QuickView for clozapine (compound)

Summary
General Info

PubChem

PubChem Compound 10404560

Name:	Clozapine
PubChem Compound ID:	10404560
Description:	A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.
Molecular formula:	C₁₈H₁₉ClN₄
Molecular weight:	332.847 g/mol

DrugBank

Identification

Name:	Clozapine
Name (isomeric):	DB00363
Drug Type:	small molecule
Description:	A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.
Synonyms:	Clozapin
Brand:	Asaleptin, Fazaclo ODT, Lepotex, Iprox, Clozaril, Leponex
Category:	GABA Antagonists, Serotonin Antagonists, Antipsychotic Agents, Antipsychotics
CAS number:	5786-21-0

Pharmacology

Indication:	For use in patients with treatment-resistant schizophrenia.
Pharmacology:	Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT₂), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts ... show more » Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT₂), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT₂ with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. show less «
Mechanism of Action:	Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.
Absorption:	Rapid and almost complete
Protein binding:	97% (bound to serum proteins)
Biotransformation:	Hepatic
Route of elimination:	Approximately 50% of the administered dose is excreted in the urine and 30% in the feces.
Half Life:	8 hours (range 4-12 hours)
Toxicity:	Clozapine carries a black-box warning for agranulocytosis.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Limit caffeine intake (may reduce clozapine matabolism).

Take without regard to meals.

Drug interaction:

Tamoxifen	Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tetrabenazine	May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Josamycin	Erythromycin increases the effect of clozapine
Flurazepam	Increased risk of toxicity
Erythromycin	Erythromycin increases the effect of clozapine

Tamoxifen	Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tetrabenazine	May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Josamycin	Erythromycin increases the effect of clozapine
Flurazepam	Increased risk of toxicity
Erythromycin	Erythromycin increases the effect of clozapine
Diazepam	Increased risk of toxicity
Trimethobenzamide	Trimethobenzamide and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Chlordiazepoxide	Increased risk of toxicity
Trospium	Trospium and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Fosphenytoin	Hydantoin decreases the effect of clozapine
Bromazepam	Bromazepam may increase the adverse effects of clozapine. Consider alternate therapy or a reduction in the bromazepam dose. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
Lorazepam	Increased risk of toxicity
Triprolidine	Triprolidine and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Lamotrigine	Lamotrigine increases the effect and toxicity of clozapine
Sertraline	The antidepressant increases the effect of clozapine
Galantamine	Possible antagonism of action
Tamsulosin	Clozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed.
Thiabendazole	The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clozapine by decreasing Clozapine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clozapine if Thiabendazole is initiated, discontinued or dose changed.
Ciprofloxacin	Ciprofloxacin may increase clozapine serum levels
Triazolam	Increased risk of toxicity
Rivastigmine	Possible antagonism of action
Modafinil	Modafinil increases the effect and toxicity of clozapine
Prazepam	Increased risk of toxicity
Quazepam	Increased risk of toxicity
Flunitrazepam	Increased risk of toxicity
Fluvoxamine	The antidepressant increases the effect of clozapine
Alprazolam	Increased risk of toxicity
Mephenytoin	Hydantoin decreases the effect of clozapine
Nitrazepam	Increased risk of toxicity
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Clozapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Phenytoin	Phenytoin may decrease the effect of clozapine.
Cimetidine	Cimetidine may increase the serum concentratin of clozapine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if cimetidine is initiated, discontinued or dose changed.
Oxazepam	Increased risk of toxicity
Donepezil	Possible antagonism of action
Halazepam	Increased risk of toxicity
Rifabutin	Rifabutin decreases the effect of clozapine
Temazepam	The benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
Estazolam	Increased risk of toxicity
Norfloxacin	Ciprofloxacin may increase clozapine serum levels
Vilazodone	Selective Serotonin Reuptake Inhibitors may decrease the metabolism of clozapine. If concurrent use of these agents is employed, monitor for increased toxic effects of clozapine if a selective serotonin reuptake inhibitor (SSRI) is initiated/dose increased, or decreased effects if a SSRI is discontinued/dose decreased.
Tramadol	Clozapine may decrease the effect of Tramadol by decreasing active metabolite production.
Ethotoin	Hydantoin decreases the effect of clozapine
Clobazam	Increased risk of toxicity
Clorazepate	Increased risk of toxicity
Midazolam	Increased risk of toxicity
Ritonavir	Ritonavir increases the effect and toxicity of clozapine
Clonazepam	Increased risk of toxicity
Ketazolam	Increased risk of toxicity
Fluoxetine	The antidepressant increases the effect of clozapine
Caffeine	Caffeine increases the effect and toxicity of clozapine
Haloperidol	Clozapine, a moderate CYP2D6 inhibitor, may increase the serum concentration of haloperidol by decreasing its metabolism. Additive CNS despresant and anticholinergic effects may also occur. Monitor for changes in the therapeutic and adverse effects of haloperidol if clozapine is initiated, discontinued or dose changed. Also monitor for increased CNS depressant and anticholinergic effects during concomitant therapy.
Rifampin	Rifampin decreases the effect of clozapine
Carbamazepine	Carbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.
Citalopram	The antidepressant increases the effect of clozapine
Cinolazepam	Increased risk of toxicity