Drug Action
Trametinib is a protein kinase inhibitor.
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Drug reference
Trametinib is a protein kinase inhibitor.
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Unresectable or metastatic melanoma with a BRAF V600 mutation (as monotherapy or in combination with dabrafenib) (specialist use only) | Advanced non-small cell lung cancer with a BRAF V600 mutation (in combination with dabrafenib) (specialist use only) ▶BY MOUTH ▶Adult: 2 mg once daily, when used in combination with dabrafenib, the dose should be taken at the same time each day with either the morning or evening dose of dabrafenib, for dose adjustments due to side-effects, consult product literature Adjuvant treatment of stage III melanoma with a BRAF V600 mutation following complete resection (in combination with dabrafenib) (specialist use only) ▶BY MOUTH ▶Adult: 2 mg once daily for 12 months, the dose should be taken at the same time each day with either the morning or evening dose of dabrafenib, for dose adjustments due to side-effects, consult product literature
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History of retinal vein occlusion
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Concomitant antiplatelet or anticoagulant therapy—increased risk of haemorrhage. conditions that could impair left ventricular function. elderly (more frequent dose adjustments may be required). impaired left Immune system and malignant disease ventricular function. predisposing factors for retinal vein occlusion. risk factors for gastrointestinal perforation
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NICE decisions ▶Trametinib in combination with dabrafenib for treating unresectable or metastatic melanoma (June 2016) NICE TA396 Trametinib (Mekinist ®) in combination with dabrafenib (Tafinlar ®) is recommended, within its marketing authorisation, as an option for treating unresectable or metastatic melanoma in adults with a BRAF V600 mutation only when the manufacturer provides trametinib and dabrafenib with the discounts agreed in the patient access schemes. www.nice.org.uk/guidance/ta396 ▶Dabrafenib with trametinib for adjuvant treatment of resected BRAF V600 mutation-positive melanoma (October 2018) NICE TA544 Dabrafenib (Tafinlar ®) with trametinib (Mekinist ®) is recommended, within its marketing authorisation, as an option for the adjuvant treatment of resected stage III BRAF V600 mutation-positive melanoma in adults. It is recommended only if the manufacturer provides dabrafenib and trametinib with the discounts agreed in the commercial arrangements. www.nice.org.uk/guidance/ta544 Scottish Medicines Consortium (SMC) decisions SMC No. 1161/16 The Scottish Medicines Consortium has advised (August 2016) that trametinib (Mekinist ®), in combination with dabrafenib, is accepted for restricted use within NHS Scotland for first-line treatment of adults with unresectable or metastatic melanoma with a BRAF V600 mutation. This advice is contingent upon the continuing availability of the patient access scheme in NHS Scotland or a list price that is equivalent or lower.
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MHRA/CHM ADVICE (MARCH 2016): TRAMETINIB: RISK OF GASTROINTESTINAL PERFORATION AND COLITIS A review by EU medicines regulators has concluded that trametinib can cause gastrointestinal perforation or colitis. Trametinib should be used with caution in patients with risk factors for gastrointestinal perforation, such as gastrointestinal metastases, diverticulitis, or use of concomitant medicines that can cause gastrointestinal perforation. Prescribers should be vigilant for signs and symptoms of gastrointestinal perforation and should advise patients to seek urgent medical attention if they develop severe abdominal pain. RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938.
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→Appendix 1: trametinib
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▶Common or very common Abdominal pain. alopecia. anaemia. asthenia. bradycardia. constipation. cough. dehydration. diarrhoea. dry mouth. dyspnoea. eye inflammation. fever. haemorrhage. hypersensitivity. hypertension. increased risk of infection. intracranial haemorrhage. left ventricular dysfunction. lymphoedema . mucositis. nausea. oedema. respiratory disorders. skin reactions. stomatitis. vision disorders. vomiting ▶Uncommon Chorioretinopathy. gastrointestinal disorders. heart failure. retinal detachment. retinal occlusion. rhabdomyolysis SIDE-EFFECTS, FURTHER INFORMATION Additional side- effects reported when used in combination with dabrafenib include dizziness, hyperhidrosis, hyponatraemia, hypotension, leucopenia, muscle spasms, myocarditis, neutropenia, night sweats, and thrombocytopenia.
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Manufacturer advises women of child-bearing potential should use highly effective non-hormonal contraception during, and for 4 months after stopping treatment.
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Manufacturer advises avoid—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.
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Manufacturer advises avoid—no information available.
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Manufacturer advises caution in moderate to severe impairment (no information available).
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Manufacturer advises caution in severe impairment—no information available.
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Manufacturer advises measure blood pressure at baseline and monitor during treatment; evaluate left ventricular ejection fraction before treatment, after one month of treatment, and then approximately every 3 months thereafter; monitor liver function every 4 weeks for 6 months after treatment initiation, and thereafter as clinically indicated. l HANDLING AND STORAGE Manufacturer advises store in refrigerator (2–8 °C); once opened, bottle may be stored for 30 days at not more than 30 °C.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 3, 23, 25 ▶Mekinist (Novartis Pharmaceuticals UK Ltd) Trametinib 500 microgram Mekinist 0.5mg tablets | 7 tablet P £280.00 | 30 tablet P £1,200.00 Trametinib 2 mg Mekinist 2mg tablets | 7 tablet P £1,120.00 | 30 tablet P £4,800.00
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Manufacturer advises patients and their carers should be told to seek immediate medical attention if symptoms of pulmonary embolism or deep vein thrombosis occur; patients and their carers should also be advised to report new visual disturbances. Missed doses Manufacturer advises if a dose is more than 12 hours late, the missed dose should not be taken and the next dose should be taken at the normal time. Driving and skilled tasks Manufacturer advises patients and carers should be counselled on the effects on driving and performance of skilled tasks—risk of dizziness and visual disturbances.
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2 mg once daily, when used in combination with
First-line fragment. Read the complete Indications and Dose section above.
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2 mg once daily for 12 months, the dose should
First-line fragment. Read the complete Indications and Dose section above.
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