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Drug Interactions between avatrombopag and rifampin

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

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Interactions between your drugs

Major

rifAMPin avatrombopag

Applies to: rifampin and avatrombopag

ADJUST DOSE: Concomitant use of avatrombopag with moderate to potent dual inducers of CYP450 2C9 and 3A4 may decrease the systemic exposure (AUC) of avatrombopag which may lead to reduced efficacy. An open-label study evaluated the pharmacokinetic and pharmacodynamic drug-drug interactions of avatrombopag in combination with dual or selective CYP450 2C9 and 3A4 interacting drugs. Administration of a single 20 mg dose of avatrombopag to healthy subjects (n=48) who had achieved steady-state concentrations of rifampin (a moderate CYP450 2C9 and potent CYP450 3A4 inducer) resulted in a 43% reduction in avatrombopag AUC, and a shortened terminal elimination phase half-life from 20.3 hours to 9.84 hours. However, no impact on the maximum platelet count was observed.

MANAGEMENT: For the treatment of patients with chronic immune thrombocytopenia, the manufacturer recommends an increased starting dose of avatrombopag 40 mg orally once daily when used concomitantly with a moderate to potent dual CYP450 2C9 and 3A4 inducer. In patients already receiving avatrombopag therapy and starting a moderate or strong dual CYP450 2C9 and 3A4 inducer, platelet counts should be monitored and avatrombopag dose adjusted according to the manufacturer's product labeling as necessary. Dose adjustments are not recommended when prescribed for the treatment of thrombocytopenia in adult patients with chronic liver disease undergoing a procedure.

References (4)
  1. Nomoto M, Zamora CA, Schuck E, et al. (2018) "Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs." Br J Clin Pharmacol, 84, p. 952-60
  2. (2023) "Product Information. Doptelet (avatrombopag)." Swedish Orphan Biovitrum Pty Ltd
  3. (2021) "Product Information. Doptelet (avatrombopag)." Swedish Orphan Biovitrum Ltd
  4. (2021) "Product Information. Doptelet (avatrombopag)." AkaRx, Inc.

Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References (6)
  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
Moderate

avatrombopag food

Applies to: avatrombopag

ADJUST DOSING INTERVAL: Food reduces the variability in oral absorption and bioavailability of avatrombopag. According to the product labeling, avatrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) were not affected when administered with either a low-fat (500 calories; 3 g fat, 15 g proteins, 108 g carbohydrates) or high-fat (918 calories; 59 g fat, 39 g proteins, 59 g carbohydrates) meal. However, the variability of avatrombopag exposure was reduced by 40% to 60% with food, and the time to reach Cmax was delayed by 0 to 2 hours relative to the fasted state.

MANAGEMENT: To ensure consistent absorption and plasma drug levels, avatrombopag should be taken with food.

References (1)
  1. (2018) "Product Information. Doptelet (avatrombopag)." Dova Pharmaceuticals

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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