Package leaflet: Information for the patient

Trilafon 2 mg film-coated tablets, 4 mg film-coated tablets, 8 mg film-coated tablets

Perphenazine
Please read all of 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 may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Trilafon is and what it is used for
What you need to know before taking Trilafon
How to take Trilafon
Possible side effects
How to store Trilafon
Contents of the pack and other information

1. What Trilafon is and what it is used for

Trilafon contains the active substance perphenazine.
Perphenazine belongs to a group of medicines called phenothiazines which act on the central nervous system, reducing states of anxiety and distress (anxiolytic properties), providing therapeutic effects against psychotic symptoms (delusions and hallucinations), and also preventing or eliminating vomiting and nausea (antiemetic properties).
Trilafon is indicated for the treatment of the following disorders and diseases:

schizophrenia, a mental disorder characterized by various symptoms including hallucinations, delusions, tendency to withdraw socially, and difficulty in organizing thoughts;
paranoid states, personality disorders characterized by a persistent tendency to interpret the behaviour of others with distrust and suspicion;
psychological conditions manifesting with mood disturbances associated with euphoria and excitability, and characterized by obsessive ideas and behaviours (mania);
toxic psychoses, psychiatric disorders induced by the use of psychoactive substances (amphetamines, LSD, cocaine, etc.);
psychiatric disorders associated with organic causes and accompanied by delirium;
severe anxiety disorders that do not improve with anxiolytic medicines;
depression, when accompanied by agitation and delusions, in combination with antidepressants;
to reduce vomiting and persistent, continuous hiccups;
in the treatment of severe pain, generally in combination with analgesic medicines.

2. What you should know before taking Trilafon

Do not take Trilafon if:

you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
you are in a state of reduced level of consciousness (severe obtundation), coma, or severe depression;
you are taking medicines that can slow down normal brain activity (central nervous system depressants), such as alcohol, barbiturates, opioids, etc.; you are taking other medicines used to treat mental disorders (neuroleptics); in this case, inform your doctor;
you have blood disorders (hematological dyscrasias) or impaired bone marrow function, which fails to produce an adequate number of blood cells (bone marrow depression);
you have liver disease;
you have suspected or confirmed brain damage (subcortical brain damage, with or without hypothalamic involvement);
you are under 12 years of age (see section “Children and adolescents”);
you are in the first trimester of pregnancy or are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Trilafon if:

you are elderly;
you suffer from cardiovascular diseases or have a family history of cardiac dysfunction (QT prolongation);
you have a tumor of the adrenal glands (pheochromocytoma) or heart valve abnormalities (mitral insufficiency). In such cases, you will require closer monitoring during perphenazine administration due to the risk of low blood pressure (hypotension);
you have respiratory diseases caused by lung infections or chronic respiratory disorders such as severe asthma or emphysema;
you have reduced kidney function;
you suffer from a condition causing increased eye pressure (glaucoma);
you have diseases affecting the urogenital system, such as enlarged prostate (prostatic hypertrophy);
you have narrowing of the gastrointestinal or urinary tracts (stenotic diseases of the digestive and urinary systems);
you suffer from psychiatric disorders, as Trilafon may worsen mood, potentially leading to depression;
you have a breast tumor. In this case, perphenazine will be administered with particular caution, as it increases the concentration of a hormone (prolactin) that could worsen your condition;
you have Parkinson's disease or Parkinson-like conditions, or other motor disorders, since perphenazine may increase muscle rigidity;
you are experiencing alcohol withdrawal;
you suffer from seizures and are taking anticonvulsant (antiepileptic) medications. In such cases, if deemed necessary by your doctor, the dose of antiseizure medications may need to be increased;
you are exposed to extremely high or low temperatures, as Trilafon may impair the body's temperature regulation mechanisms;
you are scheduled for 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 receiving;
you are in the post-operative phase, as vomiting aspiration has occurred in a limited number of patients treated with phenothiazines;
you consume alcohol, as it may enhance the effects of the medicine, significantly lower blood pressure (hypotension), and increase the risk of suicide;
you suffer from dementia and are being treated with atypical antipsychotics, as an increased risk of cerebrovascular events (e.g., stroke, transient ischemic attack) has been observed in such cases;
you have risk factors for stroke;
you have had cardiovascular diseases associated with blood clot formation (venous thromboembolism) or have risk factors for such conditions.

The use of Trilafon for the treatment of nausea and vomiting in pregnancy should only occur in cases where alternative interventions are not possible, and not for common or frequent cases of pregnancy-related nausea, nor for the purpose of prevention.

