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PCE Dispertab and Rapamune (Sirolimus Oral Solution)

Determining the interaction of PCE Dispertab and Rapamune (Sirolimus Oral Solution) and the possibility of their joint administration.

Check result:
PCE Dispertab <> Rapamune (Sirolimus Oral Solution)
Relevance: 03.12.2022 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:

Erythromycin may significantly increase the blood levels of sirolimus. This may increase the risk of serious side effects such as infections; lymphoma and other cancers; diabetes; kidney problems; various lung disorders; high blood pressure; high cholesterol and triglycerides; swelling of the face, eyes or mouth; and water retention, especially in the hands, feet, and various tissues such as the sac around the heart or lungs. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor immediately if you develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. You should also seek medical attention if you experience nausea, vomiting, loss of appetite, increased or decreased urination, sudden weight gain or weight loss, fluid retention, swelling, shortness of breath, muscle cramps, tiredness, weakness, dizziness, confusion, and irregular heart rhythm, as these may be signs and symptoms of kidney problems. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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.

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.
PCE Dispertab

Generic Name: erythromycin

Brand name: EES. Granules, EES-400 Filmtab, EryPed 200, EryPed 400, Ery-Tab, Erythrocin Lactobionate, Erythrocin Stearate Filmtab, PCE Dispertab, E. E. S, EryPed, Erythrocin, Erythromycin Filmtabs, Erythromycin Lactobionate - IV

Synonyms: PCE Dispertab (Oral), PCE, PCE (Oral)

Rapamune (Sirolimus Oral Solution)

Generic Name: sirolimus

Brand name: Rapamune

Synonyms: Rapamune

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.