Anafranil sr 75: detailed information

Package leaflet: Information for the patient

Anafranil SR 75, 75 mg, prolonged-release coated tablets
Clomipramini hydrochloridum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others.
It may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

What Anafranil SR 75 is and what it is used for
What you need to know before taking Anafranil SR 75
How to take Anafranil SR 75
Possible side effects
How to store Anafranil SR 75
Contents of the pack and other information

1. What Anafranil SR 75 is and what it is used for

Anafranil SR 75 is a medicine in the form of prolonged-release coated tablets,
containing clomipramine hydrochloride as the active substance, which belongs to the group
of tricyclic antidepressants.
Anafranil SR 75 is used in the treatment of depressive states of various causes and symptoms,
e.g. endogenous, reactive, neurotic, organic, masked, and involutional depression; depression
associated with schizophrenia and personality disorders; depressive syndromes related to
advanced age, chronic pain conditions, and chronic somatic diseases. It is also used in the
treatment of obsessive-compulsive disorders, panic attacks, phobias, and nocturnal enuresis
in children (over 5 years of age, provided organic causes have been excluded).

2. Important information before using Anafranil SR 75

When not to use Anafranil SR 75

If the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
If the patient has cross-sensitivity to tricyclic antidepressants;
If the patient is taking monoamine oxidase inhibitor (MAOI) antidepressants, or within 14 days before or after treatment with MAOIs. Concurrent use of selective, reversible MAO-A inhibitors such as moclobemide is also not recommended;
If the patient has recently suffered a myocardial infarction;
If the patient has congenital long QT syndrome.

Warnings and precautions
Before starting treatment with Anafranil SR 75, discuss this with your doctor or pharmacist.
The patient should inform the doctor about the following conditions:

Epileptic seizures,
Irregular heartbeat, cardiovascular diseases, especially cardiac arrhythmias and circulatory failure,
Schizophrenia,
Glaucoma (increased intraocular pressure),
Liver or kidney disease,
Any blood disorders,
Difficulty urinating, e.g. due to prostate disorders,
Hyperthyroidism,
Frequent constipation,
Alcohol abuse.

It is important that the doctor regularly evaluates the treatment effects, allowing for dose adjustment and reducing the risk of adverse reactions. During follow-up visits, the doctor may recommend blood sampling for laboratory tests and measuring blood pressure and cardiac function before and during treatment.
Suicidal behaviour, suicidal thoughts, or clinical worsening of illness
The risk of suicidal thoughts, self-harm, or suicide attempts, characteristic of severe depression, may persist until significant remission occurs.
In patients with depressive disorders, both adults and children, depression and (or) suicidal tendencies may worsen, or other psychiatric symptoms may intensify, regardless of whether other antidepressants are being used or not. Short-term clinical studies have shown that antidepressant drugs increase the risk of suicidal thoughts and behaviours (suicidality) in children and adolescents with depressive disorders and other psychiatric conditions.
Particular observation is required for patients who have previously experienced suicide attempts or who show a significant degree of suicidal tendencies before starting treatment.
Every patient taking Anafranil SR 75 (regardless of indication) should remain under close medical supervision. The doctor should monitor for any worsening of the patient's condition or the emergence of suicidal tendencies or other psychiatric symptoms. Such medical monitoring should occur during the initial phase of therapy and at times of dose adjustments. In such cases, especially if symptoms are severe, onset is sudden, or changes go beyond the patient's typical disease pattern, consideration should be given to modifying the treatment regimen or even discontinuing the medicine.
Patients, as well as family members and caregivers of children and adults treated with antidepressants for psychiatric or non-psychiatric reasons, should be informed by the doctor about the need to immediately report any clinical deterioration, emergence of suicidal thoughts or behaviours, or unusual changes in behaviour (see also section Undesirable effects).

