Question

20. Rifampin is a drug that causes enzyme induction. Would you have to increase or decrease the dosage of another drug taken concurrently if it required drug metabolism for elimination?

Answer 1

Ans. The dose has to be increased for a drug that is concurrently administered along with Rifampin as it is an enzyme inducer.

Explanation:

Rifampin is a semi-synthetic congener of rifamycin B which is mainly used in the management of Tuberculosis.

Drug interactions of Rifampin: Rifampin is a microsomal enzyme inducer and increases the cytochrome oxidase P450 enzymes (namely CYP3A4, CYP2D6, CYP1A2, CYP2C). As a result of this enzyme induction, the metabolism of rifampin itself is increased manifold and if there are other drugs which are concurrently administered along with Rifampin, whose elimination also requires metabolism by cytochrome oxidases, their doses have to be increased to compensate for the extra drug loss by enzyme induction.

Examples of drugs whose metabolism is increased by Rifampin and whose does are to be increased to provide the therapeutic effect:

• Warfarin
• Oral contraceptives
• Corticosteroids
• Sulfonylureas
• Digitoxin
• Steroids
• Protease inhibitors
• Theophylline
• Metoprolol
• Fluconazole
• Ketoconazole

If the dose is not increased for a drug that is concurrently administered along with enzyme inducer drug like Rifampin, therapeutic failure occurs. For example, failure of contraception when oral contraceptives are used along with Rifampin