Package leaflet: Information for the patient

Anafranil, 10 mg, film-coated tablets
Anafranil, 25 mg, film-coated tablets
Clomipramini hydrochloridum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

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

Contents of the leaflet

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

1. What Anafranil is and what it is used for

Anafranil is a medicine in the form of film-coated tablets, containing as the active substance
clomipramine hydrochloride, which belongs to the group of tricyclic antidepressants.
Anafranil 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 conditions related to advanced age, chronic
pain states, 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

When not to use Anafranil

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 (MAO) antidepressants, or within 14 days before or after treatment with MAO inhibitors. Concomitant 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, discuss this with your doctor or pharmacist. The patient
should inform the doctor about the following conditions:

Seizures,
Irregular heartbeat, cardiovascular diseases, especially cardiac arrhythmias and circulatory failure,
Schizophrenia,
Glaucoma (increased intraocular pressure),
Liver or kidney disease,
Any blood disorders,
Difficulty in urination, 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 assessing
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 of the disease 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 taken.
Short-term clinical studies have shown that antidepressant drugs increase the risk of suicidal thoughts and behaviours (suicidal tendencies) in children and adolescents suffering from depressive disorders and other psychiatric disorders.
Particular observation is required for patients who have previously experienced suicide attempts or those showing a significant degree of suicidal tendencies before starting treatment.
Every patient taking Anafranil (regardless of indication) should be 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 dosage changes. In such cases, especially if symptoms are severe, onset is sudden, or symptoms go beyond the typical disease pattern of the patient, consideration should be given to changing the treatment regimen or even discontinuing the drug.
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 worsening, emergence of suicidal thoughts or behaviours, or unusual changes in behaviour (see also section Undesirable effects).
Use of Anafranil in patients with psychiatric disorders
In many patients with panic attacks, more pronounced anxiety symptoms may occur at the beginning of Anafranil treatment. Paradoxically, anxiety intensification is greatest during the first few days of treatment and usually subsides within two weeks.
In patients with schizophrenia receiving tricyclic antidepressants, psychotic activation has sometimes been observed.
Episodes of mania or mild manic states have also been reported during the depressive phase in patients with bipolar affective disorders treated with tricyclic antidepressants. In such cases, it may be necessary to reduce the dose of Anafranil or discontinue it and administer an antipsychotic agent. Once these symptoms resolve, treatment with low doses of Anafranil may be restarted if necessary.
Tricyclic antidepressants may induce, especially at night, psychotic symptoms (with delirium), particularly in individuals predisposed to such reactions and in elderly patients. These symptoms usually 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 observed. 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, serotonin-noradrenaline reuptake inhibitors, tricyclic antidepressants, buprenorphine or lithium.
If such symptoms (as described above) occur, contact your doctor immediately.
When switching to fluoxetine, a washout period of 2 to 3 weeks is recommended before starting fluoxetine or after discontinuing it.
Seizures
Tricyclic antidepressants may lower the seizure threshold; therefore, Anafranil should be used with particular caution in patients with epilepsy or other factors predisposing to seizures, e.g. brain damage, concomitant use of neuroleptics, alcohol or anticonvulsant withdrawal. The occurrence of seizures is dose-dependent; therefore, recommended daily doses of Anafranil should not be exceeded.
As with similar tricyclic antidepressants, concomitant treatment with Anafranil and electroconvulsive therapy should only be administered under very close supervision.
Use of Anafranil in patients with cardiovascular disorders
Anafranil 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 drugs that prolong the QTc interval with clomipramine (see section 3).
Potassium deficiency should be corrected before administering Anafranil due to the risk of cardiac disturbances.
Blood pressure should be checked before starting Anafranil, as the drug may cause hypotension in patients with orthostatic hypotension or unstable circulation.
Anticholinergic effects
Due to its anticholinergic properties, Anafranil 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, related to the anticholinergic properties of tricyclic antidepressants, may cause corneal epithelial damage in patients wearing contact lenses.
White blood cell count
In isolated cases, changes in white blood cell count have been observed in patients treated with Anafranil; therefore, periodic blood count monitoring 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, inform the anaesthesiologist that the patient is taking Anafranil.
Special patient groups
Caution is advised when using tricyclic antidepressants in patients with severe liver disease and in patients with pheochromocytoma, as these drugs may trigger a hypertensive crisis.
Anafranil should be used with caution in patients with hyperthyroidism and in patients receiving thyroid medications, due to the risk of cardiotoxic effects.
In patients with liver disease, periodic monitoring of liver enzyme activity is recommended.
Caution is advised 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 drug should be avoided due to the risk of adverse effects.
Anafranil with other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently used, as well as any medicines the patient plans to take.
They may interact with Anafranil, so dose adjustment or discontinuation of one of the medicines may be necessary.
During treatment with Anafranil, buprenorphine should not be taken without prior consultation with a doctor.
It is particularly important to inform the doctor about daily alcohol consumption and the use of 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,
Medicines used in Parkinson's disease,
Thyroid preparations,
Cimetidine,
Rifampicin,
Methylphenidate,
Oral contraceptives,
Estrogens,
Diuretics.

