FANAPT Tablet Ref.[10297] Active ingredients: Iloperidone

2.1 Recommended Dosage

Titrate FANAPT to avoid orthostatic hypotension [see Warnings and Precautions (5.7)]. Administer FANAPT orally with or without food. Table 1 includes dosage recommendations for FANAPT for the treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.

Table 1. Dosage Recommendations for FANAPT in Adults for the Treatment of Schizophrenia or Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder:

2.2 Dosage Recommendations for Use in Patients Who Are Known CYP2D6 Poor Metabolizers

Reduce the dose of FANAPT by one-half for CYP2D6 poor metabolizers [see Clinical Pharmacology (12.3, 12.5)]. Table 2 includes dosage recommendations for FANAPT in adults who are CYP2D6 poor metabolizers.

Table 2. Dosage Recommendations for FANAPT in Adults with Schizophrenia or Bipolar I Disorder Who are CYP2D6 Poor Metabolizers:

2.3 Dosage Recommendations in Patients with Hepatic Impairment

No dose adjustment for FANAPT is needed in patients with mild hepatic impairment. Patients wFANAPTsith moderate hepatic impairment may require dose reduction, if clinically indicated. FANAPT is not recommended for patients with severe hepatic impairment [see Use in Specific Populations (8.6)].

2.4 Dosage Modifications for Concomitant Use with Strong CYP2D6 Inhibitors and Strong CYP3A4 Inhibitors

Coadministration with Strong CYP2D6 Inhibitors

Reduce the dose of FANAPT one-half when administered concomitantly with strong CYP2D6 inhibitors such as fluoxetine or paroxetine. When the CYP2D6 inhibitor is withdrawn from the combination therapy, increase the dose of FANAPT to where it was before [see Drug Interactions (7.1)].

Coadministration with Strong CYP3A4 Inhibitors

Reduce the dose of FANAPT by one-half when administered concomitantly with strong CYP3A4 inhibitors such as ketoconazole or clarithromycin. When the CYP3A4 inhibitor is withdrawn from the combination therapy, increase the dose of FANAPT to where it was before [see Drug Interactions (7.1)].

Coadministration with Strong CYP2D6 and Strong CYP3A4 Inhibitors

Reduce the dose of FANAPT by about one-half if administered concomitantly with inhibitors of CYP2D6 and CYP3A4. When both CYP2D6 and CYP3A4 inhibitors are withdrawn from the combination therapy, increase the dose of FANAPT to where it was before [see Drug Interactions (7.1)].

2.5 Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that the initiation titration schedule be followed whenever patients have had an interval off FANAPT of more than 3 days.

10.1 Human Experience

In pre-marketing trials involving over 3,522 patients, accidental or intentional overdose of FANAPT was documented in 8 patients ranging from 48 mg to 576 mg taken at once and 292 mg taken over a 3-day period. No fatalities were reported from these cases. The largest confirmed single ingestion of FANAPT was 576 mg; no adverse physical effects were noted for this patient. The next largest confirmed ingestion of FANAPT was

438 mg over a 4-day period; extrapyramidal symptoms and a QTc interval of 507 msec were reported for this patient with no cardiac sequelae. This patient resumed FANAPT treatment for an additional 11 months. In general, reported signs and symptoms were those resulting from an exaggeration of the known pharmacological effects (e.g., drowsiness and sedation, tachycardia, and hypotension) of FANAPT.

10.2 Management of Overdose

There is no specific antidote for FANAPT. Therefore, appropriate supportive measures should be instituted. In case of acute overdose, the healthcare provider should establish and maintain an airway and ensure adequate oxygenation and ventilation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizures or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous ECG monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide and quinidine should not be used, as they have the potential for QT-prolonging effects that might be additive to those of FANAPT. Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of FANAPT, resulting in problematic hypotension. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of FANAPTinduced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision should continue until the patient recovers.

Consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

Store FANAPT tablets at controlled room temperature, 25°C (77°F); excursions permitted to 15° to 30 °C (59° to 86°F) [See USP Controlled Room Temperature]. Protect FANAPT tablets from exposure to light and moisture.