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Drug Interactions between amoxicillin / clarithromycin / vonoprazan and cabergoline

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

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Interactions between your drugs

Major

clarithromycin cabergoline

Applies to: amoxicillin / clarithromycin / vonoprazan and cabergoline

CONTRAINDICATED: Coadministration with certain macrolide antibiotics may significantly increase the plasma concentrations of ergot derivatives. The mechanism is macrolide inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of ergotamine and related drugs. Macrolides that may significantly inhibit CYP450 3A4 include clarithromycin, erythromycin and troleandomycin, and clinical ergotism has been reported in patients receiving ergotamine or dihydroergotamine with these agents. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4.

MANAGEMENT: Given the potential for ergot toxicity characterized by peripheral vasospasm, ischemia, thrombosis, tachycardia and hypertension, concomitant use of ergot derivatives with clarithromycin, erythromycin, or troleandomycin is considered contraindicated. Although clinical data have not been reported, some manufacturers also consider the combination of cabergoline with macrolides contraindicated or to be avoided on theoretical grounds. Azithromycin may be a safer alternative during therapy with ergot derivatives.

References (16)
  1. Leroy F, Asseman P, Pruvost P, Adnet P, Lacroix D, Thery C (1988) "Dihydroergotamine-erythromycin-induced ergotism." Ann Intern Med, 109, p. 249
  2. Matthews NT, Havill JH (1979) "Ergotism with therapeutic doses of ergotamine tartrate." N Z Med J, 89, p. 476-7
  3. Francis H, Tyndall A, Webb J (1984) "Severe vascular spasm due to erythromycin-ergotamine interaction." Clin Rheumatol, 3, p. 243-6
  4. Hayton AC (1969) "Precipitation of acute ergotism by triacetyloleandomycin." N Z Med J, 69, p. 42
  5. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  6. Ghali R, De Lean J, Douville Y, Noel HP, Labbe R (1993) "Erythromycin-associated ergotamine intoxication: arteriographic and electrophysiologic analysis of a rare cause of severe ischemia of the lower extremities and associated ischemic neuropathy." Ann Vasc Surg, 7, p. 291-6
  7. Horowitz RS, Dart RC, Gomez HF (1996) "Clinical ergotism with lingual ischemia induced by clarithromycin-ergotamine interaction." Arch Intern Med, 156, p. 456-8
  8. (2001) "Product Information. Migranal (dihydroergotamine nasal)." Novartis Pharmaceuticals
  9. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  10. Bird PA, Sturgess AD (2000) "Clinical ergotism with severe bilateral upper limb ischaemia precipitated by an erythromycin - ergotamine drug interaction." Aust N Z J Med, 30, p. 635-6
  11. Eadie MJ (2001) "Clinically significant drug interactions with agents specific for migraine attacks." Cns Drugs, 15, p. 105-18
  12. Ausband SC, Goodman PE (2001) "An unusual case of clarithromycin associated ergotism." J Emerg Med, 4, p. 411-3
  13. (2004) "Product Information. Cafergot (caffeine-ergotamine)." Novartis Pharmaceuticals
  14. Nakatsuka A, Nagai M, Yabe H, et al. (2006) "Effect of clarithromycin on the pharmacokinetics of cabergoline in healthy controls and in patients with Parkinson's disease." J Pharmacol Sci, 100, p. 59-64
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Srisuma S, Lavonas EJ, Wananukul W (2014) "Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors." Clin Toxicol (Phila), p. 1-4
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

cabergoline food

Applies to: cabergoline

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
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.

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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

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