May 5, 2016
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Erivedge

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Erivedge




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Embryo-Fetal Toxicity

Based on its mechanism of action, ERIVEDGE can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. In animal reproduction studies, vismodegib was embryotoxic, fetotoxic, and teratogenic at maternal exposures lower than the human exposures at the recommended dose of 150 mg/day.

Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE therapy. Advise females of reproductive potential to use effective contraception during therapy with ERIVEDGE and for 7 months after the final dose. Advise male patients to use condoms, even after a vasectomy, to avoid potential drug exposure in pregnant partners and female partners of reproductive potential during therapy and for 3 months after the final dose of ERIVEDGE. Advise pregnant women of the potential risk to a fetus [see Use in Specific Populations and CLINICAL PHARMACOLOGY].

Blood Donation

Advise patients not to donate blood or blood products while receiving ERIVEDGE and for 7 months after the final dose of ERIVEDGE.

Semen Donation

Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Advise male patients not to donate semen during and for 3 months after the final dose of ERIVEDGE [see Use in Specific Populations].

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide).

Administration Instructions
  • Advise patients to swallow ERIVEDGE capsules whole and not to crush or open the capsules.
Embryo-Fetal Toxicity
  • Advise pregnant women of the potential risk to a fetus [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
  • Advise females of reproductive potential to use effective contraception during therapy with and for 7 months after the final dose of ERIVEDGE [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].
  • Advise males, even those with prior vasectomy, to use condoms to avoid potential drug exposure in both pregnant partners and female partners of reproductive potential during therapy with and for 3 months after the final dose of ERIVEDGE [see WARNINGS AND PRECAUTIONS and Use in Specific Populations].
  • Advise female patients and female partners of male patients to contact their healthcare provider with a known or suspected pregnancy. Report pregnancies to Genentech at 1-888-835-2555 [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Semen Donation
  • Advise males not to donate semen during therapy with and for 3 months after the final dose of ERIVEDGE.
Lactation
  • Advise women that breastfeeding is not recommended during therapy with ERIVEDGE and for 7 months after the final dose [see Use in Specific Populations].
Blood Donation
  • Advise patients not to donate blood or blood products while taking ERIVEDGE and for 7 months after the final dose of ERIVEDGE.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenicity studies with vismodegib have not been conducted. Pilomatricoma (a benign cutaneous neoplasm) was observed in rats administered oral vismodegib for 26 weeks at 100 mg/kg/day (approximately 0.8 times the systemic exposure (AUC) in patients at the recommended human dose).

Vismodegib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro human chromosomal aberration assay in human peripheral blood lymphocytes or in the in vivo rat bone marrow micronucleus assay.

Studies to assess the potential of vismodegib to affect fertility have not been conducted; however, data from repeat-dose toxicology studies in rats and dogs indicate that male and female reproductive function and fertility may be impaired in patients receiving ERIVEDGE capsule. In a 26-week toxicology study in rats, a relative decrease in percent motile sperm was observed at ≥ 15 mg/kg/day (approximately ≥ 0.3 times the AUC in patients at the recommended human dose). In dogs, increased numbers of degenerating germ cells and hypospermia were observed in young animals administered oral vismodegib for 4 weeks at ≥ 50 mg/kg/day (approximately ≥ 2 times the AUC in patients at the recommended human dose). No corresponding findings were observed in sexually mature dogs at similar doses in 13-week and 26-week toxicology studies. A decrease in the number of corpora lutea was observed in female rats administered oral vismodegib for 26 weeks at 100 mg/kg/day (approximately 0.8 times the AUC in patients at the recommended human dose).

Use In Specific Populations

Pregnancy

Risk Summary

Based on its mechanism of action and animal reproduction studies, ERIVEDGE can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY]. In animal reproduction studies, oral administration of vismodegib during organogenesis at doses below the recommended human dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats [see Data]. There are no human data on the use of ERIVEDGE in pregnant women. Advise pregnant women of the potential risk to a fetus. Report pregnancies to Genentech at 1-888-835-2555.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In an embryo-fetal developmental toxicity study, pregnant rats were administered vismodegib orally at doses of 10, 60, or 300 mg/kg/day during the period of organogenesis. Pre- and post-implantation loss were increased at doses of ≥ 60 mg/kg/day (approximately ≥ 2 times the systemic exposure (AUC) in patients at the recommended human dose), which included early resorption of 100% of the fetuses. A dose of 10 mg/kg/day (approximately 0.2 times the AUC in patients at the recommended dose) resulted in malformations (including missing and/or fused digits, open perineum and craniofacial anomalies) and retardations or variations (including dilated renal pelvis, dilated ureter, and incompletely or unossified sternal elements, centra of vertebrae, or proximal phalanges and claws).

Lactation

No data are available regarding the presence of vismodegib in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in breastfed infants from ERIVEDGE, advise a nursing woman that breastfeeding is not recommended during therapy with ERIVEDGE and for 7 months after the final dose.

Females And Males Of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE therapy.

Contraception

Females

Based on its mechanism of action and animal data, ERIVEDGE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations]. Advise females of reproductive potential to use effective contraception during therapy and for 7 months after the final dose of ERIVEDGE.

Males

Vismodegib is present in semen [see CLINICAL PHARMACOLOGY]. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Advise male patients to use condoms, even after a vasectomy, to avoid drug exposure to pregnant partners and female partners of reproductive potential during therapy with and for 3 months after the final dose of ERIVEDGE. Advise males of the potential risk to an embryo or fetus if a female partner of reproductive potential is exposed to ERIVEDGE. Advise males not to donate semen during therapy with and for 3 months after the final dose of ERIVEDGE.

Infertility

Females

Amenorrhea can occur in females of reproductive potential. Reversibility of amenorrhea is unknown [see ADVERSE REACTIONS].

Pediatric Use

The safety and effectiveness of ERIVEDGE capsule have not been established in pediatric patients. In repeat-dose toxicology studies in rats, administration of oral vismodegib resulted in toxicities in bone and teeth. Effects on bone consisted of closure of the epiphyseal growth plate when oral vismodegib was administered for 26 weeks at ≥ 50 mg/kg/day (approximately ≥ 0.4 times the systemic exposure (AUC) in patients at the recommended human dose). Abnormalities in growing incisor teeth (including degeneration/necrosis of odontoblasts, formation of fluid-filled cysts in the dental pulp, ossification of the root canal, and hemorrhage resulting in breakage or loss of teeth) were observed after administration of oral vismodegib at ≥ 15 mg/kg/day (approximately ≥ 0.2 times the AUC in patients at the recommended human dose).

Geriatric Use

Clinical studies of ERIVEDGE capsule did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment [see CLINICAL PHARMACOLOGY].

Renal Impairment

No dose adjustment is required in patients with renal impairment [see CLINICAL PHARMACOLOGY].

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 4/27/2016

Warnings
Precautions

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