Dabrafenib

What is Dabrafenib?

• Dabrafenib (Tafinlar) is a kinase inhibitor is a medication used for the treatment of cancers associated with a mutated version of the gene BRAF.

What are the uses of this medicine?

This medicine is used: alone or in combination with a medicine called trametinib 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
• that has a certain type of abnormal “BRAF” gene.

• in combination with trametinib, to help prevent melanoma that has a certain type of abnormal “BRAF” gene from coming back after the cancer has been removed by surgery.

• in combination with trametinib to treat a type of lung cancer called non-small cell lung cancer (NSCLC):
• that has spread to other parts of the body, and
• that has a certain type of abnormal “BRAF” gene.

• in combination with trametinib to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):
• that has spread to other parts of the body and you have no satisfactory treatment options and
• that has a certain type of abnormal “BRAF” gene

How does this medicine work?

• Dabrafenib is an inhibitor of some mutated forms of BRAF kinases.
• Dabrafenib also inhibits wild-type BRAF and CRAF kinases.
• Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo.
• Dabrafenib and trametinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Use of dabrafenib and trametinib in combination resulted in greater growth inhibition of BRAF V600 mutation-positive tumor cell lines in vitro and prolonged inhibition of tumor growth in BRAF V600 mutation positive tumor xenografts compared with either drug alone.

Who Should Not Use this medicine ?

Limitations of Use:

• Tafinlar is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF NSCLC, or wild-type BRAF ATC.

What drug interactions can this medicine cause?

• Avoid concurrent administration of strong inhibitors of CYP3A4 or CYP2C8.
• Concomitant use with agents that are sensitive substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6 may result in loss of efficacy of these agents.

Is this medicine FDA approved?

• FDA approved this drug in the year of 2013.

How should this medicine be used?

• Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with Tafinlar as a single agent.
• Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with Tafinlar and trametinib'

Recommended Dosage: Recommended Dosage for Unresectable or Metastatic Melanoma

• The recommended dosage of Tafinlar is 150 mg orally taken twice daily, as a single agent or in combination with trametinib, until disease progression or unacceptable toxicity.

Recommended Dosage for the Adjuvant Treatment of Melanoma

• The recommended dosage of Tafinlar is 150 mg orally taken twice daily in combination with trametinib until disease recurrence or unacceptable toxicity for up to 1 year.

Recommended Dosage for NSCLC

• The recommended dosage of Tafinlar is 150 mg orally taken twice daily, in combination with trametinib until disease recurrence or unacceptable toxicity.

Recommended Dosage for ATC

• The recommended dosage of Tafinlar is 150 mg orally taken twice daily, in combination with trametinib until disease recurrence or unacceptable toxicity. '

Administration

• Take Tafinlar exactly as your healthcare provider tells you. Do not change your dose or stop Tafinlar unless your healthcare provider tells you.
• Your healthcare provider may change your dose of Tafinlar, temporarily stop, or completely stop your treatment with Tafinlar if you develop certain side effects.
• Take Tafinlar 2 times a day, about 12 hours apart.
• Take Tafinlar at least 1 hour before or 2 hours after a meal.
• Do not open, crush, or break Tafinlar capsules.
• If you miss a dose of Tafinlar, take it as soon as you remember. If it is within 6 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 Capsules: 50 mg, 75 mg

This medicine is available in fallowing brand namesː

• Tafinlar

What side effects can this medication cause?

The most common side effects of Tafinlar when taken alone include:

• thickening of the outer layers of the skin
• warts
• headache
• hair loss
• fever
• redness, swelling, peeling, or tenderness of hands or feet
• joint aches

The most common side effects of Tafinlar when taken with trametinib in people with melanoma that has spread to other parts of the body or cannot be removed by surgery include:

• fever
• chills
• rash
• joint aches
• headache
• cough

The most common side effects of Tafinlar when taken with trametinib to help prevent melanoma from coming back after the cancer has been removed by surgery include:

• fever
• chills
• fatigue
• diarrhea
• nausea
• vomiting
• headache
• joint aches
• rash
• muscle aches

The most common side effects of Tafinlar when taken with trametinib in people with NSCLC include:

• fever
• rash
• fatigue
• swelling of face, arms, and legs
• nausea
• chills
• vomiting
• bleeding
• diarrhea
• cough
• dry skin
• shortness of breath
• decreased appetite

Tafinlar may cause serious side effects, including:

• Risk of new cancers
• bleeding problems
• heart problems
• eye problems
• fever
• serious skin reactions
• increased blood sugar (hyperglycemia)

What special precautions should I follow?

• New Primary Malignancies, Cutaneous, and Non-cutaneous can occur when Tafinlar is administered as a single agent or with trametinib. Monitor patients for new malignancies prior to, or while on therapy, and following discontinuation of treatment.
• Increased cell proliferation can occur with BRAF inhibitors.
• Major hemorrhagic events can occur in patients receiving Tafinlar with trametinib. Monitor for signs and symptoms of bleeding.
• Assess left ventricular ejection fraction (LVEF) before treatment with Tafinlar and trametinib, after one month of treatment, then every 2 to 3 months thereafter.
• Across clinical trials, uveitis occurred in 1% of patients who received Tafinlar monotherapy and in 2% of patients who received Tafinlar administered with trametinib. Perform ophthalmologic evaluation for any visual disturbances.
• Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration, or renal failure, can occur with Tafinlar. Incidence and severity of pyrexia are increased with Tafinlar and trametinib.
• Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with Tafinlar administered with trametinib. Monitor for skin toxicities. Discontinue for intolerable Grade 2 or for Grade 3 or 4 rash not improving within 3 weeks despite interruption of Tafinlar. Permanently discontinue for severe cutaneous adverse reactions (SCARs).
• Monitor serum glucose levels upon initiation and as clinically appropriate when Tafinlar is administered in patients with preexisting diabetes or hyperglycemia.
• Tafinlar, which contains a sulfonamide moiety, confers a potential risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Monitor patients with G6PD deficiency for signs of hemolytic anemia while taking Tafinlar.
• Tafinlar can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of potential risk to a fetus and to use an effective non-hormonal method of contraception.

What to do in case of emergency/overdose?

• There is no information on overdosage of Tafinlar.

Management of Overdose

• Since dabrafenib is highly bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with Tafinlar.

Can this medicine be used in pregnancy?

• Tafinlar can cause fetal harm when administered to a pregnant woman.
• There is insufficient data in pregnant women exposed to Tafinlar to assess the risks.

Can this medicine be used in children?

• The safety and effectiveness of Tafinlar as a single agent or with trametinib have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: dabrafenib
• Inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose
• Capsule shells: hypromellose, red iron oxide (E172), titanium dioxide (E171).

Who manufactures and distributes this medicine?

• Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

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

• Store Tafinlar at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Tafinlar and all medicine out of the reach of children.

• Dailymed label info on Dabrafenib
• FDA Dabrafenib

Dabrafenib Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

Dabrafenib Resources
Latest articles Most recent articles Ongoing trials	Wikipedia