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Drug Interactions between Diabinese and nitisinone

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

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Interactions between your drugs

Major

chlorproPAMIDE nitisinone

Applies to: Diabinese (chlorpropamide) and nitisinone

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with potent or moderate inhibitors of CYP450 2C9 may significantly increase the plasma concentrations of sulfonylureas, many of which have been found to be substrates of the isoenzyme. Pharmacokinetic data are available for single-dose administration of chlorpropamide (250 mg), tolbutamide (500 mg), glipizide (2.5 mg), glyburide (5 mg), and glimepiride (0.5 mg) in combination with fluconazole, a moderate CYP450 2C9 inhibitor. In healthy study subjects, fluconazole 100 mg daily for 7 days increased the single-dose systemic exposures (AUCs) of various sulfonylureas by an average of nearly 30% (chlorpropamide, tolbutamide) to almost 50% (glipizide, glyburide). Mean changes in blood glucose levels were not statistically significant in these studies, although approximately 48% of patients treated with fluconazole experienced symptoms consistent with hypoglycemia compared to 40% of patients treated with placebo. One in four of the fluconazole-treated patients in the glyburide study also required oral glucose. A higher dosage of fluconazole (400 mg for one day, followed by 200 mg daily for 3 days) increased single-dose glimepiride AUC by 138% and prolonged its half-life from 2.0 to 3.3 hours in healthy volunteers. In another study, low-dose fluconazole (50 mg/day) given to treat vulvovaginal candidiasis in 14 postmenopausal diabetic women receiving gliclazide or glyburide therapy demonstrated no effect on blood glucose control; pharmacokinetic data were not included. Based on available data, fluconazole use does not appear to be associated with a significant risk of severe hypoglycemia at dosages <200 mg/day in sulfonylurea-treated patients. However, higher dosages may cause greater inhibition of sulfonylurea clearance and increased hypoglycemic effects, particularly in the elderly and patients with renal or hepatic impairment. There have been case reports of profound hypoglycemia, including coma and death, during treatment of sulfonylureas with fluconazole, oral miconazole, as well as voriconazole. Concomitant use of sulfonylureas with fluconazole has also been associated with increased risk of serum transaminase elevations.

MANAGEMENT: Caution is advised when sulfonylureas are used concomitantly with potent or moderate CYP450 2C9 inhibitors. Blood glucose should be closely monitored, and the sulfonylurea dosage adjusted as necessary. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypoglycemia occurs, patients should initiate appropriate remedial therapy immediately, discontinue the CYP450 2C9 inhibitor if possible, and contact their physician.

References

  1. Lazar JD, Wilner KD "Drug interactions with fluconazole." Rev Infect Dis 12 Suppl 3 (1990): s327-33
  2. Rowe BR, Thorpe J, Barnett A "Safety of fluconazole in women taking oral hypoglycaemic agents." Lancet 339 (1992): 255-6
  3. Pond SM, Birkett DJ, Wade DN "Mechanisms of inhibition of tolbutamide metabolism: phenylbutazone, oxyphenbutazone, sulfaphenazole." Clin Pharmacol Ther 22 (1977): 573-9
  4. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  5. "Product Information. Micronase (glyburide)." Pharmacia and Upjohn PROD (2002):
  6. "Product Information. Monistat 7 (miconazole topical)." Ortho McNeil Pharmaceutical
  7. "Product Information. Diflucan (fluconazole)." Roerig Division PROD (2001):
  8. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel PROD (2001):
  9. Miners JO, Birkett DJ "Cytochrome P4502C9: an enzyme of major importance in human drug metabolism." Br J Clin Pharmacol 45 (1998): 525-38
  10. Venkatakrishnan K, von Moltke LL, Greenblatt DJ "Effects of the antifungal agents on oxidative drug metabolism: clinical relevance." Clin Pharmacokinet 38 (2000): 111-80
  11. Komatsu K, Ito K, Nakajima Y, Kanamitsu S, Imaoka S, Funae Y, Green CE, Tyson CA, Shimada N, Sugiyama Y "Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments." Drug Metab Disposition 28 (2000): 475-81
  12. Niemi M, Backman JT, Neuvonen M, Laitila J, Neuvonen PJ, Kivisto KT "Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride." Clin Pharmacol Ther 69 (2001): 194-200
  13. Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7
  14. "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals (2002):
  15. Niemi M, Cascorbi I, Timm R, Kroemer HK, Neuvonen PJ, Kivisto KT "Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes." Clin Pharmacol Ther 72 (2002): 326-32
  16. Shon JH, Yoon YR, Kim MJ, et al. "Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 in vitro: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism." Br J Clin Pharmacol 59 (2005): 552-63
  17. Holstein A, Plaschke A, Ptak M, et al. "Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents." Br J Clin Pharmacol 60 (2005): 103-6
  18. "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation (2006):
  19. Jeong S, Nguyen PD, Desta Z "Comprehensive in vitro inhibition analysis of eight cytochrome P450 (CYP) enzymes by voriconazole: major effect on CYPs 2B6, 2C9, 2C19 and 3A." Antimicrob Agents Chemother 53 (2009): 541-51
  20. Ragia G, Petridis I, Tavridou A, Christakidis D, Manolopoulos VG "Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic patients treated with sulfonylureas." Pharmacogenomics 10 (2009): 1781-7
  21. Shobha JC, Muppidi MR "Interaction between voriconazole and glimepiride." J Postgrad Med 56 (2010): 44-5
  22. Back DJ, Tjia JF, Karbwang J, Colbert J "In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolones." Br J Clin Pharmacol 26 (1988): 23-9
  23. Schelleman H, Bilker WB, Brensinger CM, Wan F, Hennessy S "Anti-infectives and the risk of severe hypoglycemia in users of glipizide or glyburide." Clin Pharmacol Ther 88 (2010): 214-22
  24. Tirkkonen T, Heikkila P, Huupponen R, Laine K "Potential CYP2C9-mediated drug-drug interactions in hospitalized type 2 diabetes mellitus patients treated with the sulphonylureas glibenclamide, glimepiride or glipizide." J Intern Med 268 (2010): 359-66
  25. Niwa T, Shiraga T, Takagi A "Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, CYP3A4 activities in human liver microsomes." Biol Pharm Bull 28 (2005): 1805-8
View all 25 references

Drug and food interactions

Moderate

chlorproPAMIDE food

Applies to: Diabinese (chlorpropamide)

Alcohol may affect blood glucose levels in patients with diabetes. Both hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) may occur, depending on how much and how often you drink. You should avoid using alcohol if your diabetes is not well controlled or if you have high triglycerides, neuropathy (nerve damage), or pancreatitis. Moderate alcohol consumption generally does not affect blood glucose levels if your diabetes is under control. However, it may be best to limit alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with your normal meal plan. Avoid drinking alcohol on an empty stomach or following exercise, as it may increase the risk of hypoglycemia. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Moderate

nitisinone food

Applies to: nitisinone

Grapefruit juice may increase the blood levels of certain medications such as nitisinone. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with nitisinone. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

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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.

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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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