Profile
Fanapt (iloperidone) - 2 indications
Scroll down for more information on each indication:
- for the treatment of schizophrenia in adults; approved May of 2009
- for the treatment of manic or mixed episodes associated with bipolar I disorder in adults; approved April of 2024
General Information
Fanapt is a psychotropic agent belonging to the chemical class of piperidinyl-benzisoxazole derivatives.
Fanapt is specifically indicated:
- for the treatment of schizophrenia in adults
- for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults
Mechanism of Action
The mechanism of action of iloperidone in schizophrenia and bipolar I disorder is unknown. However, the efficacy of iloperidone could be mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonism. Iloperidone forms an active metabolite, P88, that has an in vitro receptor binding profile similar to the parent drug.
Side Effects
Adverse events associated with the use of Fanapt for adults with schizophrenia may include, but are not limited to, the following:
- dizziness
- somnolence
- dry mouth
- nausea
- tachycardia
- diarrhea
- orthostatic hypotension
- weight gain
Adverse events associated with the use of Fanapt for adults with bipolar mania may include, but are not limited to, the following:
- tachycardia
- dizziness
- dry mouth
- hepatic enzymes increased
- nasal congestion
- weight increased
- hypotension
- somnolence
Indication 1 - adults with schizophrenia
approved May 2009
Fanapt is supplied as a tablet designed for oral administration. Fanapt must be titrated slowly from a low starting dose to avoid orthostatic hypotension.
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Recommended dose |
1mg twice daily | 2mg twice daily | 4mg twice daily | mg twice daily | 8mg twice daily | 10mg twice daily | 12mg twice daily | 6 mg to 12 mg twice daily |
FDA approval of Fanapt was based on the results of two clinical studies.
Six-Week Study
This placebo-controlled trial enrolled 706 subjects who met the DSM-III/IV criteria for schizophrenia. The subjects received two dose ranges of Fanapt (12-16 mg/day or 20-24 mg/day) compared to placebo and an active control. Fanapt was titrated starting 1 mg twice daily on day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, as needed. The primary endpoint was change from baseline on the Brief Psychiatric Rating Scale (BPRS) total score at the end of treatment (Day 42). Both the 12-16 mg/day and the 20-24 mg/day dose ranges of Fanapt were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to Fanapt in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug.
Four-Week Study
This placebo-controlled trial enrolled 604 subjects who met the DSM-III/IV criteria for schizophrenia. The subjects one fixed dose of Fanapt (24 mg/day) compared to placebo and an active control. Fanapt was titrated starting 1 mg twice daily on day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment (Day 28). The 24 mg/day Fanapt dose was superior to placebo in the PANSS total score. Fanapt appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.
Indication 2 - the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults
approved April 2024
Fanapt is supplied as a tablet designed for oral administration. Fanapt must be titrated slowly from a low starting dose to avoid orthostatic hypotension.
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 and 7 | Recommended dose |
1 mg twice daily | 3 mg twice daily | 6 mg twice daily | 9 mg twice daily | 12 mg twice daily | Titration complete | 12 mg twice daily |
Clinical Trial Results
The FDA approval of Fanapt for the active treatment of manic or mixed episodes associated with bipolar 1 disorder in adults was based on a randomized phase 3 trial in approximately 400 patients with a history of bipolar I disorder suffering from a current episode of mania. Patients were randomized to receive either Fanapt or placebo in a 1:1 ratio. The primary endpoint measured in Week 4 of treatment was assessed by the Young Mania Rating Scale (YMRS), a rating scale of clinical severity in the core symptoms of mania. At the end of the study (Week 4), Fanapt treated patients showed a larger improvement than placebo treated patients, and this difference was highly statistically significant. Statistically significant benefit in the Fanapt treated group over placebo was observed as early as the Week 2 assessment.