istradefylline

Therapeutic Classification: antiparkinson agents

Pharmacologic Classification: adenosine receptor antagonist

Indications ⬆ ⬇

REMS

Adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing "off" episodes.

Action ⬆ ⬇

Acts as an adenosine receptor antagonist; the mechanism by which these effects exert beneficial effects in patients with Parkinson's disease is unknown.

Therapeutic effects:

Reduction in "off" time.

Pharmacokinetics ⬆ ⬇

Absorption: Unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: 98%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP1A1 and CYP3A4 isoenzymes. 48% excreted in feces, 39% in urine.

Half-Life: 83 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe psychotic disorders (may worsen psychosis);
Severe hepatic impairment;
OB: Pregnancy.

Use Cautiously in:

End-stage renal disease;
Moderate hepatic impairment;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

Endo: hyperglycemia

GI: ↓appetite, constipation, diarrhea, nausea

Metab: hyperuricemia

Neuro: dyskinesia, aggression, agitation, confusion, delirium, delusions, disorientation, dizziness, hallucinations, impulse control disorders (gambling, sexual), insomnia, mania, paranoid ideation

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with levodopa may cause or exacerbate dyskinesia.
Cigarette smoking may ↓ levels; if patient smokes ≥20 cigarettes/day, ↑ dose to 40 mg once daily.
Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, and ketoconazole, may ↑ levels and risk of toxicity.
Strong CYP3A4 inducers, including carbamazepine, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Higher doses (40 mg/day) may ↑ levels and risk of toxicity of CYP3A4 substrates, including atorvastatin.
May ↑ levels and risk of toxicity of P-glycoprotein substrates, including digoxin.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 20 mg once daily; may ↑ to 40 mg once daily, if needed, based on clinical response. Concurrent use of strong CYP3A4 inhibitors: Do not exceed 20 mg/day.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: Do not exceed 20 mg/day.

Availability ⬆ ⬇

Tablets: 20 mg; 40 mg

Assessment ⬆ ⬇

Assess parkinsonian symptoms (akinesia, rigidity, tremors, pill rolling, shuffling gait, mask-like face, twisting motions, and drooling) during therapy. "On-off phenomenon" may cause symptoms to appear or improve suddenly.
Assess for signs and symptoms of dyskinesia (abnormal movements, uncontrolled sudden movements) before and during therapy.
Monitor for signs and symptoms of behavior changes (hallucinations, psychotic behavior, paranoid ideation, delusions, confusion, mania, disorientation, aggressive behavior, agitation, delirium) during therapy. Consider reducing dose or discontinuing therapy.

Implementation ⬆ ⬇

PO: Administer once daily without regard for food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication at regular intervals as directed. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise patient and family to notify health care professional if signs and symptoms of hallucinations or psychosis (being overly suspicious or feeling people want to harm you, disorientation, believing things that are not real, aggressive behavior, seeing or hearing things that are not real, agitation, confusion, delirium, increased activity or talking, or if new or increased gambling, sexual, or other intense urges occur). Dose reduction may be required.
Rep: Advise females of reproductive potential to use effective contraception and avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