- Capsules, oral 150 mg
Vismodegib binds to and inhibits Smoothened, a transmembrane protein involved in hedgehog signal transduction.
Absolute bioavailability is 31.8% (single dose).
The Vd ranges from 16.4 to 26.6 L. Plasma protein binding is greater than 99%, both to human serum albumin and alpha-1 acid glycoprotein.
Metabolic pathways of vismodegib in humans include oxidation, glucuronidation, and pyridine ring cleavage.
Eliminated primarily by the hepatic route with 82% recovered in the feces and 4.4% recovered in urine. The estimated elimination half-life is 4 days (once-daily dosing) and 12 days (single dose).
Special PopulationsRenal Function Impairment
The effect of renal impairment on the systemic exposure of vismodegib has not been studied. Population pharmacokinetic analyses showed that CrCl (range, 30 to 80 mL/min) does not have a clinically meaningful influence on the systemic exposure of vismodegib.Hepatic Function Impairment
The effect of hepatic impairment on the systemic exposure of vismodegib has not been studied.Elderly
Population pharmacokinetic analyses showed that age (range, 26 to 89 y) does not have a clinically meaningful influence on the systemic exposure of vismodegib.Gender
Population pharmacokinetic analyses showed that sex does not have a clinically meaningful influence on the systemic exposure of vismodegib.Weight
Population pharmacokinetic analyses showed that weight (range, 41 to 140 kg) does not have a clinically meaningful influence on the systemic exposure of vismodegib.
Indications and Usage
For the 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, and who are not candidates for radiation.
None well documented.
Dosage and AdministrationBasal Cell Carcinoma
PO 150 mg once daily until disease progression or unacceptable toxicity occurs.
- Administer with or without food. Swallow capsule whole; do not open or crush.
- If a dose is missed, do not make up that dose; resume dosing with the next scheduled dose.
Store between 59° and 86°F.
Drug InteractionsCYP-450 system
Vismodegib is an inhibitor of CYP2C8, CYP2C9, CYP2C19, and the transporter BCRP. However, systemic exposure of rosiglitazone (a CYP2C8 substrate) was not altered with coadministration.Drugs that affect gastric pH (eg, antacids [eg, magnesium hydroxide], histamine H 2 receptor antagonists [eg, famotidine], proton pump inhibitors [eg, omeprazole])
The bioavailability of vismodegib may be reduced. Clinical significance is unknown.P-glycoprotein inhibitors (eg, azithromycin, clarithromycin, erythromycin)
May increase vismodegib systemic exposure and adverse reactions.
Dysgeusia (55%); nausea (30%); diarrhea (29%); constipation (21%); vomiting (14%); ageusia (11%).
Hyponatremia (4%); azotemia (2%); hypokalemia (1%).
Weight loss (45%); decreased appetite (25%).
Muscle spasms (72%); arthralgias (16%).
WarningsEmbryo-fetal death and severe birth defects
Vismodegib can result in embryo-fetal death or severe birth defects. Vismodegib is embryotoxic and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations.
Verify pregnancy status prior to the initiation of vismodegib. Advise male and female patients of these risks. Advise female patients of the need for contraception and advise male patients of the potential risk of vismodegib exposure through semen.
Category D . Can cause embryo-fetal death and/or severe birth defects. Determine pregnancy status within 7 days prior to initiation of treatment.
Safety and efficacy not established.
Has been observed in females of reproductive potential. Reversibility of amenorrhea is unknown.
Advise patients not to donate blood or blood products while receiving vismodegib and for at least 7 mo after the last dose.
No information available.
- Advise patients to read the Medication Guide before starting therapy and with each refill.
- Advise patients that vismodegib exposure during pregnancy can cause embryo-fetal death or severe birth defects.
- Instruct female patients of reproductive potential to use a highly effective form of contraception (failure rate of less than 1%) prior to the first dose of vismodegib and for at least 7 mo after the last dose of vismodegib.
- Instruct all male patients, even those with prior vasectomy, to use condoms with spermicide, during sexual intercourse with female partners while taking vismodegib and for at least 2 mo after the last dose of vismodegib.
- Instruct patients to immediately contact their health care provider if they (or, for males, their female partner) become pregnant or if pregnancy is suspected following exposure to vismodegib.
- Instruct patients to immediately report any pregnancy exposure to vismodegib and encourage participation in the vismodegib pregnancy pharmacovigilance program by calling the manufacturer at 1-888-835-2555.
- Inform female patients of the potential for serious adverse reactions in breast-feeding infants from vismodegib, taking into account the importance of the drug to the mother.
- Advise patients not to donate blood or blood products while taking vismodegib and for at least 7 mo after the last dose of vismodegib.
- Advise patients to swallow vismodegib whole and to not crush or open the capsules.
- Inform patients that if a dose is missed, not to make up that dose; advise patients to resume dosing with the next scheduled dose.
Copyright © 2009 Wolters Kluwer Health.