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Doravirine and Zema-Pak

Determining the interaction of Doravirine and Zema-Pak and the possibility of their joint administration.

Check result:
Doravirine <> Zema-Pak
Relevance: 28.06.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Consumer information for this interaction is not currently available.GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 100 mg dose of doravirine with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 57%, 88% and 97%, respectively, compared to administration of doravirine alone. When doravirine was administered with the moderate CYP450 3A4 inducer rifabutin (300 mg once daily) in 12 study subjects, doravirine Cmax did not change, but AUC and C24hr decreased by an average of 50% and 68%, respectively. In addition, when doravirine 100 mg once daily was initiated following cessation of treatment with efavirenz (600 mg once daily) in 17 study subjects, doravirine Cmax, AUC, and C24hr decreased by an average of 35%, 62% and 85%, respectively, on the first day and 14%, 32% and 50%, respectively, 14 days later. Although coadministration of doravirine with other moderate CYP450 3A4 inducers has not been evaluated, reduced efficacy of doravirine may occur. The extent to which other, less potent CYP450 3A4 inducers may affect doravirine is unknown. MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of doravirine with moderate CYP450 3A4 inducers should generally be avoided. If coadministration is necessary, some authorities recommend that the doravirine dose be increased to 100 mg twice daily (approximately 12 hours apart) (UK). References "Product Information. Pifeltro (doravirine)." Merck & Company Inc, Whitehouse Station, NJ. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" ([2013 - ]): Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

Professional:

GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 100 mg dose of doravirine with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 57%, 88% and 97%, respectively, compared to administration of doravirine alone. When doravirine was administered with the moderate CYP450 3A4 inducer rifabutin (300 mg once daily) in 12 study subjects, doravirine Cmax did not change, but AUC and C24hr decreased by an average of 50% and 68%, respectively. In addition, when doravirine 100 mg once daily was initiated following cessation of treatment with efavirenz (600 mg once daily) in 17 study subjects, doravirine Cmax, AUC, and C24hr decreased by an average of 35%, 62% and 85%, respectively, on the first day and 14%, 32% and 50%, respectively, 14 days later. Although coadministration of doravirine with other moderate CYP450 3A4 inducers has not been evaluated, reduced efficacy of doravirine may occur. The extent to which other, less potent CYP450 3A4 inducers may affect doravirine is unknown.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of doravirine with moderate CYP450 3A4 inducers should generally be avoided. If coadministration is necessary, some authorities recommend that the doravirine dose be increased to 100 mg twice daily (approximately 12 hours apart) (UK).

References
  • "Product Information. Pifeltro (doravirine)." Merck & Company Inc, Whitehouse Station, NJ.
  • EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" ([2013 - ]):
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
Doravirine

Generic Name: doravirine

Brand name: Pifeltro

Synonyms: n.a.

Zema-Pak

Generic Name: dexamethasone

Brand name: Baycadron, Dexamethasone Intensol, DexPak 10 Day Taperpak, DexPak 13 DayTaperpak, DexPak 6 DayTaperpak, De-Sone LA, Dexacen-4, Dexasone, Dexasone LA, Solurex, Solurex LA, Decadron, DexPak, TaperDex, Zema-Pak, ZoDex, Zonacort

Synonyms: Zema-Pak (Oral)

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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