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Drug Interactions between repaglinide and tigecycline

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

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Interactions between your drugs

Moderate

repaglinide tigecycline

Applies to: repaglinide and tigecycline

MONITOR: Tetracyclines may enhance the hypoglycemic effects of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). The exact mechanism is unknown; however, proposed mechanisms include increasing the sensitivity of insulin, increasing the half-life of insulin via inhibition of insulin degradation in the liver, interference with epinephrine-induced hyperglycemia via inhibition of glycogenolysis, and tetracycline-induced hepatotoxicity. The authors of one study suggest that tetracycline may also be able to inhibit alpha-amylase and/or alpha-glucosidase, as substrates for these enzymes have similar functional groups to those found in tetracycline. There are case reports available documenting hypoglycemia for patients on doxycycline and one case report demonstrating improved insulin sensitivity in a patient on minocycline. It is possible that other tetracyclines may possess similar abilities to lower glucose levels.

MANAGEMENT: Blood glucose should be monitored more closely during therapy with a tetracycline antibiotic. As the effects of the antibiotic may persist beyond the last dose, it is possible that patients may need to be monitored more closely until the antibiotic is fully eliminated from their body, which will differ depending on the half-life of the antibiotic involved. Insulin and insulin secretagogues may require dosage adjustments if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their doctor if it occurs unexpectedly. Conversely, patients should be observed for loss of glycemic control following completion of tetracycline therapy.

References (12)
  1. Dalpe-Scott M, Heick HM, Begin-Heick N (1983) "Insulin secretion in the obese (ob/ob) mouse: the effect of oxytetracycline on insulin release." Diabetes, 32, p. 932-7
  2. Dalpe-Scott M, Begin-Heick N (1982) "Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat." Diabetes, 31, p. 53-9
  3. Begin-Heick N, Heick HM, Norman MG (1979) "Regranulation of Islets of Langerhans and normalization of in vivo insulin secretion in ob/ob mice treated with oxytetracycline." Diabetes, 28, p. 65-70
  4. Phillips PJ, Easterbrook G (1977) "Phenformin, tetracycline and lactic acidosis." Ann Intern Med, 86, p. 111
  5. Miller JB (1966) "Hypoglycaemic effect of oxytetracycline." BMJ, 2, p. 1007
  6. Hiatt N, Bonorris G (1970) "Insulin response in pancreatectomized dogs treated with oxytetracycline." Diabetes, 19, p. 307-11
  7. Amiri B, Hosseini NS, Taktaz F, et al. (2019) "Inhibitory effects of selected antibiotics on the activities of alpha-amylase and alpha-glucosidase: In-vitro, in-vivo and theoretical studies" Eur J Pharm Sci, 138, p. 1-16
  8. Kennedy KE, Teng C, Patek TM, Frei CR (2020) "Hypoglycemia associated with antibiotics alone and in combination with sulfonylureas and meglitinides: an epidemiologic surveillance study of the FDA adverse event reporting system (FAERS)." Drug Saf, 43, p. 363-9
  9. Ashraf S, Saberinia H, Desimone M (2018) "Doxycycline induced hypoglycemia in an adult without diabetes." J Basic Clin Pharma, 9, p. 115-7
  10. Douglas Y, grant mb, Moshiree B (2023) Case report open access minocycline attenuates severe hyperglycemia in patient with lipodystrophy. https://www.omicsonline.org/open-access/minocycline-attenuates-severe-hyperglycemia-in-patient-with-lipodystrophy-ijm-1000136.php?aid=76310
  11. Ijete E, Hosni M, Dadey E, Nikookam K, Rehmani H, Mlawa G (2022) "Uncommon side effect of a common drug: doxycyline induced hypoglycemia." Endocrine Abstracts, 81, P347
  12. (2020) "Product Information. Tetracycline (tetracycline)." Sigma Pharmaceuticals Australia Pty Ltd

Drug and food interactions

Moderate

repaglinide food

Applies to: repaglinide

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (32)
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  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. 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
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. 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
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  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286

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.

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