SIROLIMUS (Generic for RAPAMUNE)

Sirolimus 1mg, Oral tablet

High Fat Foods

· Severity: Major

· Notes for Consumers: Sirolimus may be taken with or without food, but it is critical that you always take sirolimus consistently with or without food to maintain consistent blood levels of this drug. Avoid grapefruit while taking Sirolimus as grapefruits or grapefruit juice can increase sirolimus concentrations, causing side effects.

· Notes for Professionals: Food may affect the exposure to sirolimus. As compared with the fasted state, administration of sirolimus oral solution with a high-fat meal decreased the peak blood concentration of sirolimus by 34%, increased the Tmax 3.5-fold, and increased the AUC by 35%. As compared with the fasted state, administration of sirolimus tablets with a high-fat meal increased the peak blood concentration of sirolimus by 65%, increased the Tmax by 32%, and increased the AUC by 23%. To minimize variability, sirolimus should be taken consistently with or without food.

Sirolimus 1mg, Oral tablet

Grapefruit juice

· Severity: Severe

· Notes for Consumers: Avoid Grapefruit Juice while taking Sirolimus. Grapefruits and Grapefruit juice may increase Sirolimus blood levels significantly leading to side effects like abdominal pain, confusion, decreased urination, dizziness, headache, mood changes, nausea-vomiting, tremor, yellowing of skin or eyes, weakness, or other problems.

· Notes for Professionals: Food may affect the exposure to sirolimus. As compared with the fasted state, administration of sirolimus oral solution with a high-fat meal decreased the peak blood concentration of sirolimus by 34%, increased the Tmax 3.5-fold, and increased the AUC by 35%. As compared with the fasted state, administration of sirolimus tablets with a high-fat meal increased the peak blood concentration of sirolimus by 65%, increased the Tmax by 32%, and increased the AUC by 23%. To minimize variability, sirolimus should be taken consistently with or without food. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level. According to the manufacturer, because grapefruit juice inhibits the CYP3A4-mediated metabolism of sirolimus, grapefruit juice should not be used to dilute sirolimus or taken concurrently with sirolimus.

<b>DISCLAIMER:</b><em> This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Drug information is sourced from GSDD (Gold Standard Drug Database ) provided by Elsevier.</em>