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U.S. Department of Health and Human Services

Safety

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Fanapt (iloperidone) Tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  

 

April 2014

Summary View

7 DRUG INTERACTIONS

7.2 Potential of Fanapt to Affect Other Drugs
  • In vitro studies in human liver microsomes showed that iloperidone does not substantially inhibit the metabolism of drugs metabolized by the following cytochrome P450 isozymes: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, or CYP2E1. Furthermore, in vitro studies in human liver microsomes showed that iloperidone does not have enzyme inducing properties, specifically for the following cytochrome P450 isozymes: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.
  • Dextromethorphan: A study in healthy volunteers showed that changes in the pharmacokinetics of dextromethorphan (80 mg dose) when a 3 mg dose of iloperidone was co-administered resulted in a 17% increase in total exposure and a 26% increase in the maximum plasma concentrations (Cmax )of dextromethorphan. Thus, an interaction between iloperidone and other CYP2D6 substrates is unlikely.
  • Fluoxetine: A single 3 mg dose of iloperidone had no effect on the pharmacokinetics of fluoxetine (20 mg twice daily).
  • Midazolam (a sensitive CYP 3A4 substrate): A study in patients with schizophrenia showed a less than 50% increase in midazolam total exposure at iloperidone steady state (14 days of oral dosing at up to 10 mg iloperidone twice daily) and no effect on midazolam Cmax. Thus, an interaction between iloperidone and other CYP3A4 substrates is unlikely.

8 USE IN SPECIFIC POPULATIONS

8.7 Hepatic Impairment
  • No dose adjustment to FANAPT is needed in patients with mild hepatic impairment. Exercise caution when administering it to patients with moderate hepatic impairment. FANAPT is not recommended for patients with severe hepatic impairment [see Dosage in Special Populations (2.2)]. In adult subjects with mild hepatic impairment no relevant difference in pharmacokinetics of iloperidone, P88 or P95 (total or unbound) was observed compared to healthy adult controls. In subjects with moderate hepatic impairment a higher (2-fold) and more variable free exposure to the active metabolites P88 was observed compared to healthy controls, whereas exposure to iloperidone and P95 was generally similar (less than 50% change compared to control). Since a study in severe liver impaired subjects has not been conducted, FANAPT is not recommended for patients with severe hepatic impairment.

 

January 2013

Summary View

5 WARNINGS AND PRECAUTIONS

5.3 Neuroleptic Malignant Syndrome (NMS)
  • A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including FANAPT.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience
  • The information below is derived from a clinical trial database for FANAPT consisting of 2070 patients exposed to FANAPT at doses of 10 mg/day or greater, for the treatment of schizophrenia. Of these, 806 received FANAPT for at least 6 months, with 463 exposed to FANAPT for at least 12 months.

7 DRUG INTERACTIONS

7.2 Potential for FANAPT to Affect Other Drugs
  • In vitro studies in human liver microsomes showed that iloperidone does not substantially inhibit the metabolism of drugs metabolized by the following cytochrome P450 isozymes: CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, or CYP2E1. Based on in vitro studies, iloperidone is a time-dependent inhibitor of CYP3A at therapeutic exposure levels. Co-administration of iloperidone may lead to an increase in plasma levels of drugs that are predominantly eliminated by CYP3A4 

 

 

January 2012

Summary View

5 WARNINGS AND PRECAUTIONS

5.5 Metabolic Changes
  • new section added; see PI for details