the dose until a satisfactory response is achieved.

  • opioids, barbiturates, or other sedatives, antihistamines, anaesthetics, tranquillisers, and meperidine (and other opioid analgesics). Concomitant administration with Mutabon Forte may enhance the central nervous system depressant effects of these medicines, including respiratory depression. Conversely, these medicines may enhance the effects of Mutabon Forte. Therefore, you must not take Mutabon Forte together with these medicines (see section "Do not take Mutabon Forte if").

Talk to your doctor or pharmacist if you are taking:

  • medicines that may reduce white blood cell count (leukopenic drugs), as Mutabon Forte may cause disturbances in blood cell production (see section "Do not take Mutabon Forte if" and "Warnings and precautions");
  • other psychotropic medicines, medicines with anticholinergic action (inhibition of acetylcholine, a substance acting on the nervous system), or medicines acting on the autonomic nervous system (sympathomimetics), due to the possible occurrence of adverse effects from their interaction with Mutabon Forte;
  • medicines with anticholinergic action, such as atropine, or antihistamines, as this may enhance effects on the cholinergic system, increasing the risk of intestinal blockages (paralytic ileus), blurred vision, and possible changes in eye pressure in the presence of glaucoma;
  • medicines acting on the autonomic nervous system (sympathomimetic amines) such as epinephrine combined with local anaesthetics, as this may increase the activity of these medicines or of Mutabon Forte. Your doctor will closely monitor you and adjust the dose to avoid adverse effects on blood pressure and heart function, which may sometimes be fatal;
  • reserpine, methyldopa, other medicines for high blood pressure (hypertension) such as guanethidine (concomitant use requires dose adjustment by the doctor), beta-blockers that block adrenergic receptors such as propranolol or similar medicines, as this may cause low blood pressure (hypotension). Concomitant use of Mutabon Forte and these medicines is therefore not recommended. Your doctor may require you to have your blood pressure checked before starting treatment with Mutabon Forte and weekly checks during the first month of treatment;
  • medicines for seizures (see section "Warnings and precautions");
  • phenytoin, a medicine used to treat epilepsy, as Mutabon Forte may alter its effectiveness;
  • antipsychotic medicines;
  • sedative medicines such as diazepam;
  • high doses of ethchlorvynol (a sedative and hypnotic medicine), as transient delirium has been reported with this combination. The combination with Mutabon Forte should be used with caution;
  • medicines for stomach hyperacidity containing aluminium salts, as they may reduce the absorption of Mutabon Forte;
  • medicines that prolong the QT interval, as this increases the risk of heart rhythm disturbances (cardiac arrhythmias);
  • medicines that cause electrolyte imbalances in the blood;
  • medicines containing cimetidine, as this may increase amitriptyline blood concentrations and its effects, possibly leading to severe adverse effects;
  • medicines that inhibit cytochrome P450 2D6 (an enzyme in the body involved in drug metabolism), such as quinidine, cimetidine, many other antidepressants, phenothiazines, propafenone and flecainide, and all medicines known as selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline and paroxetine, and serotonin-noradrenaline reuptake inhibitors (duloxetine). In such cases, your doctor may prescribe lower doses than recommended, both for these medicines and for Mutabon Forte. Your doctor will monitor you closely when switching from one medicine to another, especially when switching from fluoxetine to Mutabon Forte;
  • levodopa and phenylbutazone, as taking Mutabon Forte may interfere with the absorption of these medicines and lead to their inactivation;
  • valproic acid;
  • medicines containing buprenorphine. These medicines may interact with Mutabon Forte and may cause symptoms such as involuntary and rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, and fever above 38°C. Contact your doctor if you experience these symptoms.

Mutabon Forte may interfere with the absorption of various other medicines.
Inform your doctor if you are exposed to organophosphorus insecticides.
Mutabon Forte and laboratory tests
Taking Mutabon Forte may darken the urine and cause changes in the results of certain laboratory tests:

  • false positives (non-real positive results) in the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens, and 5-hydroxy-indoleacetic acid;
  • changes in electrocardiogram such as QT interval prolongation;
  • abnormalities in electroencephalogram;
  • alteration (increase) in levels of iodine bound to blood proteins;
  • changes in hypothalamic-pituitary function tests, as the medicine may cause a decrease in levels of certain hormones;
  • false positives and false negatives in urine pregnancy tests;
  • possible increases and decreases in blood sugar levels.

Mutabon Forte with alcohol
Mutabon Forte must not be taken together with alcohol (ethanol) due to a possible increase in the medicine's effects, including a reduction in blood pressure (hypotension). In addition, this combination may increase the risk of suicide and the danger of overdose.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Mutabon Forte must not be used during confirmed or suspected pregnancy due to the risk of adverse effects in the newborn (see section "Do not take Mutabon Forte if" and section 4 "Undesirable effects in children").
Breastfeeding
You must not use Mutabon Forte if you are breastfeeding (see section "Do not take Mutabon Forte if"), as Mutabon Forte passes into breast milk and may cause adverse effects in the newborn.
Driving and using machines
Mutabon Forte affects your ability to drive vehicles and operate machinery, as it may alter your reaction time (the interval between perceiving a danger and starting to react to avoid it). Therefore, exercise appropriate caution when driving or operating machinery.
Mutabon Forte contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Mutabon Forte contains the colouring Sunset Yellow (E-110), which may cause allergic reactions.

9. How to take Mutabon Forte

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The optimal dose of Mutabon Forte must be determined by your doctor, depending on the specific
condition being treated, the duration and severity of the illness, and your response to therapy.
The recommended dose is 1 tablet, 3–4 times daily. It generally takes several days to achieve a
noticeable effect from Mutabon Forte.
Please note that the tranquilizing effect appears more rapidly (after 2 or 3 days) than the antidepressant
effect (1 week or longer); therefore, symptoms of tension and anxiety disappear much earlier than
depressive symptoms.
If you suffer from severe restlessness and psychomotor agitation or persistent insomnia, it is
advisable to take 1 or 2 tablets in the evening, half an hour before going to bed; the remaining
tablets prescribed by your doctor can be taken during the course of the day.
To achieve full benefit, you must continue treatment for several weeks, as advised by your doctor.
Once symptoms are under control, your doctor will gradually reduce your dose until establishing the
most suitable maintenance dose for you.
Your doctor will periodically assess whether you still require treatment with Mutabon Forte or with
other medications at different dosages.

