Elthropa Drug Interactions

Effects of Elthropa on other medicinal products: HMG CoA reductase inhibitors: Administration of Elthropa 75 mg once daily for 5 days with a single 10 mg dose of the OATP1B1 and BCRP substrate rosuvastatin to 39 healthy adult subjects increased plasma rosuvastatin C_max 103% (90% confidence interval [CI]: 82%, 126%) and AUC_0-∞ 55% (90% CI: 42%, 69%). Interactions are also expected with other HMG-CoA reductase inhibitors, including atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin. When co-administered with Elthropa, a reduced dose of statins should be considered and careful monitoring for statin adverse reactions should be undertaken (see Pharmacology: Pharmacokinetics under Actions).
OATP1B1 and BCRP substrates: Concomitant administration of Elthropa and OATP1B1 (e.g. methotrexate) and BCRP (e.g. topotecan and methotrexate) substrates should be undertaken with caution (see Pharmacology: Pharmacokinetics under Actions).
Cytochrome P450 substrates: In studies utilising human liver microsomes, Elthropa (up to 100 µM) showed no in vitro inhibition of the CYP450 enzymes 1A2, 2A6, 2C19, 2D6, 2E1, 3A4/5, and 4A9/11 and was an inhibitor of CYP2C8 and CYP2C9 as measured using paclitaxel and diclofenac as the probe substrates. Administration of Elthropa 75 mg once daily for 7 days to 24 healthy male subjects 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 Elthropa and CYP450 substrates are co-administered (see Pharmacology: Pharmacokinetics under Actions).
HCV protease inhibitors: Dose adjustment is not required when Elthropa is co-administered with either telaprevir or boceprevir. Co-administration of a single dose of Elthropa 200 mg with telaprevir 750 mg every 8 hours did not alter plasma telaprevir exposure.
Co-administration of a single dose of Elthropa 200 mg with boceprevir 800 mg every 8 hours did not alter plasma boceprevir AUC_(0-τ), but increased C_max by 20%, and decreased C_min by 32%. The clinical relevance of the decrease in C_min has not been established, increased clinical and laboratory monitoring for HCV suppression is recommended.
Effects of other medicinal products on Elthropa: Ciclosporin: A decrease in Elthropa exposure was observed with co-administration of 200 mg and 600 mg ciclosporin (a BCRP inhibitor). The co-administration of 200 mg ciclosporin decreased the C_max and the AUC_Inf of Elthropa by 25% and 18%, respectively. The co-administration of 600 mg ciclosporin decreased the C_max and the AUC_Inf of Elthropa by 39% and 24%, respectively. Elthropa 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 Elthropa is co-administered with ciclosporin. Elthropa dose may need to be increased based on these platelet counts.
Polyvalent cations (chelation): Elthropa chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium and zinc. Administration of a single dose of Elthropa 75 mg with a polyvalent cation-containing antacid (1,524 mg aluminium hydroxide and 1,425 mg magnesium carbonate) decreased plasma Elthropa AUC_0-∞ by 70% (90% CI: 64%, 76%) and C_max by 70% (90% CI: 62%, 76%). Elthropa 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 Elthropa absorption due to chelation (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Lopinavir/ritonavir: Co-administration of Elthropa with lopinavir/ritonavir may cause a decrease in the concentration of Elthropa. A study in 40 healthy volunteers showed that the co-administration of a single 100 mg dose of Elthropa with repeat dose lopinavir/ritonavir 400/100 mg twice daily resulted in a reduction in Elthropa plasma AUC_inf by 17% (90% CI: 6.6%, 26.6%). Therefore, caution should be used when co-administration of Elthropa with lopinavir/ritonavir takes place. Platelet count should be closely monitored in order to ensure appropriate medical management of the dose of Elthropa when lopinavir/ritonavir therapy is initiated or discontinued.
CYP1A2 and CYP2C8 inhibitors and inducers: Elthropa is metabolised through multiple pathways including CYP1A2, CYP2C8, UGT1A1, and UGT1A3 (see Pharmacology: Pharmacokinetics under Actions). Medicinal products that inhibit or induce a single enzyme are unlikely to significantly affect plasma Elthropa concentrations, whereas medicinal products that inhibit or induce multiple enzymes have the potential to increase (e.g. fluvoxamine) or decrease (e.g. rifampicin) Elthropa concentrations.
HCV protease inhibitors: Results of a drug-drug pharmacokinetic (PK) interaction study show that co-administration of repeat doses of boceprevir 800 mg every 8 hours or telaprevir 750 mg every 8 hours with a single dose of Elthropa 200 mg did not alter plasma Elthropa exposure to a clinically significant extent.
Medicinal products for treatment of ITP: Medicinal products used in the treatment of ITP in combination with Elthropa in clinical studies included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin. Platelet counts should be monitored when combining Elthropa with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see Dosage & Administration).
Food interaction: The administration of Elthropa tablet with a high-calcium meal (e.g. a meal that included dairy products) significantly reduced plasma eltrombopag AUC_0-∞ and C_max. In contrast, the administration of Elthropa 2 hours before or 4 hours after a high-calcium meal or with low-calcium food [<50 mg calcium] did not alter plasma eltrombopag exposure to a clinically significant extent (see Dosage & Administration).
Administration of a single 50 mg dose of Elthropa in tablet form with a standard high-calorie, high-fat breakfast that included dairy products reduced plasma eltrombopag mean AUC_0-∞ by 59% and mean C_max by 65%.
Food low in calcium (<50 mg calcium), including fruit, lean ham, beef and unfortified (no added calcium, magnesium or iron) fruit juice, unfortified soya milk and unfortified grain, did not significantly impact plasma eltrombopag exposure, regardless of calorie and fat content (see Dosage & Administration).