Dabrafenib is a targeted therapy drug that is used to treat melanoma and non-small cell lung cancer that have a specific mutation (V600E or V600K) in the BRAF gene. This drug belongs to a class of medications called kinase inhibitors.

Dabrafenib Mesylate (Tafinlar) is a mutant BRAF-kinase inhibitor that is used as monotherapy or in combination with Trametinib (Mekinist) for the treatment of melanoma and other malignancies like anaplastic thyroid carcinoma and metastatic non-small cell lung cancer.

Dabrafenib (Tafinlar) Uses:

• Melanoma:
  • Used for the adjuvant treatment of melanoma (in combination with trametinib) in patients with a BRAF V600E or BRAF V600K mutation ( detected by an approved test), and lymph node involvement, following complete resection.
  • Used for the treatment of unresectable or metastatic melanoma in patients with a BRAF V600E mutation (single-agent therapy) or in patients with BRAF V600E or BRAF V600K mutations (in combination with trametinib);
  • confirm BRAF V600E or BRAF V600K mutation status with an approved test prior to treatment.
• Non-small cell lung cancer, metastatic:
  • Used for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients with BRAF V600E mutation as detected by an approved test (in combination with trametinib).
• Thyroid cancer, anaplastic, locally advanced or metastatic:
  • Used for the treatment of locally advanced or metastatic anaplastic thyroid cancer (ATC) (in combination with trametinib) in patients with BRAF V600E mutation and with no satisfactory locoregional treatment options.
  • Limitations of use: for patients having wild-type BRAF melanoma, wild-type BRAF NSCLC, or wild-type BRAF ATC, Trametinib is not indicated for the treatment of those patients.

Dabrafenib (Tafinlar) Dose in Adults

Note: Before starting the treatment, make sure to check if the patient has the BRAF V600 mutation.

Dabrafenib (Tafinlar) Dose in the treatment of Melanoma, adjuvant treatment (with BRAF V600E or BRAF V600K mutation):

• For treating melanoma (with specific BRAF V600E or V600K changes), take Dabrafenib as a pill: 150 mg two times a day (about every 12 hours).
• Combine it with trametinib.
• Keep taking this for up to 1 year unless the cancer gets worse or there are bad side effects.

Dabrafenib (Tafinlar) Dose in the treatment of metastatic or unresectable melanoma (with BRAF V600E mutation):

• For treating advanced melanoma (with a specific BRAF V600E change) that has spread or can't be surgically removed: Take Dabrafenib as a pill, 150 mg two times a day (about every 12 hours).
• Take it by itself.
• Keep taking it until the cancer gets worse or if there are bad side effects.

Dabrafenib (Tafinlar) Dose in the treatment of metastatic or unresectable melanoma (with BRAF V600E or BRAF V600K mutation):

• For treating advanced melanoma (with BRAF V600E or V600K changes) that has spread or can't be removed by surgery: Take Dabrafenib as a pill, 150 mg two times a day (roughly every 12 hours).
• Use it with trametinib.
• Keep taking both until the cancer gets worse or if there are strong side effects.

Dabrafenib (Tafinlar) Dose in the treatment of metastatic non-small cell lung cancer (with BRAF V600E mutation):

• For treating advanced non-small cell lung cancer (with a BRAF V600E change): Take Dabrafenib as a pill, 150 mg two times a day (about every 12 hours).
• Combine it with trametinib.
• Keep taking both until the cancer worsens or if there are severe side effects.

Dabrafenib (Tafinlar) Dose in the treatment of locally advanced or metastatic anaplastic Thyroid cancer (with BRAF V600E mutation):

• For treating advanced thyroid cancer (with a BRAF V600E change) that's spread or grown into nearby areas: Take Dabrafenib as a pill, 150 mg two times a day (roughly every 12 hours).
• Use it together with trametinib.
• Keep taking both until the cancer gets worse or if bad side effects happen.

If you forget a dose:

• If there's more than 6 hours until your next dose, you can take the missed one.
• But if it's less than 6 hours until the next dose, skip the missed one and don't try to make up for it.

Use in Children:

Not indicated.

Dabrafenib (Tafinlar) Pregnancy Category: N

• Dabrafenib might harm an unborn baby if taken by a pregnant woman, based on how it works and animal studies
• Women who can become pregnant should use a strong non-hormone birth control while on this medicine and for 2 weeks after stopping if using only dabrafenib, or 4 months if combined with trametinib
• Regular birth control pills might not work properly with this treatment
• Also, for men, this drug might affect the production of sperm, as seen in animal tests
• It's a good idea for men to discuss family planning and their ability to have children before starting the medicine.

Use of Dabrafenib while breastfeeding

• We're not sure if dabrafenib gets into breast milk
• But because there's a chance it could seriously harm a breastfeeding baby, the maker of the medicine advises not to breastfeed while taking it and for 2 weeks after stopping if only using dabrafenib, or 4 months if also using trametinib.

