Class: Biological Therapy

Generic Name:Dabrafenib
Trade Name:TAFINLAR^®

For which conditions is this drug approved? TAFINLAR isindicated as a single agent for the treatment of patients with unresectable (unable to be removed with surgery) or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test. TAFINLAR is also indicated in combination with MEKINIST® (trametinib) for the treatment of patients with unresectable or metastatic melanoma with a confirmed BRAF V600E or V600K mutation.

What is the mechanism of action? TAFINLAR is a kinase inhibitor. These drugs work by blocking the action of enzymes called kinases, which are involved in many cell functions, including cell signaling, growth, and division. These enzymes may be too active or found at high levels in some types of cancer cells, and blocking them may help keep cancer cells from growing. Specifically, TAFINLAR targets BRAF V600 kinases, which may be involved in cancer cell growth in metastatic melanoma.

How is TAFINLAR typically given (administered)?TAFINLAR should only be given as a single agent to patients with a BRAF V600E mutation that’s been confirmed through laboratory testing and in combination with MEKINIST in patients with confirmed BRAF V600E or V600K mutation. As a single agent, the recommended dose of TAFINLAR is 150 mg orally twice daily. In combination with MEKINIST, the recommended dose is 2 mg orally once daily. TAFINLAR should be taken at least 1 hour before or at least 2 hours after a meal.

How are patients typically monitored?Patients should be monitored for new malignancies before, after, and during treatment; tumor growth; symptoms of bleeding; blood clotting; heart and eye problems; fever; skin infection; and hyperglycemia (high blood sugar).

What are the common (occur in 20% or more of patients) side effects of treatment with TAFINLAR as a single agent?

• Hyperkeratosis (thickening of the outer layer of the skin)
• Headache
• Joint pain
• Papilloma (noncancerous tumor in the skin or mucous membrane)
• Alopecia (hair loss)
• Palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome) (redness, swelling, pain, and occasionally blisters on the palms of the hands and/or the soles of the feet)

What are the common (occur in 20% or more of patients) side effects of treatment with TAFINLAR in combination with MEKINIST?

• Fever
• Chills
• Fatigue
• Rash
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Peripheral edema
• Cough
• Headache
• Joint pain
• Night sweats
• Decreased appetite
• Constipation
• Pain in a muscle or group of muscles 

This is not a complete list of side effects. Some patients may experience other side effects that are not listed here. Patients may wish to discuss with their physician the other less common side effects of this drug, some of which may be serious.

Some side effects may require medical attention. Other side effects do not require medical attention and may go away during treatment. Patients should check with their physician about any side effects that continue or are bothersome.

What can patients do to help alleviate or prevent discomfort and side effects? Tell your doctor if you have or have had any medical condition, with special attention to the following:

• Bleeding problems or blood clots
• Heart problems
• Eye problems
• Liver or kidney problems
• Diabetes
• A deficiency of the glucose-6-phosphate dehydrogenase (G6PD) enzyme (an inherited condition that can put you at risk for hemolytic anemia)
• You plan to have surgery, dental, or other medical procedures
• You are pregnant or plan to become pregnant

Take TAFINLAR one time a day exactly as your healthcare provider tells you to take it. Swallow capsules whole; don’t open, crush, or break them. Do not change your dose or stop TAFINLAR unless your healthcare provider tells you to do so. If you miss a dose, take it as soon as you remember. If it is within 12 hours of your next scheduled dose, skip the missed dose and take the next dose at your regular time. If you take too much TAFINLAR, call your healthcare provider or go to the nearest hospital emergency room right away.

Are there any special precautions patients should be aware of before starting treatment? TAFINLAR can harm your unborn baby, and women who are able to become pregnant should use effective birth control during treatment and for two weeks after stopping treatment with TAFINLAR alone or for four months when taking TAFINLAR in combination with MEKINIST.Be aware that birth control using hormones (such as birth control pills, injections, or patches) may not work as well with TAFINLAR, so use a non-hormonal effective method of birth control. Tell you doctor if you are breastfeeding or plan to breastfeed; because it is not known if TAFINLAR passes into your breast milk, you should not take this drug while breastfeeding.

When should patients notify their physician?

Tell your doctor if you experience any side effects that bother you or don’t go away. Also call your healthcare provider right away if:

• You have symptoms of severe high blood sugar, such as increased thirst urinating more often than normal, or urinating an increased amount of urine.
• You have symptoms of a heart problem, including feeling like your heart is pounding or racing, shortness of breath, swelling of your ankles and feet, or feeling lightheaded.
• You have signs of a blood clot, including chest pain, sudden shortness of breath or trouble breathing, pain in your legs with or without swelling, swelling in your arms or legs, a cool or pale arm or leg
• You have unusual signs of bleeding, such as: headaches or dizziness; if you feel weak, cough up blood or blood clots, vomit blood; your vomit looks like coffee grounds; or your stools red or black stools and look like tar
• You have signs of eye problems, including: blurred vision; loss of vision; or other vision changes; seeing color dots, a halo (a blurred outline around objects); eye pain; swelling; or redness
• You any new lesions, changes to existing lesions on their skin, or other signs and symptoms of malignancies (including warts, moles, and sores).
• You have symptoms of a type of anemia called hemolytic anemia where the body does not have enough healthy red blood cells (a risk in people with G6PD deficiency). Signs of anemia or breakdown of red blood cells include: yellow skin (jaundice), weakness or dizziness, and shortness of breath.
• You develop a fever.

What is a package insert?

A package insert is required by the FDA and contains a summary of the essential scientific information needed for the safe and effective use of the drug for healthcare providers and consumers.  A package insert typically includes information regarding specific indications, administration schedules, dosing, side effects, contraindications, results from some clinical trials, chemical structure, pharmacokinetics and metabolism of the specific drug. By carefully reviewing the package insert, you will get the most complete and current information about how to safely use this drug. If you do not have the package insert for the drug you are using, your pharmacist or physician may be able to provide you with a copy.