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Drug Interactions between Nuvelle TS Phase I and Vfend

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

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Interactions between your drugs

Moderate

estradiol voriconazole

Applies to: Nuvelle TS Phase I (estradiol) and Vfend (voriconazole)

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

  1. Lazar JD, Wilner KD (1990) "Drug interactions with fluconazole." Rev Infect Dis, 12 Suppl 3, s327-33
  2. Pillans PI, Sparrow MJ (1993) "Pregnancy associated with a combined oral contraceptive and itraconazole." N Z Med J, 106, p. 436
  3. 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
  4. 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
  5. Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
  6. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
View all 6 references

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Drug and food interactions

Moderate

voriconazole food

Applies to: Vfend (voriconazole)

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References

  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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Minor

estradiol food

Applies to: Nuvelle TS Phase I (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

  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. 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

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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.

Further information

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