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Drug Interactions between clarithromycin and ramelteon

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

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Interactions between your drugs

Moderate

clarithromycin ramelteon

Applies to: clarithromycin and ramelteon

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 and/or 2C9 may increase the plasma concentrations and pharmacologic effects of ramelteon, which is partially metabolized by these isoenzymes. In healthy volunteers, administration of a single 16 mg oral dose of ramelteon following pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 4 days) increased ramelteon peak plasma concentration (Cmax) by 36% and systemic exposure (AUC) by 84% compared to administration of ramelteon alone. Likewise, coadministration with fluconazole, a potent CYP450 2C9 inhibitor, resulted in an increase of approximately 150% in the Cmax and AUC of ramelteon following a single 16 mg oral dose. Similar pharmacokinetic changes were also observed with its biologically active metabolite, known as M-II.

MANAGEMENT: Caution is advised if ramelteon is prescribed in combination with potent inhibitors of CYP450 3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, delavirdine, nefazodone, protease inhibitors, ketolide and certain macrolide antibiotics) and/or CYP450 2C9 (e.g., fluconazole, gemfibrozil, imatinib, miconazole). A reduction in the ramelteon dosage may be necessary in patients who experience excessive sedation.

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

Drug and food interactions

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
Minor

clarithromycin food

Applies to: clarithromycin

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References (1)
  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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