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Istradefylline

Medically reviewed by Drugs.com. Last updated on Apr 13, 2020.

Pronunciation

(IS tra DEF i lin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Nourianz: 20 mg, 40 mg

Brand Names: U.S.

  • Nourianz

Pharmacologic Category

  • Anti-Parkinson Agent, Adenosine Receptor Antagonist

Pharmacology

The mechanism of action of istradefylline is unknown. In in vitro studies and in in vivo animal studies, istradefylline was demonstrated to be an adenosine A2A receptor antagonist.

Distribution

Vd/F: ~557 L

Metabolism

Primarily via CYP1A1 and CYP3A4, with minor contribution from CYP1A2, 2B6, 2C8, CYP2C9, CYP2C18, and 2D6

Excretion

Feces: ~48%; urine: 39%

Time to Peak

Median: 3 to 4 hours

Half-Life Elimination

~83 hours

Protein Binding

~98%

Special Populations: Hepatic Function Impairment

Moderate hepatic impairment (Child-Pugh class B): AUC0-24 steady state exposure is predicted to be increased 3.3-fold based on estimated mean terminal half-life.

Special Populations Note

Smoking: Smoking (ie, tobacco) ≥20 cigarettes a day decreased steady-state systemic exposure by 38% to 54%.

Use: Labeled Indications

Parkinson disease, "off" episode: Treatment of Parkinson disease, in combination with levodopa/carbidopa, in adult patients experiencing "off" episodes.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Parkinson disease, "off" episode: Oral: 20 mg once daily; may further increase dose based on response and tolerability to a maximum dose of 40 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for concomitant tobacco smoking (≥20 cigarettes/day or the equivalent amount of another tobacco product): 40 mg once daily.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: May be taken with or without food.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F).

Drug Interactions

AtorvaSTATin: Istradefylline may increase the serum concentration of AtorvaSTATin. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Istradefylline. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Istradefylline. Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Digoxin: Istradefylline may increase the serum concentration of Digoxin. Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

Lomitapide: Istradefylline may increase the serum concentration of Lomitapide. Management: Decrease the initial dose of lomitapide by half in patients taking lomitapide 10 mg daily or more when used in combination with weak CYP3A4 inhibitors, including istradefylline (dose of 40 mg daily or more). The maximum dose of lomitapide is 30 mg daily. Consider therapy modification

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

St John's Wort: May decrease the serum concentration of Istradefylline. Avoid combination

Tobacco (Smoked): May decrease the serum concentration of Istradefylline. Management: The recommended dosage of istradefylline in patients who use tobacco in amounts of 20 or more cigarettes per day (or the equivalent of another tobacco product) is 40 mg once daily. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

Adverse Reactions

Frequencies noted refer to experience with combination therapy.

>10%: Neuromuscular & skeletal: Dyskinesia (15% to 17%)

1% to 10%:

Central nervous system: Insomnia (6%), dizziness (3% to 6%), auditory hallucination (≤6%), hallucination (≤6%), visual hallucination (≤6%), abnormal behavior (≤2%), abnormality in thinking (≤2%), aggressive behavior (≤2%), agitation (≤2%), confusion (≤2%), delirium (≤2%), delusion (≤2%), disorientation (≤2%), mania (≤2%), paranoid ideation (≤2%)

Dermatologic: Skin rash (2%)

Endocrine & metabolic: Increased serum glucose (1% to 2%)

Gastrointestinal: Nausea (6%), constipation (5% to 6%), decreased appetite (3%), diarrhea (2%)

Hepatic: Increased serum alkaline phosphatase (2%)

Renal: Increased blood urea nitrogen (1% to 2%)

Respiratory: Upper respiratory tract inflammation (1% to 2%)

<1%: Impulse control disorder

Postmarketing: Increased libido

Warnings/Precautions

Concerns related to adverse effects:

• Dyskinesias: May cause or exacerbate dyskinesias. Use with caution in patients with preexisting dyskinesias.

• Impulse control disorders: Has been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, compulsive buying, libido increases (hypersexuality), binge eating, and/or other intense urges. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors.

• Psychotic effects: May cause or exacerbate mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment or after starting or increasing the dose; manifestations may include paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Avoid use in patients with a major psychotic disorder.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; moderate impairment (Child-Pugh class B) requires lower maximum dose. Use is not recommended in severe hepatic impairment (Child-Pugh class C); has not been studied.

Special populations:

• Tobacco smoker: Tobacco smokers have been shown to have a decreased systemic exposure to istradefylline; a higher dose is recommended with use of ≥20 cigarettes/day or the tobacco equivalent.

Monitoring Parameters

Mental status and behavioral changes; dyskinesias.

Reproductive Considerations

Females of reproductive potential should use effective contraception during therapy.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to istradefylline may cause fetal harm.

Patient Education

What is this drug used for?

• It is used to treat Parkinson's disease.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Constipation

• Nausea

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Abnormal movements

• Mood changes

• Behavioral changes

• Sensing things that seem real but are not

• Confusion

• Uncontrollable urges

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.