Tafinlar

Dabrafenib mesilate

Monotherapy or in combination w/ trametinib for the treatment of adult patients w/ unresectable or metastatic melanoma w/ a BRAF V600 mutation. In combination w/ trametinib for the adjuvant treatment of adult patients w/ Stage III melanoma w/ BRAF V600 mutation, following complete resection. In combination w/ trametinib for the treatment of adult patients w/ advanced NSCLC w/ a BRAF V600 mutation.

150 mg bd.

Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meal. Swallow whole w/ water, do not chew/open. Do not mix w/ food or liqd. Take at the same time each day. When dabrafenib & trametinib are taken in combination, the once-daily dose of trametinib should be taken at the same time each day w/ either the morning or evening dose of dabrafenib.

Hypersensitivity.

Do not use in patients w/ wild-type BRAF melanoma or wild-type BRAF NSCLC. Consider other treatment options before initiating dabrafenib/trametinib combination in patients who have progressed on a prior BRAF inhibitor. Risk of new cutaneous & non-cutaneous malignancies. Reports of ophthalmologic reactions, including uveitis, iridocyclitis & iritis. Routinely monitor for visual signs & symptoms (eg, change in vision, photophobia & eye pain) during therapy. Reports of fever. Interrupt therapy if patient's temp is ≥38°C. Reports of granulomatous nephritis. Routinely monitor for serum creatinine during therapy. Reports of pancreatitis. Avoid concomitant use w/ potent CYP2C8 & CYP3A4 inducers; medicinal products that are sensitive substrates of certain metabolising enzymes or transporters. Caution when co-administered w/ warfarin; digoxin. Minor influence on the ability to drive & use machines. Caution in patients w/ severe renal impairment; moderate or severe hepatic impairment. Women of childbearing potential must use effective contraception during therapy & for 2 wk following discontinuation of dabrafenib & 16 wk following the last dose of trametinib when given in combination w/ dabrafenib. May decrease efficacy of hormonal contraceptives. May impair male & female fertility. Should not be administered to pregnant women unless potential benefit to the mother outweighs possible risk to the foetus. Discontinue breast-feeding or discontinue dabrafenib during lactation, taking into account the benefit of breast-feeding for the child & the benefit of therapy for the woman. Safety & efficacy have not been established in childn & adolescents <18 yr. In combination w/ trametinib: Risk of haemorrhage; retinal vein occlusion & retinal pigment epithelial detachment; left ventricular ejection fraction reduction/left ventricular dysfunction; hepatic adverse events; HTN; ILD/pneumonitis; rash; rhabdomyolysis; DVT/pulmonary embolism; severe cutaneous adverse reactions, including SJS & DRESS; colitis & GI perforation; sarcoidosis; haemophagocytic lymphohistiocytosis. Monitor liver function every 4 wk for 6 mth after treatment initiation w/ trametinib, & as clinically indicated thereafter.

Monotherapy: Papilloma; decreased appetite; headache; cough; nausea, vomiting, diarrhoea; hyperkeratosis, alopecia, rash, palmar-plantar erythrodysaesthesia syndrome; arthralgia, myalgia, pain in extremity; pyrexia, fatigue, chills, asthenia. Cutaneous squamous cell carcinoma, seborrhoeic keratosis, acrochordon (skin tags), basal cell carcinoma; hypophosphataemia, hyperglycaemia; constipation; dry skin, pruritus, actinic keratosis, skin lesion, erythema, photosensitivity; flu-like illness. In combination w/ trametinib: Nasopharyngitis; decreased appetite; headache, dizziness; HTN, haemorrhage; cough; abdominal pain, constipation, diarrhoea, nausea, vomiting; dry skin, pruritus, rash, erythema; arthralgia, myalgia, pain in extremity, muscle spasms; fatigue, chills, asthenia, oedema peripheral, pyrexia, flu-like illness; increased ALT & AST. UTI, cellulitis, folliculitis, paronychia, rash pustular; cutaneous squamous cell carcinoma, papilloma, seborrhoeic keratosis; neutropenia, anaemia, thrombocytopenia, leukopenia; dehydration, hyponatraemia, hypophosphataemia, hyperglycaemia; vision blurred, visual impairment, uveitis; decreased ejection fraction; hypotension, lymphoedema; dyspnoea; dry mouth, stomatitis; dermatitis acneiform, actinic keratosis, night sweats, hyperkeratosis, alopecia, palmar-plantar erythrodysaesthesia syndrome, skin lesion, hyperhidrosis, panniculitis, skin fissures, photosensitivity; mucosal inflammation, face oedema; increased blood alkaline phosphatase, γ-glutamyltransferase, blood creatine phosphokinase.

Increased conc w/ strong CYP2C8 or CYP3A4 inhibitors eg, ketoconazole, gemfibrozil, nefazodone, clarithromycin, ritonavir, saquinavir, telithromycin, itraconazole, voriconazole, posaconazole, atazanavir. Decreased conc w/ potent CYP2C8 or CYP3A4 inducers eg, rifampicin, phenytoin, carbamazepine, phenobarb or St. John's wort. Reduced plasma levels of substrates of CYP3A4, CYP2Cs, CYP2B6, UGT or transporter (eg, Pgp or MRP-2). Decreased exposure of oral midazolam, digoxin, warfarin.

Targeted Cancer Therapy

L01EC02 - dabrafenib ; Belongs to the class of B-Raf serine-threonine kinase (BRAF) inhibitors. Used in the treatment of cancer.

P₁S₁S₃