Use in children and adolescents
Mutabon Forte is not recommended for children under 12 years of age (see section “Children and
adolescents”).

Use in the elderly
The dose and frequency of administration of Mutabon Forte in elderly patients must be carefully
determined by the doctor, who will consider reducing the above-mentioned dose according to
individual needs.

If you take more Mutabon Forte than you should
In case of accidental or intentional overdose of Mutabon Forte, contact your doctor or pharmacist
immediately, or go to the nearest hospital.
Symptoms of overdose appear rapidly, so hospital monitoring is required as soon as possible.
Overdose with Mutabon Forte, as with other medicines in the same class, may result in death.
Symptoms of overdose may correspond to any of the adverse effects listed for the two active
substances, perphenazine or amitriptyline hydrochloride (see section “Possible side effects”).

Symptoms of perphenazine overdose include motor system abnormalities (extrapyramidal symptoms),
such as involuntary muscle movements (dyskinesia) and abnormal muscle contractions (dystonia);
however, these may be masked by the anticholinergic effects of amitriptyline. Other symptoms may
include partial loss of consciousness (stupor) or coma; children may experience epileptic seizures.

Symptoms of amitriptyline overdose include irregular heartbeat (cardiac arrhythmias), severe drop in
blood pressure (severe hypotension), involuntary muscle contractions (convulsions), and reduced
activity of the nervous system (central nervous system depression), including coma.
Abnormalities in cardiac conduction detectable on electrocardiogram (ECG) have also been reported.

Other symptoms of overdose include: confusion, difficulty concentrating, temporary visual
hallucinations, dilated pupils, agitation, hyperactive reflexes, drowsiness, muscle rigidity, vomiting,
decreased body temperature (hypothermia), fever, or any of the symptoms listed among the
adverse effects.

Overdose with amitriptyline in children may lead to serious consequences. Children are particularly
susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low blood sodium
levels, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.

Treatment in case of overdose with Mutabon Forte
There is no specific antidote to counteract the effects of Mutabon Forte overdose. In case of
accidental or intentional overdose, contact your doctor or pharmacist immediately, or go to the
nearest hospital. Your doctor will initiate appropriate emergency measures, such as gastric lavage
and electrocardiographic (ECG) monitoring, and will closely observe you for any signs of central
nervous system involvement, breathing difficulties, low blood pressure, abnormal heart rhythm
and/or heart conduction block, and epileptic seizures.
Your doctor may decide to contact the local poison control center.

If you forget to take Mutabon Forte
Do not take a double dose to make up for a missed tablet. Continue your treatment as prescribed.

If you stop taking Mutabon Forte
Do not stop taking Mutabon Forte without first consulting your doctor.
Phenothiazines (perphenazine) generally do not cause psychological dependence. However,
sudden discontinuation of high-dose treatment may lead to gastritis, nausea, vomiting, dizziness,
tremors, and motor hyperactivity. If you experience any of these symptoms, consult your doctor, who
will prescribe appropriate treatment.

Sudden discontinuation of high-dose tricyclic antidepressant therapy (amitriptyline hydrochloride)
may cause symptoms such as: malaise, chills, cold-like symptoms, muscle pain, headache, nausea,
vomiting, anxiety, instability, dizziness, and a constant urge to move (akathisia). These symptoms are
not indicative of addiction.

If high-dose treatment with Mutabon Forte is suddenly stopped, inform your doctor and pay attention
to any symptoms you may experience.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

10. Possible side effects

Like all medicines, Mutabon Forte can cause side effects, although not everyone experiences them.
The side effects of Mutabon Forte are the same as those associated with the two active substances (perphenazine and amitriptyline) when taken individually. No side effects specifically due to their combination in Mutabon Forte have been reported.
In very rare cases, patients with hypersensitivity to phenothiazines (perphenazine) have developed excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse, and death.
Occasionally, treatment with phenothiazines may cause paralysis of intestinal muscles leading to cessation of intestinal content progression (adynamic ileus), which, if severe, may result in complications and death.
Stop treatment with Mutabon Forte and contact your doctor immediately if you experience:

  • Neuroleptic Malignant Syndrome (NMS), a potentially fatal condition characterized by symptoms such as elevated body temperature, muscle rigidity, reduced movement (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), cardiac rhythm disturbances (arrhythmias)), and altered mental status that may progress to stupor and coma (see "Stop taking Mutabon Forte and inform your doctor if" in section 2);
  • persistent abnormalities in muscle contractions and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia) (see "Stop taking Mutabon Forte and inform your doctor if" in section 2);
  • swelling of the hands, feet, ankles, or face, lips, tongue, and/or throat, causing difficulty in swallowing or breathing (angioedema);
  • markedly increased body temperature (hyperpyrexia);
  • allergic reactions with skin rashes (urticaria), irritation and appearance of red spots on the skin (erythema), itchy inflammatory skin reactions (eczema), skin inflammation with lesion formation and loss of the superficial skin layer (exfoliative dermatitis), itching, skin sensitivity to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoid), swelling due to fluid accumulation in the upper airways (laryngeal edema), contact dermatitis;
  • formation of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the legs), which may travel through blood vessels to the lungs, causing chest pain and difficulty breathing (the frequency of this side effect cannot be determined from available data);
  • worsening of depressive state, including, rarely, suicidal thoughts or behavior (see section “Warnings and precautions”).

Side effects related to perphenazine
The most common symptoms reported during treatment with perphenazine, as with all medicines belonging to the same pharmacological class as perphenazine, are disturbances and abnormalities of the motor system (extrapyramidal reactions), such as:

  • abnormal posture characterized by hyperextension of the neck, rigidity, and severe arching of the back (opisthotonos), abnormal contraction of jaw muscles with difficulty opening the mouth (trismus), limited mobility or blockage of the neck accompanied by cervical pain and contraction of lateral neck muscles (torticollis), torticollis associated with a deviated head posture and sudden muscle spasms causing abrupt head rotations (spastic torticollis), pain and tingling in limbs, restlessness with excessive motor activity (motor restlessness), eye deviation in one direction (oculogyric crisis), hyper-reflexia characterized by abnormal muscle contractions, movement disorder involving involuntary muscle contractions (dystonia), including tongue abnormalities (color changes, pain, protrusion or rolling), sudden involuntary contractions of masticatory muscles, sensation of throat tightness, difficulty in speaking and swallowing (dysphagia), inability to sit still, a group of symptoms including tremor, muscle rigidity, slowed movement execution, and postural abnormalities (parkinsonism), and loss of muscle coordination (ataxia).
    The frequency and severity of these symptoms generally increase with higher doses of Mutabon Forte.
    Additionally, the following may occur:

