Presentation and Status in Health Basket
30 X 25 mg
20 X 75 mg
Before initiating treatment with Anafranil, hypokalemia should be treated. The dosage should be adapted to the individual patient’s condition. The aim is to achieve an optimum effect while keeping the doses as low as possible and increasing them cautiously. After a response has been obtained, maintenance therapy should be continued at the optimum dose to avoid relapse. Patients with a history of recurrent depression require maintenance treatment for a longer duration. Duration of maintenance treatment and need for further treatment should be reviewed periodically. As a precaution against possible QTc prolongation and serotonergic toxicity, adherence to the recommended doses of Anafranil is advised and any increase in dose should be made with caution if drugs that prolong QT interval or other serotonergic agents are co-administered. Abrupt discontinuation of Anafranil therapy should be avoided because of possible withdrawal symptoms. Therefore, dosage should be stopped gradually after regular use for long duration and the patient should be monitored carefully when Anafranil therapy is discontinued. Immediate release formulations (coated tablets) and sustained-release tablets can be used inter-changeably in equivalent doses.
Depression and obsessive-compulsive syndromes: Start treatment with 50-75 mg/day (1 coated tablet of 25 mg 2-3 times daily or 1 sustainedrelease tablet of 75 mg once daily [preferably in the evening]). Raise the daily dosage stepwise, e.g. 25 mg every few days, (depending on how the medication is tolerated) to 100- 150 mg, during the first week of treatment. In severe cases this dosage can be increased up to a maximum of 250 mg daily. Once there is a distinct improvement, adjust the daily dosage to a maintenance level of about 50-100 mg.
Dosage and administration in special populations
Geriatric population: Elderly patients generally show a stronger response to Anafranil than patients of intermediate age groups, Anafranil should be used with caution in elderly patients and doses should be increased cautiously. Start treatment with 10 mg daily. Gradually raise the dosage to an optimum level of 30-50 mg daily, which should be reached after about 10 days and then maintained until the end of treatment.
Children and Adolescents: Adolescents generally show a stronger response to Anafranil than patients of intermediate age groups, Anafranil should be used with caution in adolescents and doses should be increased cautiously.
Obsessive-compulsive syndromes: The starting dose is 25 mg daily and should be gradually increased (also given in divided doses) during the first 2 weeks, as tolerated, up to a daily maximum of 3 mg/kg or 100 mg, whichever is smaller. Thereafter, the dosage may be increased gradually over the next several weeks up to a daily maximum of 3 mg/kg or 200 mg, whichever is smaller. No experience is available in children under 5 years.
Renal impairment: Anafranil should be given with caution in patients with renal impairment.
Hepatic impairment: Anafranil should be given with caution in patients with hepatic impairment.
Method of administration: The method of administration should be adapted to the individual patient’s condition. The Divitabs (sustained-release tablets divisible) can be halved, allowing the dosage to be adapted individually, but they should not be chewed. Anafranil can be administered with or without food.
Depression of varying origin: In children and adolescents, there is not sufficient evidence of safety and efficacy for the treatment of depressive states of varying aetiology and symptomatology. The use in children and odolescents (0-17 years of age) in this indication is therefore not recommended.
Obsessive compulsive syndromes: No experience is available in children younger than 5 years of age.
Hypersensitivity to clomipramine or any of the excipients, or cross-sensitivity to tricyclic antidepressants of the dibenzazepine group. In combination with, or within 14 days before or after treatment with, a MAOI. The concomitant treatment with selective, reversible MAO-A inhibitors, such as moclobemide. Recent myocardial infarction, congenital long QT syndrome, lactation.
Risk of suicide: All patients being treated with Anafranil for any indication should be observed closely for clinical worsening, suicidality and other psychiatric symptoms, especially during the initial phase of therapy or at times of dose changes. Modifying the therapeutic regimen, including possibly discontinuing the medication, should be considered in these patients especially if these changes are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Other psychiatric effects: Many patients with panic disorder experience more marked anxiety at the start of the treatment with Anafranil. This paradoxical initial increase in anxiety is most pronounced during the first few days of treatment and generally subsides within two weeks.
