Vemurafenib

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

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.

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.

Distributed by: Genentech USA, Inc., A Member of the Roche Group,1 DNA Way, South San Francisco, CA 94080-4990. Revised: Aug 2016

Included as part of the "PRECAUTIONS" Section

Avoid exposure to sunlight or tanning beds. Vemurafenib can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Vemurafenib is part of the drug class:

• Protein kinase inhibitors

• Take vemurafenib exactly as your healthcare provider tells you. Do not change your dose or stop vemurafenib unless your healthcare provider tells you.
• Vemurafenib is taken in the morning and in the evening, about 12 hours apart.
• Take vemurafenib with or without a meal.
• Swallow the tablets whole with a glass of water. Do not chew or crush vemurafenib tablets.
• If you miss a dose, 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.
• Do not take 2 doses of vemurafenib at the same time.
• If you take too much vemurafenib, call your healthcare provider right away.

If you take too much vemurafenib call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If vemurafenib is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Avoid exposure to sunlight or tanning beds. Vemurafenib can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

General

• Distribution of vemurafenib is restricted; drug is available only through designated specialty pharmacies.12 Specific information available from the manufacturer at or at 1-888-249-4918.12

• Confirm presence of BRAF V600E mutation prior to initiation of therapy.1

Administration

Oral Administration

Administer orally twice daily without regard to meals.1

Do not crush or chew tablets.1

If a dose is missed, it may be taken up to 4 hours prior to next dose.1 Do not take 2 doses at the same time.1

If vomiting occurs following administration, do not take a replacement dose.1 Administer next dose at regularly scheduled time.1

Dosage

Adults

960 mg twice daily.1 Clinical studies continued therapy for as long as the patient derived clinical benefit or until unacceptable toxicity occurred.1

If intolerable grade 2 or 3 toxicity occurs, temporarily interrupt vemurafenib therapy.1 When toxicity resolves or improves to grade 1 or less, resume therapy at a reduced dosage of 720 mg twice daily.1

If toxicity recurs at a dosage of 720 mg twice daily, temporarily interrupt therapy again until toxicity resolves to grade 1 or less, and resume therapy at a reduced dosage of 480 mg twice daily.1

If grade 4 toxicity occurs, permanently discontinue or temporarily interrupt therapy until toxicity resolves to grade 1 or less, and resume therapy at a reduced dosage of 480 mg twice daily if clinically appropriate.1

If toxicity recurs at a reduced dosage of 480 mg twice daily, permanently discontinue vemurafenib.1 Dosages <480 mg twice daily not recommended.1

If the corrected QT interval (QTc) is >500 msec, temporarily interrupt vemurafenib therapy.1

When QTc interval returns to ≤500 msec, resume therapy at a reduced dosage.1

If QTc interval >500 msec and increases >60 msec from baseline despite correction of electrolyte abnormalities and control of other risk factors (e.g., CHF, bradyarrhythmias), permanently discontinue vemurafenib.1

No dosage adjustment necessary.1

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No initial dosage adjustment required.1

Renal Impairment

Mild or moderate renal impairment: No initial dosage adjustment required.1

Geriatric Patients

No specific dosage adjustment recommendations at this time.1

Vemurafenib is a moderate inhibitor of CYP1A2, and a weak inhibitor of 2D6 in vivo.1 Vemurafenib inhibits CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 in vitro.1 The drug also is an inhibitor and substrate of CYP3A4.1

Vemurafenib is a substrate and inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Possible pharmacokinetic interaction (increased plasma concentrations of vemurafenib).1 Avoid concomitant use; selection of alternative drug with no or minimal CYP3A4 inhibition potential recommended.1

CYP3A4 inducers: Possible pharmacokinetic interaction (decreased plasma concentrations of vemurafenib).1 Avoid concomitant use; selection of alternative drug with no or minimal CYP3A4 induction potential recommended.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A2: Possible pharmacokinetic interaction (increased plasma concentrations of CYP1A2 substrate and possible toxicity).1 Concomitant use of vemurafenib and CYP1A2 substrates with a narrow therapeutic index not recommended.1 If concomitant use cannot be avoided, consider dosage reduction of the CYP1A2 substrate and closely monitor for adverse effects.1

Substrates of CYP2D6: Possible pharmacokinetic interaction (increased plasma concentrations of CYP2D6 substrate and possible toxicity).1

Substrates of CYP3A4: Possible pharmacokinetic interaction (decreased plasma concentrations of CYP3A4 substrate and possible decreased efficacy).1

Substrates of CYP2C9: Possible pharmacokinetic interaction (increased plasma concentrations of CYP2C9 substrate and possible toxicity).1

Substrates of CYP2C19: No clinically important interaction reported.1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT prolongation).1 Avoid concomitant use.1 4 (See Prolongation of QT Interval under Cautions.)

Specific Drugs

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair loss.
• Muscle or joint pain.
• Back pain.
• Itching.
• Headache.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Change in taste.
• Feeling tired or weak.
• Not hungry.
• Cough.
• Dry skin.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time vemurafenib is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take vemurafenib or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to vemurafenib. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Mild to moderate impairment (preexisting): No dosage adjustment necessary.

Severe impairment (preexisting): There are no dosage adjustments provided in the manufacturer's labeling (data are insufficient to determine if dosage adjustment is necessary); use with caution.

Nephrotoxicity/creatinine abnormalities during treatment: Refer to dosage adjustment for toxicity and manage with dose reduction, treatment interruption, or discontinuation.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C and 30°C (59°F and 86°F). Store in the original container with the lid tightly closed.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.