  • abnormalities in the protein composition of cerebrospinal fluid, headache (cephalalgia), drowsiness;

  • worsening of psychotic symptoms such as thought disturbances, delusions and hallucinations, motor, emotional and behavioral abnormalities (catatonic-like states), thought patterns detached from reality (paranoid reactions), deep sleep state (lethargy), excitement, restlessness and hyperactivity, nocturnal confusion, bizarre dreams, sleep disturbances (insomnia);

  • abnormal milk secretion from breasts (galactorrhea), breast enlargement in women and men (gynecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), altered sexual desire, ejaculation inhibition, false positive pregnancy tests, increased and decreased blood sugar levels (hyperglycemia and hypoglycemia), presence of sugar in urine (glycosuria), excessive release of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH);

  • drop in blood pressure upon standing from sitting or lying down (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, fainting and dizziness;

  • decreased white blood cells (agranulocytosis, leukopenia), increased levels of a specific type of white blood cells (eosinophilia), reduced number of red blood cells (hemolytic anemia), abnormal destruction of platelets (thrombocytopenic purpura), reduced number of all blood cells (pancytopenia);

  • inflammation and obstruction of bile ducts (biliary stasis),

  • yellowing of the skin and whites of the eyes (jaundice).

Less frequent side effects:

  • sedation, blood disorders (hematologic dyscrasia), involuntary muscle contractions (convulsions).

Occasionally observed:

  • dry mouth and hypersalivation, nausea, vomiting and diarrhea, gastric retention, anorexia, constipation (stipsis), persistent constipation and formation of hard masses of dehydrated feces in the intestine (fecaloma), difficulty emptying the bladder (urinary retention), frequent need to urinate and involuntary urine leakage (incontinence), loss of bladder function (bladder paralysis), increased urine output (polyuria);
  • nasal congestion;
  • pallor, increased (mydriasis) and decreased (miosis) pupil size, blurred vision, eye disease characterized by increased pressure inside the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), decreased blood pressure (hypotension), altered pulse rate,
  • rarely observed: disturbances in cardiac electrical conduction (QT prolongation), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest;
  • swelling of the salivary glands (parotid swelling).

Side effects associated with long-term therapy:

  • liver damage;
  • appearance of skin spots (cutaneous pigmentation), visual disturbances due to deposition of fine particulate matter in the cornea and lens, which in severe cases may lead to star-shaped lens opacities, corneal inflammation (epithelial keratopathies), retinal changes, retinal destruction leading to vision loss (pigmentary retinopathy);
  • persistent abnormalities in muscle contractions and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia), which may also appear after treatment discontinuation.

Other side effects:

  • fluid accumulation in the lower limbs (peripheral edema), sedation state (epinephrine reversal effect), altered levels of proteins binding iodine (increased PBI not attributable to increased thyroxine), lupus erythematosus-like syndrome (an inflammatory autoimmune disease affecting multiple organs and tissues), increased appetite and weight gain, abnormal increase in food consumption (polyphagia), excessive sensitivity to light (photophobia), muscle weakness.

Sudden death has been occasionally reported in patients treated with phenothiazines.
In some patients, the cause of death could not be determined, nor could it be established whether death was attributable to phenothiazine.
In elderly patients with dementia, a slight increase in mortality has been reported in patients taking antipsychotics compared to those who did not.

Side effects related to amitriptyline hydrochloride
Treatment with antidepressant medicines, including amitriptyline hydrochloride, may trigger the onset of latent schizophrenia, which may be prevented in some cases by the antipsychotic effect of perphenazine contained in Mutabon Forte.
In patients with chronic schizophrenia, epileptic seizures (epileptiform convulsions) have been reported during treatment with amitriptyline hydrochloride.
In addition, amitriptyline hydrochloride may cause, besides some of the side effects reported for perphenazine, the following adverse effects:

  • increased risk of bone fractures;
  • skin rash;
  • pupil abnormalities (accommodation disturbances),
  • difficulty emptying the bladder (urinary retention and urinary tract dilation);
  • awareness of heartbeat (palpitations), heart attack and stroke, heart rhythm disturbances (arrhythmias), disturbances in conduction of electrical impulses in the heart that may lead to complete or partial heart block;
  • confusion, concentration disturbances, disorientation, fixations and hallucinations, excitement, nervousness, anxiety and agitation, insomnia and nightmares, hearing loss, tingling and altered perception of stimuli in limbs (paresthesia), dysfunction of the peripheral nervous system (peripheral neuropathy), tremors and convulsions, changes in electroencephalogram, hearing disturbances (tinnitus);
  • increased testicle size;
  • gastrointestinal disorders (epigastric discomfort and heartburn), inflammation of the oral cavity (stomatitis), altered taste, dark discoloration of the tongue;
  • rarely, liver inflammation (hepatitis) has occurred;
  • bone marrow suppression (when the bone marrow fails to produce sufficient blood cells), decreased white blood cells (agranulocytosis, leukopenia), capillary rupture under the skin surface (purpura), increased levels of a specific type of white blood cells (eosinophilia), reduced platelet count (thrombocytopenia);
  • a heart condition called "QT interval prolongation" (seen on electrocardiogram, ECG) (common frequency);
  • dizziness, weakness and fatigue, weight gain or loss, hair loss (alopecia);
  • dry eyes (frequency “not known”).

Abrupt discontinuation of long-term treatment may cause:

  • nausea, headache (cephalalgia), malaise.

Side effects in children
The following symptoms have been observed in newborns of mothers who took antipsychotics, including Mutabon Forte, during the last three months of pregnancy: agitation, muscle rigidity and/or weakness, hyperactive reflexes, tremor, motor system disturbances and abnormalities (extrapyramidal symptoms), drowsiness, breathing problems, feeding difficulties, and neonatal withdrawal syndrome.
If your baby shows any of these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you help provide more information on the safety of this medicine.

9. How to store Mutabon Forte

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp".
The expiry date refers to the last day of that month.
The expiry date indicated refers to the product in its original, undamaged packaging,
properly stored.
This medicine does not require any special storage temperature.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how
to dispose of medicines no longer used. This will help protect the environment.

