Label Changes for:
Orap (pimozide) 1 mg and 2 mg tablets
Changes have been made to the CONTRAINDICATIONS and PRECAUTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- Clinical drug interaction studies have demonstrated that pimozide is also metabolized by CYP 2D6. Concomitant use of ORAP with paroxetine and other strong CYP 2D6 inhibitors is contraindicated
- pharmacokinetic and safety information for pimozide as related to intrinsic defects in CYP2D6 metabolism
- Individuals with genetic variations resulting in poor CYP 2D6 metabolism (approximately 5 to 10% of the population) exhibit higher pimozide concentrations than extensive CYP 2D6 metabolizers. The concentrations observed in poor CYP 2D6 metabolizers are similar to those seen with strong CYP 2D6 inhibitors such as paroxetine. The time to achieve steady state pimozide concentrations is expected to be longer (approximately 2 weeks) in poor CYP 2D6 metabolizers because of the prolonged half-life. Alternative dosing strategies are recommended in patients who are genetically poor CYP 2D6 metabolizers
Leukopenia, Neutropenia and Agranulocytosis
- Class Effect: In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including Orap. Agranulocytosis has also been reported.
- Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of Orap should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
- Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue Orap and have their WBC followed until recovery.