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Drug Interactions between itraconazole and primidone

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

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Interactions between your drugs

Major

itraconazole primidone

Applies to: itraconazole and primidone

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the oral bioavailability and plasma concentrations of itraconazole and ketoconazole. In vitro studies have shown that CYP450 3A4 is the major enzyme involved in their metabolism, and pharmacokinetic studies as well as case reports have demonstrated decreases in itraconazole and ketoconazole systemic exposure (AUC) by at least 80% and sometimes even to undetectable levels when coadministered with potent CYP450 3A4 inducers such as rifampin or phenytoin, including reports of treatment failure.

MANAGEMENT: Concomitant use of itraconazole or ketoconazole with potent CYP450 3A4 inducers should generally be avoided. Some authorities recommend avoiding coadministration of potent CYP450 3A4 inducers from 2 weeks before and during treatment with these azole antifungal agents unless the benefits outweigh the risk of potentially reduced antifungal efficacy. If coadministration is required, clinical response and antifungal activity should be closely monitored and the itraconazole or ketoconazole dosage increased as necessary.

References (15)
  1. 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
  2. Brass C, Galgiani JN, Blaschke TF, et al. (1982) "Disposition of ketoconazole, an oral antifungal, in humans." Antimicrob Agents Chemother, 21, p. 151-8
  3. Engelhard D, Stutman HR, Marks MI (1984) "Interaction of ketoconazole with rifampin and isoniazid." N Engl J Med, 311, p. 1681-3
  4. 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
  5. 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
  6. Meunier F (1986) "Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents." Eur J Clin Microbiol, 5, p. 103-9
  7. (2002) "Product Information. Nizoral (ketoconazole)." Janssen Pharmaceuticals
  8. Schaferkorting M (1993) "Pharmacokinetic optimisation of oral antifungal therapy." Clin Pharmacokinet, 25, p. 329-41
  9. 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
  10. 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
  11. Ducharme MP, Slaughter RL, Warbasse LH, Chandrasekar PH, Vandevelde V, Mannens G, Edwards DJ (1995) "Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin." Clin Pharmacol Ther, 58, p. 617-24
  12. (2024) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  13. (2024) "Product Information. Ketoconazole (ketoconazole)." Taro Pharmaceuticals U.S.A. Inc
  14. (2024) "Product Information. Sporanox (itraconazole)." Janssen-Cilag Pty Ltd
  15. Moon SM, Park HY, Jeong BH, Jeon K, lee sy, Koh WJ (2015) "Effect of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis and coexisting nontuberculous mycobacterial infection." Antimicrob Agents Chemother, 59, p. 663-5

Drug and food interactions

Major

primidone food

Applies to: primidone

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References (5)
  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
Moderate

itraconazole food

Applies to: 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 (10)
  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

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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