10. Package contents and other information

What Mutabon Forte contains

  • The active substances are perphenazine and amitriptyline hydrochloride. Each film-coated tablet contains 4 mg of perphenazine and 25 mg of amitriptyline hydrochloride.
  • The other components are rice starch, lactose, magnesium stearate, povidone, Opadry® red (Hypromellose E-464, Macrogol, Titanium dioxide E-171, Hydroxypropylcellulose E-463, Erythrosine E-127 aluminium lake, Sunset Yellow E-110 aluminium lake).

Description of the appearance of Mutabon Forte and contents of the pack
Mutabon Forte is available in packs of 30 film-coated tablets, contained in a blister.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milano
Manufacturers
Vamfarma S.r.l.
Via Kennedy, 5
26833 Comazzo (LO)
SPECIAL PRODUCT’S LINE S.P.A.
Via Fratta Rotonda Vado Largo, 1
Anagni (Frosinone) – Italy

Patient Information Leaflet
Mutabon Mite 2 mg + 10 mg film-coated tablets
Perphenazine + Amitriptyline hydrochloride

Please read this leaflet carefully before taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
  • If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

  1. What Mutabon Mite is and what it is used for
  2. What you need to know before taking Mutabon Mite
  3. How to take Mutabon Mite
  4. Possible side effects
  5. How to store Mutabon Mite
  6. Contents of the pack and other information

4. What Mutabon Mite is and what it is used for

Mutabon Mite contains two active substances: perphenazine and amitriptyline hydrochloride.
Perphenazine belongs to a group of medicines called phenothiazines, which act on the central
nervous system, reducing anxiety states (anxiolytic property) and exerting therapeutic effects
on psychotic symptoms (delusions and hallucinations).
Amitriptyline hydrochloride belongs to a group of medicines known as "tricyclic antidepressants",
used in the treatment of depression.
Mutabon Mite is therefore an antidepressant combined with a neuroleptic, used for the
treatment of certain mental disorders, which may have genetic causes (endogenous) or may be
triggered by an unpleasant life event (reactive-type disorders), in which simple anxiety is
associated with relatively mild or limited depressive symptoms.
Due to the low content of its active substances, Mutabon Mite allows dosage adjustment according
to the individual needs of the patient, minimizing the doses used. For this reason, Mutabon Mite
can also be used in maintenance therapy.
Mutabon Mite is also effective in cases of severe insomnia associated with anxiety and depression.

11. What you need to know before taking Mutabon Mite

Do not take Mutabon Mite if:

  • you are allergic to the active substances (perphenazine and amitriptyline hydrochloride) or to other similar medicines, or to any of the other ingredients of this medicine (listed in section 6);
  • you are taking or have taken within the last two weeks medicines for depression known as monoamine oxidase inhibitors (MAOIs) (see section "Other medicines and Mutabon Mite");
  • you have increased pressure inside the eye;
  • you suffer from an eye disease due to increased intraocular pressure (glaucoma);
  • you have urogenital system disorders such as enlarged prostate (prostatic hypertrophy) or suspected or confirmed difficulty in emptying the bladder (urinary retention);
  • you have a muscle disease characterized by loss of tone and strength (myasthenia gravis);
  • you have a blood disorder characterized by changes in blood composition (blood dyscrasia);
  • you have impaired bone marrow function that fails to produce enough blood cells (bone marrow depression);
  • you suffer from disorders in blood cell production (haematopoietic disturbances). The administration of medicines that may cause a reduction in white blood cells (leukopenic drugs) must therefore be avoided;
  • you have liver disease;
  • you are taking other medicines that reduce the activity of the central nervous system (such as barbiturates, ethyl alcohol, narcotics, analgesics, antihistamines; see section "Other medicines and Mutabon Mite");
  • you are in a state of reduced level of consciousness (severe obtundation) or in coma;
  • you suffer from severe depression;
  • you have suspected or confirmed brain damage (subcortical cerebral damage), as you may develop an increase in body temperature up to over 40°C, sometimes after 14 or 16 hours after taking the medicine;
  • you are pregnant or breastfeeding (see section "Pregnancy and breastfeeding");
  • you have recently had a heart attack (myocardial infarction).

Warnings and precautions
Talk to your doctor or pharmacist before taking Mutabon Mite.
Inform your doctor if:

  • you have or have had episodes of epilepsy or seizures (involuntary muscle contractions) or are being treated with medicines used to control seizures. Your doctor will assess whether it is necessary to increase the dose of these medicines when taken together with Mutabon Mite;
  • you are taking other medicines with similar action (neuroleptics);
  • you have a tumour of the adrenal glands (pheochromocytoma) or a dysfunction of the mitral valve of the heart (mitral insufficiency). In such cases, you will require closer monitoring during perphenazine treatment due to associated risks of low blood pressure (hypotension). If you have pheochromocytoma, you may experience high blood pressure after stopping treatment with Mutabon Mite (rebound hypertension);
  • you have a tumour of the breast. In this case, perphenazine will be administered with particular caution, as it causes an increase in the concentration of a hormone (prolactin) that may worsen your condition;
  • you need to undergo surgery. Your doctor will advise you whether it is necessary to stop treatment with Mutabon Mite several days before the procedure;
  • you are in the post-operative phase, as vomiting and aspiration may occur;
  • you have recently undergone surgery and are taking high doses of this medicine. In this case, your doctor will closely monitor you due to the risk of low blood pressure (hypotension). Additionally, it may be necessary to reduce the amount of anaesthetics or sedatives you are taking;
  • you are generally exposed to extremely high or low temperatures, as perphenazine contained in Mutabon Mite may impair the body's temperature regulation mechanisms;
  • you have reduced kidney function or severe kidney disease;
  • you are predisposed to or already affected by Parkinson's disease or Parkinson-like conditions, or other motor disorders, as perphenazine may increase muscle rigidity;
  • you have previously experienced difficulty in emptying the bladder (urinary retention);
  • you have or have had difficulty in stomach emptying (pyloric stenosis) or suffer from intestinal blockage (intestinal obstruction);
  • you suffer from thyroid diseases (hyperthyroidism) or are taking medicines containing thyroid hormones. Your doctor will keep you under close surveillance;
  • you have respiratory disorders caused by lung infections or chronic respiratory conditions such as severe asthma or emphysema;
  • you consume alcohol, as it may enhance the effects of the medicine, including a significant drop in blood pressure (hypotension). If you abuse alcohol, your risk of suicide or overdose may increase (see section "Mutabon Mite with alcohol");
  • you are experiencing alcohol withdrawal;
  • you suddenly develop sore throat or other signs of infection, as Mutabon Mite may cause disturbances in blood cell production. Your doctor will perform blood tests, particularly between the 4th and 10th week of therapy. If tests show a significant decrease in white blood cells, your doctor will instruct you to stop treatment; a slight decrease in white blood cells is not in itself an indication to discontinue treatment;
  • you have cognitive impairment (dementia), as treatment with Mutabon Mite may increase the risk of cerebrovascular events (cerebrovascular problems);
  • you suffer from heart and blood vessel diseases (cardiovascular diseases), especially if you are elderly, have a family history of heart rhythm conduction abnormalities (QT prolongation), or have risk factors for stroke (pathological vascular events in the brain), because antidepressant medicines, particularly when administered at high doses, may cause heart rhythm disturbances (arrhythmias, sinus tachycardia and prolonged conduction times) or more serious events such as myocardial infarction and stroke;
  • you have had diseases associated with blood clot formation or have a family history of such diseases;
  • you have hardening, thickening, and loss of elasticity of the arterial wall in the brain (cerebral arteriosclerosis);
  • you suffer from mental disorders such as manic-depressive psychosis or a personality disorder characterized by a persistent tendency to interpret others' behaviour with suspicion and distrust (paranoid disorder), as tricyclic antidepressants like amitriptyline may exacerbate symptoms of these conditions. However, the calming effect of Mutabon Mite reduces the risk of such effects;
  • you are scheduled for electroconvulsive therapy, as concomitant use with amitriptyline may increase risks associated with this procedure; in such cases, your doctor will limit the use of Mutabon Mite to only essential cases;
  • you are taking medicines containing buprenorphine. Using these medicines together with Mutabon Mite may lead to serotonin syndrome, a potentially fatal condition (see "Other medicines and Mutabon Mite").