During treatment with Trilafon, the following may occur:

the appearance of inflammation of the mouth and upper airways. In such cases, blood tests should be performed;
changes in organ function. Safe and effective use of Trilafon requires appropriate dosage control and periodic monitoring of blood cell counts, and liver, kidney, and heart function, especially if Trilafon is taken at high doses or for prolonged periods. If abnormalities are detected, your doctor may decide to discontinue treatment;
the development of involuntary muscle movements (tardive dyskinesia). The risk of developing dyskinesia and the likelihood of it becoming irreversible increase with the duration of treatment and the total dose of medicine taken. Discontinuation of treatment may resolve these abnormalities. If you notice the onset of these symptoms, inform your doctor, who will assess whether to adjust the dose or discontinue treatment;
the occurrence of skin sensitivity reactions to light (photosensitivity). Therefore, avoid excessive exposure to sunlight or use specific protective creams during treatment with Trilafon;
an increased risk of suicidal thoughts if you suffer from depression. This condition may persist during treatment with Trilafon and until there is significant improvement in symptoms. Therefore, you will be closely monitored to prevent access to excessive amounts of Trilafon.

Stop taking Trilafon and inform your doctor immediately if you experience:

a potentially life-threatening group of symptoms known as neuroleptic malignant syndrome, which include: elevated body temperature, muscle rigidity, reduced movement (akinesia), autonomic disturbances (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), changes in heart rhythm (arrhythmias)), and altered mental status that may progress to stupor or coma. Your doctor will stop the treatment and initiate therapy to manage these symptoms;
a significant increase in body temperature not attributable to a specific cause. This temperature rise may suggest hypersensitivity to perphenazine, in which case your doctor will advise discontinuing the treatment; abnormalities in liver or kidney function tests or blood dyscrasias—in such cases, your doctor will instruct you to stop treatment. Perphenazine reduces the sensation of nausea and vomiting and may therefore mask signs of overdose of other medicines or make it more difficult to diagnose conditions such as intestinal obstruction, Reye's syndrome, and brain tumors.

Increased mortality in elderly patients with dementia
A slight increase in the risk of death has been observed in elderly patients with dementia treated with antipsychotics compared to untreated patients.
Therefore, Trilafon is not indicated for the treatment of behavioral disorders associated with dementia.

Children and adolescents
The safety of Trilafon in children under 12 years of age has not been established; therefore, its use in children is not recommended.

Other medicines and Trilafon
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Talk to your doctor or pharmacist if you are taking:

other antipsychotic medicines, as concomitant therapy with Trilafon should be avoided;
barbiturates, anxiolytics, anesthetics, antihistamines, meperidine, and other opioid analgesics;
medicines for the treatment of seizures, such as phenytoin, and lithium, used to treat certain mood disorders;
tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs);
medicines for high blood pressure, such as guanethidine, methyldopa, and beta-blockers (e.g., propranolol);
quinidine, propafenone, and flecainide (antiarrhythmics);
cimetidine (a medicine used in the treatment of ulcers);
medicines with anticholinergic action (inhibition of acetylcholine, a substance acting in the nervous system), such as atropine;
phenylbutazone (used for inflammation and muscular trauma), medicines that suppress thyroid hormone production (thiouracil derivatives), and other medicines that suppress bone marrow (myelotoxic agents);
metrizamide, a compound used as a contrast agent in certain diagnostic tests for blood disorders. Trilafon therapy must be discontinued at least 48 hours before the test due to the increased risk of seizures. Trilafon should not be restarted until at least 24 hours after the test;
levodopa, a medicine used to treat Parkinson's disease;
medicines used to reduce stomach acidity, such as aluminum salts, as their concomitant use with Trilafon may reduce its absorption;
medicines that prolong the QT interval, as this increases the risk of developing heart rhythm disturbances (cardiac arrhythmias);
medicines that cause electrolyte imbalances, such as medicines used to treat high blood pressure (hypertension).

Inform your doctor if you are exposed to organophosphorus insecticides.

Trilafon and laboratory tests
Taking Trilafon may cause darkening of the urine and alter the results of certain laboratory tests:

false positives in the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens, and 5-hydroxy-indoleacetic acid;
alterations in hypothalamic-pituitary function tests, as the medicine may cause a reduction in certain hormones;
false positives and false negatives in urine pregnancy tests;
changes in the electrocardiogram, specifically in the QT interval.

Trilafon with food, drinks, and alcohol
Do not take Trilafon with alcohol 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 overdose.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Trilafon must not be used during the first trimester of pregnancy. In subsequent months, your doctor will assess whether taking Trilafon is necessary.
Perphenazine is rapidly excreted in breast milk; therefore, your doctor will decide whether you should stop breastfeeding or discontinue Trilafon therapy, taking into account the importance of the treatment for you.