Cardiac and vascular disorders: Anafranil should be administered with particular caution in patients with cardiovascular disorders, especially those with cardiovascular insufficiency, conduction disorders, (e.g. atrioventricular block grades I to III), or arrhythmias. Monitoring of cardiac function and the ECG is indicated in such patients.
Serotonin syndrome: Due to the risk of serotonergic toxicity, it is advisable to adhere to recommended doses. Serotonin syndrome, with symptoms such as hyperpyrexia, myoclonus, agitation, seizures, delirium and coma, can possibly occur when clomipramine is administered with serotonergic co-medications such as SSRIs, SNaRIs, tricyclic antidepressants or lithium. For fluoxetine, a washout period of two to three weeks is advised before and after treatment with fluoxetine.
Convulsions: Tricyclic antidepressants are known to lower the convulsion threshold and Anafranil should, therefore, be used with extreme caution in patients with epilepsy and other predisposing factors, e.g. brain damage of varying aetiology, concomitant use of neuroleptics, withdrawal from alcohol or drugs with anticonvulsive properties (e.g. benzodiazepines). It appears that the occurrence of seizures is dose dependent. Therefore, the recommended total daily dose of Anafranil should not be exceeded.
Anticholinergic effects: Because of its anticholinergic properties, Anafranil should be used with caution in patients with a history of increased intraocular pressure, narrow-angle glaucoma, or urinary retention (e.g. diseases of the prostate).
Specific treatment populations: Caution is called for when giving tricyclic antidepressants to patients with severe hepatic disease and tumours of the adrenal medulla (e.g. phaeochromocytoma, neuroblastoma), in whom they may provoke hypertensive crises. Caution is indicated in patients with hyperthyroidism or patients receiving thyroid preparations, owing to the possibility of cardiac toxicity. In patients with hepatic and renal disease, periodic monitoring of the hepatic enzyme levels and renal function is recommended. Caution is called for in patients with chronic constipation. Tricyclic antidepressants may cause paralytic ileus, particularly in elderly and in bedridden patients. In elderly patients, tricyclic antidepressants may provoke pharmacogenic (delirious) psychoses, particularly at night. These disappear within a few days of withdrawing the drug. Monitoring of cardiac function and the ECG is indicated in elderly patients. An increase in dental caries has been reported during long-term treatment with tricyclic antidepressants. Regular dental check-ups are therefore advisable during long-term treatment.
Treatment discontinuation: Abrupt withdrawal should be avoided because of possible adverse reactions. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms.
Lactose and sucrose: Anafranil coated tablets contain lactose and sucrose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, severe lactase deficiency, sucrase-isomaltase insufficiency or glucose-galactose malabsorption should not take Anafranil coated tablets.
Driving and using machines: Patients receiving Anafranil should be warned that blurred vision, drowsiness and other nervous system and psychiatric related disorders such as somnolence, disturbance in attention, confusion, disorientation, aggravation of depression, delirium etc. have been observed.
For full details see prescribing information.
Very common: Accommodation disorder, vision blurred. Nausea, dry mouth, constipation. Fatigue. Weight increased. Increased appetite. Dizziness, tremor, headache, myoclonus, somnolence. Restlessness. Micturition disorder. Libido disorder, erectile dysfunction. Hyperhidrosis.
Common: Sinus tachycardia, palpitation, orthostatic hypotension, clinically irrelevant ECG changes (e.g. ST and T changes) in patients of normal cardiac status. Tinnitus. Mydriasis. Vomiting, abdominal disorders, diarrhea. Transaminases increased. Decreased appetite. Muscular weakness. Speech disorder, paraesthesias, muscle hypertonia, dysgeusia, memory impairment, disturbance in attention. Confusional state, disorientation, hallucinations (particularly in elderly patients and patients with Parkinson’s disease), anxiety, agitation, sleep disorder, mania, hypomania, aggression, depersonalisation, aggravation of depression, insomnia, nightmares, delirium. Galactorrhoea, breast enlargement. Yawning. Dermatitis allergic (skin rash, urticaria), photosensitivity reaction, pruritus. Hot flush.
For full details see prescribing information.
Interactions resulting in a contraindication: MAO inhibitors.
