Skip to main content

Drug Interactions between amoxicillin / clarithromycin / vonoprazan and clonazepam

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

clarithromycin clonazePAM

Applies to: amoxicillin / clarithromycin / vonoprazan and clonazepam

MONITOR: Macrolide antibiotics may increase and prolong the CNS effects of certain benzodiazepines. The mechanism is inhibition of CYP450 3A4 hepatic oxidation of the benzodiazepines. Midazolam, triazolam, and alprazolam have been specifically studied in this regard. Lorazepam, oxazepam, and temazepam are hepatically conjugated and are not expected to interact. Azithromycin and dirithromycin do not inhibit CYP450 isoenzymes.

MANAGEMENT: Patients receiving this combination should be monitored for excessive or prolonged sedation. Non-interacting benzodiazepines or antimicrobials may be considered as alternatives.

References (13)
  1. Phillips JP, Antal EJ, Smith RB (1986) "A pharmacokinetic drug interaction between erythromycin and triazolam." J Clin Psychopharmacol, 6, p. 297-9
  2. Warot D, Bergougnan L, Lamiable D, et al. (1987) "Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation." Eur J Clin Pharmacol, 32, p. 389-93
  3. Mattila MJ, Idanpaanheikkila JJ, Tornwall M, Vanakoski J (1993) "Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance." Pharmacol Toxicol, 73, p. 180-5
  4. Wrighton SA, Ring BJ (1994) "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res, 11, p. 921-4
  5. Amsden GW (1995) "Macrolides versus azalides: a drug interaction update." Ann Pharmacother, 29, p. 906-17
  6. Luurila H, Olkkola KT, Neuvonen PJ (1996) "Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam." Pharmacol Toxicol, 78, p. 117-22
  7. Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A (1996) "Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam." Arzneimittelforschung, 46, p. 213-7
  8. Yasui N, Otani K, Kaneko S, et al. (1996) "A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3a4 in alprazolam metabolism." Clin Pharmacol Ther, 59, p. 514-9
  9. Yeates RA, Laufen H, Zimmermann T (1996) "Interaction between midazolam and clarithromycin: comparison with azithromycin." Int J Clin Pharmacol Ther, 34, p. 400-5
  10. Yeates RA, Laufen H, Zimmermann T, Schumacher T (1997) "Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin clarithromycin, and the azalide azithromycin." Int J Clin Pharmacol Ther, 35, p. 577-9
  11. Gorski JC, Jones DR, HaehnerDaniels BD, Hamman MA, OMara EM, Hall SD (1998) "The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin." Clin Pharmacol Ther, 64, p. 133-43
  12. Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y (2000) "Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4." Pharmaceut Res, 17, p. 419-26
  13. Ito K, Ogihara K, Kanamitsu SI, Itoh T (2003) "Prediction of the in vivo interaction between midazolam and macrolides based on in vitro studies using human liver microsomes." Drug Metab Dispos, 31, p. 945-954
Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / vonoprazan and amoxicillin / clarithromycin / vonoprazan

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 (3)
  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

Drug and food interactions

Moderate

clonazePAM food

Applies to: clonazepam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References (7)
  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J (1979) "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol, 7, p. 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB (1984) "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol, 24, p. 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI (1984) "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol, 4, p. 106-7
  6. Staak M, Raff G, Nusser W (1979) "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm, 17, p. 205-12
  7. Nichols JM, Martin F, Kirkby KC (1993) "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl), 112, p. 475-82
Minor

clarithromycin food

Applies to: amoxicillin / clarithromycin / vonoprazan

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer