Introduction
Nourianz (istradefylline) is an oral medication approved as an adjunctive treatment to levodopa/carbidopa in adults with Parkinson's disease experiencing "off" episodes. It represents a novel therapeutic approach as a selective adenosine A2A receptor antagonist, offering a different mechanism of action from other Parkinson's medications.
Mechanism of Action
Nourianz exerts its therapeutic effects through selective antagonism of adenosine A2A receptors in the brain. In Parkinson's disease, there is an imbalance between dopaminergic and adenosineergic neurotransmission in the basal ganglia. By blocking adenosine A2A receptors, which are predominantly located in the striatum and globus pallidus, istradefylline reduces the inhibitory effects of adenosine on dopaminergic pathways. This action helps restore motor function without directly affecting dopamine receptors, providing complementary benefits to levodopa therapy.
Indications
Nourianz is indicated as adjunctive treatment to levodopa/carbidopa in adults with Parkinson's disease experiencing "off" episodes. These episodes refer to periods when Parkinson's symptoms return despite medication, typically occurring as the effect of levodopa wears off before the next dose.
Dosage and Administration
Recommended dosage: 20 mg orally once daily Maximum dosage: 40 mg once daily Administration: Can be taken with or without food Dose adjustment:- Moderate hepatic impairment (Child-Pugh B): Maximum 20 mg daily
- Severe hepatic impairment (Child-Pugh C): Not recommended
- Renal impairment: No dosage adjustment necessary
- Elderly patients: No dosage adjustment necessary
Pharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations achieved within 1.5-4 hours. Bioavailability is approximately 90%. Distribution: Extensive tissue distribution with a volume of distribution of ~797 L. Protein binding is approximately 98%. Metabolism: Primarily metabolized by CYP3A4 and CYP1A1 enzymes. Major metabolites include M1, M2, and M4. Elimination: Primarily excreted in feces (76%) with minor renal excretion (18%). Terminal elimination half-life is approximately 83 hours.Contraindications
- Hypersensitivity to istradefylline or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin)
Warnings and Precautions
Dyskinesia: Nourianz may cause or exacerbate dyskinesia. Dose reduction of levodopa may be necessary. Hallucinations/Psychosis: May exacerbate psychosis or hallucinations. Patients with major psychotic disorders should not be treated. Impulse Control Disorders: May cause compulsive behaviors including gambling, sexual urges, spending, or binge eating. Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or withdrawal may cause symptoms resembling neuroleptic malignant syndrome. Pregnancy: Based on animal data, may cause fetal harm. Use only if potential benefit justifies potential risk.Drug Interactions
Strong CYP3A4 inhibitors: Contraindicated due to significant increase in istradefylline exposure Moderate CYP3A4 inhibitors: Use with caution; consider dose reduction CYP3A4 inducers: May decrease istradefylline concentrations P-glycoprotein substrates: May increase concentrations of digoxin, dabigatran, and other P-gp substratesAdverse Effects
Most common adverse reactions (≥5% and more frequent than placebo):- Dyskinesia (17%)
- Dizziness (6%)
- Nausea (5%)
- Constipation (5%)
- Hallucinations (5%)
- Dyskinesia
- Hallucinations/psychotic behavior
- Impulse control disorders
- Withdrawal-emergent hyperpyrexia and confusion
Monitoring Parameters
- Motor function and "off" episode frequency
- Dyskinesia severity and duration
- Mental status changes, hallucinations, or psychotic behavior
- Signs of impulse control disorders
- Hepatic function in patients with hepatic impairment
- Therapeutic response and need for levodopa dose adjustment
Patient Education
- Take Nourianz exactly as prescribed, once daily with or without food
- Do not stop taking abruptly without medical supervision
- Report any new or worsening involuntary movements
- Immediately report any unusual urges (gambling, spending, sexual)
- Inform healthcare provider about all medications, including over-the-counter products
- Be aware of possible dizziness and use caution when driving or operating machinery
- Notify healthcare provider if pregnant, planning pregnancy, or breastfeeding
- Keep all follow-up appointments for monitoring
References
1. FDA Prescribing Information: Nourianz (istradefylline) tablets. Revised 2022. 2. Hauser RA, Stocchi F, Rascol O, et al. PREPARED: A randomized, double-blind, placebo-controlled phase 3 trial of istradefylline in early Parkinson's disease patients as adjunctive therapy to levodopa. Parkinsonism Relat Disord. 2021;89:10-16. 3. Kondo T, Mizuno Y; Japanese Istradefylline Study Group. A long-term study of istradefylline safety and efficacy in patients with Parkinson disease. Clin Neuropharmacol. 2015;38(2):41-46. 4. Chen JF, Cunha RA. The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson's disease. Purinergic Signal. 2020;16(2):167-174. 5. Saki M, Yamada K, Koshimura E, et al. In vitro pharmacological profile of istradefylline, a novel therapeutic agent for Parkinson's disease. J Pharmacol Sci. 2013;123(3):305-315.
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.