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

Contraindications

  • Hypersensitivity:
    • false
  • Regions: US

Food Interactions

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

Interactions

Type in a drug name to check for interaction with Vismodegib
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Vismodegib.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Vismodegib.
Abatacept
The metabolism of Vismodegib can be increased when combined with Abatacept.
Abemaciclib
Vismodegib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abiraterone
The metabolism of Vismodegib can be decreased when combined with Abiraterone.
Acenocoumarol
The metabolism of Acenocoumarol can be decreased when combined with Vismodegib.
Acetohexamide
The metabolism of Acetohexamide can be decreased when combined with Vismodegib.
Acetyl sulfisoxazole
The metabolism of Vismodegib can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acid
The metabolism of Acetylsalicylic acid can be decreased when combined with Vismodegib.
Adalimumab
The metabolism of Vismodegib can be increased when combined with Adalimumab.
Afatinib
Vismodegib may decrease the excretion rate of Afatinib which could result in a higher serum level.
Afelimomab
The metabolism of Vismodegib can be increased when combined with Afelimomab.
Agomelatine
The metabolism of Vismodegib can be decreased when combined with Agomelatine.
Albendazole
The metabolism of Albendazole can be decreased when combined with Vismodegib.
Allopurinol
Vismodegib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Almotriptan
The metabolism of Almotriptan can be decreased when combined with Vismodegib.
Alosetron
The metabolism of Alosetron can be decreased when combined with Vismodegib.
Alpelisib
The serum concentration of Alpelisib can be increased when it is combined with Vismodegib.
Alprazolam
The metabolism of Alprazolam can be decreased when combined with Vismodegib.
Alvocidib
Vismodegib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
2 References
  1. 1 . Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.PubMed: 19726763
  2. 2 . Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628.PubMed: 23662017