Interactions resulting in a concomitant use not recommended: Antiarrhythmics, Diuretics, SSRIs, Serotonergic agents.
Interactions resulting in increased effect of Anafranil: Terbinafine, Cimetidine, Oral contraceptives, Antipsychotics, Methylphenidate, Valproate, Grapefruit, grapefruit juice, or cranberry juice.
Interactions resulting in decreased effect of Anafranil: Rifampicin, Anticonvulsants, Cigarette smoking, Colestipol and cholestyramine, St. John’s wort.
Interactions affecting other drugs: Anticholinergic agents, Antiadrenergic agents, CNS depressants, Sympathomimetic drugs, Anticoagulants.
For full details see prescribing information.
Pregnancy and Lactation
Pregnancy: There is limited amount of data from the use of Anafranil in pregnant women that indicates a potential to harm the foetus or cause congenital malformation. Anafranil should be used during pregnancy only if the potential benefit outweighs the potential risk to the foetus.
Lactation: Since the active substance passes into the breast milk, Anafranil should be gradually withdrawn or the infant weaned if the patient is breast-feeding.
For full details see prescribing information.
The signs and symptoms of overdose with Anafranil are similar to those reported with other tricyclic antidepressants. Cardiac abnormalities and neurological disturbances are the main complications. In children, accidental ingestion of any amount should be regarded as serious and potentially fatal.
Signs and symptoms: Symptoms generally appear within 4 hours of ingestion and reach maximum severity after 24 hours. Owing to delayed absorption (anticholinergic effect), long half-life, and enterohepatic recycling of the drug, the patient may be at risk for up to 4-6 days. The following signs and symptoms may be seen:
Central nervous system: Drowsiness, stupor, coma, ataxia, restlessness, agitation, enhanced reflexes, muscular rigidity and choreoathetoid movements, convulsions. In addition, symptoms consistent with serotonin syndrome (e.g. hyperpyrexia, myoclonus, delirium and coma) may be observed.
Cardiovascular system: Hypotension, tachycardia, arrhythmias, QTc prolongation and arrhythmias including torsades de pointes, conduction disorders, shock, heart failure; in very rare cases cardiac arrest.
Respiratory depression, cyanosis, vomiting, fever, mydriasis, sweating, and oliguria or anuria may also occur.
Treatment: There is no specific antidote, and treatment is essentially symptomatic and supportive. Anyone suspected of receiving an overdose of Anafranil, particularly children, should be hospitalised and kept under close surveillance for at least 72 hours. Perform gastric lavage or induce vomiting as soon as possible if the patient is alert. If the patient is not alert, secure the airway with a cuffed endotracheal tube before beginning lavage, and do not induce vomiting. These measures are recommended for up to 12 hours or even longer after the overdose, since the anticholinergic effect of the drug may delay gastric emptying. Administration of activated charcoal may help to reduce drug absorption. Treatment of symptoms is based on modern methods of intensive care, with continuous monitoring of cardiac function, blood gases, and electrolytes, and if necessary emergency measures such as anticonvulsive therapy, artificial respiration, and resuscitation.
Treatment of Torsade de Pointes: If Torsade de Pointes should occur during treatment with Anafranil, the drug should be discontinued and hypoxia, electrolyte abnormalities and acid base disturbances should be corrected. Persistent Torsade de Pointes may be treated with magnesium sulphate 2g (20ml of 10% solution) intravenously over 30-120 seconds, repeated twice at intervals of 5-15 minutes if necessary. Alternatively, if these measures fail, the arrhythmia may be abolished by increasing the underlying heart rate. This can be achieved by atrial and ventricular pacing or by isoprenaline (isproterenol) infusion to achieve a heart rate of 90-110 beats/minute. Torsade de Pointes is usually not helped by antiarrhythmic drugs and those which prolong the QTc interval (e.g. amiodarone, quinidine) may make it worse. Since it has been reported that physostigmine may cause severe bradycardia, asystole and seizures, its use is not recommended in cases of overdose with Anafranil. Haemodialysis or peritoneal dialysis are ineffective because of the low plasma concentrations of clomipramine.
Storage: Store below 25°C, protect from moisture.