ERIVEDGE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERIVEDGE (ERIVEDGE).
Inhibitor of the hedgehog signaling pathway by binding to and inhibiting Smoothened (SMO), a transmembrane protein involved in the transduction of hedgehog signals.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C9; also undergoes metabolism via CYP2C8 and CYP2C19 to a lesser extent. |
| Excretion | Primarily hepatic metabolism via CYP3A4/5, with 70% of dose excreted in feces as metabolites and 13% in urine as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life ranges from 4 to 5 days, supporting once-daily dosing for continuous Hedgehog pathway inhibition. |
| Protein binding | >99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 9–11 L/kg, indicating extensive distribution into tissues beyond plasma. |
| Bioavailability | Oral bioavailability is approximately 30–40% due to first-pass metabolism; absorption is increased with a high-fat meal. |
| Onset of Action | Not applicable for oral administration; clinical effect (e.g., tumor shrinkage) observed after weeks of continuous dosing. |
| Duration of Action | Duration corresponds to drug exposure; sustained suppression of Hedgehog signaling occurs with daily dosing, with clinical effects persisting as long as therapy continues. |
150 mg orally once daily on a continuous schedule.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate to severe hepatic impairment (Child-Pugh B or C): Not recommended due to lack of data. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to increased risk of adverse effects (e.g., muscle spasms, dysgeusia). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERIVEDGE (ERIVEDGE).
| Breastfeeding | No data on the presence of vismodegib in human milk, effects on the breastfed infant, or effects on milk production. Due to the potential for serious adverse reactions in breastfeeding infants, women should not breastfeed during treatment and for at least 24 months after the last dose. M/P ratio not available. |
| Teratogenic Risk | ERIVEDGE (vismodegib) is an inhibitor of the Hedgehog signaling pathway. It is embryotoxic and teratogenic in animals. In pregnant women, it can cause fetal harm when administered during pregnancy. There is a risk of severe birth defects or embryo-fetal death. Use is contraindicated in pregnancy. Risks are present throughout all trimesters due to the drug's mechanism of action. Effective contraception is required before, during, and after treatment. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Pregnancy: May cause fetal harm.","Women of childbearing potential not using effective contraception."]
| Precautions | ["Embryofetal toxicity: Can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for at least 20 months after the last dose.","Premature fusion of the epiphyses: Reported in pediatric patients exposed to hedgehog pathway inhibitors. Monitor growth in pediatric patients.","Blood donation: Advise patients not to donate blood or blood products during treatment and for at least 20 months after the last dose."] |
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| Fetal Monitoring | Confirm pregnancy status prior to initiation. Advise women of reproductive potential to use effective contraception during therapy and for at least 24 months after the last dose. Monitor for pregnancy in women of childbearing potential at monthly intervals during treatment. If pregnancy occurs, drug should be discontinued and the patient apprised of potential hazard to the fetus. |
| Fertility Effects | Vismodegib may impair fertility in males and females based on animal studies. In rats, decreased fertility and mating indices were observed. In humans, no specific fertility studies have been conducted. Oligospermia has been reported in male patients. Effects may be reversible upon discontinuation, but recovery timeline is unknown. |