There are no adequate or well-controlled studies of clozapine in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 0.4 and 0.9 times, respectively, the maximum recommended human dose (MRHD) of 900 mg/day on a mg/m2 body surface area basis. The studies revealed no evidence of impaired fertility or harm to the fetus due to clozapine. Because animal reproduction studies are not always predictive of human response, CLOZARIL should be used during pregnancy only if clearly needed.^L905

Consider the risk of exacerbation of psychosis when discontinuing or changing treatment with antipsychotic medications
during pregnancy and postpartum. Consider early screening for gestational diabetes for patients treated with antipsychotic
medications see Warnings and Precautions (5.11). Neonates exposed to antipsychotic drugs during the third trimester of
pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Monitor neonates for symptoms
of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding difficulties. The severity of
complications can vary from self-limited symptoms to some neonates requiring intensive care unit support and prolonged
hospitalization.^L905

The most commonly reported signs and symptoms associated with clozapine overdose are: sedation, delirium, coma,
tachycardia, hypotension, respiratory depression or failure; and hypersalivation. There are reports of aspiration
pneumonia, cardiac arrhythmias, and seizure. Fatal overdoses have been reported with clozapine, generally at doses above
2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. There is no available specific antidote to an overdose of CLOZARIL. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Monitor cardiac status and vital signs. Use general symptomatic and supportive measures. Consider the possibility of multiple-drug involvement.^L905

No carcinogenic potential was demonstrated in long-term studies in mice and rats at doses up to 0.3 times and 0.4 times,
respectively, the maximum recommended human dose (MRHD) of 900 mg/day on an mg/m2 body surface area basis. Clozapine was not genotoxic when tested in the following gene mutation and chromosomal aberration tests: the bacterial Ames test, the in vitro mammalian V79 in Chinese hamster cells, the in vitro unscheduled DNA synthesis in rat hepatocytes or the in vivo micronucleus assay in mice. Clozapine had no effect on any parameters of fertility, pregnancy, fetal weight, or postnatal development when
administered orally to male rats 70 days before mating and to female rats for 14 days before mating at doses up to 0.4 times the MRHD of 900 mg/day on an mg/m2 body surface area basis.^L905