ANAFRANIL 25 mg Tablets

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Anafranil, 10 mg, Coated Tablets
3. Anafranil, 25 mg, Coated Tablets
   1. Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.
   2. Table of Contents of the Package Leaflet
4. What is Anafranil and what is it used for
5. Important information before taking Anafranil
   1. When not to take Anafranil
   2. Warnings and precautions
   3. Anafranil and other medications
   4. Using Anafranil in the elderly
   5. Children and adolescents
   6. Pregnancy and breastfeeding
   7. Driving and operating machinery
6. How to take Anafranil
   1. Taking a higher dose of Anafranil than recommended
   2. Missing a dose of Anafranil
   3. Discontinuing Anafranil treatment
7. Possible side effects
   1. The patient should contact their doctor as soon as possible if they experience any of the following side effects, as medical intervention may be necessary:
   2. Reporting side effects
8. How to store Anafranil
9. Package contents and other information
   1. What Anafranil contains
   2. What Anafranil looks like and package contents
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer
   6. Date of the last revision of the package leaflet:

Package Leaflet: Information for the Patient

Anafranil, 10 mg, Coated Tablets

Anafranil, 25 mg, Coated Tablets

Clomipramine Hydrochloride

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• The package leaflet should be kept in case it needs to be read again.
• In case of any doubts, the patient should consult a doctor, pharmacist, or nurse.
• This medication has been prescribed for a specific person. It should not be given to others. The medication may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those not listed in this package leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Anafranil and what is it used for
• 2. Important information before taking Anafranil
• 3. How to take Anafranil
• 4. Possible side effects
• 5. How to store Anafranil
• 6. Package contents and other information

1. What is Anafranil and what is it used for

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

2. Important information before taking Anafranil

When not to take Anafranil

• If the patient is allergic to the active substance or any of the other ingredients of this medication (listed in section 6);
• If the patient has cross-sensitivity to tricyclic antidepressants;
• If the patient is taking monoamine oxidase inhibitor (MAOI) medications and for 14 days before starting or after stopping MAOI treatment. It is also not recommended to take selective, reversible MAO-A inhibitors, such as moclobemide, at the same time;
• If the patient has recently had a myocardial infarction;
• If the patient has a congenital long QT syndrome.

Warnings and precautions

Before starting Anafranil, the patient should discuss it with their doctor or pharmacist. The patient should inform their doctor about the following conditions:

• seizures,
• irregular heartbeat, cardiovascular diseases, especially rhythm disorders and heart failure,
• schizophrenia,
• glaucoma (increased eye pressure),
• liver or kidney diseases,
• any blood diseases,
• difficulties in urinating, e.g., due to prostate diseases,
• hyperthyroidism,
• constipation,
• alcohol abuse.

It is essential for the doctor to regularly assess the treatment effects, which allows for adjusting the medication dose and reducing the possibility of side effects. During the follow-up visit, the doctor may recommend a blood test and measure blood pressure and heart rate before and during treatment.

Suicidal thoughts, suicidal ideation, or clinical worsening

The risk of suicidal thoughts, self-harm, or suicidal attempts, characteristic of severe depression, may persist until significant remission of the disease. In patients with depressive disorders, both adults and children, there may be an increase in depression and (or) suicidal tendencies, or an increase in other psychiatric symptoms, regardless of whether other antidepressant medications are being taken. Short-term clinical trials have shown that antidepressant medications increase the risk of suicidal thoughts and behaviors (suicidal ideation) in children and adolescents with depressive disorders and other psychiatric disorders.

Patients who have had suicidal attempts or show a significant degree of suicidal tendencies before starting treatment require special observation. Every patient taking Anafranil (regardless of the indication) should be under close medical supervision. The doctor should pay attention to any worsening of the patient's condition or the occurrence of suicidal tendencies or other psychiatric symptoms. Such medical supervision should take place at the initial stage of therapy and when changing the dosage. In such situations, especially if the changes are severe, their onset is sudden, or they exceed the characteristic symptoms of the patient's disease, it is necessary to consider changing the treatment regimen, or even discontinuing the medication.

