Dabrafenib

About Dabrafenib

• The US FDA approved dabrafenib on May 29, 2013. 
• Dabrafenib is a kinase inhibitor prescribed as a monotherapy for treating patients with unresectable or metastatic melanoma carrying the BRAF V600E mutation. 
• In combination with trametinib, Dabrafenib is indicated for patients with unresectable or metastatic melanoma harboring BRAF V600E or V600K mutations, based on demonstrated durable response rates. 
• However, there is no evidence of improved disease-related symptoms or overall survival with Dabrafenib in combination with trametinib. 
• It is important to note that Dabrafenib is not intended for treating patients with wild-type BRAF melanoma. 
• Dabrafenib is a cancer growth blocker targeting specific proteins produced by the mutated BRAF gene, inhibiting the growth of cancer cells.

Strength: 

Dabrafenib capsules are available in strengths of 50 mg and 75 mg. 

Recommended Dosage:

Before commencing treatment with Dabrafenib as a standalone therapy, ensure the presence of the BRAF V600E mutation in tumor specimens. Similarly, prior to initiating treatment with Dabrafenib in combination with trametinib, confirm the presence of BRAF V600E or V600K mutation in tumor specimens.

• The recommended dosage regimens for Dabrafenib are as follows: 150 mg orally taken twice daily, approximately 12 hours apart, when used as a single agent, and 150 mg orally taken twice daily, approximately 12 hours apart, in combination with trametinib 2 mg orally taken once daily. 
• Treatment should be continued until disease progression or unacceptable toxicity occurs. Take Dabrafenib, either as a single agent or in combination with trametinib, at least 1 hour before or 2 hours after a meal. 
• Do not take a missed dose of Dabrafenib within 6 hours of the next scheduled dose, and avoid opening, crushing, or breaking the Dabrafenib capsule. 
• When used in combination with trametinib, the once-daily dose of trametinib should be taken at the same time each day, aligning with either the morning or evening dose of Dabrafenib.

No dose modifications are required for new primary cutaneous malignancies. However, for new primary non-cutaneous malignancies, Dabrafenib should be permanently discontinued in patients who develop RAS mutation-positive non-cutaneous malignancies. If Dabrafenib is used in combination with trametinib and patients develop non-cutaneous malignancies, there is no need for dose modifications for trametinib. 

• The recommended dose reductions for Dabrafenib, whether administered alone or with trametinib, include a first dose reduction to 100 mg orally twice daily, a second dose reduction to 75 mg orally twice daily, and a third dose reduction to 50 mg orally twice daily. 
• Subsequently, Dabrafenib should be permanently discontinued if a patient is unable to tolerate 50 mg orally twice daily. 
• For trametinib administered in combination with Dabrafenib, the recommended dose reductions involve a first dose reduction to 1.5 mg orally once daily, a second dose reduction to 1 mg orally once daily, and permanent discontinuation if unable to tolerate trametinib 1 mg orally once daily.

Important: 

It is advisable to refrain from the simultaneous use of potent inhibitors of CYP3A4 or CYP2C8, as well as strong inducers of CYP3A4 or CYP2C8, in conjunction with Dabrafenib. Additionally, the concurrent administration of agents sensitive to CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6 should be avoided to prevent any potential loss of efficacy for these agents. Careful consideration and monitoring are essential to ensure the appropriate management of drug interactions.

Adhering to protocols is crucial in Dabrafenib treatment. Healthcare providers must monitor and address adverse reactions promptly. Regular follow-ups and open communication ensure a responsible approach. Before starting the treatment inform your doctor about all the pre existing condition to about adverse effects. 

Warnings & Precaution:

• When administering Dabrafenib as a single agent or in combination with trametinib, it is crucial to monitor patients for the occurrence of new malignancies before the initiation of therapy, during treatment, and after discontinuation of Dabrafenib or the combination therapy. 
• Increased cell proliferation can occur with BRAF inhibitors, posing a risk of tumor promotion in BRAF wild-type melanoma. 
• Additionally, major hemorrhagic events, venous thromboembolism, cardiomyopathy, ocular toxicities, serious febrile reactions, serious skin toxicity, hyperglycemia, and glucose-6-phosphate dehydrogenase deficiency are potential risks associated with Dabrafenib, especially in combination with trametinib. 
• Healthcare providers should carefully monitor for signs and symptoms related to these adverse events, conducting regular assessments to ensure patient safety. Discontinuation and appropriate management should be considered in cases of intolerable skin toxicity or other severe adverse reactions.

Common Dabrafenib Side Effects:

• Hyperkeratosis
• Headache
• Pyrexia
• Arthralgia
• Papilloma
• Alopecia
• Palmar-plantar erythrodysesthesia syndrome
• Pyrexia
• Chills
• Fatigue
• Rash
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Peripheral edema
• Cough
• Headache
• Arthralgia
• Night sweats
• Decreased appetite
• Constipation
• Myalgia

Use in Specific Population

• Dabrafenib, based on its mechanism of action, poses a risk of fetal harm when administered to pregnant women. 
• The presence of this drug in human milk is unknown, and considering the potential for severe adverse reactions in nursing infants, a decision should be made regarding whether to discontinue nursing or cease the drug, considering its importance to the mother. 
• The safety and efficacy of Dabrafenib in pediatric patients have not been established. 
• Female patients of reproductive potential are advised to use highly effective contraception during treatment and for at least 2 weeks after the last dose of Dabrafenib or at least 4 months after the last dose of Dabrafenib taken with trametinib. 
• Non-hormonal contraception is recommended due to the potential impact of Dabrafenib on the effectiveness of hormonal contraceptives. 
• In case of pregnancy or suspicion of pregnancy during Dabrafenib treatment, patients should contact their healthcare provider. 
• Female patients are informed that Dabrafenib in combination with trametinib may affect fertility. 
• Effects on spermatogenesis have been observed in male animals, and male patients are advised on the potential risk of impaired spermatogenesis, seeking counseling on fertility and family planning options before starting Dabrafenib treatment. 
• Dose adjustment is not recommended for patients with mild hepatic or renal impairment, and appropriate doses have not been established for patients with moderate to severe hepatic or renal impairment.

Storage and Handling

• Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F). 
• Store the capsule in its original container. 
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.