Driving and using machines
Trilafon may cause sedation and drowsiness. Keep this in mind when driving or operating machinery.

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

3. How to take Trilafon

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.

The optimal dose of Trilafon must be determined by the doctor, depending on the severity of the illness and your response to treatment.
It is always preferable to use the lowest effective dose, since the frequency and severity of adverse effects are proportional to dose increases.
The need to continue treatment should be periodically reviewed by the doctor.

The recommended dose for the treatment of outpatients is 4–8 mg of Trilafon three times daily or 8–16 mg twice daily.
For hospitalized patients, the recommended dose is 8–16 mg two to four times daily, or 8–32 mg twice daily. In any case, the daily oral dose of perphenazine must not exceed 64 mg.

The use of Trilafon for the control of vomiting requires doses of 8–12 mg divided throughout the day.

Use in children and adolescents
Trilafon must not be used in children and adolescents under 12 years of age (see section “Children and adolescents”).
For adolescents over 12 years of age, the same treatment regimen applicable to adults should be followed (see previous section).

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

If you take more Trilafon than you should
If you have taken or ingested an excessive dose of Trilafon, contact your doctor immediately or go to the nearest hospital.

Symptoms of perphenazine overdose may include motor system abnormalities (extrapyramidal symptoms). There may be a progressive slowing of mental functions (central nervous system depression), ranging from drowsiness to temporary detachment from external reality (stupor) or coma with absence of reflexes. Seizures may occur in children. Patients with moderate or early-stage intoxication may experience restlessness, confusion, and agitation. Other symptoms of overdose include: low blood pressure (hypotension), increased heart rate (tachycardia), reduced body temperature (hypothermia), reduced pupil size (miosis), tremors, muscle contractions, involuntary muscle contractions (spasms), muscle rigidity, or reduced muscle tone (hypotonia), seizures, difficulty swallowing and breathing, bluish discoloration of the skin and mucous membranes (cyanosis), respiratory and/or vasomotor collapse, sometimes with sudden apnea.

Treatment in case of Trilafon overdose
There is no specific antidote available to counteract the effects of Trilafon overdose. In hospital, you will immediately receive appropriate emergency treatments (e.g. induction of vomiting or gastric lavage) and will be kept under close medical supervision with continuous monitoring of your condition.

If you forget to take Trilafon
Do not take a double dose to make up for the missed dose.

If you stop taking Trilafon
Do not stop taking Trilafon without first consulting your doctor.
Phenothiazines generally do not cause dependence. However, if you suddenly stop treatment, you may experience symptoms such as gastritis, nausea, vomiting, dizziness, tremors, and motor hyperactivity.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Trilafon can cause side effects, although not everybody will experience them.
Stop treatment with Trilafon and contact your doctor immediately if you experience:

Neuroleptic Malignant Syndrome (NMS), 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), changes in heart rhythm (arrhythmias)), altered mental status which may progress to stupor and coma;
persistent abnormalities in muscle contraction and movement, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (tardive dyskinesia);
skin rash, similar to hives, accompanied by swelling of the hands, feet, ankles, or even the face, lips, tongue and/or throat, leading to difficulty swallowing or breathing (angioedema);
increased body temperature (hyperpyrexia);
excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse, and death due to hypersensitivity to phenothiazines (extremely rare adverse reactions);
swelling, pain, and redness in the legs, possibly accompanied by chest pain and difficulty breathing. These symptoms are due to blood clot formation in the veins, especially in the legs, which may migrate through blood vessels to the lungs (the frequency of this adverse reaction cannot be determined from available data).

The most commonly reported symptoms 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 excessive extension 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 the limbs, restlessness with excessive motor activity (motor restlessness), deviation of the eyes in one direction (oculogyric crisis), hyper-reactivity of reflexes characterized by abnormal muscle contractions (hyperreflexia), movement disorder characterized by

involuntary muscle contractions (dystonia), including spinal column deformation (protrusion),
tongue abnormalities (color, pain, and involuntary movements), sudden and involuntary contractions of
the masticatory muscles, sensation of throat tightness, difficulty in speaking and swallowing
(dysphagia), inability to sit still, abnormalities in movement and muscle contraction (dyskinesia),
muscle rigidity and slowness in movement execution (parkinsonism), and loss of muscular
coordination (ataxia).
Additionally, the following may occur:

abnormalities in the protein composition of the fluid in the central nervous system (cerebrospinal fluid), seizures, 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), worsening of symptoms for which treatment was initiated (paradoxical excitement), restlessness and hyperactivity, nocturnal confusion with bizarre dreams, sleep disturbances (insomnia);
abnormal milk secretion (galactorrhea), breast enlargement in women and men (gynaecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhoea), changes in sexual desire, inhibition of ejaculation, increased and decreased blood sugar levels (hyperglycaemia and hypoglycaemia), presence of sugar in urine (glycosuria), excessive release of an antidiuretic hormone which may cause headache, nausea, and malaise (syndrome of inappropriate antidiuretic hormone secretion, SIADH);
false positive results in pregnancy tests;
drop in blood pressure upon standing from a sitting or lying position (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, transient loss of consciousness and dizziness, non-specific changes in electrocardiogram, abnormalities in cardiac conduction (QT prolongation, rarely observed), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation, and cardiac arrest;
decrease in white blood cells (agranulocytosis, leucopenia), increase in a specific type of white blood cells (eosinophilia), decrease in red blood cells (haemolytic anaemia), abnormal destruction of platelets (thrombocytopenic purpura), reduction in all blood cell types (pancytopenia);
inflammation and obstruction of specific ducts carrying bile (biliary stasis), yellowing of the skin and whites of the eyes (jaundice).

Less frequent side effects:

sedation, blood disorders (haematological dyscrasia), loss of consciousness associated with involuntary muscle contractions (seizures), and effects on the autonomic nervous system. Occasionally, the following may occur:
dry mouth and hypersalivation, feeling of discomfort (nausea), vomiting and diarrhoea, gastric retention, loss of appetite, constipation (stipsis), persistent constipation and formation of a hard mass of dehydrated faeces (faecaloma), 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);
stuffy nose (nasal congestion);
pallor, increased (mydriasis) and decreased (miosis) pupil size, blurred vision, eye disease causing increased pressure inside the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), decreased blood pressure (hypotension), altered pulse rate, intestinal muscle disturbances and blockage (adynamic ileus), which in severe cases may lead to complications and death;
skin allergic reactions (urticaria), irritation and appearance of red spots on the skin (erythema), inflammatory skin reactions causing itching (eczema), skin inflammation with lesion formation and loss of superficial layers (exfoliative dermatitis), itching, skin sensitivity to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoid), accumulation of fluid in the upper airways (laryngeal oedema), contact dermatitis.

Side effects associated with long-term therapy:

appearance of skin spots (cutaneous pigmentation), visual disturbances which, in more severe cases, lead to stellate opacities of the lens, corneal inflammation (epithelial keratopathies), retinal abnormalities, retinal destruction up to vision loss (pigmentary retinopathy).

Other side effects:

fluid accumulation in the lower limbs (peripheral oedema), sedative state (epinephrine reversal effect), changes in levels of proteins binding iodine (increased PBI not attributable to increased thyroxine), swelling of salivary glands (parotid swelling), 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 due to phenothiazine treatment.

Side effects in children
Newborns whose mothers have taken antipsychotics, including Trilafon, during the last three months of pregnancy are at risk of motor system disturbances and abnormalities (extrapyramidal symptoms) and neonatal withdrawal syndrome. Additionally reported symptoms include: agitation, muscle rigidity and/or weakness, tremor, drowsiness, breathing difficulties, feeding problems, and hyperactive reflexes.
If your baby shows any of these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the website www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Trilafon

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, unopened packaging,
correctly stored.
This medicine does not require any special storage 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 Trilafon contains
The active substance is perphenazine.
Each tablet of Trilafon 2 mg coated tablets contains 2 mg of perphenazine.
Each tablet of Trilafon 4 mg coated tablets contains 4 mg of perphenazine.
Each tablet of Trilafon 8 mg coated tablets contains 8 mg of perphenazine.
The other components are:
Trilafon 2 mg coated tablets: maize starch, lactose, magnesium stearate, pregelatinized starch,
hypromellose, macrogol, white opaspray, paraffin.
Trilafon 4 mg coated tablets and Trilafon 8 mg coated tablets: maize starch, lactose,
magnesium stearate, pregelatinized starch, Opadry white (hypromellose, macrogol, titanium dioxide,
hydroxypropylcellulose).

Description of the appearance of Trilafon and contents of the pack
Trilafon is available as coated tablets contained in a blister. Each pack contains 20 tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Neopharmed Gentili S.r.l.
Via San Giuseppe Cottolengo, 15
20143 Milan
Manufacturer
VAMFARMA S.r.l.
Via Kennedy, 5
26833 Comazzo (CO)