Use of the medicine in patients with psychiatric disorders
In many patients with panic attacks, more pronounced anxiety symptoms occur at the beginning of Anafranil SR 75 treatment. Paradoxically, the intensification of anxiety is greatest during the first few days of treatment and usually subsides within two weeks.
In patients with schizophrenia receiving tricyclic antidepressants, activation of psychosis has sometimes been observed.
Episodes of mania or mild manic states have also been reported during depressive phases in patients with bipolar affective disorders treated with tricyclic antidepressants. In such cases, it may be necessary to reduce the dose of Anafranil SR 75 or discontinue it and administer an antipsychotic agent. Once these symptoms have resolved, treatment with low doses of Anafranil SR 75 may be restarted if needed.
Tricyclic antidepressants may induce psychoses (with delirium), especially at night, particularly in individuals predisposed to such reactions and in elderly patients. These symptoms resolve within a few days after discontinuation of the drug.

Serotonin syndrome
Due to the risk of toxic effects on the serotonergic system, recommended doses should be strictly followed. Serotonin syndrome, characterized by high fever, tremors, muscle rigidity, agitation, seizures, delirium, and coma, may occur when clomipramine is used concomitantly with serotonergic drugs such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, buprenorphine, or lithium.
If such symptoms (as described above) occur, the patient should contact their doctor.
When switching to or from fluoxetine, a waiting period of 2 to 3 weeks is recommended before starting or after stopping fluoxetine.

Seizures
Tricyclic antidepressants may lower the seizure threshold and therefore Anafranil SR 75 should be used with particular caution in patients with epilepsy or other factors predisposing to seizures, e.g. brain injury, concomitant use of neuroleptics, alcohol or anticonvulsant withdrawal. The occurrence of seizures is dose-dependent; therefore, recommended daily doses of Anafranil SR 75 should not be exceeded.
As with similar tricyclic antidepressants, concomitant treatment with Anafranil SR 75 and electroconvulsive therapy should only be administered under very close supervision.

Use of the medicine in patients with cardiovascular diseases
Anafranil SR 75 should be administered with particular caution to patients with cardiovascular diseases, especially those with circulatory failure, conduction disorders (e.g. first to third-degree atrioventricular block) or arrhythmias. In these patients, as well as in elderly patients, monitoring of cardiac function and electrocardiographic examination are recommended.
Concomitant use of drugs that increase clomipramine levels should be avoided, as well as concomitant administration of QT-prolonging drugs with clomipramine (see section 3).
Potassium deficiency should be corrected prior to administration of Anafranil SR 75 due to the risk of cardiac disturbances.
Blood pressure should be checked before starting treatment with Anafranil SR 75, as the drug may cause hypotension in patients with orthostatic hypotension or unstable circulation.

Anticholinergic effects
Due to anticholinergic properties, Anafranil SR 75 should be used cautiously in patients with a history of elevated intraocular pressure, narrow-angle glaucoma, or conditions associated with urinary retention (e.g. prostate disorders).
Reduced tear production and accumulation of mucus secretion, associated with the anticholinergic properties of tricyclic antidepressants, may cause corneal epithelial damage in patients wearing contact lenses.

White blood cell count
Changes in white blood cell count have been observed in isolated cases in patients treated with Anafranil SR 75; therefore, periodic monitoring of blood counts and observation for symptoms such as fever and sore throat are recommended. These recommendations particularly apply during the first months of treatment and during long-term therapy.

Anaesthesia
Before undergoing general or local anaesthesia, the anaesthesiologist should be informed about the use of Anafranil SR 75.

Special patient groups
Caution is advised when using tricyclic antidepressants in patients with severe liver disease and in patients with adrenal gland tumours, in whom these drugs may trigger hypertensive crisis.
Anafranil SR 75 should be used with caution in patients with hyperthyroidism and in those taking thyroid medications, due to the risk of cardiotoxic effects.
In patients with liver disease, periodic monitoring of liver enzyme activity is recommended.
Caution is required when administering the drug to patients with chronic constipation. Tricyclic antidepressants may cause paralytic ileus, especially in elderly and severely ill patients.
During long-term use of tricyclic antidepressants, an increased incidence of dental caries has been observed. Therefore, regular dental check-ups are recommended during prolonged treatment with these drugs.

