Description

Simple

A medication used to treat patients with a rare condition called Erdheim-Chester Disease and a type of skin cancer called melanoma.

Clinical

A kinase inhibitor used to treat patients with Erdheim-Chester Disease who have the BRAF V600 mutation, and melanoma in patients who have the BRAF V600E mutation.

Overview

Vemurafenib is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E.[2] It exerts its function by binding to the ATP-binding domain of the mutant BRAF.[3] Vemurafenib was co-developed by Roche and Plexxikon and it obtained its FDA approval on August 17, 2011, under the company Hoffmann La Roche. After approval, Roche in collaboration with Genentech launched a broad development program. [8]

Pharmacology

Indication

Vemurafenib is approved since 2011 for the treatment of metastatic melanoma with a mutation on BRAF in the valine located in the exon 15 at codon 600, this mutation is denominated as V600E.[ Read more

Pharmacodynamic

BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to redu... Read more

Mechanism of action

Vemurafenib is an orally available inhibitor of mutated BRAF-serine-threonine kinase. Vemurafenif is a small molecule that interacts as a competitive inhibitor of the mutated species of BRAF. It is especially potent against the BRAF V600E mutation. Vemurafenib blocks downstream processes to inhibit... Read more

Absorption

Vemurafenib is well absorbed after oral administration.[6] Peak concentrations are reached in 3 hou... Read more

Protein binding

Vemurafenib highly binds to plasma proteins where >99% of the administered dose will be found protein bound to serum albumin and alpha-1 acid glycoprotein.[ Read more

Volume of distribution

The estimation of the volume of distribution for Vemurafenib is 106 L.[ Read more

Clearance

The total body clearance is 31 L/day.[ Read more

Half life

The elimination half-life of Vemurafenib is estimated to be 57 hours (range of 30-120 hours).[ Read more

Route of elimination

Analysis showed that 94% of administered Vemurafenib is excreted via feces and 1% is excreted by urine.[ Read more

Toxicity

In the few toxicity reports, it has been shown an increased in the development of cutaneous squamous cell carcinomas or acceleration in pre-existant tumor growth.[FDA label]

Adverse Effects

Contraindications

  • Hypersensitivity:
    • false
  • Regions: US

Food Interactions

    Information currently not available.

Interactions

Type in a drug name to check for interaction with Vemurafenib
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Vemurafenib.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Vemurafenib.
2,4-thiazolidinedione
The therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Vemurafenib.
3,5-diiodothyropropionic acid
The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Vemurafenib.
3,5-Diiodotyrosine
The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Vemurafenib.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Vemurafenib.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Vemurafenib.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Vemurafenib.
6-O-benzylguanine
The serum concentration of 6-O-benzylguanine can be increased when it is combined with Vemurafenib.
8-azaguanine
The serum concentration of 8-azaguanine can be increased when it is combined with Vemurafenib.
8-chlorotheophylline
The serum concentration of 8-chlorotheophylline can be increased when it is combined with Vemurafenib.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Vemurafenib.
9-Deazaguanine
The serum concentration of 9-Deazaguanine can be increased when it is combined with Vemurafenib.
9-Methylguanine
The serum concentration of 9-Methylguanine can be increased when it is combined with Vemurafenib.
Abaloparatide
The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Vemurafenib.
Abemaciclib
Vemurafenib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Abexinostat
The risk or severity of QTc prolongation can be increased when Abexinostat is combined with Vemurafenib.
Acarbose
The therapeutic efficacy of Acarbose can be increased when used in combination with Vemurafenib.
Acebutolol
The risk or severity of QTc prolongation can be increased when Acebutolol is combined with Vemurafenib.
Acefylline
The serum concentration of Acefylline can be increased when it is combined with Vemurafenib.
10 References
  1. 1 . Jordan EJ, Kelly CM: Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43. doi: 10.1517/14656566.2012.737780. Epub 2012 Oct 24.PubMed: 23094782
  2. 2 . Kim G, McKee AE, Ning YM, Hazarika M, Theoret M, Johnson JR, Xu QC, Tang S, Sridhara R, Jiang X, He K, Roscoe D, McGuinn WD, Helms WS, Russell AM, Miksinski SP, Zirkelbach JF, Earp J, Liu Q, Ibrahim A, Justice R, Pazdur R: FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation. Clin Cancer Res. 2014 Oct 1;20(19):4994-5000. doi: 10.1158/1078-0432.CCR-14-0776. Epub 2014 Aug 5.PubMed: 25096067
  3. 3 . Luke JJ, Hodi FS: Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma. Clin Cancer Res. 2012 Jan 1;18(1):9-14. doi: 10.1158/1078-0432.CCR-11-2197. Epub 2011 Nov 14.PubMed: 22083257
  4. 4 . Schirosi L, Strippoli S, Gaudio F, Graziano G, Popescu O, Guida M, Simone G, Mangia A: Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients? BMC Cancer. 2016 Nov 18;16(1):905.PubMed: 27863476
  5. 5 . Stempel JM, Bustamante Alvarez JG, Carpio AM, Mittal V, Dourado C: Erdheim-Chester disease, moving away from the orphan diseases: A case report. Respir Med Case Rep. 2016 Dec 3;20:55-58. eCollection 2017.PubMed: 27995058
  6. 6 . Zhang W, Heinzmann D, Grippo JF: Clinical Pharmacokinetics of Vemurafenib. Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7.PubMed: 28255850
  7. 7 . Goldinger SM, Rinderknecht J, Dummer R, Kuhn FP, Yang KH, Lee L, Ayala RC, Racha J, Geng W, Moore D, Liu M, Joe AK, Bazan SP, Grippo JF: A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma. Pharmacol Res Perspect. 2015 Mar;3(2):e00113. doi: 10.1002/prp2.113.PubMed: 25729580
  8. 8 . Roche news Link
  9. 9 . FDA News and Events Link
  10. 10 . FDA Vemurafenib application Link