Suicide/Suicidal thoughts
Depression is associated with an increased risk of suicidal thoughts, self-harm (self-injury), and suicide. The risk of experiencing such thoughts may increase in the early stages of improvement and persist until your symptoms significantly improve. Since improvement may not occur during the first few weeks of treatment or immediately thereafter, you will be closely monitored by your doctor until improvement occurs.
Other mental disorders for which Mutabon Mite is prescribed may also increase the risk of suicidal behaviour and major depressive disorder (a depressive disorder characterized by alternating periods of well-being and depressive phases). If you suffer from major depressive disorder, your doctor will follow the same precautions as for patients with other psychiatric conditions.
You are more likely to experience suicidal thoughts if:

  • you have previously considered suicide;
  • you are a young person under 25 years of age being treated with antidepressants. Your doctor will closely monitor you throughout the treatment period, especially during the initial phase and after dose changes, particularly if you are at high risk of suicidal thoughts. Contact your doctor immediately if you experience worsening of symptoms, emergence of suicidal thoughts or behaviour, or behavioural changes.

It is possible that during treatment with Mutabon Mite the following may occur:

  • development of involuntary muscle movements (tardive dyskinesia), especially if you are elderly. Both the risk of developing dyskinesia and the possibility that it becomes irreversible increase with the duration of treatment and total amount of medicine taken, although it may less frequently occur after short treatment periods and at low doses. Discontinuation of treatment may resolve this condition.
    If you notice the onset of these symptoms, inform your doctor, who will evaluate whether to adjust the dose or discontinue treatment;

  • increased or decreased blood sugar levels;

  • development of skin sensitivity to light (photosensitivity). Therefore, avoid excessive exposure to sunlight during treatment with Mutabon Mite.

Cardiac problems, known as "QT interval prolongation" (seen on electrocardiogram, ECG) and heart rhythm disorders (accelerated or irregular heartbeat), have been reported in connection with the use of Mutabon Mite. Contact your doctor if:

  • you have a slow heart rate,
  • you have or have had a condition in which your heart is unable to pump blood properly through your body (a condition called heart failure),
  • you are taking other medicines that may cause heart problems, or
  • you have a condition causing abnormally low levels of potassium or magnesium or abnormally high levels of potassium in the blood.

Stop taking Mutabon Mite and contact your doctor immediately if you experience:

  • a significant increase in body temperature not attributable to a specific cause. This temperature rise may suggest hypersensitivity to perphenazine, and your doctor will instruct you to stop treatment;
  • a potentially fatal group of symptoms known as neuroleptic malignant syndrome, characterized by: increased body temperature, muscle rigidity, reduced or loss of ability to perform spontaneous movements (akinesia), autonomic disturbances (pulse and blood pressure irregularities, sweating, increased heart rate (tachycardia), heart rhythm disturbances (arrhythmias)), and altered mental status that may progress to partial loss of consciousness (stupor) and coma. Your doctor will instruct you to stop treatment and initiate therapy to manage these symptoms;
  • abnormal blood urea levels.

During treatment with Mutabon Mite, you will need periodic check-ups to monitor red blood cell counts and liver and kidney function. If abnormalities occur, your doctor will discontinue treatment.
Taking Mutabon Mite may mask signs of overdose of other medicines or make diagnosis of conditions such as intestinal obstruction, Reye's syndrome (an acute illness generally seen in patients under 18 years of age, potentially fatal, characterized by symptoms mainly affecting the brain and liver), brain tumours, or other diseases altering brain structure and/or function (encephalopathies) more difficult.

Children and adolescents
The use of Mutabon Mite is not recommended in children under 12 years of age due to lack of safety and efficacy data.

Other medicines and Mutabon Mite
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not take Mutabon Mite together with the following medicines:

  • monoamine oxidase inhibitors (MAOIs). Do not take Mutabon Mite simultaneously or within two weeks after stopping treatment with monoamine oxidase inhibitors, as serious reactions may occur, including a marked increase in body temperature (hyperpyretic crisis), seizures, coma, and death (see section "Do not take Mutabon Mite if"). After this period has passed, your doctor will cautiously start treatment with Mutabon Mite, gradually increasing the dose until a satisfactory response is achieved;
  • opioids, barbiturates, or other sedatives, antihistamines, anaesthetics, tranquillisers, and meperidine (and other opioid analgesics). Concomitant administration with Mutabon Mite may enhance the central nervous system depressant effects of these medicines, including respiratory depression. Conversely, these medicines may enhance the effects of Mutabon Mite. Therefore, you must not take Mutabon Mite together with these medicines (see section "Do not take Mutabon Mite if").

