Buspirone
Adverse Effect: an increased risk of gastrointestinal bleeding and hyperglycemia Clinical Management: Caution should be observed when clozapine and buspirone are coadministered.
Carbamazepine
Adverse Effect: an increased risk of bone marrow suppression, asterixis, or decreased serum clozapine levels Clinical Management: Avoid concurrent use; an alternative anticonvulsant agent should be considered. If coadministration of these agents is necessary, monitor patients for decreased response to clozapine.
Cimetidine
Adverse Effect: An increased risk of clozapine side effects (dizziness, vomiting, hypotension, bone marrow suppression) Clinical Management: With concurrent use, monitor patients for clozapine toxicity. Consider selecting another H2 antagonist (eg, ranitidine or famotidine) that has less potential to alter drug metabolism or switching to another anti-ulcer medication such as sucralfate.
Erythromycin
Adverse Effect: Increased clozapine serum concentrations and risk of side effects (sedation, incoordination, slurred speech, seizures, hematologic abnormalities) Clinical Management: Monitor patients for signs and symptoms of clozapine intoxication (sedation, incoordination, slurred speech, seizures, hematologic abnormalities). Doses of clozapine may need to be reduced when erythromycin is added to therapy. Alternatively, consider using azithromycin, which is less likely to interfere with clozapine metabolism, or a non-macrolide antibiotic.
Fluoxetine
Adverse Effect: An increased risk of clozapine toxicity (sedation, seizures, hypotension) Clinical Management: Monitor the therapeutic efficacy of clozapine and for any evidence of toxicity, particularly when the daily clozapine dose exceeds 300 mg or 3.5 mg/kg. Lower clozapine dosage may be required in some clinical situations.
Lithium
Adverse Effect: weakness, dyskinesias, increased extrapyramidal symptoms, encephalopathy, and brain damage
Lorazepam
Adverse Effect: CNS depression Clinical Management: Monitor for signs of intoxication (eg, marked sedation, dizziness, ataxia, weakness, decreased cognition or motor performance, excessive salivation). If symptoms are present, reduce lorazepam dose.
Phenobarbitone
Adverse Effect: Decreased clozapine plasma levels associated with marked worsening of psychosis Clinical Management: When adding phenobarbital therapy to patients stabilized on clozapine, monitor patient closely for worsening of psychotic symptoms. If needed, increase the clozapine dose cautiously on the basis of psychotic symptoms. Conversely, when discontinuing phenobarbital, levels of clozapine may increase significantly.
Phenytoin
Adverse Effect: Decreased clozapine plasma levels associated with marked worsening of psychosis Clinical Management: When adding phenytoin therapy to patients stabilized on clozapine, monitor patient closely for worsening of psychotic symptoms. If needed, increase the clozapine dose cautiously on basis of psychotic symptoms. Conversely, when phenytoin is discontinued, levels of clozapine may significantly increase.
Rifampicin
Adverse Effect: Subtherapeutic concentrations of clozapine Clinical Management: Monitor clozapine levels when rifampin therapy is added, changed, or discontinued.
Risperidone
Adverse Effect: Decreased risperidone clearance Clinical Management: Monitor patients for increased adverse effects of risperidone when these drugs are given concurrently.
Sertraline
Adverse Effect: Increased risk of clozapine toxicity (sedation, seizures, hypotension) Clinical Management: Monitor the therapeutic efficacy of clozapine and for any evidence of toxicity, particularly when the daily clozapine dose exceeds 300 mg or 3.5 mg/kg. Lower clozapine dosage may be required in some clinical situations.
Tramadol
Adverse Effect: an increased risk of seizures Clinical Management: Caution should be used if tramadol is to be administered to patients receiving neuroleptic therapy. If possible, avoid this combination |