Dabrafenib (Tafinlar) Dose in Kidney Disease:

• If your kidney function is good (GFR ≥30 mL/minute/1.73 m), you don't need to change the dose.

• If your kidney function is poor (GFR <30 mL/minute/1.73 m), the medicine's label doesn't give specific dose changes because it hasn't been studied enough in this situation.

Dabrafenib (Tafinlar) Dose in Liver disease:

• If you have a mild problem with how your liver works, you can take the usual dose.
• But if you have a moderate to serious liver problem, the medicine's label doesn't tell how to adjust the dose because it hasn't been tested enough. But, since the liver mainly handles the drug, those with bigger liver issues might have more of the drug in their system.

Common Side Effects of Dabrafenib (Tafinlar):

• Cardiovascular:
  • Hypertension
  • Peripheral Edema
• Central Nervous System:
  • Headache
  • Chills
• Dermatologic:
  • Hyperkeratosis
  • Skin Rash
  • Alopecia
  • Palmarplantar Erythrodysesthesia
  • Xeroderma
• Endocrine & Metabolic:
  • Hyperglycemia
  • Hypophosphatemia
  • Hypoalbuminemia
  • Hyponatremia
• Gastrointestinal:
  • Nausea
  • Diarrhea
  • Abdominal Pain
  • Vomiting
  • Constipation
• Hematologic & Oncologic:
  • Anemia
  • Lymphocytopenia
  • Papilloma
  • Neutropenia
  • Hemorrhage
  • Malignant Neoplasm Of Skin
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Aspartate Aminotransferase
• Neuromuscular & Skeletal:
  • Arthralgia
  • Myalgia
  • Back Pain
• Respiratory:
  • Cough
• Miscellaneous:
  • Fever

Less Common Side Effects Of Dabrafenib (Tafinlar):

• Cardiovascular:
  • Cardiomyopathy
• Central Nervous System:
  • Dizziness
• Gastrointestinal:
  • Pancreatitis
  • Gastrointestinal Hemorrhage
• Hematologic & Oncologic:
  • Thrombocytopenia
  • Basal Cell Carcinoma
  • Malignant Neoplasm
  • Malignant Melanoma
• Hypersensitivity:
  • Hypersensitivity
• Ophthalmic:
  • Uveitis
• Renal:
  • Interstitial Nephritis
• Respiratory:
  • Nasopharyngitis
• Miscellaneous:
  • Febrile Reaction

Contraindications to Dabrafenib (Tafinlar):

• The U.S. label doesn't list any reasons not to take the drug.

• But in Canada, you shouldn't take it if you're allergic to dabrafenib or any part of the medicine.

Warnings and precautions

Cardiomyopathy

• Heart muscle problems (cardiomyopathy) can happen when using dabrafenib alone or with trametinib.
• Before starting the combo treatment, and then every 2 to 3 months during treatment, check the heart's pumping ability.
• If there are heart issues, you might need to pause dabrafenib (and check trametinib's guidelines for any changes needed there).
• For some, the heart problem went away after adjusting the dose, taking a break, or stopping the drug completely.

Dermatologic toxicities:

• Skin problems (like rashes, redness, or even conditions that cause hand and foot discomfort) can happen when using dabrafenib with trametinib.
• These issues also occur when using just trametinib.
• Some people had to go to the hospital because of severe skin problems or infections.
• Watch for skin issues and signs of infection.
• Depending on how bad it is, you might need to pause the treatment, take a smaller dose, or stop the medicine.

Febrile reactions

• Sometimes, serious fevers and fever-related issues like low blood pressure, shaking, dehydration, and kidney problems can happen with dabrafenib, either alone or with trametinib.
• If your fever is 38.5°C (101.3°F) or higher or if you have a serious fever with other problems, stop dabrafenib treatment.
• Check for signs of infection and kidney function.
• You might need to take less medicine or stop it.
• If you get fevers again, corticosteroids can help if your temperature doesn't get back to normal in 3 days, or if the fever causes issues like dehydration or low blood pressure.

Hemorrhage

• Bleeding, sometimes in important areas like the brain or stomach, can happen when using dabrafenib alone or with trametinib.
• Some serious bleedings have even caused death.
• If this happens, you might need to pause the treatment or take a smaller dose.
• Stop dabrafenib (and trametinib) for the worst bleeding events or if a serious bleeding doesn't get better after pausing the drug.

Hyperglycemia

• High blood sugar can happen when using dabrafenib, whether on its own or with trametinib.
• If this occurs, you might need to start or increase diabetes medicines like insulin.
• If you already have diabetes or high blood sugar, check your blood sugar levels before starting and during the treatment as needed.

Malignancy

• Certain skin cancers and new melanomas were seen more often in people using just dabrafenib compared to those on other treatments in studies.
• Some patients got these more than once.
• Using dabrafenib with trametinib reduced the chance of these skin cancers.
• Some lung cancer patients also got these skin cancers.
• Even though it's rare, basal cell skin cancer happened too, sometimes more than once for a patient.
• Before starting the drug, get a skin check, then every 2 months while on the drug, and for 6 months after stopping.
• There have been a few cases of cancers in other parts of the body with the combined treatment.
• Look out for signs of these.
• If you get a certain type of non-skin cancer with a RAS mutation, stop dabrafenib for good, but you don't need to change the trametinib dose.