Patients, as well as family members and caregivers of children and adults being treated with antidepressants for psychiatric and non-psychiatric reasons, will be informed by the doctor about the need to immediately report any worsening of the patient's clinical condition, the occurrence of suicidal thoughts or behaviors, or unusual changes in behavior (see also section 4, Possible side effects).

Using Anafranil in patients with mental disorders

In many patients suffering from panic attacks, at the beginning of Anafranil treatment, more pronounced anxiety symptoms occur. Paradoxically, the intensification of anxiety is greatest during the first few days of treatment and usually subsides within two weeks.

In patients with schizophrenia, taking tricyclic antidepressants has sometimes led to the activation of psychosis.

There have also been reports of manic or mild manic episodes during the depressive phase in patients with cyclical 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 medication to the patient. Once these symptoms have subsided, treatment with Anafranil can be restarted with small doses if necessary.

Tricyclic antidepressants may cause, especially at night, psychoses (with delirium), particularly in people prone to such reactions and in elderly patients. These symptoms subside within a few days after discontinuing the medication.

Serotonin syndrome

Due to the risk of toxic effects on the serotonergic system, the recommended doses should be followed. Serotonin syndrome, characterized by high fever, seizures, muscle spasms, agitation, seizures, delirium, and coma, may occur during concomitant use of clomipramine with serotonergic medications, such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, buprenorphine, or lithium.

If the patient experiences such symptoms (as above), they should contact their doctor.

In the case of fluoxetine, it is recommended to wait 2 to 3 weeks before taking fluoxetine or after taking it.

Seizures

Tricyclic antidepressants may lower the seizure threshold, and therefore, Anafranil should be used with caution in patients with epilepsy or other factors predisposing to seizures, such as brain damage, concomitant administration of neuroleptics, or a history of alcohol or anticonvulsant drug withdrawal (e.g., benzodiazepines). The occurrence of seizures is dose-dependent, so the recommended daily doses of Anafranil should not be exceeded.

As with similar tricyclic antidepressants, concomitant treatment with Anafranil and electroconvulsive therapy should only be used under very close supervision.

Using Anafranil in patients with cardiovascular diseases

Anafranil should be administered with caution to patients with cardiovascular diseases, especially those with heart failure, conduction disorders (e.g., first- to third-degree atrioventricular block), or cardiac arrhythmias.

In these patients, as well as in the elderly, it is recommended to monitor heart function and perform an electrocardiogram.

Concomitant use of medications that may increase clomipramine levels should be avoided, and medications that prolong the QTc interval should not be administered with clomipramine (see section 3).

Before administering Anafranil, potassium deficiencies should be corrected due to the risk of cardiac arrhythmias.

Before starting Anafranil treatment, it is recommended to check blood pressure, as the medication may cause a drop in blood pressure in patients with orthostatic hypotension or unstable circulation.

Anticholinergic effects

Due to its anticholinergic properties, Anafranil should be administered with caution to patients with a history of increased intraocular pressure, narrow-angle glaucoma, or diseases associated with urinary retention (e.g., prostate diseases).

The decreased production of tear fluid and the accumulation of mucous secretions, associated with the anticholinergic properties of tricyclic antidepressants, may cause damage to the corneal epithelium in patients wearing contact lenses.

White blood cell count

In patients treated with Anafranil, changes in white blood cell count have been reported in individual cases, so it is recommended to periodically monitor the white blood cell count and observe for symptoms such as fever and sore throat. These recommendations are particularly important during the first months of treatment and during long-term treatment.

Anesthesia

Before undergoing general or local anesthesia, the patient should inform the anesthesiologist about taking Anafranil.

Special patient groups

Caution is recommended when using tricyclic antidepressants in patients with severe liver diseases and adrenal gland tumors, as these medications may cause a hypertensive crisis.

Anafranil should be used with caution in patients with hyperthyroidism and those taking thyroid preparations, due to the possibility of toxic effects on the heart.

In patients with liver diseases, it is recommended to periodically monitor liver enzyme activity.

