Vemurafenibum

Vemurafenibum Uses, Dosage, Side Effects, Food Interaction and all others data.

Vemurafenibum is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E. It exerts its function by binding to the ATP-binding domain of the mutant BRAF. Vemurafenibum 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.

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. Vemurafenibum has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity. All the different reports indicate thet Vemurafenibum generates an almost complete inhibition of the MAPK pathway.

Trade Name Vemurafenibum
Availability Prescription only
Generic Vemurafenib
Vemurafenib Other Names Vemurafenib, Vémurafénib, Vemurafenibum
Related Drugs Keytruda, pembrolizumab, Opdivo, nivolumab, ipilimumab, Yervoy, Zelboraf
Type
Formula C23H18ClF2N3O3S
Weight Average: 489.922
Monoisotopic: 489.072546264
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.

Groups Approved
Therapeutic Class
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Vemurafenibum
Vemurafenibum

Uses

Vemurafenibum is 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.

Vemurafenibum 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. The V600E mutation, a substitution of glutamic acid for valine, accounts for 54% of the cases of cutaneous melanoma. Vemurafenibum approval was extended in 2017, for its use as a treatment of adult patients with Erdheim-Chester Disease whose cancer cells present BRAF V600 mutation. Erdheim-Chester disease is an extremely rare histiocyte cell disorder that affects large bones, large vessels, central nervous system, as well as, skin and lungs. It is reported an association of Erdheim-Chester disease and V600E mutation.

Vemurafenibum is also used to associated treatment for these conditions: Metastatic Melanoma, Unresectable Melanoma, Refractory Erdheim-Chester disease, Refractory Non-small cell lung cancer

How Vemurafenibum works

Vemurafenibum 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. Vemurafenibum blocks downstream processes to inhibit tumour growth and eventually trigger apoptosis. Vemurafenibum does not have antitumour effects against melanoma cell lines with the wild-type BRAF mutation.

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.

Food Interaction

  • Do not take with or immediately after a high-fat meal. Taking vemurafenib with a high-fat meal may increase the AUC and Cmax by approximately 5 fold and 2.5 fold, respectively.
  • Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of vemurafenib, which may increase its serum concentration.
  • Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of vemurafenib and may reduce its serum concentration.
  • Limit caffeine intake. Vemurafenibum inhibits CYP1A2, which may increase the serum levels and adverse effects of caffeine.
  • Take with or without food.

Volume of Distribution

The estimation of the volume of distribution for Vemurafenibum is 106 L.

Elimination Route

Vemurafenibum is well absorbed after oral administration. Peak concentrations are reached in 3 hours when an oral dose of 960 mg twice daily for 15 days has been given to patients. In the same conditions, Vemurafenibum presents a Cmax of 62 mcg/ml and AUC of 601 mcg h/ml. It is unknown how food affects the absorption of vemurafenib. It presents an accumulation ratio of 7.36 after repeating doses of 960 mg

Half Life

The elimination half-life of Vemurafenibum is estimated to be 57 hours (range of 30-120 hours).

Clearance

The total body clearance is 31 L/day.

Elimination Route

Analysis showed that 94% of administered Vemurafenibum is excreted via feces and 1% is excreted by urine.

Innovators Monograph

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*** Taking medicines without doctor's advice can cause long-term problems.
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