FDA approves new add-on drug to treat off episodes in adults with Parkinson’s disease

Latest FDA approval for Parkinson’s disease

The U.S. Food and Drug Administration approved Nourianz (istradefylline) tablets as an add-on treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “off” episodes.

An “off” episode is a time when a patient’s medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.
According to the National Institutes of Health, PD is the second-most common neurodegenerative disorder in the U.S. after Alzheimer’s disease. An estimated 50,000 Americans are diagnosed with PD each year, and about one million Americans have the condition. The neurological disorder typically occurs in people over age 60, although it can occur earlier.

It happens when cells in the brain, which produce a chemical called dopamine, become impaired or die. Dopamine helps transmit signals between the areas of the brain that produce smooth, purposeful movements – such as eating, writing, and shaving. Early symptoms of the disease are subtle and typically worsen gradually; however, the disease progresses more quickly in some people than in others.

DESCRIPTION

NOURIANZ contains istradefylline, an adenosine receptor antagonist, which has a xanthine derivative structure. The chemical name is (E)-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methyl-3,7­
dihydro-1H-purine-2,6-dione.

Its molecular formula is C20H24N4O4. The molecular weight is 384.43.

Mechanism of Action

The precise mechanism by which istradefylline exerts its therapeutic effect in Parkinson disease is
unknown. In in vitro studies and in in vivo animal studies, istradefylline was demonstrated to be an
adenosine A2A receptor antagonist.

The effectiveness of Nourianz in treating “off” episodes in patients with PD who are already being treated with levodopa/carbidopa was shown in four 12-week placebo-controlled clinical studies that included a total of 1,143 participants. In all four studies, patients treated with Nourianz experienced a statistically significant decrease from baseline in daily “off” time compared to patients receiving a placebo.

The most common adverse reactions observed in patients taking Nourianz were involuntary muscle movement (dyskinesia), dizziness, constipation, nausea, hallucination and sleeplessness (insomnia). Patients should be monitored for development of dyskinesia or exacerbation of existing dyskinesia. If hallucinations, psychotic behavior, or impulsive/compulsive behavior occurs, a dosage reduction or stoppage of Nourianz should be considered. Use of Nourianz during pregnancy is not recommended. Women of childbearing potential should be advised to use contraception during treatment.

Important Safety Information

Warnings and Precautions

Dyskinesia: NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In clinical trials, 1% of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

Hallucinations / Psychotic Behavior: Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with NOURIANZ. Consider dosage reduction or discontinuation if a patient develops hallucinations or psychotic behaviors while taking NOURIANZ.

Impulse Control / Compulsive Behaviors: Patients treated with NOURIANZ and one or more medication(s) for the treatment of Parkinson’s disease (including levodopa) may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges. In clinical trials, 1 patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on NOURIANZ 20 mg or placebo.

Drug Interactions

The maximum recommended dosage in patients taking strong CYP3A4 inhibitors is 20 mg once daily. Avoid use of NOURIANZ with strong CYP3A4 inducers.

Specific Populations

Pregnancy: Based on animal data, may cause fetal harm.

Hepatic impairment: The maximum recommended dosage of NOURIANZ in patients with moderate hepatic impairment is 20 mg once daily. Avoid use in patients with severe hepatic impairment.

Adverse Reactions

The most common adverse reactions with an incidence ≥5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.

Before you take NOURIANZ, tell your healthcare provider about all your medical conditions, including if you:
 have a history of abnormal movement (dyskinesia).
 have reduced liver function.
 smoke cigarettes.
 are pregnant or plan to become pregnant. NOURIANZ may harm your unborn baby.
 are breastfeeding or plan to breastfeed. It is not known if NOURIANZ passes into breast milk. You and your healthcare
provider should decide if you will take NOURIANZ or breastfeed.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
NOURIANZ and other medicines may affect each other causing side effects. NOURIANZ may affect the way other
medicines work, and other medicines may affect how NOURIANZ works.

The FDA granted approval of Nourianz to Kyowa Kirin, Inc.

Reference:

FDA Label