Clozapine (Dosage)

Clozapine is an atypical antipsychotic high-potency neuroleptic. It belongs to the second generation (SGA) or atypical antipsychotic and is the most effective antipsychotic against the persistent positive symptoms of schizophrenia. It presents minimal extrapyramidal symptoms (unlike first generation antipsychotics, FGA). Its main indications are schizophrenia that does not respond or does not tolerate treatment with other antipsychotics. It is also prescribed for bipolar disorder and for other mental disorders, such as psychotic disorders in Parkinson's disease, in cases where standard treatment has failed.

Clozapine exerts a weak blocking action on dopaminergic receptors (D1, D2, D3 and D5), and potent effects on the D4 receptor, in addition, it has a potent anti-alpha-adrenergic, anticholinergic, antihistamine and also decrease the patient's level of wakefulness.

CONTRAINDICATIONS

Treatment with clozapine is contraindicated in the following cases: Hypersensitivity to clozapine; patients who can not be analyzed periodically; history of granulocytopenia/toxic or idiosyncratic agranulocytosis (with the exception of that produced by prior chemotherapy); history of clozapine-induced agranulocytosis; impaired function of the bone marrow; uncontrolled epilepsy; alcoholic psychosis or other toxic psychoses, drug intoxication, comatose states; circulatory collapse and/or depression of the CNS (central nervous system); severe renal or cardiac disorders; liver disease; paralytic ileus; concomitance with drugs that cause agranulocytosis. Avoid clozapine with depot antipsychotics.

PRECAUTIONS

Precautions should be taken in patients under 16 years old (efficacy and safety has not been established) and in the elderly patients. Precautions in patients with hepatic insufficiency.

Stop the treatment in individuals with eosinophilia or thrombocytopenia.

Clozapine can cause agranulocytosis, restrict its use to patients with an initial normal white blood cell count, and who can receive regular white blood cell counts and absolute neutrophil counts every week for the first 18 weeks of treatment and at 4-week intervals thereafter.

Before starting treatment, make sure that the patient has not experienced an adverse haematological reaction to clozapine. If the white blood cell count is less than 3000/mm3 or the absolute neutrophil count is less than 1500/mm3, discontinue the treatment.

Exert caution if flu-like symptoms or evidence of infection appear as well as in patients with a history of epilepsy, prostate hypertrophy or narrow-angle glaucoma, constipation, history of colon disease or a history of low abdominal surgery.

Assess risk/benefit in patients with a history of primary disorders of the bone marrow. Use in benign ethnic neutropenia only if the hematologist gives consent. Do not re-expose those patients who have been suspended in the clozapine treatment for alteration in leukocyte or neutrophil count. If the onset of myocarditis or cardiomyopathy is suspected, stop treatment and do not re-expose

SIDE EFFECTS

Leukopenia/decreased white blood cell count/neutropenia, eosinophilia, leukocytosis. Weight gain. Drowsiness/sedation, dizziness, blurred vision, headache, tremor, stiffness, akathisia, extrapyramidal symptoms, epileptic seizures/convulsions/myoclonic spasms. Tachycardia, changes in ECG (electrocardiogram); hypertension, postural hypotension, syncope. Constipation, hypersalivation, nausea, vomiting, anorexia, dry mouth. Increase in liver enzymes; incontinence and urinary retention. Fatigue, fever, benign hyperthermia, sweating disorders/temperature regulation disorders.

PHARMACOLOGIC INTERACTIONS

Increased risk and/or severity of bone marrow suppression with: bone marrow suppressors, pyrazolone analgesics, penicillamine, cytotoxic agents and depot long-acting injectable antipsychotics.

Increased risk of circulatory collapse if clozapine is taken together with benzodiazepines.

Clozapine potentiates the action of anticholinergics and antihypertensives.

The plasma concentration of clozapine may be decreased by phenytoin.

Clozapine increases the risk of developing neuroleptic malignant syndrome (NMS) if ingested concomitantly with lithium.

The plasma level of clozapine is decreased with CYP1A2 inducers (eg, omeprazole).

The plasma level of clozapine can be increased with CYP1A2 inhibitors (fluvoxamine, caffeine, ciprofloxacin).

BRAND NAMES

  • Leponex ®
  • Nemea ®
  • Clozaril ®
  • FazaClo ®
  • Versacloz ®

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CYP1A2 CYP2D6

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