Composition:

Each tablet contains 25 or 100mg Clozapine.

Mechanism of Action:

Clozapine belongs to dibenzodiazepines and it is classified as antipsychotic agent. It has weak dopamine blocking activity at D1,D2,D3 and D5 receptors, but shows high potency for the D4 receptor.

Indications:

Clozanex is indicated in treatment of resistant schizophrenic patients who are non-responsive to, or intolerant of conventional neuroleptics.

Dosage:

The dosage must be adjusted individually for each patient, the lowest effective dose should be used.

Initial dose: 12.5mg 1-2 times daily in the first day, then 25mg 1-2 times daily in the second day, and increased slowly to maximum 300mg daily within 2 – 3 weeks. Then in some cases the doses can be increased to 50-100mg per week. In most patients anti-psychotic effect can be expected with 200 – 450mg in divided doses with large portion at bedtime.

Maintenance dose: 150 – 300mg daily in divided doses. A few patients may require a maximum dose of 900mg daily. Adverse reaction may increase at this dose especially particular seizures.

A gradual reduction in dose is recommended over a 1 – 2 weeks period. The product is not recommended for children, and when uses in the elderly initiate treatment with low dose.

Side Effects:

It may occur at the beginning of therapy: Orthostatic hypotension, sedation or restless, headache, disturbance in sweating and temperature regulation, temperature elevation above 38°C, fatigue, drowsiness, myoclonic convulsion, agitation, tachycardia, respiratory depression, nausea, vomiting, constipation, dry mouth, extrapyramidal symptoms are limited mainly to tremor mild and transient, rare of leucocyte including eosinophilia especially in the initial week of treatment, isolated cases of thrombocytopenia, weight gain, elevated prolactin levels, urinary retention. Elevation in liver enzymes may occur particularly in the fist three months of treatment.

ContraIndications:

Allergy, progressive liver disease or hepatic failure, bone marrow disorders, epilepsy, renal or cardiac failure, alcoholic, in patients whom the product may cause agranulocytosis , acute CNS depression.

Drug Interactions:

The product should not be used in combination with non-conventional neuroleptica. It lowers the seizure threshold, patient with epilepsy should be closely monitored. It should not be used concurrently with drugs known to have a substantial potence to depress bone marrow function such as co-trimaxazole, chloramphenicol, sulphonamide and carbamazepine. It may increase warfarin concentration since it is highly bound to plasma protein. Cimetidine, fluoxetine and carbamazepine may increase the drug concentration in the plasma. Caution should be taken in concomitant administration with anti-cholinergic, hypotensive or respiratory depressant. The product may enhance the central effects of MAO inhibitors, CNS depressants, benzodiazepines and antihistamine.

Precautions:

• Before starting the treatment, a white blood cells count and differential count must be preformed. If any symptoms or signs of infection developed, a white blood cell count must be obtained.
• The product has anti-cholinergic activity, careful must be taken by prostate enlargement, narrow angle glaucoma.
• Patient with pre-existing liver disorders may receive the drug but they need regular liver function test monitoring especially when they have nausea or jaundice, the treatment should be immediately discontinued.
• Orthostatic hypotension can occur with the drug treatment especially during initial therapy, the treatment require close medical supervision. Patient with fever should be checked out of the possibility of an infection.
• Caution must be taken by driving or operating machinery.

Use in Pregnancy or Lactation:

The drug is not recommended for use in pregnancy or lactation.