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Drug Interactions between elbasvir / grazoprevir and eltrombopag

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

eltrombopag grazoprevir

Applies to: eltrombopag and elbasvir / grazoprevir

CONTRAINDICATED: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may significantly increase the plasma concentrations of grazoprevir, which is a substrate of the hepatic uptake transporters. In 12 study subjects, administration of a single 200 mg dose of grazoprevir with a single 600 mg intravenous dose of rifampin, a potent OATP1B1 inhibitor, resulted in greater than 10-fold increases in grazoprevir peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration of grazoprevir alone. A single 600 mg oral dose of rifampin administered during multiple-dosing of grazoprevir 200 mg once daily increased the Cmax and AUC of grazoprevir by 6.5- and 8.4-fold, respectively. Pharmacokinetic studies with other OATP1B1 inhibitors have reported similar results. In one study, administration of grazoprevir 200 mg once daily with atazanavir/ritonavir 300 mg/100 mg once daily increased grazoprevir Cmax, AUC and Cmin by 6.2-, 10.6- and 11.6-fold, respectively (n=12). Likewise, administration with darunavir/ritonavir 600 mg/100 mg twice daily increased grazoprevir Cmax, AUC and Cmin by 5.3-, 7.5- and 8.1-fold, respectively (n=13), while administration with lopinavir/ritonavir 400 mg/100 mg twice daily increased grazoprevir Cmax, AUC and Cmin by 7.3-, 12.9- and 21.7-fold, respectively (n=13). A single 400 mg dose of cyclosporine increased grazoprevir Cmax, AUC and Cmin by 17.0-, 15.2- and 3.4-fold, respectively (n=14). High plasma levels of grazoprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) elevations.

MANAGEMENT: Concomitant use of elbasvir-grazoprevir with OATP 1B1 or 1B3 inhibitors is considered contraindicated.

References (5)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc
  4. (2020) "Product Information. Nexlizet (bempedoic acid-ezetimibe)." Esperion Therapeutics
  5. (2020) "Product Information. Nexletol (bempedoic acid)." Esperion Therapeutics

Drug and food interactions

Moderate

eltrombopag food

Applies to: eltrombopag

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of eltrombopag. In healthy volunteers, a standard high-fat breakfast significantly decreased plasma eltrombopag peak plasma concentration (Cmax) by 65% and systemic exposure (AUC) by 59% and delayed Tmax by one hour. The calcium content of this meal may have also contributed to this decrease in exposure. In another study, adult subjects administered a single 25 mg dose of eltrombopag for oral suspension with a high-calcium, moderate-fat, moderate-calorie meal exhibited a 79% decrease in Cmax and 75% decrease in AUC of eltrombopag. Administration of eltrombopag 2 hours after the high-calcium meal decreased eltrombopag Cmax by 48% and AUC by 47%, while administration 2 hours before the high-calcium meal decreased eltrombopag Cmax by 14% and AUC by 20%.

ADJUST DOSING INTERVAL: Polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc can significantly reduce the gastrointestinal absorption of eltrombopag due to chelation. In one clinical trial, administration of a single 75 mg dose of eltrombopag with an antacid containing 1524 mg aluminum hydroxide and 1425 mg magnesium carbonate resulted in an approximately 70% decrease in eltrombopag Cmax and AUC.

MANAGEMENT: Eltrombopag should be taken on an empty stomach one hour before or two hours after a meal. Additionally, eltrombopag should be taken at least 2 hours before or 4 hours after any products that contain polyvalent cations such as antacids, mineral supplements, dairy products, and fortified juices.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2008) "Product Information. Promacta (eltrombopag)." GlaxoSmithKline
Minor

grazoprevir food

Applies to: elbasvir / grazoprevir

Food does not appear to have clinically significant effects on the pharmacokinetics of elbasvir and grazoprevir. When a single 50 mg-100 mg dose of elbasvir-grazoprevir was administered to healthy study subjects with a high-fat meal (900 kcal; 500 kcal from fat), elbasvir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 15% and 11%, respectively, while grazoprevir Cmax and AUC increased by 2.8- and 1.5-fold, respectively, compared to administration under fasting conditions. According to the product labeling, elbasvir-grazoprevir may be administered with or without food.

References (1)
  1. (2016) "Product Information. Zepatier (elbasvir-grazoprevir)." Merck & Co., Inc

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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