TAFINLAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAFINLAR (TAFINLAR).
TAFINLAR (dabrafenib) is a selective inhibitor of BRAF V600E, V600K, and V600D mutant kinases, leading to inhibition of the MAPK pathway and reduced cell proliferation in BRAF-mutant tumors.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4; forms active metabolites (hydroxy-dabrafenib and desmethyl-dabrafenib) via CYP3A4. |
| Excretion | Primarily metabolized, with 45% of the dose recovered in feces and 32% in urine (mostly as metabolites). Unchanged drug accounts for <1% in urine and <2% in feces. |
| Half-life | Terminal elimination half-life is approximately 8.2 hours (range 5.6–11.2 hours) following oral administration, supporting twice-daily dosing. |
| Protein binding | 99.7% bound to human plasma proteins, primarily to albumin (99.4%) and alpha-1-acid glycoprotein (98.1%). |
| Volume of Distribution | Mean apparent volume of distribution (Vd/F) is 78.4 L (approximately 1.1 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability is approximately 70% after oral administration. Food (high-fat meal) reduces Cmax by 51% and AUC by 24%; therefore, take consistently with respect to food. |
| Onset of Action | Not defined for clinical effect; pharmacodynamic effects (pERK inhibition) observed within hours. Therapeutic response (tumor shrinkage) typically assessed after 6–8 weeks of continuous dosing. |
| Duration of Action | Sustained pERK suppression persists for at least 12 hours post-dose, consistent with twice-daily dosing interval. Clinical duration of response varies; median progression-free survival in trials approximately 6.9 months. |
150 mg orally twice daily, at least 1 hour before or 2 hours after a meal.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 75 mg twice daily. Child-Pugh C: Not recommended. |
| Pediatric use | For children ≥1 year: 150 mg/m² orally twice daily (maximum 300 mg/day) based on BSA; administer with dabrafenib. Capsules should not be opened. |
| Geriatric use | No specific dose adjustment; monitor renal function and electrolyte disturbances more frequently due to age-related physiological changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAFINLAR (TAFINLAR).
| Breastfeeding | There is no information regarding the presence of dabrafenib in human milk, its effects on the breastfed infant, or effects on milk production. Dabrafenib and its metabolites are excreted in the milk of lactating rats at concentrations 2.4- to 8.5-fold higher than in maternal plasma. The M/P ratio is not reported in humans. Due to the potential for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with TAFINLAR and for 2 weeks after the last dose. |
| Teratogenic Risk | In animals, dabrafenib (TAFINLAR) was teratogenic at exposures below human exposures at the recommended dose. In pregnant rats, dabrafenib caused embryo-fetal toxicity including post-implantation loss, reduced fetal weight, and visceral and skeletal malformations. Fetal malformations included absent or small kidney, anophthalmia/microphthalmia, and dilated cerebral ventricles. In rabbits, increased post-implantation loss and reduced fetal body weight were observed. Based on its mechanism of action (RAF kinase inhibitor), dabrafenib can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy should be avoided, and if used, the patient should be apprised of potential hazard to the fetus. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to dabrafenib or any excipients"]
| Precautions | ["New primary malignancies (cutaneous and non-cutaneous) due to paradoxical MAPK activation","Hemorrhage including major bleeding events","Venous thromboembolism","Cardiomyopathy (monitor LVEF)","Serious febrile reactions (fever, rigors) requiring management","Severe dermatologic reactions (Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms)","Hyperglycemia (in diabetic patients)","Interstitial lung disease/pneumonitis","Ocular toxicities (including uveitis, retinal vein occlusion)"] |
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| Fetal Monitoring | Pregnancy status should be verified in females of reproductive potential prior to initiating TAFINLAR. Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose. Monitor for signs of fetal toxicity if exposed during pregnancy. Additionally, monitor liver function, glucose levels (due to risk of hyperglycemia), and for ocular toxicities (e.g., uveitis, retinal vein occlusion) as part of general monitoring. |
| Fertility Effects | Based on animal studies, dabrafenib may impair fertility in females. In female rats, dabrafenib disrupted estrous cycling and decreased fertility at exposures lower than human exposure at the recommended dose. Reversibility of these effects was not assessed. Effects on male fertility have not been adequately studied, but testicular degeneration was observed in dogs at clinically relevant exposures. Therefore, TAFINLAR may impair both male and female fertility. |