Home » Drug Information » FDA Approved Drugs » 2006
Medical Areas: Neurology | Psychiatry/Psychology
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Janssen Pharmaceuticals
Approval Status: Approved December 2006
Treatment Area: Schizophrenia
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
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.
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
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
Adverse events associated with the use of Invega may include,
but are not limited to, the following:
- Extrapyramidal disorder
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.
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
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.
For additional information regarding Invega or schizophrenia,
please visit the Invega web page.