Ocular toxicities:

• Some eye problems can happen when using dabrafenib with trametinib, like parts of the retina detaching
• This might affect your central vision
• If you notice vision problems, see an eye doctor within a day
• You don't need to change the dabrafenib dose for this, but trametinib might need adjustment
• Get regular eye checks during the combo treatment
• Uveitis, which affects the middle part of the eye, can also happen with these drugs
• If you experience symptoms like eye pain, light sensitivity, or vision changes, use eye drops and see a doctor
• This could require a break from dabrafenib or stopping it, but trametinib doesn't have to change.

Extension of QT

• Using dabrafenib, alone or with trametinib, can sometimes cause the heart's QT interval to lengthen, which might lead to heart rhythm problems
• This is rare but be careful if you're already at risk for irregular heartbeats.

Venous thromboembolism

• When using dabrafenib with trametinib, there's a chance of blood clots forming in veins, which can be deadly
• These clots and lung problems from clots happen more often with the combo treatment
• If you feel short of breath, have chest pain, or swelling in an arm or leg, get medical help fast
• For simple blood clots, you can keep using dabrafenib
• But if there's a very serious clot in the lungs, stop using trametinib for good.

Dabrafenib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

General Checks:

• Mutation Status: Confirm BRAFV600K or V600E before treatment.
• Blood Sugar: Keep an eye on sugar levels, especially if you have diabetes or high sugar.
• Electrolytes and Kidney: Check salt levels and kidney function.
• Skin Checks: Examine the skin before starting, every 2 months during treatment, and 6 months after stopping to look for new skin cancers.
• Fever and Infections: Look out for high temperatures and signs of infections.
• Eye Issues: Watch for eye pain, sensitivity to light, and vision changes.
• Other Symptoms: Check for signs of anemia, skin problems (and related infections), and cancers outside the skin.

For Combination with Trametinib:

• Liver Check: Monitor liver function.
• Blood Check: Look at the complete blood count regularly.
• Heart Check: Test heart function (LVEF) at the start, after 1 month, and then every 2-3 months.
• Bleeding & Clots: Look out for signs of heavy bleeding and blood clots.
• Lung Issues: Watch for symptoms of lung problems.
• Eye Problems: Check for RPED or issues with retinal veins.

Always: Make sure patients are taking their medicine as directed.

How to administer Dabrafenib (Tafinlar)?

• Take the pill by mouth.
• Make sure to take it 1 hour before eating or 2 hours after eating.
• Doses should be spaced out by about 12 hours.
• Don't open, crush, or break the capsules.
• If you're taking it with trametinib, take trametinib's once-a-day dose at the same time every day. This can be with either the morning or evening dose of dabrafenib.

Mechanism of action of Dabrafenib (Tafinlar):

• Dabrafenib targets mutated forms of a protein called B-raf (BRAF).
• Certain mutations in the BRAF gene (like V600) cause it to stay active all the time, leading to abnormal cell growth.
• Dabrafenib blocks this abnormal growth by stopping the overactive BRAF.
• Dabrafenib on its own slows down cancer cell growth by hitting this target.

Combination with Trametinib:

• Dabrafenib is even more effective when combined with trametinib.
• Together, they strongly block a pathway called MAPK, which is critical for cancer cell growth.
• This combo works especially well in melanoma with BRAF V600 mutations, causing the cells to die.
• In lung cancer with the same mutation, this combo also stops cell growth significantly.

In short, dabrafenib hampers mutated BRAF, while combining it with trametinib boosts its effects against cancer cells.

Absorption:

• It's best not to take with a high-fat meal (like one with ~1,000 calories and 58 to 75 grams of fat) because the body takes in less of the drug.

Distribution:

• It spreads out in the body, occupying about 70.3 L of space.

Binding:

• It tightly sticks to plasma proteins at a rate of 99.7%.

Metabolism:

• The liver changes it into its active form called hydroxy-dabrafenib through enzymes CYP2C8 and CYP3A4. This active form is further changed to another active form, desmethyl-dabrafenib, by the CYP3A4 enzyme.

Bioavailability:

• About 95% of the drug gets into the body's circulation after it's taken orally.

Half-life:

• The original drug lasts about 8 hours in the body. The first active form (hydroxy-dabrafenib) stays around for 10 hours. The second active form (desmethyl-dabrafenib) remains for 21 to 22 hours.

Peak Time:

• The drug reaches its highest level in the body in 2 hours. A high-fat meal can delay this peak.

Excretion:

• The body gets rid of it mostly through feces (71%) and a bit in urine (23%), but only the changed forms, not the original drug.

International Brand Names of Dabrafenib:

• Tafinlar

Dabrafenib Brands Names in Pakistan: 

Not available.