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Drug Interactions between itraconazole and mirtazapine

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

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Interactions between your drugs

Moderate

itraconazole mirtazapine

Applies to: itraconazole and mirtazapine

MONITOR: Coadministration of mirtazapine with drugs that inhibit one or more of its metabolic pathways may result in increased plasma concentrations of mirtazapine. In vitro data from human liver microsomes indicate that CYP450 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite, while CYP450 3A4 is primarily responsible for the formation of the N-desmethyl and N-oxide metabolites. When cimetidine, a weak inhibitor of CYP450 1A2, 2D6 and 3A4, was given at 800 mg twice daily for 14 days to twelve healthy male subjects in combination with mirtazapine 30 mg once daily on days 6 to 12, mean steady-state mirtazapine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 22% and 54%, respectively. Mirtazapine had no effect on the pharmacokinetics of cimetidine. In another study with 24 healthy male Caucasian subjects, administration of the potent CYP450 3A4 inhibitor ketoconazole at 200 mg twice daily for 6.5 days increased Cmax and AUC of a single 30 mg dose of mirtazapine by approximately 40% and 50%, respectively. A case report described increases in serum mirtazapine concentrations of three- to fourfold in two patients following the addition of fluvoxamine, a potent CYP450 1A2 and weak CYP450 2D6/3A4 inhibitor. One patient reported feeling more anxious with the combination.

MANAGEMENT: The possibility of prolonged and/or increased pharmacologic effects of mirtazapine should be considered during coadministration of drugs that inhibit CYP450 1A2, 2D6 and/or 3A4. Therapeutic response to mirtazapine should be monitored more closely following initiation, discontinuation, or dosing change of CYP450 inhibitors, and the mirtazapine dosage adjusted as necessary. A prolonged duration of monitoring for adverse effects may be required depending on the elimination half-life of the concomitant drug. For example, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, can increase plasma concentrations and the risk of adverse effects of mirtazapine for at least 28 days after administration of rolapitant.

References (5)
  1. (2001) "Product Information. Remeron (mirtazapine)." Organon
  2. Sitsen JM, Maris FA, Timmer CJ (2000) "Concomitant use of mirtazapine and cimetidine: a drug-drug interaction study in healthy male subjects." Eur J Clin Pharmacol, 56, p. 389-94
  3. Okubo M, Murayama N, Miura J, Chiba Y, Yamazaki H (2015) "Effects of cytochrome P450 2D6 and 3A5 genotypes and possible coadministered medicines on the metabolic clearance of antidepressant mirtazapine in Japanese patients." Biochem Pharmacol, 93, p. 104-9
  4. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.
  5. Stormer E, von Moltke LL, Shader RI, Greenblatt DJ (2000) "Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4" Drug Metab Dispos, 28, p. 1168-75

Drug and food interactions

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
Moderate

mirtazapine food

Applies to: mirtazapine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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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