Caution should be exercised when administering the medication to patients with chronic constipation. Tricyclic antidepressants may cause paralytic ileus, especially in the elderly and bedridden patients.

During long-term use of tricyclic antidepressants, an increased frequency of tooth decay has been reported. Therefore, during long-term use of these medications, regular dental check-ups are recommended.

Discontinuing treatment

It is recommended to avoid sudden discontinuation of the medication due to the possibility of side effects.

Anafranil and other medications

The patient should inform their doctor or pharmacist about all medications they are currently taking or have recently taken, as well as any medications they plan to take.

These medications may interact with Anafranil, so it may be necessary to adjust the dose or discontinue one of the medications.

While taking Anafranil, the patient should not take buprenorphine without consulting their doctor first.

It is particularly important to inform the doctor about daily alcohol consumption and the use of the following medications:

• those affecting blood pressure or heart function,
• other antidepressant medications (e.g., fluoxetine),
• neuroleptics,
• sedatives,
• barbiturates,
• benzodiazepines,
• monoamine oxidase inhibitors (MAOIs), such as moclobemide,
• antiepileptic medications,
• anticoagulant medications,
• asthma or allergy medications,
• medications used in Parkinson's disease,
• thyroid preparations,
• cimetidine,
• rifampicin,
• methylphenidate,
• oral contraceptives,
• estrogens,
• diuretics.

The information in this package leaflet may also apply to medications used in the past or those that will be used in the future.

Using Anafranil in the elderly

Elderly patients require smaller doses of the medication than younger patients. Side effects occur more frequently in elderly patients. The treating doctor should provide the patient with information about the exact dosage and the need for careful self-observation.

Children and adolescents

Anafranil is indicated for the treatment of nocturnal enuresis in children over 5 years old (provided that organic causes have been excluded).

Pregnancy and breastfeeding

Pregnancy

Before taking any medication, the patient should consult their doctor or pharmacist.

The patient should inform their doctor about the pregnancy or suspected pregnancy. Anafranil should not be used during pregnancy unless explicitly prescribed by the doctor.

Breastfeeding

Before taking any medication, the patient should consult their doctor or pharmacist.

The patient should inform their doctor about breastfeeding. The active substance in Anafranil passes into breast milk, so the medication should be gradually discontinued or breastfeeding should be stopped.

Driving and operating machinery

Anafranil may cause drowsiness and reduced concentration in some individuals, as well as decreased visual acuity. If such symptoms are observed, the patient should not drive vehicles, operate machinery, or perform other activities that require high concentration. Alcohol consumption may increase drowsiness.

Anafranil contains lactose and sucrose. If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking the medication.

3. How to take Anafranil

This medication should always be taken according to the doctor's instructions. In case of doubts, the patient should consult their doctor or pharmacist.

The dosage and administration method should be individualized and adjusted according to the patient's condition. To achieve the optimal effect, the smallest possible dose should be used. If necessary, the dose should be increased cautiously. This recommendation is particularly important for elderly patients and adolescents, as they usually show greater sensitivity to Anafranil than other patients.

Due to the possibility of QTc interval prolongation and toxic effects on the serotonergic system, the recommended doses of Anafranil should be followed.

In the case of concomitant administration of medications that prolong the QT interval or affect the serotonergic system with Anafranil, the dose of Anafranil should be increased with caution.

Adults

Depression, obsessive-compulsive disorders, and phobias

Treatment should be started with 1 tablet of 25 mg, 2-3 times a day, or 1 tablet of 75 mg with prolonged release, 1 time a day (preferably in the evening). The daily dose should be increased gradually, e.g., by 25 mg every few days (depending on the patient's tolerance to the medication), up to 4-6 tablets of 25 mg or 2 tablets of 75 mg with prolonged release during the first week of treatment. In severe cases, the dose can be increased up to a maximum of 250 mg per day. Once significant improvement is achieved, the daily dose should be adjusted to the maintenance dose, usually around 2-4 tablets of 25 mg or 1 tablet of 75 mg with prolonged release.

