Clozapine
Mechanism :
Clozapine is classified as an atypical antipsychotic drug, because its binding to dopamine receptors and its effects on various dopamine mediated behaviours differ from those exhibited by more typical antipsychotic drug products. Clozapine does interfere with the binding of dopamine at D1, D2, D3, and D5 receptors, and has a high affinity for the D4 receptor. Clozapine also acts as an antagonist at adrenergic, cholinergic, histaminergic and serotonergic receptors.
Indication :
Contraindications :
Clozapine is contraindicated in patients with a previous hypersensitivity to clozapine or any other component of this drug, in patients with myeloproliferative disorders, uncontrolled epilepsy, paralytic ileus, or a history of clozapine-induced agranulocytosis or severe granulocytopenia. As with more typical antipsychotic drugs, contraindicated in severe central nervous system depression or comatose states. Should not be used simultaneously with other agents having a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function. The mechanism of clozapine-induced agranulocytosis is unknown; nonetheless, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression.
Dosing :
Oral: 12-18 years: Initially on the first day, 12.5 mg/dose, 1-2 times daily and from the second day 25 mg/dose 1-2 times dally. If tolerated well, gradually increase by 25-50 mg over 14-21 days to maintenance dose of 300 mg/day in divided doses, Max: 900 mg/day if necessary.
Adverse Effect :
Neutropenia, drowsiness anti-muscarinic effects, hypotension, tachycardia, cardiac dysrhythmias, extra pyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, hypothermia, gynaecomastia, galactorrhoea, impotence, menstrual disturbances, weight gain, lowered threshold for seizures, bone marrow depression, hemolytic anemia, contact hypersensitivity, photosensitivity, rashes, cholestatic jaundice, corneal and lens opacities.
Interaction :
Cotrimoxazole, carbamazepine: Avoid drugs known to depress leucopoiesis.
Benzodiazepines: Orthostatic hypotension in patients taking clozapine can, be accompanied by profound collapse and respiratory and/or cardiac arrest.
Antihypertensive drugs: May potentiate the hypotensive effects.
Atropine-type drugs: May potentiate the anticholinergic effects.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function; use with caution |
| 10-20 | Dose as in normal renal function; use with caution |
| <10 | Start with a low dose and titrate slowly |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Use with caution. Start with lower dose and adjust as per clinical response. Monitor LFT. On treatment if there is elevated transaminases or jaundice, discontinue treatment.