Each Azaleptine, 100 mg tablet contains:

active ingredient: clozapine – 100 mg;

For a full list of excipients see section List of Excipients.

Posology

The dosage must be adjusted individually. For each patient the lowest effective dose should be used. For doses not realisable/practicable with one strength, other strengths of this medicinal product are available. Cautious titration and a divided dosage schedule are necessary to minimise the risks of hypotension, seizure and sedation.

Initiation of Azaleptine treatment must be restricted to those patients with a WBC count ≥ 3500/mm³ (3.5×10⁹/L) and an ANC ≥ 2000/mm³ (2.0×10⁹/L) within standardised normal limits. Dose adjustment is indicated in patients who are also receiving medicinal products that have pharmacodynamic and pharmacokinetic interactions with Azaleptine, such as benzodiazepines or selective serotonin re-uptake inhibitors (see section Interaction with other medicinal products and other forms of interaction).

Switching from a previous antipsychotic therapy to Azaleptine

It is generally recommended that Azaleptine should not be used in combination with other antipsychotics. When Azaleptine therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that the other antipsychotic should first be discontinued by tapering the dosage downwards.

The following dosages are recommended:

Treatment-resistant schizophrenic patients

Starting therapy

12.5 mg once or twice on the first day, followed by 25 mg once or twice on the second day. If well tolerated, the daily dose may then be increased slowly in increments of 25 to 50 mg in order to achieve a dose level of up to 300 mg/day within 2 to 3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50 to 100 mg at half-weekly or, preferably, weekly intervals.

Therapeutic dose range

In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. The total daily dose may be divided unevenly, with the larger portion at bedtime.

Maximum dose

To obtain full therapeutic benefit, a few patients may require larger doses, in which case judicious increments (not exceeding 100 mg) are permissible up to 900 mg/day. However, the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.

Maintenance dose

After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses. Careful downward titration is therefore recommended. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, once daily administration in the evening may be appropriate.

Ending therapy

In the event of planned termination of Azaleptine therapy, a gradual reduction in dose over a 1- to 2-week period is recommended. If abrupt discontinuation is necessary, the patient should be carefully observed for the occurrence of withdrawal reactions (see section Special warnings and precautions for use).

Re-starting therapy

In patients in whom the interval since the last dose of Azaleptine exceeds 2 days, treatment should be re-initiated with 12.5 mg given once or twice on the first day. If this dose is well tolerated, it may be feasible to titrate the dose to the therapeutic level more quickly than is recommended for initial treatment. However, in any patient who has previously experienced respiratory or cardiac arrest with initial dosing (see section Special warnings and precautions for use), but was then able to be successfully titrated to a therapeutic dose, re-titration should be carried out with extreme caution.

Psychotic disorders occurring during the course of Parkinson’s disease, in cases where standard treatment has failed

Starting therapy

The starting dose must not exceed 12.5 mg/day, taken in the evening. Subsequent dose increases must be by 12.5 mg increments, with a maximum of two increments a week up to a maximum of 50 mg, a dose that cannot be reached until the end of the second week. The total daily amount should preferably be given as a single dose in the evening.

Therapeutic dose range

The mean effective dose is usually between 25 and 37.5 mg/day. In the event that treatment for at least one week with a dose of 50 mg fails to provide a satisfactory therapeutic response, dosage may be cautiously increased by increments of 12.5 mg/week.

Maximum dose

The dose of 50 mg/day should only be exceeded in exceptional cases, and the maximum dose of 100 mg/day must never be exceeded.

Dose increases should be limited or deferred if orthostatic hypotension, excessive sedation or confusion occurs. Blood pressure should be monitored during the first weeks of treatment.

Maintenance dose

When there has been complete remission of psychotic symptoms for at least 2 weeks, an increase in anti-parkinsonian medication is possible if indicated on the basis of motor status. If this approach results in the recurrence of psychotic symptoms, Azaleptine dosage may be increased by increments of 12.5 mg/week up to a maximum of 100 mg/day, taken in one or two divided doses (see above).

Ending therapy

A gradual reduction in dose by steps of 12.5 mg over a period of at least one week (preferably two) is recommended.

Treatment must be discontinued immediately in the event of neutropenia or agranulocytosis (see section Special warnings and precautions for use). In this situation, careful psychiatric monitoring of the patient is essential since symptoms may recur quickly.

Special populations:

Hepatic impairment

Patients with hepatic impairment should receive Azaleptine with caution along with regular monitoring of liver function tests (see section Special warnings and precautions for use).

Paediatric population

No paediatric studies have been performed. The safety and efficacy of Azaleptine in children and adolescents under the age of 16 years have not yet been established. It should not be used in this group until further data become available.

Patients 60 years of age and older

Initiation of treatment is recommended at a particularly low dose (12.5 mg given once on the first day) with subsequent dose increments restricted to 25 mg/day.

Method of administration

Azaleptine is administered orally.

Pharmacotherapeutic group: Antipsychotics; Diazepines, oxazepines and thiazepines

ATC code: N05AH02

List of Excipients:

microcrystalline cellulose

lactose monohydrate

maize (corn) starch

povidone

sodium starch glycolate

magnesium stearate

For more detailed information about the drug, click: http://pharm.cals.am/pharm/data/drug_134425/1736329537406.pdf