Panic attacks, agoraphobia

Treatment should be started with 1 tablet of 10 mg per day. Depending on the patient's tolerance to the medication, the dose should be increased until a satisfactory clinical condition is achieved. The daily dose is determined individually for each patient and ranges from 25 mg to 100 mg. If necessary, the dose can be increased up to 150 mg per day. It is recommended not to discontinue treatment for at least 6 months. During this period, the maintenance dose should be gradually reduced.

Elderly patients

Treatment should be started with 1 tablet of 10 mg per day. The dose should be increased gradually to achieve the optimal dose, ranging from 30 to 50 mg per day, within 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 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 should be used in patients who do not show a full response to treatment within 1 week. The tablets should be administered as a single dose after the evening meal. In cases of nocturnal enuresis occurring in the early hours of the night, part of the dose should be administered earlier (around 4 pm). After achieving the desired clinical response, treatment should be continued (for 1-3 months), and the dose should be gradually reduced.

There is no data on the use of Anafranil in children under 5 years old.

The tablets should be swallowed whole and washed down with a large amount of liquid.

Taking a higher dose of Anafranil than recommended

In case of taking more tablets than prescribed by the doctor, the patient should immediately seek medical help. Usually, within a few hours after overdosing, the following symptoms appear: increased drowsiness; impaired concentration; rapid, slow, or irregular heart rhythm; restlessness and agitation; loss of muscle coordination and stiffness; shortness of breath; seizures; vomiting; fever. Overdosing is particularly dangerous in small children.

Missing a dose of Anafranil

In case of missing a dose, the patient should take the missed dose as soon as possible and return to the regular dosing schedule. If there is not much time left before the next dose, the patient should not take the missed dose, but take the next dose according to the schedule. In case of doubts, the patient should consult their doctor.

The patient should not take a double dose to make up for the missed dose.

Discontinuing Anafranil treatment

The following symptoms usually occur after sudden discontinuation of the medication or dose reduction: nausea, vomiting, abdominal pain, diarrhea, insomnia, headache, nervousness, and anxiety.

In case of any further doubts about the use of this medication, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medications, Anafranil can cause side effects, although not everybody gets them. Usually, they do not require medical intervention and may subside during treatment as the patient's body gets used to the medication.

The patient should immediately inform their doctor about any unexpected symptoms during Anafranil treatment. This includes symptoms that do not seem to be related to the medication.

The patient should contact their doctor as soon as possible if they experience any of the following side effects, as medical intervention may be necessary:

jaundice, skin reactions (itching or redness), fever and sore throat, balance disorders, eye pain, severe abdominal pain, muscle weakness or stiffness, muscle spasms, urinary retention, breast swelling and galactorrhea, rapid or irregular heart rhythm (tachycardia, palpitations), speech difficulties, confusion or delirium, hallucinations, seizures.

Suicidal thoughts, worsening of depression or anxiety disorders

Patients with depression or anxiety disorders may sometimes have thoughts of self-harm or suicide. Such symptoms or behavior may worsen at the beginning of antidepressant treatment, as these medications usually start working after 2 weeks, sometimes later.

Cases of suicidal behavior and thoughts have been reported during clomipramine treatment or shortly after discontinuing treatment.

The occurrence of suicidal thoughts, self-harm, or suicidal attempts is more likely if:

• the patient has had suicidal thoughts or self-harm in the past;
• the patient is a young adult; clinical trials indicate an increased risk of suicidal behavior in people under 25 years old with psychiatric disorders who have been treated with antidepressant medications.

If the patient experiences suicidal thoughts or self-harm, they should immediately contact their doctor or go to the hospital.

Side effects are listed in order of frequency:

Very common (more than 1 in 10 patients)

Drowsiness, fatigue, restlessness, increased appetite, lethargy, dizziness, tremors, headache, seizures, muscle spasms, dry mouth, excessive sweating, constipation, accommodation disorders, blurred vision, urinary retention, nausea, weight gain, sexual dysfunction.

