Mekinist

Trametinib

Monotherapy or in combination w/ dabrafenib for unresectable or metastatic melanoma w/ BRAF V600 mutation. In combination w/ dabrafenib for advanced NSCLC w/ BRAF V600 mutation; in ped patients ≥6 yr w/ low-grade glioma (LGG) w/ BRAF V600E mutation who require systemic therapy; for adult & ped patients ≥6 yr w/ unresectable or metastatic solid tumors w/ BRAF V600E mutation who have progressed following prior treatment & no satisfactory alternative treatment options; as adjuvant treatment of stage III melanoma w/ BRAF V600E or V600K mutation & involvement of lymph node(s), following complete resection.

Duration of treatment: Unresectable or metastatic melanoma or solid tumors, or metastatic NSCLC Until disease progression or unacceptable toxicity. LGG Ped patient Until loss of clinical benefit or unacceptable toxicity. Adjuvant melanoma Max: 1 yr. Adult Monotherapy or in combination w/ dabrafenib 2 mg once daily. Dose reduction: 1st dose reduction: 1.5 mg once daily. 2nd dose reduction: 1 mg once daily. Ped patient weighing ≥51 kg 2 mg once daily, 38-50 kg 1.5 mg once daily, 26-37 kg 1 mg once daily. Dose reduction: 1 mg once daily starting dose: 1st dose reduction: 0.5 mg once daily. 1.5 mg once daily starting dose: 1st dose reduction: 1 mg once daily, 2nd dose reduction: 0.5 mg once daily. 2 mg once daily starting dose: 1st dose reduction: 1.5 mg once daily, 2nd dose reduction: 1 mg once daily.

Should be taken on an empty stomach: Take at least 1 hr before or 2 hr after meals.

Hypersensitivity.

Interrupt treatment immediately if retinal abnormality is noted. Permanently discontinue if retinal vein occlusion (RVO) occurs. W/draw treatment if signs & symptoms of severe cutaneous adverse reactions (SCARs) appear. Interrupt therapy if patient's temp is ≥38°C (100.4°F), & at 1st symptom of pyrexia in case of recurrence; if hemophagocytic lymphohistiocytosis (HLH) is suspected. Discontinue treatment if HLH is confirmed. Not recommended in patients w/ history of RVO. Hemorrhagic events including major hemorrhagic events; disorders associated w/ visual disturbances including chorioretinopathy or retinal pigment epithelial detachment & RVO; rash; SCARs including SJS & DRESS; VTE including DVT & pulmonary embolism; pyrexia; colitis & GI perforation; HLH; tumor lysis syndrome (TLS). Patients w/ conditions impairing left ventricular ejection fraction (LVEF); risk factors for GI perforation including history of diverticulitis & GIT metastases, & concomitant use of medications w/ recognized risk of GI perforation. Evaluate LVEF in all patients prior to initiation of treatment w/ periodic follow-up w/in 8 wk of initiating therapy, & continuously during treatment. Perform thorough ophthalmological evaluation at baseline & during treatment. Closely monitor patients for skin reactions; w/ risk factors for TLS eg, rapidly growing tumors, high tumor burden, renal dysfunction & dehydration. Monitor serum creatinine & other evidence of renal function during & following severe events of pyrexia. Moderate or severe hepatic, & severe renal impairment. Sexually-active females of reproductive potential should use effective contraception during, & for at least 16 wk after stopping treatment. Male patients should use condoms during sexual intercourse during & for at least 16 wk after stopping treatment. Pregnancy & lactation. Not recommended in ped patients <6 yr.

HTN, haemorrhage, hypotension; cough, dyspnea; diarrhoea, nausea, vomiting, constipation, abdominal pain, dry mouth; rash, dermatitis acneiform, dry skin, pruritus, alopecia, erythema, hyperkeratosis; fatigue, peripheral oedema, oedema, pyrexia, chills, asthenia, flu-like illness; UTI, nasopharyngitis; neutropenia; decreased appetite, hyponatraemia; headache, dizziness; arthralgia, myalgia, pain in extremity, muscle spasms; increased ALT, AST & blood alkaline phosphatase. Folliculitis, paronychia, cellulitis, pustular rash; anaemia, thrombocytopenia, leukopenia; hypersensitivity; dehydration, hyperglycaemia, hypophosphataemia; blurred vision, periorbital oedema, visual impairment, uveitis, chorioretinopathy, retinal detachment; left ventricular dysfunction, decreased ejection fraction, bradycardia, AV block; lymphoedema, pulmonary embolism, VTE; epistaxis, pneumonitis; stomatitis, acute pancreatitis; chapped skin, palmar-plantar erythrodysaesthesia syndrome, skin fissures, actinic keratosis, night sweats, skin lesion, hyperhidrosis, panniculitis, photosensitivity; increased blood creatine phosphokinase; face oedema, mucosal inflammation; cutaneous squamous cell carcinoma (SCC) including SCC of skin, in situ (Bowen's disease) & keratoacanthoma, papilloma including skin papilloma, seborrhoeic keratosis, acrochordon (skin tags); increased γ-glutamyltransferase; renal failure, tubulointerstitial nephritis; peripheral neuropathy.

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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