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Drug Interactions between carbamazepine and clarithromycin

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

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Interactions between your drugs

Major

carBAMazepine clarithromycin

Applies to: carbamazepine and clarithromycin

MONITOR CLOSELY: Some macrolide antibiotics can significantly increase serum carbamazepine levels. The mechanism is probably inhibition of hepatic CYP450 3A4 isoenzymes. Severe carbamazepine toxicity has been reported. At the same time, carbamazepine may induce the CYP450 3A4 metabolism of macrolides. This may lead to sub-therapeutic levels of macrolides and a decreased antibiotic effect.

MANAGEMENT: Monitoring of carbamazepine blood levels is recommended, and the patient should be carefully observed for signs of carbamazepine toxicity. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians. The carbamazepine dosage may require reduction. Monitor for a reduction in the antimicrobial effects of the macrolide if this combination must be used. Alternative antimicrobial therapy, if available, is generally recommended for patients on carbamazepine.

References (19)
  1. Jaster PJ, Abbas D (1986) "Erythromycin-carbamazepine interaction." Neurology, 36, p. 594-5
  2. Vajda FJ, Bladin PF (1984) "Carbamazepine-erythromycin-base interaction." Med J Aust, Jan, p. 81
  3. Wong YY, Ludden TM, Bell RD (1983) "Effect of erythromycin on carbamazepine kinetics." Clin Pharmacol Ther, 33, p. 460-4
  4. Berrettini WH (1986) "A case of erythromycin-induced carbamazepine toxicity." J Clin Psychiatry, 47, p. 147
  5. Mesdjian E, Dravet C, Cenraud B, Roger J (1980) "Carbamazepine intoxication due to triacetyloleandomycin administration in epileptic patients." Epilepsia, 21, p. 489-96
  6. Hedrick R, Williams F, Morin R, Lamb WA, Cate JC (1983) "Carbamazepine-erythromycin interaction leading to carbamazepine toxicity in four epileptic children." Ther Drug Monit, 5, p. 405-7
  7. Goulden KJ, Camfield P, Dooley JM, et al. (1986) "Severe carbamazepine intoxication after coadministration with erythromycin." J Pediatr, 109, p. 135-8
  8. Dravet C, Mesdjian E, Cenraud B, Roger J (1977) "Interaction between carbamazepine and triacetyloleandomycin." Lancet, 1, p. 810-1
  9. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  10. (2022) "Product Information. Ery-Tab (erythromycin)." Abbott Pharmaceutical
  11. Albani F, Riva R, Baruzzi A (1993) "Clarithromycin-carbamazepine interaction: a case report." Epilepsia, 34, p. 161-2
  12. Stafstrom CE, Nohria V, Loganbill H, Nahouraii R, Boustany RM, Delong GR (1995) "Erythromycin-induced carbamazepine toxicity: a continuing problem." Arch Pediatr Adolesc Med, 149, p. 99-101
  13. Metz DC, Getz HD (1995) "Helicobacter pylori gastritis therapy with omeprazole and clarithromycin increases serum carbamazepine levels." Dig Dis Sci, 40, p. 912-5
  14. Amsden GW (1995) "Macrolides versus azalides: a drug interaction update." Ann Pharmacother, 29, p. 906-17
  15. Dammann HG (1996) "Therapy with omeprazole and clarithromycin increases serum carbamazepine levels in patients with h-pylori gastritis." Dig Dis Sci, 41, p. 519
  16. Keranen T, Jolkkonen J, Jensen PK, Menge GP, Andersson P (1992) "Absence of interaction between oxcarbazepine and erythromycin." Acta Neurol Scand, 86, p. 120-3
  17. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  18. Cerner Multum, Inc. "Australian Product Information."
  19. "Product Information. Equetro (carBAMazepine)." Validus Pharmaceuticals LLC

Drug and food interactions

Moderate

carBAMazepine food

Applies to: carbamazepine

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

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References (3)
  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
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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