Talk to your doctor or pharmacist if you are taking:

  • medicines that may cause a reduction in white blood cells (leukopenic drugs), as Mutabon Mite may cause disturbances in blood cell production (see section "Do not take Mutabon Mite if" and "Warnings and precautions");
  • other psychotropic medicines, medicines with anticholinergic action (inhibition of acetylcholine, a substance acting on the nervous system), or medicines acting on the autonomic nervous system (sympathomimetics), due to the possible occurrence of adverse effects due to interaction with Mutabon Mite;
  • medicines with anticholinergic action, such as atropine, or antihistamines, as this may enhance effects on the cholinergic system, increasing the risk of intestinal obstruction (paralytic ileus), blurred vision, and possible changes in intraocular pressure in the presence of glaucoma;
  • medicines acting on the autonomic nervous system (sympathomimetic amines) such as epinephrine combined with local anaesthetics, as this may increase the activity of these medicines or of Mutabon Mite. Your doctor will closely monitor you and adjust the dose to avoid adverse effects on blood pressure and cardiac function, which may sometimes be fatal;
  • reserpine, methyldopa, other medicines for high blood pressure (hypertension) such as guanethidine (concomitant use requires dose adjustment by the doctor), beta-blockers blocking adrenergic receptors such as propranolol or similar medicines, as this may cause low blood pressure (hypotension). Concomitant use of Mutabon Mite and these medicines is therefore not recommended. Your doctor may require blood pressure monitoring before starting Mutabon Mite and weekly checks during the first month of treatment;
  • medicines for the treatment of seizures (see section "Warnings and precautions");
  • phenytoin, a medicine used for epilepsy, as Mutabon Mite may alter its effectiveness;
  • antipsychotic medicines;
  • sedative medicines such as diazepam;
  • high doses of ethchlorvynol (a sedative and hypnotic medicine), as transient delirium has been reported with this combination. The combination with Mutabon Mite should be used with caution;
  • medicines for stomach hyperacidity containing aluminium salts, as they may reduce the absorption of Mutabon Mite;
  • medicines that prolong the QT interval, as this increases the risk of developing heart rhythm disturbances (cardiac arrhythmias);
  • medicines that cause electrolyte imbalances in the blood;
  • medicines containing cimetidine, as it may increase amitriptyline concentrations in the blood and its effects, possibly leading to serious adverse effects;
  • medicines that inhibit cytochrome P450 2D6 (an enzyme in the body involved in drug metabolism), such as quinidine, cimetidine, many other antidepressants, phenothiazines, propafenone and flecainide, and all medicines known as selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline and paroxetine, or serotonin-norepinephrine reuptake inhibitors (duloxetine). In such cases, your doctor may prescribe lower than recommended doses for both these medicines and Mutabon Mite. Your doctor will monitor you closely, especially when switching from one medicine to another, particularly when switching from fluoxetine to Mutabon Mite;
  • levodopa and phenylbutazone, as the anticholinergic effects of tricyclic antidepressants may slow gastrointestinal motility, interfering with the absorption of these medicines;
  • valproic acid;
  • medicines containing buprenorphine. These medicines may interact with Mutabon Mite and may cause symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle contraction, fever above 38°C. Contact your doctor if you experience these symptoms.

Mutabon Mite may interfere with the absorption of various other drugs.
Inform your doctor if you are exposed to organophosphorus insecticides.

Mutabon Mite and laboratory tests
Taking Mutabon Mite may darken the urine and cause changes in the results of certain laboratory tests:

  • false-positives (non-real positive results) in the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens, and 5-hydroxyindoleacetic acid;
  • changes in electrocardiogram such as QT interval prolongation;
  • abnormalities in electroencephalogram;
  • alteration (increase) in levels of iodine bound to blood proteins;
  • changes in hypothalamic-pituitary function tests, as the medicine may cause a decrease in levels of certain hormones;
  • false-positives and false-negatives in urine pregnancy tests;
  • possible increases and decreases in blood sugar levels.

Mutabon Mite with alcohol
Mutabon Mite must not be taken together with alcohol (ethanol) due to a possible increase in the medicine's effects, including a reduction in blood pressure (hypotension). In addition, this combination may increase the risk of suicide and overdose.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Mutabon Mite must not be used during pregnancy, confirmed or suspected, due to the risk of adverse effects in the newborn (see section "Do not take Mutabon Mite if" and section 4 "Undesirable effects in children").
Breastfeeding
You must not use Mutabon Mite if you are breastfeeding (see section "Do not take Mutabon Mite if"), as Mutabon Mite passes into breast milk and may cause adverse effects in the newborn.

Driving and using machines
Mutabon Mite affects your ability to drive vehicles and use machinery, as it may alter reaction time (the interval between perceiving a danger and beginning to react to avoid it). Therefore, exercise appropriate caution when driving vehicles or operating machinery.

Mutabon Mite contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

12. How to take Mutabon Mite

Take this medicine exactly as directed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The optimal dose of Mutabon Mite must be determined by your doctor, depending on the specific
condition being treated, the duration and severity of the illness, and your response to therapy.
The recommended dose is 1 tablet, 1–3 times daily. Several days are generally required before a noticeable effect of Mutabon Mite is achieved.
If you suffer from persistent insomnia, it may be advisable—especially during the first days of treatment—to take 1 or 2 tablets in the evening, half an hour before going to bed; the remaining tablets prescribed by your doctor can be taken during the day.
To achieve a full therapeutic effect, you must continue treatment for several weeks, as advised by your doctor. Once symptoms are under control, your doctor will gradually reduce your dose until the most suitable maintenance dose for you is established.
Your doctor will periodically assess whether continued treatment with Mutabon Mite is necessary.

Use in children and adolescents
Mutabon Mite is not recommended for children under 12 years of age (see section “Children and adolescents”).

Use in the elderly
The dose and frequency of administration of Mutabon Mite in elderly patients must be carefully determined by the doctor, who may consider reducing the above-mentioned dose based on individual needs.

If you take more Mutabon Mite than you should
In case of accidental or intentional overdose of Mutabon Mite, contact your doctor or pharmacist immediately or go to the nearest hospital.
Signs and symptoms of overdose appear rapidly, so hospital monitoring is required as soon as possible.
Overdose with Mutabon Mite, as with other medicines in the same class, may result in death.
Symptoms of overdose may correspond to any of the adverse effects listed for the two active substances, perphenazine or amitriptyline hydrochloride (see section “Possible side effects”).

