Approved July 31, 2009

PALIPERIDONE PALMITATE
(FDA Category 3S)

INVEGA(R) SUSTENNA (TM) (Ortho-McNeil-Janssen, Pharmaceuticals). is an extended-release injectable atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives.

DOSING INFORMATION: After establishing tolerability to oral paliperidone or oral risperidone, the initial dose of paliperidone palmitate is 234 mg IM on day 1 and 156 mg IM one week later, both administered into deltoid muscle. The monthly maintenance dose is 117 mg IM administered into the deltoid or gluteal muscle, although some patients may benefit from lower or higher doses within the recommended range of 39 mg to 234 mg monthly.

PHARMACOKINETICS: Paliperidone palmitate is hydrolyzed to paliperidone, the major active metabolite of risperidone. Due to its extremely low water solubility, paliperidone palmitate dissolves slowly after IM injection before being hydrolyzed to paliperidone and absorbed into systemic circulation. Following IM administration, Tmax is reached in 13 days with release of drug starting as early as day 1 and lasting for as long as 126 days. IM injection into the deltoid muscle provides a 28% higher Cmax compared to IM injection into the gluteal muscle. The 2 initial deltoid IM injections help to attain therapeutic concentrations rapidly. The release profile of paliperidone palmitate and the recommended dosing regimen result in sustained therapeutic concentrations. AUC is dose proportional within the 39 mg to 234 mg dose range. The apparent Vd is 391 L and plasma protein binding is 74%. Paliperidone is not extensively metabolized. Approximately 80% of radio-labeled paliperidone was recovered in the urine and 11% in the feces. The median apparent half-life following a single IM dose over the range of 39 mg to 234 mg was 25 to 49 days.

CAUTIONS: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death in clinical trials were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that antipsychotic drugs may increase mortality. It is unclear from the observational studies to what extent these mortality findings may be attributed to the antipsychotic drug as opposed to patient characteristics. Paliperidone palmitate is not approved for the treatment of patients with dementia-related psychosis Avoid using paliperidone palmitate with any drug class that is known to prolong QTc interval, and in patients with risk factors for prolonged QT interval. Monitor blood sugars in diabetic patients and patients at risk for high blood sugars. Significant weight gain has been reported. Commonly observed adverse events included injection site reactions, somnolence, dizziness, akathisia and extrapyramidal disorder.

FDA APPROVED INDICATIONS: Paliperidone palmitate is indicated for the acute and maintenance treatment of schizophrenia in adults.