Dabrafenib

Dabrafenib is a prescription medication used to treat the symptoms of Melanoma, Non-Small Cell Lung Cancer, and locally advanced or metastatic Thyroid Cancer. Dabrafenib may be used alone or with other medications.

• Dabrafenib is available under the following different brand names: Tafinlar 

Common side effects of Dabrafenib include:

• Headache,
• Muscle or joint pain,
• Bleeding,
• Fever,
• Chills,
• Tiredness,
• Dry skin,
• Thickened skin,
• Warts,
• Rash,
• Swelling in the legs, arms, and face,
• Redness, swelling, peeling, or tenderness of hands or feet,
• Nausea,
• Vomiting,
• Diarrhea,
• Decreased appetite,
• Cough,
• Shortness of breath, and
• Hair loss

Serious side effects of Dabrafenib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Little or no urination,
• Fever,
• Chills,
• Lightheadedness,
• Shortness of breath,
• Pale or yellowed skin,
• Dark-colored urine,
• Fever,
• Confusion,
• Weakness,
• Eye pain or swelling,
• Vision changes,
• Seeing halos around lights,
• Seeing color “dots” in your vision,
• Severe skin rash,
• Skin pain or swelling,
• Redness and peeling skin on the hands or feet,
• Increased thirst or urination,
• Dizziness,
• Headache,
• Bloody or tarry stools,
• Coughing up blood,
• Vomit that looks like coffee grounds,
• Pounding heartbeats, and
• Swelling in your feet or ankles

Rare side effects of Dabrafenib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule

• 50 mg
• 75 mg

Melanoma

Adult dosage

• BRAF V600E mutation-positive unresectable or metastatic melanoma
  • Indicated as a single agent
  • 150 mg orally two times a day
• BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma
  • Indicated, in combination with trametinib
  • 150 mg orally two times a day plus trametinib 2 mg orally once a day
• Adjuvant treatment of BRAF V600E or V600K mutation-positive melanoma
  • Indicated in combination with trametinib when lymph node(s) involved following complete resection
  • 150 mg orally two times a day plus trametinib 2 mg orally once a day

Non-Small Cell Lung Cancer

Adult dosage

• BRAF V600E mutation-positive
  • Indicated in combination with trametinib
  • 150 mg orally two times a day plus trametinib 2 mg orally once a day

BRAF V600E mutation-positive

• Indicated, in combination with trametinib, for locally advanced or metastatic anaplastic thyroid cancer (ATC) in adults with no satisfactory locoregional treatment options
• 150 mg orally two times a day plus trametinib 2 mg orally once a day

Thyroid Cancer, Locally Advanced or Metastatic

Adult dosage

• Indicated, in combination with trametinib, for locally advanced or metastatic anaplastic thyroid cancer (ATC) in adults with no satisfactory locoregional treatment options
• 150 mg orally two times a day plus trametinib 2 mg orally once a day
• BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors

Adult dosage

• 150 mg orally two times a day plus trametinib 2 mg orally once a day
• Continue until disease recurrence or unacceptable toxicity

Pediatric dosage

• Children below 6 years OR below 26 kg: Safety and efficacy not established
• Children above 6 years and above or equal to 26 kg
• 26-37 kg: Dabrafenib 75 mg orally two times a day with trametinib 1 mg orally once a day
• 38-50 kg: Dabrafenib 100 mg orally two times a day with trametinib 1.5 mg orally once a day
• Above 51 kg: Dabrafenib 150 mg orally two times a day with trametinib 2 mg orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Dabrafenib has severe interactions with the following drugs:
  • cariprazine
  • cobimetinib
  • doravirine
  • elbasvir/grazoprevir
  • fostemsavir
  • isavuconazonium sulfate
  • lefamulin
  • lonafarnib
  • lorlatinib
  • lumacaftor/ivacaftor
  • mavacamten
  • naloxegol
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • panobinostat
  • praziquantel
  • regorafenib
  • tacrolimus ointment
• Dabrafenib has serious interactions with at least 147 other drugs.
• Dabrafenib has serious interactions with at least 280 other drugs.
• Dabrafenib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dabrafenib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dabrafenib?”

