Company: GlaxoSmithKline.
Legal category: Prescription. High Tech. Sport permitted.
Active ingredient: Dabrafenib (as mesilate) 50mg, 75mg.
Description: Opaque, dark red or dark pink hard capsules marked GS TEW or GS LHF and strength, respectively.
Presentation: 120, price pending reimbursement.
Indication: Unresectable or metastatic melanoma with a BRAF V600 mutation.
Pharmacology: Dabrafenib is an inhibitor of RAF kinases. Oncogenic mutations in BRAF lead to constitutive activation of the RAS/RAF/MEK/ERK pathway. BRAF mutations have been identified at a high frequency in specific cancers, including approximately 50% of melanoma. The most commonly observed BRAF mutation is V600E which accounts for approximately 90% of the BRAF mutations seen in melanoma.
Dosage: Adult: 150mg twice daily at same time each day. Leave 12 hours between doses. Continue until patient no longer derives benefit or unacceptable toxicity develops. See SPC for dose reductions and modifications. Elderly: As per adults. Children: Under 18 years, safety and efficacy not established.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy (assess risk/benefit).
Special precautions: Caution: Severe renal impairment, moderate or severe hepatic impairment. Safety and efficacy not established in wild-type BRAF melanoma or in non-Caucasians. Interrupt if temperature ≥38.5°C; evaluate for signs of infection. Monitor for cutaneous squamous cell carcinoma and new primary melanomas, and non-cutaneous malignancies (head and neck exam, chest/abdomen computerised tomography scan, anal exam, pelvic exam (for women), complete blood cell counts) prior to initiation, during therapy and for up to 6 months after discontinuation or until initiation of another anti-neoplastic therapy. Monitor serum creatinine routinely; may need to interrupt if increases. Ophthalmologic reactions including uveitis and iritis reported; monitor routinely. Pancreatitis reported; investigate unexplained abdominal pain promptly. Not recommended: Uncorrectable electrolyte abnormalities (including magnesium) or long QT syndrome. Monitor electrocardiogram and electrolytes in all patients before treatment, after one month and after dose modification; further monitoring recommended in moderate to severe hepatic impairment monthly during first 3 months followed by every 3 months thereafter or more often as indicated. Women of childbearing potential must use effective methods of contraception during therapy and for 4 weeks following discontinuation. May impair male and female fertility; may cause irreversible impaired spermatogenesis. Driving/using machines. Lactation (assess risk/benefit).
Drug interactions: Not recommended: Drugs known to prolong QT interval. Avoid: Potent inducers of CYP2C8 and CYP3A4, agents that increase gastric pH. Caution: Strong inhibitors of CYP2C8 and CYP3A4, warfarin, digoxin, OATB1B1 or OATP1B3 substrates such as statins; drugs metabolised by enzymes including CYP3A4, CYP2Cs and CYP2B6 or transported by proteins including P-glycoprotein, MRP-2, BCRP and OATP1B1/1B3; analgesics, antibiotics, anticancer agents, anticoagulants, antipsychotics, calcium channel blockers, cardiac glycosides, corticosteroids, HIV antivirals, hormonal contraceptives, hypnotics, immunosuppressants, statins metabolised by CYP3A4, see SPC. Take at least one hour prior to or two hours after food.
Adverse drug reactions: Papilloma, cutaneous squamous cell carcinoma, seborrhoeic keratosis, skin tags, basal cell carcinoma, decreased appetite, hypophosphataemia, hyperglycaemia, headache, cough, GI upset, hyperkeratosis, alopecia, rash, palmar-plantar erythrodysaesthesia syndrome, dry skin, pruritus, actinic keratosis, skin lesion, erythema, arthralgia, myalgia pain in extremity, pyrexia, fatigue, chills, influenza-like illness, decreased left ventricular ejection fraction.
Full prescribing information and references available from GlaxoSmithKline. Telephone: (01) 4955000.