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Drug Interactions between Celebrex and metoprolol

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

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Interactions between your drugs

Moderate

metoprolol celecoxib

Applies to: metoprolol and Celebrex (celecoxib)

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of metoprolol. The mechanism is celecoxib inhibition of metoprolol metabolism via CYP450 2D6. In 12 healthy male volunteers, pretreatment with celecoxib (200 mg orally twice daily for 7 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of metoprolol (50 mg single dose) by 38% and 64%, respectively, compared to administration of metoprolol alone. One patient had a 204% increase in metoprolol AUC following celecoxib pretreatment. The magnitude of the interaction was significantly greater in subjects with 2 fully functional alleles associated with CYP450 2D6 activity (i.e., homozygous extensive metabolizers (EMs) of CYP450 2D6) than in subjects with only 1 fully functional allele (i.e., heterozygous EMs). The relative increase in metoprolol AUC by celecoxib was 103% and 36%, respectively, while relative decrease in metoprolol oral clearance by celecoxib was 46% and 25%, respectively, in homozygous EMs versus heterozygous EMs. Poor metabolizers of CYP450 2D6 were excluded from the study.

MANAGEMENT: Although metoprolol has a wide therapeutic range, caution is advised during coadministration with celecoxib because hemodynamic effects of metoprolol may be related to plasma concentration. Patients should be monitored for increased pharmacologic effects that may result in bradycardia or hypotension.

References

  1. Bengtsson C, Johnsson G, Regardh C-G "Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long-term treatment." Clin Pharmacol Ther 17 (1975): 400-8
  2. "Product Information. Celebrex (celecoxib)." Searle PROD (2001):
  3. Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K "Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans." Clin Pharmacol Ther 74 (2003): 130-137

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Drug and food interactions

Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

References

  1. "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals PROD (2001):
  2. Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-54

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Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

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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.

See also

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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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