Symptoms of perphenazine overdose include motor system disturbances (extrapyramidal symptoms), such as involuntary muscle movements (dyskinesia) and abnormal muscle contractions (dystonia); however, these may be masked by the anticholinergic effects of amitriptyline. Other symptoms may include partial loss of consciousness (stupor) or coma; children may experience epileptic seizures.

Symptoms of amitriptyline overdose include irregular heartbeat (cardiac arrhythmias), severe drop in blood pressure (severe hypotension), involuntary muscle contractions (seizures), and reduced activity of the nervous system (central nervous system depression), including coma.
Abnormalities in cardiac conduction detectable on electrocardiogram (ECG) have also been reported.

Other symptoms of overdose include: confusion, difficulty concentrating, temporary visual hallucinations, dilated pupils, agitation, hyperactive reflexes, drowsiness, muscle rigidity, vomiting, lowered body temperature (hypothermia), fever, or any of the side effects listed.
Overdose of amitriptyline in children may lead to severe consequences. Children are particularly susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low sodium levels in the blood, lethargy, drowsiness, nausea, vomiting, and high blood sugar levels.

Management in case of Mutabon Mite overdose
There is no specific antidote to counteract the effects of Mutabon Mite overdose. In case of accidental or intentional overdose, contact your doctor or pharmacist immediately or go to the nearest hospital. Your doctor will initiate appropriate emergency measures, such as gastric lavage and electrocardiographic (ECG) monitoring, and will closely observe you for any signs of central nervous system involvement, breathing difficulties, low blood pressure, heart rhythm abnormalities and/or conduction blocks, and epileptic seizures.
Your doctor may decide to contact the local poison control center.

If you forget to take Mutabon Mite
Do not take a double dose to make up for a missed tablet. Continue your treatment as prescribed.

If you stop taking Mutabon Mite
Do not stop taking Mutabon Mite without first consulting your doctor.
Phenothiazines (perphenazine) generally do not cause psychological dependence. However, sudden discontinuation of high-dose treatment may lead to gastritis, nausea, vomiting, dizziness, tremors, and motor hyperactivity. If you experience such symptoms, consult your doctor, who will prescribe appropriate treatment.
Sudden discontinuation of high-dose tricyclic antidepressant therapy (amitriptyline hydrochloride) may cause symptoms such as: malaise, chills, cold-like symptoms, muscle pain, headache, nausea, vomiting, anxiety, instability, dizziness, and a constant urge to move (akathisia). These symptoms are not indicative of addiction.
If you abruptly stop high-dose treatment with Mutabon Mite, inform your doctor and pay attention to any symptoms you may experience.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

13. Possible adverse effects

Like all medicines, Mutabon Mite can cause adverse effects, although not everybody experiences them.
The adverse effects of Mutabon Mite are the same as those associated with the two active substances (perphenazine and amitriptyline) when taken individually. No adverse effects due solely to their combination in Mutabon Mite have been reported.
In very rare cases, patients hypersensitive to phenothiazines (perphenazine) have experienced excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse, and death.
Occasionally, treatment with phenothiazines may cause intestinal muscle paralysis leading to cessation of intestinal content progression (adynamic ileus), which, if severe, may result in complications and death.
Stop treatment with Mutabon Mite and contact your doctor immediately if you experience:

  • Neuroleptic Malignant Syndrome (NMS), a potentially fatal condition characterized by symptoms such as increased body temperature, muscle rigidity, reduced movement (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), cardiac rhythm abnormalities (arrhythmias)), altered mental status,
    which may progress to stupor and coma (see "Stop treatment with Mutabon Mite and inform your doctor if you experience" in section 2);

  • persistent abnormalities in muscle contraction and movement, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia) (see "Stop treatment with Mutabon Mite and inform your doctor if" in section 2);

  • swelling of the hands, feet, ankles, or even face, lips, tongue, and/or throat, leading to difficulty swallowing or breathing (angioedema);

  • marked increase in body temperature (hyperpyrexia);

  • allergic reaction with skin rash (urticaria), irritation and appearance of red spots on the skin (erythema), itchy inflammatory skin reactions (eczema), skin inflammation with formation of lesions and shedding of the superficial layer (exfoliative dermatitis), itching, skin sensitivity to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoid), swelling due to fluid accumulation in the upper airways (laryngeal edema), contact dermatitis;

  • formation of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the legs), which may travel through blood vessels to the lungs, causing chest pain and difficulty breathing (the frequency of this adverse effect cannot be determined from available data);

  • worsening of depressive state, including, rarely, suicidal thoughts or behavior (see section "Warnings and precautions").

Adverse effects related to perphenazine
The most common symptoms reported during treatment with perphenazine, as with all medicines belonging to the same pharmacological class as perphenazine, are disturbances and abnormalities of the motor system (extrapyramidal reactions), such as:

  • abnormal posture characterized by hyperextension of the neck, rigidity, and severe arching of the back (opisthotonus), abnormal contraction of jaw muscles with difficulty opening the mouth (trismus), limited mobility or blockage of the neck accompanied by cervical pain and contraction of lateral neck muscles (torticollis), torticollis associated with a deviated head posture and sudden muscle spasms causing abrupt head rotation (spastic torticollis), pain and tingling in limbs, agitation with excessive motor activity (motor restlessness), eye deviation in one direction (oculogyric crisis), hyper-reactivity of reflexes characterized by abnormal muscle contractions (hyperreflexia), movement disorder characterized by involuntary muscle contractions (dystonia), including abnormalities affecting the tongue (color changes, protrusion, or rolling), sudden and involuntary contractions of masticatory muscles, sensation of throat tightness, difficulty in speaking and swallowing (dysphagia), inability to sit still, a group of symptoms including tremor, muscle rigidity, slowed movement, and postural abnormalities (parkinsonism), and loss of muscle coordination (ataxia). The frequency and severity of these symptoms generally increase with higher doses of Mutabon Mite.

