Product InformationRegistration Status: Active
TAFINLAR HARD CAPSULE 50MG is approved to be sold in Singapore with effective from 2015-08-24. It is marketed by NOVARTIS (SINGAPORE) PTE LTD, with the registration number of SIN14830P.
This product contains Dabrafenib 50mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Glaxo Operations UK Limited (trading as Glaxo Wellcome Operations) in SPAIN, andGlaxo Wellcome in UNITED KINGDOM.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Dabrafenib mesylate (Tafinlar) is a reversible ATP-competitive kinase inhibitor and targets the MAPK pathway. It was approved on May 29, 2013 for the treatment of melanoma [L2718]. In May 2018, Tafinlar (dabrafenib) and Mekinist ([DB08911]) in combination have been approved to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [L2714].
Tafinlar is a kinase inhibitor that was initially indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test [FDA label]. Tafinlar in combination with [DB08911] is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. The use in combination is based on the demonstration of durable response rate. Improvement in disease-related symptoms or overall survival has not been demonstrated for Tafinlar in combination with trametinib [FDA label]. In May 2018, Tafinlar (dabrafenib) and Mekinist ([DB08911]) have been approved in combination to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [L2712].
Mechanism of Action
Dabrafenib is an orally bioavailable inhibitor of B-raf (BRAF) protein with antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/Extracellular Signal-regulated Kinases signaling pathway, which may be constitutively activated due to BRAF gene mutations [FDA label].
- After oral administration, median time to achieve peak plasma concentration (Tmax) is 2 hours. Mean absolute bioavailability of oral dabrafenib is 95% [L2711].
- Apparent volume of distribution (Vd/F) = 70.3 L [FDA label]. Distribution to the brain is restricted because dabrafenib is a substrate and undergoes efflux by P-glycoprotein and breast cancer resistance protein [FDA label].
- Dabrafenib is metabolized in the liver. The biotransformation process of this drug is primarily regulated by _CYP2C8_ and _CYP3A4_ to form _hydroxy-debrafenib_. This metabolite is further oxidized via CYP3A4 to form _carboxy-dabrafenib_ and subsequently excreted in bile and urine. Carboxy-dabrafenib can also undergo decarboxylation to form _desmethyl-dabrafenib_, which may be reabsorbed from the gastrointestinal tract. _Desmethyl-dabrafenib_ is further metabolized by CYP3A4 to oxidative metabolites [L2711], [FDA label].
The clearance of dabrafenib is 17.0 L/h after single dosing and 34.4 L/h after 2 weeks of twice daily dosing [FDA label]
LD50 in rats is > 2000 mg/kg [MSDS]. The most common side effects of Daretinib (Tafinlar) as a single agent include: hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome [FDA label]. The most common adverse reactions (≥20%) for Tafinlar in combination with [DB08911] are pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia [FDA label]. The following is a list of toxicities that may occur with the combination of Daretinib and [DB08911]: **New primary malignancies**: These may occur when Tafinlar is administered as a single agent or in combination with [DB08911]. Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and following discontinuation of TAFINLAR or the combination therapy. Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors [FDA label]. **Hemorrhage:** Major hemorrhagic events can occur in patients receiving TAFINLAR in combination with trametinib. Monitor for signs and symptoms of bleeding [FDA label]. **Venous Thromboembolism**: Deep vein thrombosis and pulmonary embolism can occur in patients receiving the drug combination [FDA label]. **Cardiomyopathy **: Assess LVEF before treatment with TAFINLAR in combination with trametinib, after one month of treatment, then every 2 to 3 months thereafter [FDA label]. **Ocular toxicities**: Perform an ophthalmologic evaluation for any visual disturbances [FDA label]. **Serious Febrile Reactions:** Incidence and severity of pyrexia are increased with TAFINLAR in combination with trametinib [FDA label]. **Serious Skin Toxicity:** Monitor for skin toxicities and for secondary infections. Discontinue for intolerable Grade 2, or Grade 3 or 4 rash not improving within 3 weeks despite the interruption of TAFINLAR [FDA label]. **Hyperglycemia:** Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia [FDA label]. **Glucose-6-Phosphate Dehydrogenase Deficiency**: Closely monitor for hemolytic anemia [FDA label]. **Embryofetal Toxicity**: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus. TAFINLAR may render hormonal contraceptives less effective and an alternative method of contraception should be used [FDA label].
Dabrafenib | Dabrafenib |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.