The 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 in elderly patients
Elderly patients require lower doses of the drug than younger or middle-aged patients. Adverse effects 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 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 your doctor or pharmacist.
Inform your doctor if you are pregnant or suspect pregnancy. Anafranil 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 your doctor or pharmacist.
Inform your doctor if you are breastfeeding. The active substance in Anafranil passes into breast milk; therefore, the drug should be gradually discontinued or breastfeeding should be stopped.
Driving and operating machinery
Anafranil may cause drowsiness, reduced concentration ability, and blurred vision in some individuals. If such symptoms occur, do not drive, operate machinery, or perform other tasks requiring high attention. Alcohol consumption may worsen drowsiness.
Anafranil contains lactose and sucrose.
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking the medicine.

3. How to take Anafranil

This medicine should always be taken exactly as directed by your 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 possible dose should be used. If necessary, the dose should be increased cautiously. This recommendation applies particularly to elderly patients and adolescents, who generally show greater sensitivity to Anafranil than other patients.
Due to the potential for QTc interval prolongation and toxic effects on the serotonergic system, the recommended doses of Anafranil must be strictly observed.
When Anafranil is used concomitantly with medicines that prolong the QT interval or affect the serotonergic system, any dose increase should be performed with caution.

Adults
Depression, obsessive disorders, and phobias
Treatment should be initiated with 1 coated tablet of 25 mg taken 2–3 times daily, or 1 extended-release tablet of 75 mg once daily (preferably in the evening). The daily dose should be gradually increased, e.g., by 25 mg every few days (depending on tolerance) to 4–6 tablets of 25 mg or 2 extended-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 daily. Once a clear improvement is achieved, the daily dose should be adjusted to a maintenance dose, usually around 2–4 coated tablets of 25 mg or 1 extended-release tablet of 75 mg.

Panic attacks, agoraphobia
Treatment should be initiated with 1 coated tablet of 10 mg daily. Depending on the patient's tolerance, the dose should be gradually increased until a satisfactory clinical response is achieved. The daily dose is individually determined for each patient and typically ranges from 25 mg to 100 mg. If necessary, the dose may be increased up to 150 mg/day. It is recommended that 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 1 coated tablet of 10 mg daily. 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
Night 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 show a full response to treatment within 1 week. Coated tablets should be administered as a single dose after the evening meal. In children who wet the bed early in the night, part of the dose should be given earlier (around 4 p.m.). After achieving the desired clinical response, treatment should be continued for 1–3 months, with a gradual reduction of the dose.

There are no data on the use of Anafranil in children below 5 years of age.

Coated tablets should be swallowed whole and taken with plenty of fluid.

Taking more Anafranil than prescribed
If you take more tablets than prescribed by your doctor, seek medical help immediately. Symptoms usually appear within a few hours after overdose and may include pronounced drowsiness; difficulty concentrating; fast, slow, or irregular heartbeat; restlessness and agitation; loss of muscle coordination and muscle stiffness; shortness of breath; seizures; vomiting; fever. Overdose is particularly dangerous in young children.

If you forget to take Anafranil
If you miss a dose of Anafranil, take the missed dose as soon as possible and then return to your regular dosing schedule. If it is almost time for your next dose, do not take the missed dose; instead, take the next dose at the regular time. If in doubt, consult your doctor.
Do not take a double dose to make up for a missed dose.

