Drug Interactions between Adgyn Estro and itraconazole
This report displays the potential drug interactions for the following 2 drugs:
- Adgyn Estro (estradiol)
- itraconazole
Interactions between your drugs
itraconazole estradiol
Applies to: itraconazole and Adgyn Estro (estradiol)
MONITOR: Azole antifungal agents may increase the plasma concentrations of estrogens and progestins. The mechanism is decreased clearance of the hormones due to inhibition of CYP450 3A4 activity by azole antifungals. Coadministration of voriconazole (200 mg every 12 hours) and an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone increased the steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol by an average of 36% and 61%, respectively, and Cmax and AUC of norethindrone by 15% and 53%, respectively, in healthy volunteers. Fluconazole doses of 150 mg and 200 mg have also been shown to increase the serum concentrations of ethinyl estradiol and levonorgestrel in healthy women receiving low-dose oral contraceptives, while single and multiple doses of fluconazole 50 mg had no significant effect on the pharmacokinetics of a high-dose oral contraceptive containing 150 mcg ethinyl estradiol and norgestrel 300 mcg. Ironically, there have been isolated reports of breakthrough bleeding and unintended pregnancy during use of oral contraceptives with itraconazole, which would suggest decreased rather than increased effect of the contraceptives. However, the association to itraconazole is questionable.
MANAGEMENT: During concomitant therapy with azole antifungal agents, patients should be observed for increased or altered pharmacologic response to estrogens and progestins, and dosage(s) adjusted accordingly as necessary.
References
- Lazar JD, Wilner KD (1990) "Drug interactions with fluconazole." Rev Infect Dis, 12 Suppl 3, s327-33
- Pillans PI, Sparrow MJ (1993) "Pregnancy associated with a combined oral contraceptive and itraconazole." N Z Med J, 106, p. 436
- Devenport MH, Crook D, Wynn V, Lees LJ (1989) "Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives." Br J Clin Pharmacol, 27, p. 851-9
- Sinofsky FE, Pasquale SA (1998) "The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives." Am J Obstet Gynecol, 178, p. 300-4
- Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
- (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
Drug and food interactions
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
- 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
- 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
- (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
- 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
- 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
- (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
- 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
- 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
- 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
- Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32
estradiol food
Applies to: Adgyn Estro (estradiol)
Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.
References
- Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
- Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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