Dosing and uses of Erivedge (vismodegib)
Adult dosage forms and strengths
capsule
- 150mg
Basal Cell Carcinoma
Indicated for treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery or radiation
150 mg PO qDay
Renal & Hepatic Impairment
No dose adjustment is required in patients with renal impairment
Hepatic Impairment
No dose adjustment required in patients with hepatic impairment
Administration
May take with or without food
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Clinical trials did not include sufficient numbers of patient 65 years or older to evaluate if a different dose is required
Erivedge (vismodegib) adverse (side) effects
>10%
Muscle spasms (71.7%)
Alopecia (63.8%)
Dysgeusia (55.1%)
Weight loss (44.9%)
Fatigue (39.9%)
Nausea (30.4%)
Diarrhea (29%)
Decreased appetite (25.4%)
Constipation (21%)
Arthralgias (15.9%)
Vomiting (13.8%)
Ageusia (10.9%)
1-10%
Hyponatremia (4%)
Azotemia (2%)
Hypokalemia (1%)
Frequency not defined
Amenorrhea
Warnings
Black box warnings
Embryo-fetal death and severe birth defects
- Can cause fetal harm when administered to a pregnant woman based on its mechanism of action
- Shown to be teratogenic, embryotoxic, and fetotoxic in rats at maternal exposures lower than the human exposures at the recommended dose of 150 mg/day; embryolethal in rats at exposures within the range achieved at the recommended human dose
- Rat malformations included craniofacial anomalies, open perineum, and absent or fused digits; fetal retardations and variations were also observed
- Verify pregnancy status prior to the initiation
- Advise male and female patients of the risks of embryo-fetal death and severe birth defects and the need for contraception during and after treatment
- Advise patients to contact their healthcare provider immediately if they suspect they (or, for males, their female partner) may be pregnant
- Report exposure during pregnancy to the Genentech Adverse Event Line at 1-888-835-2555
Contraindications
None
Cautions
Can cause fetal harm when administered to pregnant women, or if pregnant women are exposed to vismodegib via seminal fluid
Patient should not donate blood while taking vismodegib or for at least 7 months after last dose
Drugs that increase gastric pH may alter solubility of vismodegib resulting in decreased bioavailability
Drugs that inhibit P-gp efflux transporter may increase systemic exposure to vismodegib and incidence of adverse effects
Advise patients not to donate blood or blood products while receiving therapy and for 7 months after final dose
Advise males not to donate semen during and for 3 months after therapy
Verify pregnancy status of females of reproductive potential within 7 days prior to initiating therapy; advise females of reproductive potential to use effective contraception during therapy and for 7 months after 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; advise pregnant women of the potential risk to a fetus
Pregnancy and lactation
Pregnancy category: D; Can cause fetal harm when administered to a pregnant woman based on its mechanism of action (by either direct exposure or exposure from seminal fluid); see Black box warnings
Shown to be teratogenic, embryotoxic, and fetotoxic in rats at maternal exposures lower than the human exposures at the recommended dose of 150 mg/day; embryolethal in rats at exposures within the range achieved at the recommended human dose
Lactation: Unknown whether distributed in breast milk; a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Erivedge (vismodegib)
Mechanism of action
Hedgehog (Hh) pathway inhibitor; the Hedgehog signaling pathway is important in embryogenesis, but in adults, it is mostly inactive; signaling is relayed by key proteins including Smoothened (SMO)
Hh ligand-expressing cancerous epithelial cells that are activated by the Hh signaling pathway may cause growth-promotion; vismodegib binds to and inhibits SMO, a transmembrane protein involved in Hedgehog signal transduction
Absorption
Bioavailability: 31.8%
Distribution
Protein Bound: >99%, binds to both albumin and alpha-1-acid glycoprotein
Vd: 16.4-26.6 L
Metabolism
>98% of total circulating drug components are the parent drug
Minimally metabolized by oxidation, glucuronidation, and pyridine ring cleavage
Minor substrate of CYP2C9 and CYP3A4 Minor inhibitor of CYP2C8, CYP2C9, and CYP2C19
Elimination
Half-life: 4 days (at steady-state)
Excretion: feces 82%, urine 4.4%
