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Drug Interactions between nateglinide and Onmel

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

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Interactions between your drugs

Minor

itraconazole nateglinide

Applies to: Onmel (itraconazole) and nateglinide

Itraconazole, a potent inhibitor of CYP450 3A4, does not appear to significantly affect the pharmacokinetics of available oral hypoglycemic agents, most of which are primarily metabolized by CYP450 2C8 (pioglitazone, rosiglitazone, repaglinide) or 2C9 (nateglinide, sulfonylureas). Modest increases in systemic exposure (AUC) have been reported for repaglinide and nateglinide, which are partially metabolized by CYP450 3A4. A retrospective analysis of pharmacokinetic and safety data from postmarketing surveillance and clinical trials over a 10-year period suggests that itraconazole is generally safe for use in diabetic patients. Specifically, a review of all postmarketing adverse event reports in patients receiving itraconazole concomitantly with insulin or an oral antidiabetic agent revealed 15 reports suggestive of hyperglycemia and 9 reports suggestive of hypoglycemia. In most patients, no change in antidiabetic effect was reported. From clinical trials including a total of 189 diabetic patients treated with itraconazole for various infections, only one itraconazole-related adverse event was recorded: a case of aggravated diabetes in a renal transplant recipient who was also receiving cyclosporine. No specific precautions should be necessary during coadministration of most oral hypoglycemic agents with itraconazole. However, dosage adjustments may be necessary if an interaction is suspected.

References

  1. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  2. Miners JO, Birkett DJ "Cytochrome P4502C9: an enzyme of major importance in human drug metabolism." Br J Clin Pharmacol 45 (1998): 525-38
  3. Venkatakrishnan K, von Moltke LL, Greenblatt DJ "Effects of the antifungal agents on oxidative drug metabolism: clinical relevance." Clin Pharmacokinet 38 (2000): 111-80
  4. 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
  5. 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
  6. Verspeelt J, Marynissen G, Gupta AK, De Doncker P "Safety of itraconazole in diabetic patients." Dermatology 198 (1999): 382-4
  7. Niemi M, Backman JT, Neuvonen M, Neuvonen PJ "Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide." Diabetologia 46 (2003): 347-51
  8. Hatorp V, Hansen KT, Thomsen MS "Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide." J Clin Pharmacol 43 (2003): 649-60
  9. Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT "CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide." Br J Clin Pharmacol 56 (2003): 305-14
  10. 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
  11. Jaakkola T, Backman JT, Neuvonen M, Neuvonen PJ "Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone." Clin Pharmacol Ther 77 (2005): 404-14
  12. Niemi M, Backman JT, Juntti-Patinen L, Neuvonen M, Neuvonen PJ "Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide." Br J Clin Pharmacol 60 (2005): 208-17
  13. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 13 references

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Drug and food interactions

Moderate

itraconazole food

Applies to: Onmel (itraconazole)

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

References

  1. Van Peer A, Woestenborghs R, Heykants J, et al. "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol 36 (1989): 423-6
  2. Wishart JM "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol 17 (1987): 220-3
  3. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals PROD (2002):
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother 37 (1993): 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res 14 (1994): 87-93
  6. "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals (2022):
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther 36 (1998): 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy 18 (1998): 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit 21 (1999): 304-9
  10. Katz HI "Drug interactions of the newer oral antifungal agents." Br J Dermatol 141 (1999): 26-32
View all 10 references

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Moderate

nateglinide food

Applies to: nateglinide

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their 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 their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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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.

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