Drug Interaction:
1. Effects of Other Drugs on Vismodegib
Drugs that Inhibit or Induce Drug Metabolizing Enzymes
Vismodegib elimination involves multiple pathways. Vismodegib is predominantly
excreted as an unchanged drug. Several minor metabolites are produced by
multiple CYP enzymes.
Although vismodegib is a substrate of CYP2C9 and CYP3A4 in vitro, CYP inhibition
is not predicted to alter vismodegib systemic exposure since similar
steady-state plasma vismodegib concentrations were observed in patients in
clinical trials concomitantly treated with CYP3A4 inducers (i.e., carbamazepine,
modafinil, phenobarbital) and those concomitantly treated with CYP3A4 inhibitors
(i.e., erythromycin, fluconazole).
2.Drugs that Inhibit Drug Transport Systems
In vitro studies indicate that vismodegib is a substrate of the efflux transporter
P-glycoprotein (P-gp). When ERIVEDGE is coadministered with drugs that inhibit
P-gp (e.g. clarithromycin, erythromycin, azithromycin), systemic exposure of
vismodegib and incidence of adverse events of ERIVEDGE may be increased.
3.Drugs that Affect Gastric pH
Drugs that alter the pH of the upper GI tract (e.g. proton pump inhibitors, H2-receptor
antagonists, and antacids) may alter the solubility of vismodegib and reduce its
bioavailability. However, no formal clinical study has been conducted to evaluate
the effect of gastric pH altering agents on the systemic exposure of vismodegib.
Increasing the dose of ERIVEDGE when coadministered with such agents
is not likely to compensate for the loss of exposure.
When ERIVEDGE is coadministered with a proton pump inhibitor, H2-receptor
antagonist or antacid, systemic exposure of vismodegib may be decreased
and the effect on efficacy of ERIVEDGE is unknown.
4. Effects of Vismodegib on Other Drugs
Results of a drug-drug interaction study conducted in cancer patients demonstrated
that the systemic exposure of rosiglitazone (a CYP2C8 substrate) or oral contraceptives
(ethinyl estradiol and norethindrone) is not altered when either drug is co-administered
with vismodegib.
I
Indication:
ERIVEDGE (vismodegib) capsule for oral use
Initial U.S. Approval: 2012
Drug Name- Erivedge
Active Ingredient - Visomodegib
To treat adult patients with basal cell carcinoma the most common
type of skin cancer
Indication-
To treat adult patients with basal cell carcinoma the most common
type of skin cancer
Approved by FDA on 30-1-2012 (Ref- FDA Approved List- 2012)
Adverse Reaction:
The most common adverse reactions (incidence of . 10%) are muscle spasms,
alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite,
constipation, arthralgias, vomiting, and ageusia.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Embryo-fetal death and severe birth defects: ERIVEDGE can cause embryo-fetal
death or severe birth defects.
Blood donation: Advise patients not to donate blood or blood products while
receiving ERIVEDGE and for at least 7 months after the last dose of ERIVEDGE.
Dosages/ Overdosage Etc:
Indication-
To treat adult patients with basal cell carcinoma the most common
type of skin cancer
INDICATIONS AND USAGE
ERIVEDGE. (vismodegib) capsule is a hedgehog pathway inhibitor indicated 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.
DOSAGE AND ADMINISTRATION
The recommended dose is 150 mg orally once daily.
DOSAGE FORMS AND STRENGTHS
150 mg capsules.
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Advise patients that ERIVEDGE 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%) while taking ERIVEDGE and
for at least 7 months after the last dose of ERIVEDGE.
Instruct all male patients, even those with prior vasectomy, to use condoms
with spermicide, during sexual intercourse with female partners while taking
ERIVEDGE and for at least 2 months after the last dose of ERIVEDGE.
Instruct patients to immediately contact their healthcare provider if they
(or, for males, their female partner) become pregnant or if pregnancy
is suspected following exposure to ERIVEDGE.
Instruct patients to immediately report any pregnancy exposure to ERIVEDGE
and encourage participation in the ERIVEDGE pregnancy
pharmacovigilance program by calling the Genentech.
.
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Vismodegib is an inhibitor of the Hedgehog pathway. Vismodegib binds to and inhibits
Smoothened, a transmembrane protein involved in Hedgehog signal transduction.
2. Pharmacokinetics
Absorption
Vismodegib is a highly permeable compound with low aqueous solubility
(BCS Class 2). The single dose absolute bioavailability of vismodegib
is 31.8%. Absorption is saturable as evidenced by the lack of dose proportional
increase in exposure after a single dose of 270 mg or 540 mg vismodegib.
ERIVEDGE capsule may be taken without regard to meals because the
systemic exposure of vismodegib at steady state is not affected by food.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
ERIVEDGE capsule can cause fetal harm when administered to a pregnant female based
on its mechanism of action. Vismodegib is teratogenic in rats at doses corresponding
to an exposure of 20% of the exposure at the recommended human dose
2. Nursing Mothers
It is not known whether vismodegib is excreted in human breast milk. Because many
drugs are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from ERIVEDGE, 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.
3. 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.
4. 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
Manufacturer Details