Additionally, the following may occur:

  • abnormalities in the protein composition of cerebrospinal fluid, headache (cephalalgia), drowsiness;

  • worsening of psychotic symptoms such as thought disturbances, delusions and hallucinations, motor, emotional, and behavioral abnormalities (catatonic-like states), thought patterns detached from reality (paranoid reactions), deep sleep state (lethargy), paradoxical excitement, restlessness and hyperactivity, nocturnal confusion, bizarre dreams, sleep disturbances (insomnia);

  • abnormal milk secretion from the breasts (galactorrhea), increased breast size in women and men (gynecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), changes in sexual desire, inhibition of ejaculation, false positives in pregnancy tests, increased and decreased blood sugar levels (hyperglycemia and hypoglycemia), presence of sugar in urine (glycosuria), excessive release of an antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH);

  • drop in blood pressure upon standing from sitting or lying down (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, fainting and dizziness;

  • decrease in white blood cells (agranulocytosis, leukopenia), increase in a specific type of white blood cells (eosinophilia), reduction in red blood cell count (hemolytic anemia), abnormal destruction of platelets (thrombocytopenic purpura), reduction in all blood cell types (pancytopenia);

  • inflammation and obstruction of specific bile-carrying ducts (biliary stasis);

  • yellowing of the skin and whites of the eyes (jaundice).

Less frequent adverse effects:

  • sedation, blood disorders (hematologic dyscrasia), involuntary muscle contractions (seizures).

Occasionally, the following may occur:

  • dry mouth and hypersalivation, nausea, vomiting, and diarrhea, gastric retention, anorexia, constipation (stasis), persistent constipation and formation of a hard mass of dehydrated feces in the intestine (fecaloma), difficulty emptying the bladder (urinary retention), frequent need to urinate and involuntary urine leakage (incontinence), loss of bladder function (bladder paralysis), increased urine output (polyuria);
  • nasal congestion;
  • pallor, increased (mydriasis) and decreased (miosis) pupil size, blurred vision, eye disease characterized by increased pressure inside the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), decreased blood pressure (hypotension), altered pulse rate.

Rarely observed:

  • abnormalities in cardiac conduction (QT prolongation), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation, and cardiac arrest;
  • swelling of the salivary glands (parotid swelling).

Adverse effects associated with long-term therapy:

  • liver damage;

  • appearance of skin spots (cutaneous pigmentation), visual disturbances due to deposition of fine particulate matter in the cornea and lens, which in severe cases may lead to star-shaped lens opacities, corneal inflammation (epithelial keratopathies), retinal abnormalities, retinal destruction leading to vision loss (pigmentary retinopathy);

  • persistent abnormalities in muscle contraction and movement, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia), which may also appear after discontinuation of treatment.

Other adverse effects:

  • fluid accumulation in lower limbs (peripheral edema), sedation state (reverse epinephrine effect), alteration in levels of proteins binding iodine (increased PBI not attributable to increased thyroxine), lupus-like syndrome (an inflammatory autoimmune disease affecting multiple organs and tissues), increased appetite and weight gain, abnormally increased food intake (polyphagia), excessive sensitivity to light (photophobia), muscle weakness.

In patients treated with phenothiazines, sudden death has been occasionally reported.
In some patients, the cause of death could not be determined, nor could it be established whether death was attributable to phenothiazine.
In elderly patients with dementia, a slight increase in mortality has been reported among those taking antipsychotics compared to those who did not.

Adverse effects related to amitriptyline hydrochloride
Treatment with antidepressant medicines, including amitriptyline hydrochloride, may trigger the onset of latent schizophrenia, which may be prevented in some cases by the antipsychotic effect of perphenazine contained in Mutabon Mite. In patients with chronic schizophrenia, epileptic seizures (epileptiform convulsions) have been observed during treatment with amitriptyline hydrochloride.
Furthermore, amitriptyline hydrochloride may cause, in addition to some of the adverse effects reported for perphenazine, the following:

  • increased risk of bone fractures;
  • skin rash;
  • pupil abnormalities (accommodation disturbances), difficulty emptying the bladder (urinary retention and urinary tract dilation);
  • awareness of heartbeats (palpitations), heart attack and stroke, heart rhythm disturbances (arrhythmias), conduction disturbances of the heart's electrical impulses that may lead to partial or complete heart stoppage (cardiac block);
  • confusion, concentration difficulties, disorientation, fixations and hallucinations, excitement, nervousness, anxiety and agitation, insomnia and nightmares, hearing loss, tingling and altered sensation in limbs (paresthesia), dysfunction of the peripheral nervous system (peripheral neuropathy), tremors and seizures, abnormalities in electroencephalogram, hearing disturbances (tinnitus);
  • increased testicle size;
  • gastrointestinal disorders (epigastric discomfort and heartburn), anorexia, inflammation of the oral cavity (stomatitis), dark discoloration of the tongue;
  • rarely, liver inflammation (hepatitis);
  • bone marrow depression (when bone marrow fails to produce sufficient blood cells), decrease in white blood cells (agranulocytosis, leukopenia), capillary rupture under the skin surface (purpura), increase in a specific type of white blood cells (eosinophilia), reduction in platelet count (thrombocytopenia);
  • a heart condition called "QT interval prolongation" (seen on electrocardiogram, ECG) (common frequency);
  • dizziness, weakness and fatigue, weight gain or loss, hair loss (alopecia);
  • dry eyes (frequency "not known").

Sudden discontinuation of long-term treatment may cause:

  • nausea, headache (cephalalgia), malaise.

Adverse effects in children
The following symptoms have been observed in newborns of mothers who took antipsychotics, including Mutabon Mite, during the last three months of pregnancy: agitation, muscle rigidity and/or weakness, hyperactive reflexes, tremor, motor system disturbances and abnormalities (extrapyramidal symptoms), drowsiness, breathing difficulties, feeding problems, and neonatal withdrawal syndrome.
If your baby shows any of these symptoms, contact your doctor immediately.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse effects, you can help provide more information on the safety of this medicine.

11. How to store Mutabon Mite

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp".
The expiry date refers to the last day of that month.
The stated expiry date applies to the product in its original, unopened packaging,
correctly stored.
This medicine does not require any special storage temperature.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

12. Package contents and other information

What Mutabon Mite contains

  • The active substances are perfenazine and amitriptyline hydrochloride.
  • Each film-coated tablet contains 2 mg of perfenazine and 10 mg of amitriptyline hydrochloride.
  • The other components are corn starch, lactose, magnesium stearate, pregelatinized starch, Opadry white (hypromellose E-464, macrogol, titanium dioxide E-171, hydroxypropylcellulose E-463).

Description of the appearance of Mutabon Mite and contents of the pack
Mutabon Mite is available in packs of 30 film-coated tablets, contained in a blister.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan
Manufacturers
Vamfarma S.r.l.
Via Kennedy, 5
26833 Comazzo (LO)
SPECIAL PRODUCT’S LINE S.P.A.
Via Fratta Rotonda Vado Largo, 1
Anagni (Frosinone) – Italy