Common (less than 1 in 10 patients)

Delirium, confusion (altered consciousness), disorientation, hallucinations (especially in the elderly and patients with Parkinson's disease), anxiety states, agitation, sleep disturbances, manic states, aggression, memory disorders, depersonalization (feeling of loss of identity), worsening of depression, concentration disorders, insomnia, nightmares, yawning, speech disorders, paresthesia (tingling or burning sensation), muscle weakness, increased muscle tone, hot flashes, dilated pupils, sinus tachycardia, palpitations, orthostatic hypotension (sudden drop in blood pressure when changing body position), changes in ECG in patients with normal heart function, vomiting, abdominal complaints, diarrhea, loss of appetite, increased liver enzyme activity, allergic skin reactions (rash, urticaria), photosensitivity, itching, galactorrhea, breast enlargement, taste disorders, tinnitus.

Uncommon (less than 1 in 100 patients)

Activation of psychotic symptoms, seizures, ataxia (coordination disorders), cardiac arrhythmias, increased blood pressure.

Rare (less than 1 in 1000 patients)

Conduction disorders in the heart, especially in patients with hypokalemia (low potassium levels in the blood).

Very rare (less than 1 in 10,000 patients)

Changes in EEG, hyperpyrexia (significant elevation of body temperature), glaucoma (increased eye pressure), urinary retention, hepatitis with or without jaundice, edema (local or generalized), hair loss, syndrome of inappropriate antidiuretic hormone secretion (SIADH), pulmonary inflammation with eosinophilia (increased white blood cell count) or without eosinophilia, systemic anaphylactic or anaphylactoid reactions, including hypotension, abnormal blood cell count (leukopenia, agranulocytosis, thrombocytopenia, eosinophilia), purpura.

Frequency not known (frequency cannot be estimated from available data)

Suicidal thoughts, suicidal behavior, fractures.

An increased risk of fractures has been observed in patients taking selective serotonin reuptake inhibitors and tricyclic antidepressants.

Reporting side effects

If any side effects occur, including those not listed in this package leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, 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. By reporting side effects, more information can be collected on the safety of the medication.

Side effects can also be reported to the marketing authorization holder.

5. How to store Anafranil

Anafranil, 10 mg, coated tablets – there are no special storage recommendations for this medication.

Anafranil, 25 mg, coated tablets – protect from moisture.

The medication should be stored in a place that is inaccessible to children.

The medication should not be used after the expiration date stated on the package. The expiration date refers to the last day of the specified month.

Medications should not be disposed of in wastewater or household waste. The patient should ask their pharmacist how to dispose of unused medications. This will help protect the environment.

6. Package contents and other information

What Anafranil contains

The active substance of Anafranil is clomipramine hydrochloride.

One coated tablet of Anafranil 10 mg contains 10 mg of clomipramine hydrochloride. The other ingredients of the medication are:

Colloidal silica

Hypromellose

Lactose monohydrate

Magnesium stearate

Cornstarch

Coating:

Hypromellose

Microcrystalline cellulose

Yellow iron oxide

Titanium dioxide

Povidone K 30

Sucrose

Talc

Copovidone

Macrogol 8000

One coated tablet of Anafranil 25 mg contains 25 mg of clomipramine hydrochloride. The other ingredients of the medication are:

Glycerol

Magnesium stearate

Lactose monohydrate

Colloidal silica

Cornstarch

Talc

Stearic acid

Coating:

Hypromellose

Copovidone

Talc

Yellow iron oxide

Titanium dioxide

Povidone K 30

Sucrose

Macrogol 8000

Microcrystalline cellulose

What Anafranil looks like and package contents

Anafranil, 10 mg

Light yellow, triangular, biconvex coated tablets.

30 coated tablets in a cardboard box.

Anafranil, 25 mg

Light yellow, round, biconvex coated tablets.

30 coated tablets in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Teva Pharmaceuticals Polska Sp. z o.o.

ul. Emilii Plater 53

00-113 Warsaw, Poland

tel.: (22) 345 93 00

Manufacturer

Teva Operations Poland Sp. z o.o.

ul. Mogilska 80

31-546 Krakow

Date of the last revision of the package leaflet: