Pharmacy & Therapeutics - April 2008 - (Page 207) E ATING 50 Y E BR S AR Plus additional features to consider Metabolism and Excretion M EN TA L H E • CYP450 isozymes play a limited role in the overall metabolism of INVEGA — Less than 10% of the dose is metabolized by each of the 4 identified metabolic pathways* • Primarily excreted unchanged via the kidneys — Dosing must be individualized according to the patient’s renal function status. The maximum recommended dose of INVEGA is 6 mg for patients with mild renal impairment and 3 mg for patients with moderate to severe renal impairment *Dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Innovative Drug Delivery System • Innovative OROS® extended-release technology for reduced peak/ trough fluctuations†1 PLASMA LEVEL VARIATION AT STEADY STATE Oral risperidone (Immediate Release) INVEGA (Extended Release) Plasma concentration INVEGA peak INVEGA trough † Correlation to clinical effect has not been established. Days Pharmacokinetic simulation. OROS is a registered trademark of ALZA Corporation. Potential for Gastrointestinal Obstruction: INVEGA should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing. Rare instances of obstructive symptoms have been reported in patients with known strictures taking nondeformable formulations. INVEGA should only be used in patients who are able to swallow the tablet whole. Orthostatic Hypotension: INVEGA may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dosetitration period. Monitoring should be considered in patients for whom this may be of concern. INVEGA should be used with caution in patients with known cardiovascular disease, and conditions that would predispose patients to hypotension. Potential for Cognitive and Motor Impairment: INVEGA has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA does not affect them adversely. Seizures: INVEGA should be used cautiously in patients with a history of seizures. Suicide: The possibility of suicide attempt is inherent in psychotic illnesses and close supervision of high-risk patients should accompany drug therapy. Maintenance Treatment: Physicians who elect to use INVEGA for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient. Drug Interactions: Given the primary CNS effects of INVEGA, INVEGA should be used with caution in combination with other centrally acting drugs and alcohol. Extrapyramidal Symptoms (EPS): Total EPS-related adverse events in the higher 9-mg and 12-mg treatment groups were 25% and 26%, respectively, versus 11% for the placebo group. Weight Gain: The proportion of subjects having a weight gain of ≥7% body weight were comparable to placebo (5%) for 3 mg (7%) and 6 mg (6%). A higher incidence was seen for 9 mg (9%) and 12 mg (9%). Renal Impairment: Dosing must be individualized according to the patient’s renal function status. The maximum recommended dose of INVEGA is 6 mg for patients with mild renal impairment and 3 mg for patients with moderate to severe renal impairment (see Dosing for Special Populations). Elderly: No dosage adjustment is recommended based on age alone. However, dose adjustment may be required because of age-related decreases in creatinine clearance (see Dosing for Special Populations). Commonly Observed Adverse Reactions: The most commonly observed adverse reactions, occurring at an incidence of ≥5% and at least 2 times placebo, were akathisia and extrapyramidal disorder. Use with Risperidone: Concomitant use of paliperidone with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is co-administered. Reference: 1. Conley R, Gupta SK, Sathyan G. Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin. 2006;22(10):1879-1892. Please see brief summary of full Prescribing Information for INVEGA on adjacent page. LT A H INVEGA—Powerful Efficacy With Safety and Tolerability CE L TM IN
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