ISTRADEFYLLINE Drug Interactions: What You Need to Know

INTERACTIONS Strong CYP3A4 inhibitors: Recommended maximum dosage with concomitant use is 20 mg once daily ( 2.2 , 7.1 ). Strong CYP3A4 inducers: Avoid use ( 2.3 , 7.1 ).

7.1 Effect of Other Drugs on NOURIANZ Strong CYP3A4 Inhibitors Coadministration of NOURIANZ with a strong CYP3A4 inhibitor (ketoconazole) increased istradefylline AUC inf by 2.5-fold <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Therefore, the recommended maximum dosage of NOURIANZ in patients concomitantly using strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin) is 20 mg once daily <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span>. Strong CYP3A4 Inducers Coadministration of NOURIANZ with a strong CYP3A4 inducer (rifampin) decreased istradefylline C max and AUC inf by 45% and 81%, respectively <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Therefore, it is recommended to avoid use of NOURIANZ with strong CYP3A4 inducers (e.g., carbamazepine, rifampin, phenytoin, St. John&apos;s wort) <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>.

7.2 Effect of NOURIANZ on Other Drugs CYP3A4 Substrates Coadministration of NOURIANZ 20 mg with a CYP3A4 substrate (midazolam) did not affect the CYP3A4 substrate exposure, while concomitant administration of NOURIANZ 40 mg increased the CYP3A4 substrate (atorvastatin) C max and AUC inf by 1.5-fold <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Monitor for an increase in adverse reactions of concomitant drugs that are CYP3A4 substrates when coadministering with NOURIANZ 40 mg. P-glycoprotein (P-gp)

Substrates

Coadministration of NOURIANZ with a P-gp substrate (digoxin) increased the P-gp substrate C max and AUC inf by 33% and 21%, respectively [see Clinical Pharmacology (12.3) ] . Monitor for an increase in adverse reactions of concomitant drugs that are P-gp substrates when coadministering with NOURIANZ.

None. None ( 4 ).

AND PRECAUTIONS Dyskinesia: Monitor patients for dyskinesia or exacerbation of existing dyskinesia ( 5.1 ). Hallucinations / Psychotic Behavior: Consider dosage reduction or stopping NOURIANZ if occurs ( 5.2 ).

Impulse

Control / Compulsive Behaviors: Consider dosage reduction or stopping NOURIANZ if occurs ( 5.3 ).

5.1 Dyskinesia NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In controlled clinical trials (Studies 1, 2, 3, and 4) <span class="opacity-50 text-xs">[see Clinical Studies (14) ]</span> , the incidence of dyskinesia was 15% for NOURIANZ 20 mg, 17% for NOURIANZ 40 mg, and 8% for placebo, in combination with levodopa. One percent of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

5.2 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. In controlled clinical trials (Studies 1, 2, 3, and 4) <span class="opacity-50 text-xs">[see Clinical Studies (14) ]</span> , the incidence of hallucinations was 2% for NOURIANZ 20 mg, 6% for NOURIANZ 40 mg, and 3% for placebo. In patients treated with NOURIANZ 40 mg, 1% discontinued because of hallucinations, compared to 0% for placebo and 0% for patients treated with NOURIANZ 20 mg. The incidence of &quot;abnormal thinking and behavior&quot; (paranoid ideation, delusions, confusion, mania, disorientation, aggressive behavior, agitation, or delirium) reported as an adverse reaction was 1% for NOURIANZ 20 mg, 2% for NOURIANZ 40 mg, and 1% for placebo.

5.3 Impulse Control / Compulsive Behaviors Patients treated with NOURIANZ and one or more medication(s) for the treatment of Parkinson&apos;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 controlled clinical trials (Studies 1, 2, 3 and 4) <span class="opacity-50 text-xs">[see Clinical Studies (14) ]</span> , one patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on placebo or NOURIANZ 20 mg. In some postmarketing cases, these urges were reported to have stopped when the dose was reduced, or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with NOURIANZ. Consider dose reduction or discontinuation if a patient develops such urges while taking NOURIANZ <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> .