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Drug Interactions between repaglinide and Uricalm Intensive

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

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Moderate

aspirin repaglinide

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine) and repaglinide

MONITOR: The hypoglycemic effect of insulin secretagogues (e.g., sulfonylureas, meglitinides) may be potentiated by certain drugs, including ACE inhibitors, 4-aminoquinolines, amylin analogs, anabolic steroids, fibrates, monoamine oxidase inhibitors (MAOIs, including linezolid), nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, selective serotonin reuptake inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinine, quinidine, and ginseng. These drugs may increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, fibrates, ginseng); stimulating insulin secretion (salicylates, NSAIDs, disopyramide, quinine, quinidine, MAOIs, ginseng); decreasing insulin clearance and resistance (4-aminoquinolines); increasing peripheral glucose utilization (SSRIs, insulin-like growth factor); inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor); slowing the rate of gastric emptying (amylin analogs); and/or suppressing postprandial glucagon secretion (amylin analogs). Or, they may increase plasma concentration of insulin secretagogues by displacing them from plasma protein binding sites and/or inhibiting their metabolism (fibrates, NSAIDs, salicylates, sulfonamides). Clinical hypoglycemia has been reported during use of some of these agents alone or with insulin and/or sulfonylureas. Use of SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are coadministered with insulin secretagogues, particularly in patients with advanced age and/or renal impairment. The oral antidiabetic dosage(s) may require adjustment 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. Patients should be observed for loss of glycemic control when these drugs are withdrawn.

References

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  64. Aleyassine H, Lee SH (1972) "Inhibition of insulin release by substrates and inhibitors of monoamine oxidase." Am J Physiol, 222, p. 565-9
  65. Cooper AJ, Ashcroft G (1966) "Potentiation of insulin hypoglycaemia by M.A.O.I. antidepressant drugs." Lancet, 1, p. 407-9
  66. Lozada A, Dujovne CA (1994) "Drug interactions with fibric acids." Pharmacol Ther, 63, p. 163-76
  67. Kradjan WA, Witt DM, Opheim KE, Wood FC (1994) "Lack of interaction between glipizide and co-trimoxazole." J Clin Pharmacol, 34, p. 997-1002
  68. Herings RMC, Deboer A, Stricker BHC, Leufkens HGM, Porsius A (1995) "Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme." Lancet, 345, p. 1195-8
  69. Ahmad S (1995) "Drug interaction induces hypoglycemia." J Fam Pract, 40, p. 540-1
  70. Feher MD, Amiel S (1995) "ACE inhibitors and hypoglycaemia." Lancet, 346, p. 125-6
  71. Paolisso G, Balbi V, Gambardella A, Varricchio G, Tortoriello R, Saccomanno F, Amato L, Varricchio M (1995) "Lisinopril administration improves insulin action in aged patients with hypertension." J Hum Hypertens, 9, p. 541-6
  72. Darcy PF, Griffin JP (1995) "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev, 14, p. 211-31
  73. Kubacka RT, Antla EJ, Juhl RP, Welshman IR (1996) "Effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy subjects." Ann Pharmacother, 30, p. 20-6
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  77. Hellman B (1974) "Potentiating effects of drugs on the binding of glibenclamide to pancreatic beta cells." Metabolism, 23, p. 839-46
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  79. Hekimsoy Z, Biberoglu S, Comlekci A, Tarhan O, Mermut C, Biberoglu K (1997) "Trimethoprim/sulfamethoxazole-induced hypoglycemia in a malnourished patient with severe infection." Eur J Endocrinol, 136, p. 3046
  80. (2001) "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc
  81. Iida H, Morita T, Suzuki E, Iwasawa K, Toyooka T, Nakajima T (1999) "Hypoglycemia induced by interaction between clarithromycin and disopyramide." Jpn Heart J, 40, p. 91-6
  82. Morris AD, Newton RW, Boyle DI, et al. (1997) "ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes." Diabetes Care, 20, p. 1363-7
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  88. Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D (2001) "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol, 52, p. 456-7
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Minor

aspirin caffeine

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine) and Uricalm Intensive (acetaminophen / aspirin / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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Drug and food interactions

Major

acetaminophen food

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA (1985) "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med, 145, p. 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA (1986) "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA, 255, p. 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med, 104, p. 399-404
  4. Thummel KE, Slattery JT, Nelson SD (1988) "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther, 245, p. 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA, 244, p. 251-3
  6. Kartsonis A, Reddy KR, Schiff ER (1986) "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med, 105, p. 138-9
  7. Prescott LF, Critchley JA (1983) "Drug interactions affecting analgesic toxicity." Am J Med, 75, p. 113-6
  8. (2002) "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical
  9. Whitcomb DC, Block GD (1994) "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA, 272, p. 1845-50
  10. Bonkovsky HL (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  11. Nelson EB, Temple AR (1995) "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA, 274, p. 301
  12. Zimmerman HJ, Maddrey WC (1995) "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology, 22, p. 767-73
View all 12 references

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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

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  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
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
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Moderate

aspirin food

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

caffeine food

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy, 16, p. 1046-52

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Minor

aspirin food

Applies to: Uricalm Intensive (acetaminophen / aspirin / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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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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