Stopping Anafranil
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 reactions

Like any medicine, this medicine can cause adverse reactions, 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.
Any unexpected symptoms occurring during treatment with Anafranil should be reported to the doctor immediately.
This also includes symptoms that do not appear to be related to taking the medicine.
Contact your doctor as soon as possible if any of the following adverse reactions 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 urinating, 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.
Such symptoms or behaviours may worsen at the beginning of treatment with antidepressants, as these medicines usually take about 2 weeks, sometimes longer, to start working.
Cases of suicidal behaviour and suicidal thoughts have been observed during treatment with clomipramine or shortly after discontinuation of therapy.
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 indicate an increased risk of suicidal behaviour in individuals under 25 years of age with psychiatric disorders who are treated with antidepressant medicines.

If a patient experiences suicidal thoughts or thoughts of self-harm, immediate contact should be made with a doctor or the patient should go to a hospital.
Adverse reactions are listed starting with the most frequent:
Very common (affects more than 1 in 10 patients)
Drowsiness, fatigue, restlessness, increased appetite, somnolence, dizziness, tremor, headache, convulsions, clonic muscle spasms, dry mouth, excessive sweating, constipation, accommodation disorders of the eye, blurred vision, urinary disorders, nausea, weight gain, disturbances in sexual desire, erectile dysfunction.
Common (affects less than 1 in 10 patients)
Delirium, confusion (impaired consciousness), disorientation, hallucinations (especially in elderly patients and those with Parkinson's disease), anxiety states, agitation, sleep disturbances, manic excitement, aggression, memory disturbances, depersonalization (feeling of loss of self-identity), worsening of depression, difficulty concentrating, insomnia, nightmares, yawning, speech disorders, paresthesia (tingling, burning sensation), 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 recording 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, convulsions, ataxia (impaired motor coordination), arrhythmia, increased blood pressure.
Rare (affects less than 1 in 1000 patients)
Cardiac conduction disturbances, particularly in patients with hypokalaemia (low potassium levels in blood).
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, swelling (local or generalized), hair loss, syndrome of inappropriate antidiuretic hormone secretion (SIADH), allergic alveolitis (lung inflammation) with or without eosinophilia (increased levels 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, damage to the heart muscle (cardiomyopathy), heart failure.
An increased risk of bone fractures has been observed in patients taking selective serotonin reuptake inhibitors and tricyclic antidepressants.
Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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 reactions helps to provide more information on the safety of the medicine.
Adverse reactions can also be reported to the marketing authorization holder.

5. How to store Anafranil

Anafranil 10 mg, coated tablets – no special storage instructions.
Anafranil 25 mg, coated tablets – protect from moisture.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after: Expiry
date (EXP)/EXP. The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Anafranil contains
The active substance is clomipramine hydrochloride.
One Anafranil 10 mg coated tablet contains 10 mg of clomipramine hydrochloride.
The other ingredients are:
Colloidal silicon dioxide
Hypromellose
Lactose monohydrate
Magnesium stearate
Corn starch
Coating ingredients:
Hypromellose
Microcrystalline cellulose
Iron oxide yellow
Titanium dioxide
Povidone K 30
Sucrose
Talc
Copovidone
Macrogol 8000

One Anafranil 25 mg coated tablet contains 25 mg of clomipramine hydrochloride.
The other ingredients are:
Glycerol
Magnesium stearate
Lactose monohydrate
Colloidal silicon dioxide
Corn starch
Talc
Stearic acid
Coating ingredients:
Hypromellose
Copovidone
Talc
Iron oxide yellow
Titanium dioxide
Povidone K 30
Sucrose
Macrogol 8000
Microcrystalline cellulose

What Anafranil looks like and contents of the pack
Anafranil 10 mg
Light yellow, triangular, biconvex coated tablets.
Packaged as 30 coated tablets in a cardboard box.

Anafranil 25 mg
Light yellow, round, biconvex coated tablets.
Packaged as 30 coated tablets in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
Emilii Plater 53
00-113 Warsaw, Poland
Tel.: (22) 345 93 00

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