Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The information below is derived from a clinical trial database for FANAPT consisting of 3,229 patients exposed to FANAPT at doses of 10 mg/day or greater, for the treatment of schizophrenia and from a clinical trial database for FANAPT consisting of 312 patients exposed to FANAPT at doses of 24 mg/day, for the treatment of bipolar mania

The information presented in this section was derived from pooled data from 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies in patients who received FANAPT at daily doses within a range of 10 to 24 mg (n=874).

Based on the pooled data from 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies, adverse reactions in patients with schizophrenia that occurred with a greater than 2% incidence in the patients treated with FANAPT, and for which the incidence in patients treated with FANAPT

Based on the pooled data from 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies of patients with schizophrenia, the following adverse reactions occurred in ≥5% incidence in the patients treated with FANAPT and at least twice the placebo rate for at least 1 dose: dizziness, dry mouth, fatigue, nasal congestion, somnolence, tachycardia, orthostatic hypotension, and weight increased. Dizziness, tachycardia, and weight increased were at least twice as common on 20-24 mg/day as on 10-16 mg/day.

In a short-term, placebo-controlled trial in patients with bipolar mania the following adverse reactions occurred in ≥5% incidence in the patients treated with FANAPT and at least twice the placebo rate: tachycardia, dizziness, dry mouth, hepatic enzymes increased, nasal congestion, weight increased, hypotension, and somnolence.

Pooled data from the 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies of patients with schizophrenia provided information regarding EPS. Adverse event data collected from those trials showed the following rates of EPS-related adverse events as shown in

Based on the pooled data from 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies in patients with schizophrenia, there was no difference in the incidence of discontinuation due to adverse reactions between FANAPT-treated (5%) and placebo-treated (5%) patients. The types of adverse reactions that led to discontinuation were similar for the FANAPT- and placebo-treated patients.

In a 4-week, placebo-controlled study in patients with bipolar mania, the incidence of discontinuation due to adverse reactions was higher in FANAPT-treated (8.7%) patients than placebo-treated (5.3%) patients. Adverse reactions that led to discontinuation in more than one FANAPT-treated subject were liver enzyme elevations, nausea and vomiting, dizziness and hypotension.

An examination of population subgroups in the 4 placebo-controlled, 4- or 6-week, fixed- or flexible-dose studies of patients with schizophrenia did not reveal any evidence of differences in safety on the basis of age, sex or race.

There were no differences between FANAPT and placebo in the incidence of discontinuation due to changes in hematology, or urinalysis.

In a short-term placebo-controlled trial, asymptomatic alanine aminotransferase (ALT) elevations ≥3x ULN occurred in 9.2% of FANAPT-treated patients with acute mania compared to 1.5% of placebo treated subjects. AST elevations were less common.

In short-term placebo-controlled trials (4- to 6-weeks) in patients with schizophrenia, there were 1.0% (13/1342) FANAPT-treated patients with hematocrit at least one time below the extended normal range during post-randomization treatment, compared to 0.3% (2/585) on placebo. The extended normal range for lowered hematocrit was defined in each of these trials as the value 15% below the normal range for the centralized laboratory that was used in the trial. 

In a short-term placebo-controlled trial (4 weeks) in patients with bipolar mania, there were 3.5% (7/200) FANAPT-treated patients with hematocrit at least one time below the extended normal range (<0.85xLLN) during post-randomization treatment, compared to 0.5% (1/196) on placebo.

Analysis of clinical laboratory data following administration of FANAPT suggested the mechanism of hemodilution based on consistent decreases in hematocrit, hemoglobin, white blood cells, total protein, and albumin. Decreases in hematocrit and total protein have been observed with other alpha receptor antagonists and are attributed to hemodilution

In a 4-week placebo-controlled trial in patients with bipolar mania, treatment with FANAPT 12 mg twice a day resulted in an increase of serum urate levels of approximately 27.2 umol/L (0.457 mg/dL) compared to 0.1 umol/L (0.002 mg/dL) in placebo group.

The following is a list of MedDRA terms that reflect adverse reactions in patients treated with FANAPT at multiple doses ≥ 4 mg/day during any phase of a trial with the database of 3,210 FANAPT-treated patients with schizophrenia. All reported reactions are included except those already listed in

Reactions are further categorized by MedDRA system organ class and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/100 patients (only those not listed in

The following adverse reactions have been identified during post-approval use of FANAPT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: retrograde ejaculation and hypersensitivity reactions (including anaphylaxis; angioedema; throat tightness; oropharyngeal swelling; swelling of the face, lips, mouth, and tongue; urticaria; rash; and pruritus).