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Drug Interactions between clotrimazole and PMB

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

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Interactions between your drugs

Moderate

conjugated estrogens clotrimazole

Applies to: PMB (conjugated estrogens / meprobamate) and clotrimazole

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 "Drug interactions with fluconazole." Rev Infect Dis 12 Suppl 3 (1990): s327-33
  2. Pillans PI, Sparrow MJ "Pregnancy associated with a combined oral contraceptive and itraconazole." N Z Med J 106 (1993): 436
  3. Devenport MH, Crook D, Wynn V, Lees LJ "Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives." Br J Clin Pharmacol 27 (1989): 851-9
  4. Sinofsky FE, Pasquale SA "The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives." Am J Obstet Gynecol 178 (1998): 300-4
  5. Weisberg E "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet 36 (1999): 309-13
  6. "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals (2002):
View all 6 references

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Drug and food interactions

Moderate

meprobamate food

Applies to: PMB (conjugated estrogens / meprobamate)

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

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

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Minor

conjugated estrogens food

Applies to: PMB (conjugated estrogens / meprobamate)

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. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 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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