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Drug Interactions between Mycobutin and Onmel

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

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Interactions between your drugs

Major

itraconazole rifabutin

Applies to: Onmel (itraconazole) and Mycobutin (rifabutin)

GENERALLY AVOID: Coadministration with rifamycins may significantly decrease the plasma concentrations of itraconazole, levoketoconazole and ketoconazole. The proposed mechanism is accelerated clearance of the azoles due to induction of CYP450 3A4-mediated metabolism by rifamycins. Pharmacokinetic studies and case reports have demonstrated that rifampin can reduce itraconazole and ketoconazole systemic exposure by at least 80% and sometimes even to undetectable levels. Treatment failure has been reported. Rifabutin, a less potent CYP450 3A4 inducer, has been found in one study to decrease itraconazole systemic exposure by 74%. Conversely, itraconazole, levoketoconazole and ketoconazole are potent inhibitors of CYP450 3A4 and may substantially increase the plasma levels of rifabutin and its pharmacologically active metabolite, 25-O-desacetylrifabutin. This may increase the risk of adverse effects such as leukopenia, uveitis, arthralgia, joint disorder, and skin discoloration. By contrast, itraconazole reportedly has no effect on rifampin pharmacokinetics. Ketoconazole has been found in some studies to decrease rifampin plasma levels, but interaction is apparently minimized when they are given 12 hours apart.

MANAGEMENT: The manufacturers recommend that itraconazole and ketoconazole not be used concomitantly or within 2 weeks of treatment with rifamycins, unless the benefits outweigh the risk of potentially reduced antifungal efficacy. If coadministration is required, the antifungal activity should be monitored and the azole dosage increased as necessary. With rifabutin, however, consideration should also be given to the potential for increased risk of rifabutin toxicity, particularly when the azole dosage is increased. Therapeutic drug monitoring for rifabutin is therefore advisable, and the dosage adjusted if needed. In addition, a complete blood count should be performed at least weekly and as clinically indicated to monitor for development of neutropenia. Levoketoconazole manufacturer recommends avoiding its concomitant use or within 2 weeks of treatment with rifamycins.

References

  1. Venkatesan K (1992) "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet, 22, p. 47-65
  2. Borcherding SM, Baciewicz AM, Self TH (1992) "Update on rifampin drug interactions." Arch Intern Med, 152, p. 711-6
  3. Abadie-Kemmerly S, Pankey GA, Dalvisio JR (1988) "Failure of ketoconazole treatment of blastomyces dermatidis due to interaction of isoniazid and rifampin." Ann Intern Med, 109, p. 844-5
  4. Blomley M, Teare E, De Belder A, et al. (1990) "Itraconazole and anti-tuberculosis drugs." Lancet, 336, p. 1255
  5. Brass C, Galgiani JN, Blaschke TF, et al. (1982) "Disposition of ketoconazole, an oral antifungal, in humans." Antimicrob Agents Chemother, 21, p. 151-8
  6. Engelhard D, Stutman HR, Marks MI (1984) "Interaction of ketoconazole with rifampin and isoniazid." N Engl J Med, 311, p. 1681-3
  7. Tucker RM, Denning DW, Hanson LH, et al. (1992) "Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations." Clin Infect Dis, 14, p. 165-74
  8. Doble N, Shaw R, Rowland-Hill C, et al. (1988) "Pharmacokinetic study of the interaction between rifampicin and ketoconazole." J Antimicrob Chemother, 21, p. 633-5
  9. (2001) "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceuticals, 1992
  10. Meunier F (1986) "Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents." Eur J Clin Microbiol, 5, p. 103-9
  11. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  12. Schaferkorting M (1993) "Pharmacokinetic optimisation of oral antifungal therapy." Clin Pharmacokinet, 25, p. 329-41
  13. Drayton J, Dickinson G, Rinaldi MG (1994) "Coadministration of rifampin and itraconazole leads to undetectable levels of serum itraconazole." Clin Infect Dis, 18, p. 266
  14. Lefort A, Launay O, Carbon C (1996) "Uveitis associated with rifabutin prophylaxis and itraconazole therapy." Ann Intern Med, 125, p. 939-40
  15. Strayhorn VA, Baciewicz AM, Self TH (1997) "Update on rifampin drug interactions, III." Arch Intern Med, 157, p. 2453-8
  16. Jaruratanasirikul S, Sriwiriyajan S (1998) "Effect of rifampicin on the pharmacokinetics of itraconazole in normal volunteers and AIDS patients." Eur J Clin Pharmacol, 54, p. 155-8
  17. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  18. Pharmaceutical Society of Australia (2006) APPGuide online. Australian prescription products guide online. http://www.appco.com.au/appguide/default.asp
  19. Cerner Multum, Inc. "Australian Product Information."
View all 19 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. (1989) "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol, 36, p. 423-6
  2. Wishart JM (1987) "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol, 17, p. 220-3
  3. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V (1993) "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother, 37, p. 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A (1994) "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res, 14, p. 87-93
  6. (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H (1998) "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther, 36, p. 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L (1998) "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy, 18, p. 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M (1999) "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit, 21, p. 304-9
  10. Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32
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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