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Drug Interactions between cenobamate and Omeclamox-Pak

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

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Interactions between your drugs

Moderate

clarithromycin cenobamate

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and cenobamate

MONITOR: Coadministration with cenobamate may decrease the plasma concentrations and pharmacologic effects of CYP450 3A4 substrates. The proposed mechanism is cenobamate-mediated induction of the CYP450 3A4 isoenzyme. According to the manufacturer, multiple doses of cenobamate (200 mg once daily) reduced the mean Cmax and AUC of midazolam, a CYP450 3A4 substrate, by 61% and 72%, respectively.

MANAGEMENT: Caution is advised if cenobamate is used concomitantly with drugs that are substrates of CYP450 3A4, particularly those with a narrow therapeutic index. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cenobamate is added to or withdrawn from therapy.

References

  1. (2020) "Product Information. Xcopri (cenobamate)." SK Life Science, Inc.

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Moderate

omeprazole cenobamate

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and cenobamate

MONITOR: Coadministration with cenobamate may increase the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 2C19. The proposed mechanism is cenobamate-mediated inhibition of CYP450 2C19. According to the manufacturer, multiple doses of cenobamate (200 mg once daily) increased the mean Cmax and AUC of omeprazole, a CYP450 2C19 substrate, by 83% and 107%, respectively.

MANAGEMENT: Caution is advised when cenobamate is used concurrently with drugs that are substrates of CYP450 2C19, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cenobamate is added to or withdrawn from therapy.

References

  1. (2020) "Product Information. Xcopri (cenobamate)." SK Life Science, Inc.

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Minor

amoxicillin clarithromycin

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References

  1. Strom J (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
  2. Cohn JR, Jungkind DL, Baker JS (1980) "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother, 18, p. 872-6
  3. Penn RL, Ward TT, Steigbigel RT (1982) "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother, 22, p. 289-94

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Minor

clarithromycin omeprazole

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

References

  1. Zhou Q, Yamamoto I, Fukuda T, Ohno M, Sumida A, Azuma J (1999) "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol, 55, p. 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW (1995) "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother, 39, p. 2078-83
  3. Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E (1999) "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther, 66, p. 265-74

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Drug and food interactions

Minor

clarithromycin food

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

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

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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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