Description

Simple

A chemotherapy drug used to treat a type of cancer called basal cell carcinoma.

Clinical

A hedgehog pathway inhibitor used to treat patients with locally advanced or metastatic basal cell carcinoma.

Overview

Vismodegib inhibits the hedgehog signalling pathway and is indicated for treatment of adult basal cell carcinoma. FDA approved on Jan 30, 2012.

Pharmacology

Indication

Vismodegib is used for treating locally advanced or metastatic basal cell carcinoma in patients whose carcinoma has recurred after surgery, and in patients who are not candidates for surgery or radiation.

Pharmacodynamic

Vismodegib selectively binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.

Mechanism of action

Mutations of the Hedgehog pathway may results in uncontrolled proliferation of skin basal cells. Vismodegib binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway.

Absorption

The absolute bioavailability of a single dose is 31.8%. Absorption is saturable and is not affected by food.

Protein binding

Vismodegib is highly protein bound with plasma protein binding at about 99%. Vismodegib binds to the plasma proteins, albumin and alpha-1-acid glycoprotein (saturable bnding).

Volume of distribution

Vismodegib has a volume of distribution of 16.4 to 26.6 L.

Clearance

Information currently not available.

Half life

The half-life after a single dose is 12 days, and after continuous daily dosing is 4 days.

Route of elimination

Vismodegib is mostly excreted unchanged, and the main route of elimination is by the feces (82%) and the urine accounts for 4.4%.

Toxicity

Increased risk of embryo-fetal death and significant birth defects. Common adverse event include muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Muscle Spasms US
  • adult
  • Kind: experimental
    • Percent: 72%
  • Clinical Trial
    Alopecia US
    • adult
  • Kind: experimental
    • Percent: 64%
  • Clinical Trial
    Dysgeusia US
    • adult
  • Kind: experimental
    • Percent: 55%
  • Clinical Trial
    Weight Loss US
    • adult
  • Kind: experimental
    • Percent: 45%
  • Clinical Trial
    Fatigue US
    • adult
  • Kind: experimental
    • Percent: 40%
  • Clinical Trial
    Nausea US
    • adult
  • Kind: experimental
    • Percent: 30%
  • Clinical Trial
    Amenorrhea US
    • adult
  • Kind: experimental
    • Percent: 30%
  • Clinical Trial
    Diarrhea US
    • adult
  • Kind: experimental
    • Percent: 29%
  • Clinical Trial
    Decreased appetite US
    • adult
  • Kind: experimental
    • Percent: 25%
  • Clinical Trial
    Constipation US
    • adult
  • Kind: experimental
    • Percent: 21%
  • Clinical Trial
    Arthralgias US
    • adult
  • Kind: experimental
    • Percent: 16%
  • Clinical Trial
    Vomiting US
    • adult
  • Kind: experimental
    • Percent: 14%
  • Clinical Trial
    Ageusia US
    • adult
  • Kind: experimental
    • Percent: 11%
  • Clinical Trial
    Hyponatremia US
    • adult
  • Kind: experimental
    • Percent: 4%
  • Clinical Trial
    Elevated creatine phosphokinase (CPK) US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Unclassified
    Elevated creatine phosphokinase (CPK) US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Unclassified
    Azotemia US
    • adult
  • Kind: experimental
    • Percent: 2%
  • Clinical Trial
    Hypokalemia US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Clinical Trial
    Premature fusion of the epiphyses US
    • pediatric
    Post Marketing
    Blood creatine phosphokinase increased US
    Post Marketing

    Contraindications

    • Hypersensitivity:
      • false
    • Regions: US

    Food Interactions

    Take with or without food. Food does not affect absorption.