A closer look at new FDA actions: Janssen's Invega

Author: Monica Holmberg, PharmD

Janssen's Invega

The FDA has granted approval to Janssen's Invega (paliperidone) for long-term maintenance treatment of schizophrenia in adults. The extended-release formulation of this atypical antipsychotic allows for once-daily dosing. Invega had previously been approved for short-term treatment only.1

More than 2 million Americans are affected by schizophrenia.2 Symptoms can include hallucinations, delusions, depression, and social withdrawal. Schizophrenia affects men and women equally.1

Mechanism of Action

The exact mechanism of action of Invega is not known. The drug is believed, however, to have an antagonistic effect at the central dopamine type 2 and serotonin type 2 receptors. It also has been shown to be an a1 and a2 adrenergic receptor antagonist and a histamine1 histaminergic receptor antagonist. Invega is the active metabolite of risperidone.3

Clinical Trial

A total of 207 patients were studied in a clinical trial of long-term treatment with Invega. Patients with acute schizophrenia were initially treated for 8 weeks with the drug. Doses ranged from 3 mg daily to 15 mg daily with a starting dose of 9 mg. After the 8 weeks, patients continued on their maintenance dose for an additional 6 weeks to establish stabilization. At the end of the 6 weeks, patients were randomized to receive either their treatment dose of Invega or placebo.1 The double-blind study was discontinued early, because Invega was determined to be more effective than placebo in 2 areas: maintaining symptom control and delaying the time until relapse.1,3

Dosage

Treatment with Invega should begin with 6 mg once a day. If a higher dose is needed, dosage increases should be made in increments of 3 mg every 5 days up to a maximum daily dose of 12 mg.

Patients with renal insufficiency (creatinine clearance between 10 and 50 mL/min) should receive a maximum daily dose of 3 mg. Patients with creatinine clearance of greater than or equal to 50 mL/min and less than 80 mL/min should receive a maximum daily dose of 6 mg.3

Contraindications, Warnings, and Precautions

Invega is contraindicated in patients with a known hypersensitivity to any of its components. Invega carries a boxed warning about its use in elderly patients with dementia-related psychosis. When compared with placebo, these patients are at a greater risk for death when treated with an atypical antipsychotic agent.

Invega has been shown to increase the corrected QT interval. Concomitant use with other medications that prolong the corrected QT interval--such as Class 1A or Class III antiarrhythmic agents, antipsychotic agents, or certain antibiotics--should be avoided.

Neuroleptic malignant syndrome has been associated with Invega and other antipsychotic medications. As with other antipsychotic medications, patients using Invega may experience tardive dyskinesia.

Patients using Invega may be at a higher risk for developing hyperglycemia or diabetes; appropriate monitoring may be warranted. Invega should not be given to patients with severe gastrointestinal narrowing.

Patients using Invega may be at a greater risk for orthostatic hypotension, seizures, hyperprolactinemia, and somnolence or sedation.3 Elderly patients receiving Invega may be at a greater risk for cerebrovascular events.

Invega is not approved for use in pediatric patients. Invega is in pregnancy category C and should not be taken by patients who are breast-feeding.

In clinical trials, the most commonly reported side effects were restlessness and extrapyramidal disorders.1 Other side effects included rapid heartbeat and drowsiness.2

Invega may be taken with or without food. The tablet should never be crushed, chewed, broken, or split, because any damage to the integrity of the tablet may disturb its extended-release formulation.

References

1. FDA Approves INVEGA for Long-term Maintenance Treatment of Schizophrenia Available at: www.janssen.com/janssen/news_release.html?item=042707_2. Accessed July 2007.

2. FDA approves new drug for schizophrenia. Available at: www.fda.gov/bbs/topics/NEWS/2006/NEW01534.html. Accessed July 2007.

3. Invega complete prescribing information. Available at: www.janssen.com/janssen/shared/pi/invega.pdf. Accessed July 2007.