Discontinuation of treatment
Abrupt discontinuation of the medicine should be avoided due to the risk of adverse reactions.

Anafranil SR 75 and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines planned for future use.
They may interact with Anafranil SR 75, and therefore dose adjustment or discontinuation of one of the medicines may be necessary.
During treatment with Anafranil SR 75, buprenorphine should not be taken without prior consultation with a doctor.
It is particularly important to inform the doctor about daily alcohol consumption and about taking the following medicines:

Those affecting blood pressure or heart function,
Other antidepressants (e.g. fluoxetine),
Neuroleptics,
Sedatives,
Barbiturates,
Benzodiazepines,
MAO inhibitors, e.g. moclobemide,
Antiepileptic drugs,
Anticoagulants,
Antiasthmatic or antiallergic drugs,
Drugs used in Parkinson's disease,
Thyroid preparations,
Cimetidine,
Rifampicin,
Methylphenidate,
Oral contraceptives,
Estrogens,
Diuretics.

Information contained in this leaflet may also apply to medicines used in the past or those to be used in the future.

Use of Anafranil SR 75 in elderly patients
Elderly patients require lower doses than younger or middle-aged patients. Adverse reactions occur more frequently in elderly patients. The treating physician should provide the patient with information regarding precise dosing and the necessity of careful self-monitoring.

Children and adolescents
Anafranil SR 75 is indicated for the treatment of nocturnal enuresis in children over 5 years of age (provided organic causes have been excluded).

Pregnancy and breastfeeding
Pregnancy
Before taking any medicine, consult a doctor or pharmacist.
Inform the doctor if pregnancy has occurred or is suspected. Anafranil SR 75 should not be used during pregnancy unless clearly recommended by a doctor.
Available data do not indicate an increased risk of general congenital malformations in offspring. However, some data from medical registries suggest an increased risk of heart defects in children of women who used clomipramine during the first three months of pregnancy (2 cases per 100 pregnancies) compared to the general population (1 case per 100 pregnancies).

Breastfeeding
Before taking any medicine, consult a doctor or pharmacist.
Inform the doctor if breastfeeding. The active substance in Anafranil SR 75 passes into breast milk; therefore, the medicine should be gradually discontinued or breastfeeding should be stopped.

Driving and operating machinery
Anafranil SR 75 may cause drowsiness, reduced concentration, and blurred vision in some individuals. If such symptoms occur, driving, operating machinery, or performing other tasks requiring high concentration should be avoided. Alcohol consumption may intensify drowsiness.

Anafranil SR 75 contains macrogol glycerol hydroxystearate.
The medicine may cause indigestion and diarrhoea.

3. How to use Anafranil SR 75

This medicine should always be used exactly as prescribed by the doctor.
If in doubt, consult your doctor or pharmacist.
Dosage and method of administration should be individually determined and adjusted according to the patient's condition. To achieve the optimal effect, the lowest effective dose should be used whenever possible. If necessary, the dose should be increased cautiously. This recommendation applies especially to elderly patients and adolescents, who are generally more sensitive to Anafranil SR 75 than other patients.

Due to the risk of QTc interval prolongation and toxic effects on the serotonergic system, the recommended doses of Anafranil SR 75 must be strictly observed.
When Anafranil SR 75 is used concomitantly with drugs that prolong the QT interval or drugs acting on the serotonergic system, any dose increase should be carried out with caution.

Adults
Depression, obsessive-compulsive disorders and phobias
Treatment should be initiated with one 25 mg coated tablet taken 2–3 times daily or one 75 mg prolonged-release tablet once daily (preferably in the evening). The daily dose should be gradually increased, e.g. by 25 mg every few days (depending on drug tolerance), to 4–6 tablets of 25 mg or 2 prolonged-release tablets of 75 mg during the first week of treatment. In severe cases, the dose may be increased up to a maximum of 250 mg per day.
Once a clear clinical improvement is achieved, the daily dose should be adjusted to a maintenance level, usually about 2–4 coated tablets of 25 mg or 1 prolonged-release tablet of 75 mg.

