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Drug Interactions between ramelteon and rifampin

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

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Interactions between your drugs

Moderate

rifAMPin ramelteon

Applies to: rifampin and ramelteon

MONITOR: Coadministration with inducers of CYP450 isoenzymes may decrease the plasma concentrations and pharmacologic effects of ramelteon, which is metabolized by CYP450 1A2 and, to a lesser extent, by CYP450 3A4 and the 2C subfamily of isoenzymes. When a single 32 mg oral dose of ramelteon was administered to healthy volunteers following pretreatment with the potent CYP450 inducer rifampin (600 mg orally once daily for 11 days), total systemic exposure (AUC) to ramelteon and its pharmacologically active metabolite was decreased by an average of approximately 80% (range 40% to 90%). Use with other inducers has not been adequately studied.

MANAGEMENT: The efficacy of ramelteon may be reduced when prescribed with potent inducers of CYP450 isoenzymes such as carbamazepine, enzalutamide, phenobarbital, phenytoin, rifampin, and St. John's wort. Other known inducers include aminoglutethimide, bexarotene, bosentan, dabrafenib, dexamethasone, efavirenz, etravirine, mitotane, modafinil, nafcillin, nevirapine, rifabutin, rifapentine, barbiturates and various other anticonvulsants, although the extent to which they interact with ramelteon is unknown.

References (1)
  1. (2005) "Product Information. Rozerem (ramelteon)." Takeda Pharmaceuticals America

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

ramelteon food

Applies to: ramelteon

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of ramelteon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of ramelteon with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In study subjects, administration of a 16 mg dose of ramelteon with a high-fat meal decreased the peak plasma drug concentration (Cmax) by 22% and delayed the median time to reach peak plasma drug concentration (Tmax) by approximately 45 minutes compared to administration in a fasted state.

MANAGEMENT: Patients receiving ramelteon should be advised to avoid the consumption of alcohol. For faster sleep onset, ramelteon should not be administered with or immediately after a high-fat/heavy meal.

References (1)
  1. (2005) "Product Information. Rozerem (ramelteon)." Takeda Pharmaceuticals America

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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