Vemurafenib

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

Vemurafenib 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. 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.

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 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 Vemurafenib generates an almost complete inhibition of the MAPK pathway.

Vemurafenib
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Vemurafenib
Availability	Prescription only
Generic	Vemurafenib
Vemurafenib Other Names	Vemurafenib, Vémurafénib, Vemurafenibum
Related Drugs	Keytruda, pembrolizumab, Opdivo, nivolumab, ipilimumab, Yervoy, Zelboraf
Weight	240mg
Type	Oral tablet
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	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Vemurafenib 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.

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. The V600E mutation, a substitution of glutamic acid for valine, accounts for 54% of the cases of cutaneous melanoma. Vemurafenib 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.

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

How Vemurafenib works

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 tumour growth and eventually trigger apoptosis. Vemurafenib 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. Vemurafenib inhibits CYP1A2, which may increase the serum levels and adverse effects of caffeine.
Take with or without food.

Vemurafenib Drug Interaction

Major: doxorubicin, lithiumModerate: paclitaxel protein-bound, fentanyl, metoprolol, acetaminophenUnknown: charcoal, aspirin, bevacizumab, arginine, levocarnitine, cysteine, enoxaparin, valproic acid, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone

Vemurafenib Disease Interaction

Moderate: lung toxicity, cutaneous malignancies, dermatological reactions, hepatic impairment, QT prolongation, renal impairment, visual complications

Volume of Distribution

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

Elimination Route

Vemurafenib 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, Vemurafenib 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