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Drug Interactions between letermovir 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 letermovir

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

MONITOR: Coadministration with letermovir may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. In vitro and in vivo studies have shown that both estrogens and progestins are partially metabolized by CYP450 3A4. Studies of letermovir with midazolam, a CYP450 3A4 probe substrate, have shown the net effect of letermovir on the CYP450 3A4 isoenzyme is moderate inhibition. Theoretically, concomitant administration of letermovir with CYP450 3A4 substrates, such as estrogens and progestins, may result in clinically relevant increases in the plasma concentration of the CYP450 3A4 substrate. The interaction between letermovir and ethinyl estradiol and levonorgestrel has been evaluated in clinical drug-drug interaction studies and no clinically significant interaction was found.

MANAGEMENT: Monitor estrogen/progestin therapy for altered pharmacologic response and adjust dosage(s) accordingly whenever letermovir is added to or withdrawn from therapy. When choosing an oral contraceptive, consider choosing an ethinyl estradiol-levonorgestrel product as this combination has been studied with letermovir and no clinically significant interaction has been found.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2017) "Product Information. Prevymis (letermovir)." Merck & Co., Inc

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 (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
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 (2)
  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

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.