Mekinist

As monotherapy or in combination w/ dabrafenib for the treatment of unresectable or metastatic melanoma w/ BRAF V600 mutation in adults. In combination w/ dabrafenib for the adjuvant treatment of stage III melanoma w/ BRAF V600 mutation in adults, following complete resection. In combination w/ dabrafenib for the treatment of advanced NSCLC w/ BRAF V600 mutation in adults.

2 mg once daily.

Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meals. Swallow w/ a full glass of water, do not chew/crush. Take at the same time every day. When taken in combination w/ dabrafenib, the once-daily dose of trametinib should be taken at the same time each day w/ either the morning dose or the evening dose of dabrafenib.

Hypersensitivity.

Efficacy & safety have not been evaluated in patients whose melanoma tested -ve for BRAF V600 mutation. Trametinib monotherapy has not demonstrated clinical activity in patients w/ BRAF V600 mutation +ve unresectable or metastatic melanoma who have progressed on prior BRAF inhibitor therapy. Limited data in patients taking trametinib in combination w/ dabrafenib who have progressed on prior BRAF inhibitor. Risk of new malignancies (cutaneous & non-cutaneous); haemorrhage; decreased left ventricular ejection fraction (LVEF); pyrexia; HTN; ILD or pneumonitis; disorders associated w/ visual disturbance, including retinal pigment epithelial detachment (RPED), retinal vein occlusion (RVO), uveitis, iridocyclitis; rash; rhabdomyolysis; renal failure; pancreatitis; hepatic events; pulmonary embolism or DVT; severe cutaneous adverse reactions, including SJS & DRESS; colitis & GI perforation; sarcoidosis; haemophagocytic lymphohistiocytosis; tumour lysis syndrome. Increased risk of haemorrhage w/ concomitant use of antiplatelet or anticoagulant therapy. Caution in patients w/ impaired left ventricular function. Safety of use is unknown in patients w/ left ventricular dysfunction, NYHA class II, III, or IV heart failure, acute coronary syndrome w/in past 6 mth, clinically significant uncontrolled arrhythmias, & uncontrolled HTN. Evaluate LVEF in all patients prior to treatment initiation, 1 mth after treatment initiation, & then at approx 3-mthly intervals while on treatment. Interrupt therapy if patient's temp is ≥38°C. Measure BP at baseline & monitor during treatment. Not recommended in patients w/ history of RVO. Safety has not been established in patients w/ predisposing factors for RVO, including uncontrolled glaucoma or ocular HTN, uncontrolled HTN, uncontrolled DM, or history of hyperviscosity or hypercoagulability syndromes. Prompt ophthalmological assessment is recommended in case of new visual disturbances at any time while on therapy. Monitor liver function every 4 wk for 6 mth after treatment initiation & thereafter as clinically indicated. Caution in patients w/ risk factors for GI perforation, including history of diverticulitis, GIT metastases & concomitant use of medicinal products w/ recognised risk of GI perforation. Minor influence on ability to drive & use machines. Caution in patients w/ severe renal impairment; moderate or severe hepatic impairment. Female patients of reproductive potential must use effective contraception during treatment & for 16 wk after stopping treatment. Use w/ dabrafenib may render hormonal contraceptives less effective. Do not administer to pregnant women & breast-feeding mothers. May impair fertility. Safety & efficacy in childn & adolescents <18 yr have not been established.

Monotherapy: HTN, haemorrhage; cough, dyspnoea; diarrhoea, nausea, vomiting, constipation, abdominal pain, dry mouth; rash, dermatitis acneiform, dry skin, pruritus, alopecia; fatigue, peripheral oedema, pyrexia; increased AST. Folliculitis, paronychia, cellulitis, rash pustular; anaemia; hypersensitivity; dehydration; peripheral neuropathy (including sensory & motor neuropathy); blurred vision, periorbital oedema, visual impairment; left ventricular dysfunction, decreased ejection fraction, bradycardia; lymphoedema; pneumonitis; stomatitis; erythema, palmar-plantar erythrodysaesthesia syndrome, skin fissures, chapped skin; face oedema, mucosal inflammation, asthenia; increased ALT, blood alkaline phosphatase & blood creatine phosphokinase. In combination w/ dabrafenib: 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, peripheral oedema, 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; peripheral neuropathy (including sensory & motor neuropathy); blurred vision, 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.

Possible increased levels w/ strong P-gp inhibitors (eg, verapamil, cyclosporine, ritonavir, quinidine, itraconazole). May result in transient inhibition of BCRP substrates (eg, pitavastatin) in the gut. Food has effect on trametinib absorption.

Targeted Cancer Therapy

L01EE01 - trametinib ; Belongs to the class of mitogen-activated protein kinase (MEK) inhibitors. Used in the treatment of cancer.

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