Invega (paliperidone)
Company: Janssen LP
Approval Status: Approved December 2006
Treatment for: Schizophrenia
Areas: Neurology; Psychiatry/Psychology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Invega is an oral extended-release (ER) major active metabolite of risperidone. It is an antagonist and thus interferes with neurotransmitter communication in the brain. It blocks dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors, all of which have been implicated in schizophrenia.
Invega is specifically indicated for the treatment of schizophrenia.
Invega is supplied as an extended release tablet available in 3 mg, 6 mg and 9 mg strengths, designed for oral administration. The recommended initial dose of the drug is 6 mg once daily, administered in the morning. The drug was observed to have dose-dependent efficacy, however this related to dose-dependent increases in adverse events. Dose increases above 6 mg/day should be made only after clinical reassessment. The maximum recommended dose is 12 mg/day.
Clinical Results
FDA Approval
FDA approval of Invega was based on the results of three clinical
trials. These placebo-controlled, active-controlled (olanzapine),
fixed-dose trials enrolled 1,665 non-elderly adult subjects who met
DSM-IV criteria for schizophrenia, internationally. Subjects
received placebo or Invega at 3, 6, 9, 12, and 15 mg/day for six
weeks. Efficacy was evaluated using the Positive and Negative
Syndrome Scale (PANSS) and the Personal and Social Performance
(PSP) scale. Results revealed all doses of Invega to be superior to
placebo on both the PANSS and PSP scales. The mean effects at all
doses were fairly similar, although the higher doses in all studies
were numerically superior.
Ongoing Study Commitments
- Janssen has agreed to repeat the study in postmarketing using
doses that include a maximally tolerated dose for the dams, as the
original pre- and postnatal developmental study in rats did not use
high enough doses to adequately evaluate the effects of
paliperidone on this phase of reproduction.
Protocol Submission: January 2007
Study Start: July 2007
Final Report Submission: December 2008 - Janssen has agreed to conduct a study to better explore for a
minimal effective dose being that in the one study that included a
3 mg dose of paliperidone ER, the dose was shown to be about as
effective as higher doses. The FDA therefore believes that Janssen
has not fully evaluated the lower end of the dose response
curve.
Protocol Submission: April 2007
Study Start: November 2007
Final Report Submission: January 2011 - Janssen has agreed to submit deferred pediatric studies under
PREA for the treatment of adolescent schizophrenia ages 12 to 17
years, and to develop other information, e.g., pharmacokinetic,
pertinent to using the drug in the pediatric population.
Final Report Submission: December 2009
Side Effects
Adverse events associated with the use of Invega may include, but are not limited to, the following:
- Parkinsonism
- Akathisia
- Dyskinesia
- Tachycardia
- Headache
- Somnolence
- Anxiety
- Hyperkinesia
- Extrapyramidal disorder
- Dystonia
In addition, Invega was shown to induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. Thus, it should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that predispose the patient to hypotension.
Mechanism of Action
Invega uses osmotic pressure to deliver paliperidone at a controlled rate. It is an oral extended-release (ER) major active metabolite of risperidone. Although the exact mechanism of action is unknown, it is thought that Invega acts as an antagonist and thus interferes with neurotransmitter communication in the brain. It blocks dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors, all of which have been implicated in schizophrenia.
Literature References
Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, Eerdekens M Paliperidone Extended-Release Tablets for Prevention of Symptom Recurrence in Patients With Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. Journal of clinical psychopharmacology 2007 Feb;27(1):6-14.
Kane J, Canas F, Kramer M, Ford L, Gassmann-Mayer C, Lim P, Eerdekens M Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial. Schizophrenia research 2006 Nov 7.
Zhu HJ, Wang JS, Markowitz JS, Donovan JL, Gibson BB, Devane CL Risperidone and Paliperidone Inhibit P-Glycoprotein Activity In Vitro. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2006 Aug 23.
Riedel M, Schwarz MJ, Strassnig M, Spellmann I, Muller-Arends A, Weber K, Zach J, Muller N, Moller HJ Risperidone plasma levels, clinical response and side-effects. European archives of psychiatry and clinical neuroscience 2005 Aug;255(4):261-8. Epub 2004 Nov 29.
Verma SK, Tan CH, Chan YH, Chong SA Plasma risperidone levels and clinical response in patients with first-episode psychosis. Journal of clinical psychopharmacology 2005 Dec;25(6):609-11.
Spina E, Avenoso A, Facciola G, Salemi M, Scordo MG, Ancione M, Madia AG, Perucca E Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. Psychopharmacology 2001 Jan 1;153(2):238-43.
Additional Information
For additional information regarding Invega or schizophrenia, please visit the Invega web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