Cautions

• Also, see Dosage Modifications
• Increases incidence of cutaneous squamous cell carcinoma, keratoacanthoma, and new incidence melanoma; perform dermatologic evaluations before initiation of therapy, every 2 months while on treatment, and for up to 6 months following discontinuation
• BRAF inhibitors may cause paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells; confirm evidence of BRAF V600E mutation status before initiation
• Based on its mechanism of action, dabrafenib may promote the growth and development of malignancies with activation of RAS through mutation or other mechanisms
• Hemorrhage, including major hemorrhages, can occur when used in combination with trametinib; permanently discontinue therapy for all Grade 4 hemorrhagic events and for any Grade 3 hemorrhagic events that do not improve; withhold therapy for Grade 3 hemorrhagic events; if improved, resume at next lower dose level
• Venous thromboembolism can occur when used in combination with trametinib
• Serious febrile reactions and fever of any severity complicated by hypotension, rigors, or chills reported
• Hyperglycemia reported; monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia; initiate or optimize anti-hyperglycemic medications as clinically indicated
• Contains a sulfonamide moiety which increases the risk of hemolytic anemia in patients with G6PD deficiency
• Based on its mechanism of action, dabrafenib can cause fetal harm; advise females of the reproductive potential of the potential risk to a fetus
• Febrile reactions
  • Incidence and severity of pyrexia are increased when dabrafenib is administered with trametinib compared with dabrafenib as a single agent
  • Withhold dabrafenib when used as monotherapy, and with trametinib when used in combination, if the patient’s temperature is greater than or equal to 100.4°F
  • In case of recurrence, therapy can be interrupted at the first symptom of pyrexia; fever may be complicated by hypotension, rigors or chills, dehydration, or renal failure; evaluate for signs and symptoms of infection, and monitor serum creatinine and other evidence of renal function during and following severe pyrexia
  • Dabrafenib, or both dabrafenib and trametinib when used in combination, may be restarted if the patient has recovered from the febrile reaction for at least 24 hours, either at the same or lower dose
  • Administer antipyretics as secondary prophylaxis when resuming dabrafenib if the patient had a prior episode of severe febrile reaction or fever associated with complications
  • Administer corticosteroids (. g, prednisone 10 mg daily) for at least 5 days for second or subsequent pyrexia if the temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications, such as dehydration, hypotension, renal failure or severe chills/rigors, and there is no evidence of active infection
• Skin toxicity
  • Risk of serious skin toxicity including rash, dermatitis, acneiform rash, palmar-plantar erythrodysesthesia syndrome, and erythema
  • Withhold treatment for intolerable or severe skin toxicity
  • Resume treatment at a lower dose in patients with improvement or recovery from skin toxicity within 3 weeks
  • Permanently discontinue therapy for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS) if skin toxicity not improved within 3 weeks
• Uveitis
  • Uveitis, iritis, and retinal pigment epithelial detachment (RPED) reported; monitor patients routinely for visual symptoms
  • If iritis is diagnosed, administer ocular therapy, and continue therapy without dose modification
  • If severe uveitis (. e., iridocyclitis) or if mild or moderate uveitis does not respond to ocular therapy, withhold treatment and treat as clinically indicated
  • Resume treatment at the same or lower dose if improves to Grade 0 or 1
  • Permanently discontinue therapy for persistent Grade 2 or greater uveitis of above 6 weeks
• Cardiomyopathy
  • Risk increases when used as a single agent or with trametinib
  • Reassess LVEF after 1 month of treatment and then approximately every 2-3 months thereafter
  • Withhold therapy for symptomatic cardiomyopathy or asymptomatic LV dysfunction of above 20% from baseline that is below the institutional lower limit of normal (LLN)
  • Resume treatment at the same dose level upon recovery of cardiac function to at least the institutional LLN for LVEF and an absolute decrease of 10% compared to baseline
• Drug interaction overview
  • Dabrafenib may render hormonal contraceptives less effective, and an alternative method of contraception should be used
  • Coadministration with potent inhibitors or inducers of CYP3A4 or CYP2C8 is not recommended
  • Drugs that increase gastric pH may decrease dabrafenib concentrations
  • Dabrafenib inhibits certain CYP isoenzymes; concomitant use with drugs that are sensitive substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6 may result in loss of efficacy of these drugs

Pregnancy and Lactation

• Verify pregnancy status in females of reproductive potential before initiating therapy
• Based on data from animal studies and its mechanism of action, it can cause fetal harm when administered to pregnant women
• Dabrafenib was teratogenic and embryotoxic in rats at doses three times greater than the human exposure
• Contraception
  • Advise female patients of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose
  • Counsel patients to use a nonhormonal method of contraception since dabrafenib can render hormonal contraceptives ineffective
  • To avoid potential drug exposure to pregnant partners and female partners of reproductive potential, advise male patients (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment and for at least 2 weeks after the last dose
• Infertility
  • Females: Advise female patients of reproductive potential that dabrafenib may impair fertility
  • Males: Advise male patients of the potential risk for impaired spermatogenesis which may be irreversible
• Lactation
  • Data are not available regarding the presence in human milk, effects on breastfed infants, or effects on milk production
  • Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 2 weeks after the last dose