Revolade Drug Interactions

Effects of other drugs on Revolade: Cyclosporine: A decrease in eltrombopag exposure was observed with co-administration of 200 mg and 600 mg cyclosporine (a BCRP inhibitor). Administration of a single dose of Revolade 50 mg with 200 mg cyclosporine (a BCRP inhibitor) decreased the Cmax and the AUCinf of eltrombopag by 25% (90% CI: 15%, 35%) and 18% (90% CI: 8%, 28%), respectively. The co-administration of 600 mg cyclosporine decreased the Cmax and the AUCinf of eltrombopag by 39% (90% CI: 30%, 47%) and 24% (90% CI: 14%, 32%), respectively. This decrease in exposure is not considered clinically meaningful. Eltrombopag dose adjustment is permitted during the course of the treatment based on the patient's platelet count (see Dosage & Administration). Platelet count should be monitored at least weekly for 2 to 3 weeks when eltrombopag is co-administered with cyclosporine. Eltrombopag dose may need to be increased based on these platelet counts.
Polyvalent Cations (Chelation): Eltrombopag chelates with polyvalent cations such as aluminium, calcium, iron, magnesium, selenium and zinc (see Pharmacology under Actions). Administration of a single dose of Revolade 75 mg with a polyvalent cation-containing antacid (1524 mg aluminium hydroxide and 1425 mg magnesium carbonate) decreased plasma eltrombopag AUCinf by 70% (90% CI: 64%, 76%) and Cmax by 70% (90% CI: 62%, 76%) (see Dosage & Administration, Interactions). Eltrombopag should be taken at least two hours before or four hours after any products such as antacids, dairy products, or mineral supplements containing polyvalent cations to avoid significant reduction in eltrombopag absorption (see Dosage & Administration).
Lopinavir/ritonavir: Co-administration of eltrombopag with lopinavir/ritonavir may cause a decrease in the concentration of eltrombopag. A study in 40 healthy volunteers showed that the co-administration of a single 100 mg dose of Revolade with repeat dose lopinavir/ritonavir 400 /100 mg twice daily resulted in a reduction in eltrombopag plasma AUCinf by 17% (90% CI: 6.6%, 26.6%).
Therefore, caution should be used when co-administration of Revolade with lopinavir/ritonavir takes place. Platelet count should be monitored at least weekly for 2 to 3 weeks in order to ensure appropriate medical management of the dose of Revolade when lopinavir/ritonavir therapy is initiated or discontinued.
HCV protease inhibitors: Co-administration of repeat doses of boceprevir 800 mg every 8 hours or telaprevir 750 mg every 8 hours with a single dose of Revolade 200 mg did not alter plasma eltrombopag exposure to a clinically significant extent.
Effects of Revolade on other drugs: Rosuvastatin: Administration of eltrombopag 75 mg once daily for 5 days with a single 10 mg dose of the OATP1B1 and BCRP substrate rosuvastatin to 39 healthy adults increased plasma rosuvastatin Cmax 103% (90% CI: 82%, 126%) and AUCinf 55% (90% CI: 42%, 69%) (see Interactions).
When co-administered with Revolade, a reduced dose of rosuvastatin should be considered and careful monitoring should be undertaken. In clinical trials with Revolade, a dose reduction of rosuvastatin by 50% was recommended for co-administration of rosuvastatin and eltrombopag. Concomitant administration of Revolade and other OATP1B1 and BCRP substrates should be undertaken with caution.
Cytochrome P450 substrates: Administration of Revolade 75 mg once daily for 7 days to 24 healthy males did not inhibit or induce the metabolism of probe substrates for 1A2 (caffeine), 2C19 (omeprazole), 2C9 (flurbiprofen), or 3A4 (midazolam) in humans. No clinically significant interactions are expected when eltrombopag and CYP450 substrates, inducers or inhibitors are co-administered.
HCV Protease inhibitors: Co-administration of a single dose of Revolade 200 mg with telaprevir 750 mg every 8 hours did not alter plasma telaprevir exposure. Co-administration of a single dose of Revolade 200 mg with boceprevir 800 mg every 8 hours did not alter plasma boceprevir AUCtau, increased Cmax by 19%, and decreased Cmin by 32 %. Dose adjustment is not required when Revolade is co-administered with either telaprevir or boceprevir.
Drug-food interaction: Administration of a single 50 mg-dose of eltrombopag tablet with a standard high-calorie, high-fat breakfast that included dairy products reduced plasma eltrombopag AUCinf by 59% (90% CI: 54%, 64%) and Cmax by 65% (90% CI: 59%, 70%). Significant reductions in plasma eltrombopag AUCinf and Cmax were also observed when a single 25 mg-dose of eltrombopag powder for oral suspension was administered with a high-calcium meal. Administration of a single 25 mg-dose of eltrombopag powder for oral suspension 2 hours before a high-calcium meal attenuated the effect, where plasma eltrombopag AUCinf was decreased by 20% (90% CI: 9%, 29%) and Cmax by 14% (90% CI: 2%, 25%). Food low in calcium (<50 mg calcium) including fruit, lean ham, beef and unfortified (no added calcium, magnesium, iron) fruit juice, unfortified soy milk, and unfortified grain did not significantly impact plasma eltrombopag exposure, regardless of calorie and fat content (see Dosage & Administration).