Clozapine
- Clozapine
- -
- Tablet
- 100mg
- Blister
- 100 Tablets
-
• Schizophrenia
Mechanism of Action
Demonstrates weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic, antihistaminic, and arousal reaction inhibiting effects are significant, also possesses antiserotoninergic (5-HT1C, 5-HT2, 5-HT3) properties
Affinity for mesolimbic dopamine D4 receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of EPS, histamine receptor blockade accounts for increased incidence of sleep disturbances
Pharmacokinetics
Bioavailability: 50-60%
Onset: 15 min
Duration: 4-12 hr
Peak plasma time: 1.5-2.5 hr
Excretion: Urine (50%), feces (30%)
Contraindications
• Hypersensitivity (eg, photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome)
Adverse Reactions
Hypersalivation, Sedation/somnolence, Weight gain, Dizziness, Tachycardia, Constipation, Insomnia, Dizziness/vertigo, Nausea, Vomiting, Dyspepsia, Hypotension, Fever, Headache, Tremor, Syncope, Sweating, Dry mouth, Visual disturbances, Disturbed sleep/nightmares, Restlessness, Hypokinesia/akinesia, Agitation, Hypertension, Abdominal discomfort/heartburn, Seizures, Rigidity, Akathisia, Confusion, Leukopenia/neutropenia, Fatigue, Diarrhea, Urinary abnormalities, Rash
Major Drug Interactions
Amisulpride - Dronedarone - Eliglustat - Irinotecan - Nirmatrelvir - Nirmatrelvir/Ritonavir - Thioridazine
Warnings
• Advise patients to immediately report symptoms consistent with severe neutropenia or infection (eg, fever, weakness, lethargy, sore throat)
• Caution with history of seizure or other factors predisposing to seizure
• Fatal myocarditis and cardiomyopathy reported, discontinue and obtain cardiac evaluation if suspected
• Orthostatic hypotension, bradycardia, syncope, and cardiac arrest may occur
• Not approved for dementia-related psychosis
Recommendations for Patient
• While clozapine can provide great benefits, it can rarely cause serious, possibly fatal side effects. For this reason, clozapine is used when other treatments have not worked or you cannot take them.
Pregnancy Considerations
Category: B
Breastfeeding Considerations
Because there is little published experience with clozapine during breastfeeding, and sedation and adverse hematologic effects have been reported in breastfed infants, other agents are preferred.
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: Maybe acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Demonstrates weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic, antihistaminic, and arousal reaction inhibiting effects are significant, also possesses antiserotoninergic (5-HT1C, 5-HT2, 5-HT3) properties
Affinity for mesolimbic dopamine D4 receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of EPS, histamine receptor blockade accounts for increased incidence of sleep disturbances
Pharmacokinetics
Bioavailability: 50-60%
Onset: 15 min
Duration: 4-12 hr
Peak plasma time: 1.5-2.5 hr
Excretion: Urine (50%), feces (30%)
Contraindications
• Hypersensitivity (eg, photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome)
Adverse Reactions
Hypersalivation, Sedation/somnolence, Weight gain, Dizziness, Tachycardia, Constipation, Insomnia, Dizziness/vertigo, Nausea, Vomiting, Dyspepsia, Hypotension, Fever, Headache, Tremor, Syncope, Sweating, Dry mouth, Visual disturbances, Disturbed sleep/nightmares, Restlessness, Hypokinesia/akinesia, Agitation, Hypertension, Abdominal discomfort/heartburn, Seizures, Rigidity, Akathisia, Confusion, Leukopenia/neutropenia, Fatigue, Diarrhea, Urinary abnormalities, Rash
Major Drug Interactions
Amisulpride - Dronedarone - Eliglustat - Irinotecan - Nirmatrelvir - Nirmatrelvir/Ritonavir - Thioridazine
Warnings
• Advise patients to immediately report symptoms consistent with severe neutropenia or infection (eg, fever, weakness, lethargy, sore throat)
• Caution with history of seizure or other factors predisposing to seizure
• Fatal myocarditis and cardiomyopathy reported, discontinue and obtain cardiac evaluation if suspected
• Orthostatic hypotension, bradycardia, syncope, and cardiac arrest may occur
• Not approved for dementia-related psychosis
Recommendations for Patient
• While clozapine can provide great benefits, it can rarely cause serious, possibly fatal side effects. For this reason, clozapine is used when other treatments have not worked or you cannot take them.
Pregnancy Considerations
Category: B
Breastfeeding Considerations
Because there is little published experience with clozapine during breastfeeding, and sedation and adverse hematologic effects have been reported in breastfed infants, other agents are preferred.
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: Maybe acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
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