Panic attacks, agoraphobia
Treatment should be initiated with one 10 mg coated tablet per day. Depending on the patient's tolerance, the dose should be gradually increased until a satisfactory clinical condition is achieved. The daily dose is individually determined for each patient and ranges from 25 mg to 100 mg. If necessary, the dose may be increased to 150 mg/day. Treatment should not be discontinued for at least 6 months. During this period, the maintenance dose should be gradually reduced.

Elderly patients
Treatment should be initiated with one 10 mg coated tablet per day. The dose should then be gradually increased so that the optimal dose of 30 to 50 mg/day is reached after approximately 10 days. This dose should be maintained throughout the treatment period.

Use in children and adolescents
Nocturnal enuresis
The initial daily dose for children aged 5–8 years is 2–3 coated tablets of 10 mg; for children aged 9–12 years, 1–2 tablets of 25 mg; and for children over 12 years, 1–3 tablets of 25 mg. Higher doses may be used in patients who do not achieve a full response within 1 week of treatment. Coated tablets should be administered as a single dose after the evening meal. In children who wet the bed during the early hours of the night, part of the dose may be administered earlier (around 4 p.m.). After the desired clinical response is achieved, treatment should be continued for 1–3 months, with a gradual reduction of the dose.

There are no data on the use of Anafranil SR 75 in children under 5 years of age.

Prolonged-release coated tablets may be divided in half but must not be chewed.

Taking more Anafranil SR 75 than prescribed
If more tablets are taken than prescribed by the doctor, seek medical help immediately. Usually within a few hours after overdose, the following symptoms may occur: pronounced drowsiness; concentration disturbances; fast, slow or irregular heartbeat; motor restlessness and agitation; loss of muscle coordination and muscle stiffness; shortness of breath; seizures; vomiting; fever. Overdose is particularly dangerous in young children.

Missing a dose of Anafranil SR 75
If a dose of Anafranil SR 75 is missed, take the missed dose as soon as possible and resume the regular dosing schedule. If it is almost time for the next dose, do not take the missed dose; instead, take the next dose according to the regular schedule. If in doubt, consult your doctor or pharmacist.
Do not take a double dose to make up for a missed dose.

Stopping Anafranil SR 75
The following symptoms usually occur after abrupt discontinuation of the medicine or dose reduction: nausea, vomiting, abdominal pain, diarrhoea, insomnia, headache, nervousness and anxiety.
If a patient with cataplexy suddenly stops taking the medicine, symptoms may worsen.

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

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
They usually do not require medical intervention and may resolve during treatment as the patient's
body becomes accustomed to the medicine.
You should inform your doctor immediately of any unexpected symptoms during treatment with
Anafranil SR 75. This also includes symptoms that do not seem to be related to the use of the medicine.
Contact your doctor as soon as possible if any of the following adverse effects occur, as medical
intervention may be necessary:
jaundice, skin reactions (itching or redness), fever and sore throat, loss of balance, eye pain, severe
abdominal pain, muscle weakness or stiffness, muscle spasms, difficulty passing urine, breast
swelling and galactorrhea, rapid or irregular heartbeat (palpitations, tachycardia), difficulty
speaking, confusion or delirium, hallucinations, seizures.
Suicidal thoughts, worsening of depression or anxiety disorders
Patients with depression or anxiety disorders may sometimes experience thoughts of self-harm or
suicide. These symptoms or behaviours may worsen at the beginning of treatment with antidepressant
medicines, as these medicines usually take about 2 weeks, sometimes longer, to start working.
The occurrence of suicidal thoughts, thoughts of self-harm or suicide is more likely if:

the patient has previously experienced suicidal thoughts or self-harm;
the patient is a young adult; clinical studies have shown an increased risk of suicidal behaviour in individuals under 25 years of age with psychiatric disorders treated with antidepressant medicines.

