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Label Changes for:

Stivarga (regorafenib)

June 2016

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

June 2016

WARNINGS AND PRECAUTIONS

Hepatotoxicity
  • Severe drug-induced liver injury with fatal outcome occurred in Stivarga-treated patients in clinical trials. In most cases, liver dysfunction occurred within the first 2 months of therapy and was characterized by a hepatocellular pattern of injury.
Dermatologic Toxicity
  • In both studies, a higher incidence of HFSR was observed in Asian patients treated with Stivarga (all grades: 78.4% in Study 1 and 88.2% in Study 2 and Grade 3: 28.4% in Study 1 and 23.5% in Study 2).
Embryo-Fetal Toxicity
  • (Addition) Based on animal studies and its mechanism of action,… Stivarga…
  • (Addition) There are no available data on Stivarga use in pregnant women… Regorafenib…
  • (Addition) Advise females of reproductive potential to use effective contraception during treatment with Stivarga and for 2 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Stivarga and for 2 months after the final dose.
Race
  • Based on pooled data from three placebo-controlled trials (Studies 1 and 2, and a study conducted in East Asia), a higher incidence of HFSR and liver function test abnormalities occurred in Asian patients treated with Stivarga as compared with Whites. No starting dose adjustment is necessary based on race.

PATIENT COUNSELING INFORMATION

  • Extensive changes have been made to the Patient Counseling Information; please refer to label.

 

April 2015

ADVERSE REACTIONS

Postmarketing Experience
  • hypersensitivity reactions

 

May 2013

7 DRUG INTERACTIONS

7.1 Effect of Strong CYP3A4 Inducers on Regorafenib
  • Co-administration of a strong CYP3A4 inducer (rifampin) with a single 160 mg dose of Stivarga decreased the mean exposure of regorafenib, increased the mean exposure of the active metabolite M-5, and resulted in no change in the mean exposure of the active metabolite M-2. Avoid concomitant use of Stivarga with strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John’s Wort) [see Clinical Pharmacology]
7.2 Effect of Strong CYP3A4 Inhibitors on Regorafenib
  • Co-administration of a strong CYP3A4 inhibitor (ketoconazole) with a single 160 mg dose of Stivarga increased the mean exposure of regorafenib and decreased the mean exposure of the active metabolites M-2 and M-5. Avoid concomitant use of Stivarga with strong inhibitors of CYP3A4 activity (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and voriconazole) [see Clinical Pharmacology].

 

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