Vemurafenib

What is Vemurafenib?

Vemurafenib (Zelboraf) is a kinase inhibitor used to treat patients whose cancer has a certain mutation in the BRAF gene, including:

• Erdheim-Chester disease.
• Melanoma that cannot be removed by surgery or has spread to other parts of the body.

Vemurafenib structure

Vemurafenib ball-and-stick model

What are the uses of this medicine?

Vemurafenib (Zelboraf) is a prescription medicine used to treat: a type of skin cancer called melanoma that:

• has spread to other parts of the body or cannot be removed by surgery, and
• has a certain type of abnormal "BRAF" gene.

a type of blood cell cancer called Erdheim-Chester Disease (ECD) that:

• can affect body tissues and organs, and
• has a certain type of abnormal "BRAF" gene.

Limitation of Use:

• Zelboraf is not used to treat melanoma with a normal BRAF gene.

How does this medicine work?

• Vemurafenib (vem’ ue raf” e nib) is an orally available inhibitor of mutated forms of BRAF, a serine/threonine kinase that is a component of the mitogen-activated pathway (MAP) kinases which are important intracellular signals involved in control of cell growth and proliferation.
• BRAF kinase is an early step in the cascade of MAP kinases (RAS-RAF-MEK-ERK) and is frequently mutated in malignant conditions, including at least half of cases of melanoma.
• Vemurafenib was shown to be active against the V600E mutants of BRAF in vitro and in animal models.
• Furthermore, in clinical trials vemurafenib therapy was associated with an improvement in overall survival in patients with metastatic malignant melanoma with V600E mutations.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following:

• certain antifungals such as itraconazole (Onmel, Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend)
• clarithromycin (Biaxin, in PrevPac)
• certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase)
• certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Tegretol, others), phenobarbital, and phenytoin (Dilantin, Phenytek)
• nefazodone
• rifampin (Rifadin, Rimactane, in Rifamate, in Rifater)
• tizanidine
• warfarin (Coumadin, Jantoven)

Is this medicine FDA approved?

• Vemurafenib was approved for use in the United States in 2011 and current indications are for unresectable or metastatic melanoma with the BRAF V600E mutation and Langerhans-cell histiocytosis with BRAF V600 mutations.

How should this medicine be used?

• Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with Zelboraf.

Recommended dosage:

• The recommended dose of Zelboraf is 960 mg (four 240 mg tablets) orally every 12 hours with or without a meal.
• A missed dose can be taken up to 4 hours prior to the next dose.

Administration:

• Take Zelboraf every 12 hours with or without a meal.
• Do not crush or chew Zelboraf tablets.
• Do not take an additional dose of Zelboraf if you vomit after taking your scheduled dose. Take your next dose at your regular time.
• If you miss a dose of Zelboraf, take it as soon as you remember. If it is within 4 hours of your next scheduled dose, just take your next dose at your regular time. Do not make up for the missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablet: 240 mg

This medicine is available in fallowing brand namesː

• Zelboraf

What side effects can this medication cause?

The most common side effects of Zelboraf in melanoma include:

• joint pain
• rash
• hair loss
• tiredness
• sunburn or sun sensitivity
• nausea
• itching
• warts

The most common side effects of Zelboraf in Erdheim-Chester Disease include:

• joint pain
• rash
• warts
• tiredness
• hair loss
• QT prolongation

Zelboraf may cause serious side effects, including:

• Risk of new cancers
• Allergic reactions
• Severe skin reactions
• QT prolongation
• Liver injury
• Eye problems
• Kidney injury
• Connective tissue disorders

What special precautions should I follow?

• Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving Zelboraf. Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation of Zelboraf. Manage with excision and continue treatment without dose adjustment.
• Monitor patients receiving Zelboraf closely for signs or symptoms of other malignancies.
• Increased cell proliferation can occur with BRAF inhibitors. Confirm evidence of BRAF V600E mutation in tumor specimens prior to initiation of Zelboraf.
• Anaphylaxis and other serious hypersensitivity reactions can occur during treatment and upon re-initiation of treatment with Zelboraf. Permanently discontinue Zelboraf in patients who experience a severe hypersensitivity reaction.
• Severe dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur in patients receiving Zelboraf. Permanently discontinue Zelboraf in patients who experience a severe dermatologic reaction.
• Concentration-dependent QT prolongation occurred. Monitor ECG and electrolytes before and during treatment. Withhold Zelboraf for QTc of 500 ms or greater. Correct electrolyte abnormalities and control for cardiac risk factors for QT prolongation.
• Liver injury leading to functional hepatic impairment, including coagulopathy or other organ dysfunction, can occur with Zelboraf. Monitor transaminases, alkaline phosphatase, and bilirubin before initiation of treatment and monthly during treatment, or as clinically indicated.
• Mild to severe photosensitivity can occur in patients treated with Zelboraf. Advise patients to avoid sun exposure, wear protective clothing and use a broad spectrum UVA/UVB sunscreen and lip balm (SPF ≥ 30) when outdoors.
• Uveitis, blurry vision, and photophobia can occur in patients treated with Zelboraf. Monitor patients for signs and symptoms of uveitis.
• Based on its mechanism of action, Zelboraf can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception.
• Monitor patients closely when vemurafenib is administered concomitantly or sequentially with radiation treatment.
• Renal failure, including acute interstitial nephritis and acute tubular necrosis, can occur with Zelboraf. Measure serum creatinine before initiation of Zelboraf and periodically during treatment.
• Dupuytren's contracture and plantar fascial fibromatosis have been reported with Zelboraf. Events should be managed with dose reduction, treatment interruption, or treatment discontinuation.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on its mechanism of action, Zelboraf can cause fetal harm when administered to a pregnant woman.
• Advise pregnant women of the potential harm to a fetus.

Can this medicine be used in children?

• The safety and effectiveness of Zelboraf in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• vemurafenib

Inactive ingredients:

• Tablet Core: hypromellose acetate succinate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, and hydroxypropyl cellulose.
• Coating: pinkish white: poly (vinyl alcohol), titanium dioxide, polyethylene glycol 3350, talc, and iron oxide red.

Who manufactures and distributes this medicine?

Distributed by:

• Genentech USA, Inc., A Member of the Roche Group,1 DNA Way, South San Francisco, CA
• Zelboraf is a registered trademark of Genentech, Inc.

What should I know about storage and disposal of this medication?

• Store Zelboraf at room temperature between 68°F to 77°F (20°C to 25°C).
• Store Zelboraf in the original container with the lid tightly closed.

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• Dailymed label info on Vemurafenib
• FDA Vemurafenib

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