If the patient experiences suicidal thoughts or thoughts of self-harm, contact a doctor immediately or go to a hospital.
Adverse effects are listed below, starting with the most frequent ones:
Very common (affects more than 1 in 10 patients)
Drowsiness, fatigue, restlessness, increased appetite, somnolence, dizziness, tremor, headache,
convulsions, clonic muscle spasms, nausea, dry mouth, constipation, excessive sweating, eye
accommodation disorders, blurred vision, urinary disorders, weight gain, sexual drive disorders,
impotence.
Common (affects less than 1 in 10 patients)
Delirium, confusion (impaired consciousness), disorientation, hallucinations (especially in elderly
patients and patients with Parkinson's disease), anxiety states, agitation, sleep disturbances, manic
excitement, aggression, memory disturbances, worsening of depression, concentration disorders,
insomnia, nightmares, yawning, speech disorders, paraesthesia (prickling or burning sensations),
muscle weakness, increased muscle tension, hot flushes, dilated pupils, sinus tachycardia, palpitations,
orthostatic hypotension (sudden drop in blood pressure upon changing to upright position), changes
in ECG in patients with normal heart function, vomiting, abdominal discomfort, diarrhoea, loss of
appetite, increased liver enzyme activity (aminotransferases), allergic skin reactions (rash, urticaria),
photosensitivity, itching, galactorrhea, breast enlargement, taste disturbances, tinnitus.
Uncommon (affects less than 1 in 100 patients)
Exacerbation of psychotic symptoms, ataxia (impaired motor coordination), arrhythmia, increased
blood pressure.
Rare (affects less than 1 in 1000 patients)
Cardiac conduction disturbances.
Very rare (affects less than 1 in 10,000 patients)
Changes in EEG recording, hyperpyrexia (marked increase in body temperature), glaucoma (increased
intraocular pressure), urinary retention, hepatitis with or without jaundice, oedema (local or general),
alopecia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), allergic alveolitis (lung
inflammation) with or without eosinophilia (increased number of one type of white blood cells),
systemic anaphylactic or anaphylactoid reactions, including hypotension, abnormal blood cell counts
(leukopenia, agranulocytosis, thrombocytopenia, eosinophilia), purpura.
Frequency not known (frequency cannot be estimated from available data)
Suicidal ideation, suicidal behaviour, fractures, myocardial damage (cardiomyopathy), heart failure.
If any of the adverse effects worsen, including any possible adverse effects not listed in this leaflet,
consult a doctor, pharmacist, or nurse.
Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions,
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of the medicine.
Adverse effects can also be reported to the marketing authorisation holder.

5. How to store Anafranil SR 75

No special requirements.
The medicine should be stored in a place inaccessible and not visible to children.
Do not use this medicine after the expiry date stated on the packaging after: Expiry
(Exp). The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Anafranil SR 75 contains
The active substance in this medicine is clomipramine hydrochloride.

One prolonged-release coated tablet contains 75 mg of clomipramine hydrochloride.
Other ingredients of the medicine are: Calcium hydrogen phosphate dihydrate
Methacrylic acid and ethyl acrylate copolymer (1:1)
Eudragit NE 30 D
Calcium stearate
Colloidal silicon dioxide

Coating ingredients:
Hypromellose
Polyoxyl 35 hydrogenated castor oil (Kolliphor RH 40)
Iron oxide red
Talc
Titanium dioxide

What Anafranil SR 75 looks like and contents of the pack
Prolonged-release pink, elongated coated tablets with a score line on one side dividing the tablet into two halves, marked with "CG" on one side and "GD" on the other.
2 blisters of 10 prolonged-release coated tablets in a cardboard box (20 tablets).

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
Emilii Plater 53 Street
00-113 Warsaw
Poland

Manufacturer
Teva Operations Poland Sp. z o.o.
Mogilska 80 Street
31-546 Kraków