istradefylline (Rx)

Brand and Other Names:Nourianz
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 20mg
  • 40mg

Parkinson Disease

Indicated as adjunctive treatment to levodopa/carbidopa in adults with Parkinson disease (PD) experiencing “OFF” episodes

20 mg PO qDay; may increase to maximum of 40 mg PO qDay

Initial dose titration not required

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe (CrCl 15-89 mL/min): No dosage adjustment required
  • ESRD (CrCl <15 mL/min) or ESRD requiring hemodialysis: Not studied

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate (Child-Pugh B): Not to exceed 20 mg PO qDay
  • Severe (Child-Pugh C): Avoid use

Coadministration with strong CYP3A4 inhibitors

  • Not to exceed 20 mg PO qDay

Tobacco smokers

  • Tobacco use (≥20 cigarettes/day or equivalent tobacco product): 40 mg PO qDay

Safety and efficacy not established

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Interactions

Interaction Checker

and istradefylline

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Dyskinesia (15-17%)

            1-10%

            Constipation (5-6%)

            Nausea (4-6%)

            Dizziness (3-6%)

            Hallucination (2-6%)

            Insomnia (1-6%)

            Decreased appetite (1-3%)

            Increased alkaline phosphatase (1-2%)

            Increased blood glucose (1-2%)

            Increased blood urea (1-2%)

            Upper respiratory tract inflammation (1-2%)

            Rash (1-2%)

            Diarrhea (1-2%)

            Postmarketing Reports

            Increased libido

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            Warnings

            Contraindications

            None

            Cautions

            Coadministration with levodopa may cause dyskinesia or exacerbate preexisting dyskinesia; in clinical trials, dyskinesia incidence was higher in patients taking istradefylline compared with placebo

            May exacerbate psychosis; patients with major psychotic disorder should not be treated with istradefylline; consider dosage reduction or discontinuation if patient develops hallucinations or psychotic behaviors while receiving therapy

            Patients treated with istradefylline and ≥1 medication(s) for PD (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; consider dose reduction or discontinuation

            Based on animal studies, may cause fetal harm

            Drug interaction overview

            • CYP inhibitors or inducers
              • Istradefylline is primarily metabolized by CYP3A4 and CYP1A1
              • Coadministration with strong CYP3A4 inhibitors: Not to exceed istradefylline 20 mg qDay
              • Strong CYP3A4 inducers: Avoid coadministration
              • Increase istradefylline dose with tobacco use equivalent to ≥20 cigarettes/day
            • Istradefylline effect on other drugs
              • Istradefylline is both a weak CYP3A4 inhibitor and inducer; higher istradefylline doses (ie, 40 mg/day) may affect CYP3A4 substrates
              • Transporters: Istradefylline is a weak inhibitor for P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OCT2, MATE1, and MATE2-K; higher istradefylline doses (ie, 40 mg/day) may affect P-gp substrates (eg, digoxin)
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            Pregnancy & Lactation

            Pregnancy

            Data are unavailable regarding use in pregnant women

            Based on animal studies, may cause fetal risk

            Use during pregnancy is not recommended; advise women of childbearing potential to use contraception during treatment

            Animal studies

            • Istradefylline administered in pregnant rabbits resulted in teratogenicity (increased incidences of fetal structural abnormalities, embryofetal and offspring mortality, growth deficits) at clinically relevant exposures and in the absence of maternal toxicity
            • Teratogenic effects were substantially greater when administered in combination with levodopa/carbidopa than when administered alone

            Lactation

            There are no data on the presence in human milk, effects on breastfed infants, or effects on milk production

            Present in milk of lactating rats at concentrations up to 10 times that in maternal plasma

            Consider developmental and health benefits of breastfeeding along with the clinical need for istradefylline, and any potential adverse effects on breastfed infants from istradefylline or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Selective adenosine A2A receptor antagonist

            The precise mechanism by which istradefylline exerts its therapeutic effect in PD is unknown

            Absorption

            Peak plasma time: 4 hr

            Distribution

            Protein bound: ~98%

            Vd: 557 L

            Metabolism

            Primarily metabolized via CYP1A1 and CYP3A4

            Minor metabolism from CYP1A2, 2B6, 2C8, CYP2C9, CYP2C18, and 2D6

            Elimination

            Half-life: ~83 hr (steady-state)

            Total clearance: ~4.6 L/hr

            Excretion: 48% feces; 39% urine

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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store at 20-25ºC (68-77ºF); excursions permitted between 15-30ºC (59-86ºF)

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.