FDA Hepatitis Update - Victrelis (boceprevir) label updated for drug-drug interactions

FDA Hepatitis Update - Victrelis (boceprevir) label updated for drug-drug interactions

On July 31, 2012, FDA updated the Victrelis (boceprevir) label to include drug-drug interactions between Victrelis and cyclosporine, tacrolimus, escitalopram, atorvastatin and pravastatin. The main changes to the label are highlighted below.

Changes were also made to the Medication Guide to reflect the new interaction data.
Section 7: Drug Interactions was updated to include information regarding the following drug-drug interactions:

• Atorvastatin: Exposure to atorvastatin was increased when administered with VICTRELIS. Use the lowest effective dose of atorvastatin, but do not exceed a daily dose of 40 mg when coadministered with VICTRELIS

• Cyclosporine: Dose adjustments of cyclosporine should be anticipated when administered with VICTRELIS and should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects.

• Escitalopram: Exposure of escitalopram was slightly decreased when coadministered with VICTRELIS. Selective serotonin reuptake inhibitors such as escitalopram have a wide therapeutic index, but doses may need to be adjusted when combined with VICTRELIS

• Pravastatin: Concomitant administration of pravastatin with VICTRELIS increased exposure to pravastatin. Treatment with pravastatin can be initiated at the recommended dose when coadministered with VICTRELIS. Close clinical monitoring is warranted

• Tacrolimus: Concomitant administration of VICTRELIS with tacrolimus requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects.

Section 12: Clinical Pharmacology was updated to include the magnitude of interaction between boceprevir and these medications.

Victrelis is a protease inhibitor for the treatment of HCV infection and manufactured by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co.

The complete, revised label and Medication Guide can be viewed at Drugs@FDA.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

Drug-Drug Interactions Added to Hepatitis C Drug Label

By: ELIZABETH MECHCATIE, Family Practice News Digital Network

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.

Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.

Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.

Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.

Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.

Serious adverse events associated with boceprevir should be reported to MedWatch or by phone at 800-332-1088.

Related June 28

Drug Interactions - Telaprevir and buprenorphine.        
Drug Interactions - Boceprevir and ciclosporin or tacrolimus.

FDA Hepatitis Update - Incivek (telaprevir) product labeling revised

Also See: Hepatitis C Drug Interaction Charts