What is Zelboraf and how is it used?

Zelboraf is a prescription medicine used to treat the symptoms of Malignant Melanoma, and Erdheim-Chester Disease. Zelboraf may be used alone or with other medications.

Zelboraf belongs to a class of drugs called Antineoplastics, BRAF Kinase Inhibitor.

It is not known if Zelboraf is safe and effective in children younger than 18 years of age.

What are the possible side effects of Zelboraf?

Zelboraf may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• fever,
• sore throat,
• burning in your eyes,
• skin pain,
• red or purple skin rash that spreads and causes blistering and peeling,
• swollen glands,
• muscle aches,
• severe weakness,
• unusual bruising,
• yellowing of your skin or eyes (jaundice),
• a new wart or lesion,
• skin sore or red bump that bleeds or does not heal,
• any change in the size or color of a mole,
• unusual thickening of tissues under the skin on the palms of your hands or the soles of your feet,
• finger or fingers that feel tight or are bent inward,
• fast or pounding heartbeats,
• fluttering in your chest,
• shortness of breath,
• sudden dizziness,
• vision changes,
• eye pain or swelling,
• severe eye redness,
• small white or yellow patches on the surface of your eye,
• stomach pain (upper right side),
• nausea,
• vomiting,
• loss of appetite,
• dark urine, and
• clay-colored stools

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Zelboraf include:

• joint pain,
• tiredness,
• nausea,
• hair loss,
• mild rash,
• itching,
• skin growths,
• sunburn, and
• increased sensitivity to sunlight  

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Zelboraf. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

DESCRIPTION

ZELBORAF (vemurafenib) is a kinase inhibitor available as 240 mg tablets for oral use. Vemurafenib has the chemical name propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]- 2,4-difluoro-phenyl}-amide. It has the molecular formula C₂₃H₁₈ClF₂N₃O₃S and a molecular weight of 489.9. Vemurafenib has the following chemical structure:

Vemurafenib is a white to off-white crystalline solid. It is practically insoluble in aqueous media.

Tablets of ZELBORAF are for oral administration. Each tablet contains 240 mg of vemurafenib.

The inactive ingredients of ZELBORAF are: 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.

INDICATIONS

Unresectable Or Metastatic Melanoma

ZELBORAF® is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

Limitation Of Use

ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma [see WARNINGS AND PRECAUTIONS].

Erdheim-Chester Disease

ZELBORAF® is indicated for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation.

DOSAGE AND ADMINISTRATION

Patient Selection For Treatment Of Melanoma

Confirm the presence of BRAF V600E mutation in melanoma tumor specimens prior to initiation of treatment with ZELBORAF [see WARNINGS AND PRECAUTIONS]. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at http://www.fda.gov/CompanionDiagnostics.

Recommended Dose

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.

Treat patients with ZELBORAF until disease progression or unacceptable toxicity occurs. Do not take an additional dose if vomiting occurs after ZELBORAF administration, but continue with the next scheduled dose.

Do not crush or chew the tablets.

Dose Modifications

For New Primary Cutaneous Malignancies

No dose modifications are recommended.

For Other Adverse Reactions

Permanently discontinue ZELBORAF for any of the following:

• Grade 4 adverse reaction, first appearance (if clinically appropriate) or second appearance
• QTc prolongation > 500 ms and increased by > 60 ms from pre-treatment values [see WARNINGS AND PRECAUTIONS]

Withhold ZELBORAF for NCI-CTCAE (v4.0) intolerable Grade 2 or greater adverse reactions.

Upon recovery to Grade 0–1, restart ZELBORAF at a reduced dose as follows:

• 720 mg twice daily for first appearance of intolerable Grade 2 or Grade 3 adverse reactions
• 480 mg twice daily for second appearance of Grade 2 (if intolerable) or Grade 3 adverse reactions or for first appearance of Grade 4 adverse reaction (if clinically appropriate)

Do not dose reduce to below 480 mg twice daily.

Dose Modification For Strong CYP3A4 Inducers

Avoid concomitant use of strong CYP3A4 inducers during treatment with ZELBORAF [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]. If concomitant use of a strong CYP3A4 inducer is unavoidable, increase the dose of ZELBORAF by 240 mg (one tablet) as tolerated. After discontinuation of a strong CYP3A4 inducer for two weeks, resume the ZELBORAF dose that was taken prior to initiating the strong CYP3A4 inducer.

HOW SUPPLIED

Dosage Forms And Strengths

Tablet: 240 mg.

Storage And Handling

ZELBORAF (vemurafenib) is supplied as 240 mg film-coated tablets with VEM debossed on one side. The following packaging configurations are available:

NDC 50242-090-01 single bottle of 120 count
NDC 50242-090-02 single bottle of 112 count

Storage And Stability

Store at room temperature 20°C–25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F), See USP Controlled Room Temperature. Store in the original container with the lid tightly closed.

Disposal Of Unused/Expired Medicines

The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Use established “collection systems,” if available in your location.

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

• New Primary Malignancies [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Dermatologic Reactions [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]
• Ophthalmologic Reactions [see WARNINGS AND PRECAUTIONS]
• Radiation Sensitization and Radiation Recall [see WARNINGS AND PRECAUTIONS]
• Renal Failure [see WARNINGS AND PRECAUTIONS]
• Dupuytren's Contracture and Plantar Fascial Fibromatosis [see WARNINGS AND PRECAUTIONS]