Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Extended-Release Tablets and Sirolimus
Determining the interaction of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Extended-Release Tablets and Sirolimus and the possibility of their joint administration.
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 potent inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly increase the plasma concentrations of sirolimus following oral administration. Sirolimus is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter, thus their inhibition in the intestine can enhance the absorption of sirolimus. In 23 healthy volunteers, administration of a single 5 mg dose of sirolimus with the potent dual CYP450 3A4/P-gp inhibitor ketoconazole (200 mg/day orally for 10 days) increased mean sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 4- and 11-fold, respectively. Likewise, posaconazole (400 mg oral suspension twice a day for 16 days) increased mean Cmax and AUC of a single 2 mg dose of sirolimus by nearly 7- and 9-fold, respectively, while voriconazole (400 mg orally every 12 hours for 1 day, then 200 mg every 12 hours for 8 days) increased the same values by 7- and 11-fold, respectively. Another dual inhibitor, boceprevir (800 mg three times a day for 11 days), increased the Cmax and AUC of a single 2 mg dose of sirolimus by 10- and 17-fold, respectively. When sirolimus 2 mg once a day was coadministered with the moderate dual inhibitor erythromycin (ethylsuccinate salt 800 mg every 8 hours) in 24 study subjects, sirolimus Cmax and AUC increased by more than 4-fold each, while erythromycin Cmax and AUC also increased by more than 1.5-fold each. MANAGEMENT: Concomitant use of sirolimus with potent CYP450 3A4 and/or P-gp inhibitors should generally be avoided. The manufacturers of posaconazole and voriconazole consider coadministration with sirolimus to be contraindicated. References "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation, Kenilworth, NJ. "Product Information. Rapamune (sirolimus)" Wyeth-Ayerst Laboratories, Philadelphia, PA. Claesson K, Brattstrom C, Burke JT "Sirolimus and erythromycin interaction: two cases." Transplant Proc 33 (2001): 2136 Dodds-Ashley E "Management of drug and food interactions with azole antifungal agents in transplant recipients." Pharmacotherapy 30 (2010): 842-54 Floren LC, Christians U, Zimmerman JJ, et al "Sirolimus oral bioavailability increases ten-fold with concomitant ketoconazole." Clin Pharmacol Ther 65 (1999): 159 "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals, New York, NY. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation, Kenilworth, NJ. View all 7 references
Professional:GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly increase the plasma concentrations of sirolimus following oral administration. Sirolimus is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter, thus their inhibition in the intestine can enhance the absorption of sirolimus. In 23 healthy volunteers, administration of a single 5 mg dose of sirolimus with the potent dual CYP450 3A4/P-gp inhibitor ketoconazole (200 mg/day orally for 10 days) increased mean sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 4- and 11-fold, respectively. Likewise, posaconazole (400 mg oral suspension twice a day for 16 days) increased mean Cmax and AUC of a single 2 mg dose of sirolimus by nearly 7- and 9-fold, respectively, while voriconazole (400 mg orally every 12 hours for 1 day, then 200 mg every 12 hours for 8 days) increased the same values by 7- and 11-fold, respectively. Another dual inhibitor, boceprevir (800 mg three times a day for 11 days), increased the Cmax and AUC of a single 2 mg dose of sirolimus by 10- and 17-fold, respectively. When sirolimus 2 mg once a day was coadministered with the moderate dual inhibitor erythromycin (ethylsuccinate salt 800 mg every 8 hours) in 24 study subjects, sirolimus Cmax and AUC increased by more than 4-fold each, while erythromycin Cmax and AUC also increased by more than 1.5-fold each.
MANAGEMENT: Concomitant use of sirolimus with potent CYP450 3A4 and/or P-gp inhibitors should generally be avoided. The manufacturers of posaconazole and voriconazole consider coadministration with sirolimus to be contraindicated.
- "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation, Kenilworth, NJ.
- "Product Information. Rapamune (sirolimus)" Wyeth-Ayerst Laboratories, Philadelphia, PA.
- Claesson K, Brattstrom C, Burke JT "Sirolimus and erythromycin interaction: two cases." Transplant Proc 33 (2001): 2136
- Dodds-Ashley E "Management of drug and food interactions with azole antifungal agents in transplant recipients." Pharmacotherapy 30 (2010): 842-54
- Floren LC, Christians U, Zimmerman JJ, et al "Sirolimus oral bioavailability increases ten-fold with concomitant ketoconazole." Clin Pharmacol Ther 65 (1999): 159
- "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals, New York, NY.
- "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation, Kenilworth, NJ.
Generic Name: dasabuvir / ombitasvir / paritaprevir / ritonavir
Brand name: Viekira XR, Viekira Pak
Synonyms: Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir
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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- Sirolimus-Omega-3 Fatty Acid Capsules
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- Sirolimus-Omega-3 polyunsaturated fatty acids
- Sirolimus-Omega-3-acid ethyl esters