Trade names Rexulti Pregnancy
category US: None assigned ATC code N05AX16 (WHO) Molar mass 433.6 g/mol | License data US FDA: Brexpiprazole Routes of
administration Oral (via tablets) Legal status US: ℞-only | |
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How to pronounce brexpiprazole rexulti memorizing pharmacology video flashcard
Brexpiprazole (/brɛksˈpɪprəzoʊl/ breks-PIP-rə-zohl; brand name Rexulti recks-UL-tee, previously known as OPC-34712) is an atypical antipsychotic drug. It is a D2 dopamine partial agonist called serotonin-dopamine activity modulator (SDAM). The drug received FDA approval on July 13, 2015 for the treatment of schizophrenia, and as an adjunctive treatment for depression. Although it failed Phase II clinical trials for ADHD, it has been designed to provide improved efficacy and tolerability (e.g., less akathisia, restlessness and/or insomnia) over established adjunctive treatments for major depressive disorder (MDD).
Contents
- How to pronounce brexpiprazole rexulti memorizing pharmacology video flashcard
- Partnership with Lundbeck
- Clinical trials
- Phase II
- Phase III
- Phase I
- Conferences
- Side effects
- Drug interactions
- Pharmacology
- Patents
- References
The drug was developed by Otsuka and Lundbeck, and is considered to be a successor of Otsuka's top-selling antipsychotic agent aripiprazole (brand names: Abilify, Aripiprex). Otsuka's US patent on aripiprazole expired on October 20, 2014; however, due to a pediatric extension, a generic will become available in the near future.
Partnership with Lundbeck
In November 2011, Otsuka and Lundbeck have announced a global alliance. Lundbeck has given Otsuka an upfront payment of $200 million, and the deal includes development, regulatory and sales payments, for a potential total of $1.8 billion. Specifically for OPC-34712, Lundbeck will obtain 50% of net sales in Europe and Canada and 45% of net sales in the US from Otsuka.
Clinical trials
Brexpiprazole was in clinical trials for adjunctive treatment of MDD, adult ADHD, and schizophrenia.
Phase II
The Phase II multicenter, double-blind, placebo-controlled study randomized 429 adult MDD patients who exhibited an inadequate response to one to three ADTs in the current episode. The study was designed to assess the efficacy and safety of brexpiprazole as an adjunctive treatment to standard antidepressant treatment. The antidepressants included in the study were desvenlafaxine, escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine.
Phase III
A new Phase III study was in the recruiting stage: "Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)". Its goal is "to compare the effect of brexpiprazole to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment in patients with major depressive disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT". Estimated enrollment was 1250 volunteers.
Phase II
Phase I
Phase II
Phase III
Conferences
Side effects
The most common adverse events associated with brexpiprazole (all doses of brexpiprazole cumulatively greater than or equal to 5% vs. placebo) were upper respiratory tract infection (6.9% vs. 4.8%), akathisia (6.6% vs. 3.2%), weight gain (6.3% vs. 0.8%) and nasopharyngitis (5.0% vs. 1.6%).
Drug interactions
Based on information given on the consent forms, it seems brexpiprazole is a substrate of CYP2D6 and CYP3A4, like its predecessor aripiprazole. Participants in the clinical trials are advised to avoid grapefruit, Seville oranges and related citruses.
Pharmacology
Brexpiprazole acts as a partial agonist of the 5-HT1A, D2, and D3 receptors. Partial agonists have both blocking properties and stimulating properties at the receptor they bind to. The ratio of blocking activity to stimulating activity determines a portion of its clinical effects. Brexpiprazole has more blocking and less stimulating activity than its predecessor, aripiprazole, which may decrease its risk for agitation and restlessness. It is also an antagonist of the 5-HT2A, 5-HT2B, 5-HT7, α1A-, α1B-, α1D-, and α2C-adrenergic, and H1 receptors. It has negligible affinity for the mACh receptors.