Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: zr pharma& GmbH, Hietzinger Hauptstrasse 37, 1130 Vienna, Austria
In the management of endogenous depression including manic depression, periodic and involutional depression, reactive and neurotic depression, obsessional and phobic states and as an adjunctive treatment of cataplexy associated with narcolepsy.
Before initiating treatment with Anafranil, hypokalemia should be treated (see 4.4 Special warnings and precautions for use). 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 other serotonergic agents are co-administered (see sections 4.4 Special Warnings and Precautions for use and 4.5 Interaction with other Medicinal Products and other forms of Interaction).
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.
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 (capsules) and sustained-release tablets can be used interchangeably in equivalent doses.
The usual daily dosage is in the range of 30 to 75 mg in single or divided doses. Initial dosage should be 10 mg/day with gradual increments to 30-150 mg/day in divided doses or as a single dose at bedtime. Dosage may exceed the stated range if necessary up to a maximum of 250 mg.
The maintenance dosage of Anafranil is generally higher than that used in depression. It is recommended that the dose be built up to 100-150 mg Anafranil daily, according to the severity of the condition. This should be attained gradually over a period of 2 weeks starting with 1 × 25 mg Anafranil daily. In elderly patients and those sensitive to tricyclic antidepressants a starting dose of 1 × 10 mg Anafranil daily is recommended. Again where a higher dosage is required the Sustained-release 75 mg formulation may be preferable.
Initially 10 mg, increasing to 50 mg daily. Control of cataplexy should be achieved within 24 hours of reaching optimal dose.
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. Daily dose should generally be low, initiated at the lowest level (10 mg) with very slow cautious increments to 30-75 mg daily.
Anafranil is not recommended for use in children due to insufficient data on safety and/or efficacy (See Section 4.4 Special Warnings and Precautions for use).
Anafranil should be given with caution in patients with renal impairment (see section 4.4 special warnings and precautions for use and section 5 pharmacological properties).
Anafranil should be given with caution in patients with hepatic impairment (see section 4.4 special warnings and precautions for use and section 5 pharmacological properties).
Anafranil prolonged-release tablets should be swallowed whole.
Anafranil can be administered with or without food.
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.
Symptoms generally appear within 4 hours of ingestion and reach maximum severity after 24 hours. Owing to delayed absorption (anticholinergic effect), long half-fife, 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: Somnolence, stupor, coma, ataxia, restlessness, agitation, hyperreflexia, muscle rigidity and choreoathetosis 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.
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 ever longer after the overdose, since the anticholinergic effect of the drug may help to reduce drug absorption.
Since it has been reported that phyotigmine may cause severe bradycardia, asystole, and seizures, its use is not recommended in cases of overdosage with Anafranil. Haemodialysis or peritoneal dialysis are ineffective because of the low plasma concentrations of clomipramine.
Rare cases of pharmacobezoar, of varying severity including fatal outcome, have been reported in association with overdose of sustained release Anafranil. The pharmacobezoar may be radiopaque, facilitating radiologic (X-ray or CT scan) confirmation but cannot exclude the diagnosis. The formation of pharmacobezoar may cause slow but continual release and absorption of clomipramine which may lead to overdose complications, including death, hours after drug ingestion and initial treatment with gastric lavage and activated charcoal. Since gastric lavage may be ineffective and could further increase systemic drug levels, consideration should be given to physical removal of the pharmacobezoar by endoscopy or surgery in selected patients. Since these cases are rare, there is insufficient clinical data regarding optimal treatment which should take into account the size and location of the pharmacobezoar, patient symptoms and condition and drug levels.
5 years.
Do not store above 30°C. Store in the original package in order to protect from moisture.
PVC/Aluminium blister packs in cardboard cartons.
Pack sizes of 100, 30 and 28 tablets are available.
Not all pack sizes may be marketed.
No special requirements.
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