Trametinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of trametinib.
Drugs List
Therapeutic Indications
Uses
Advanced non-small cell lung cancer BRAFV600 mutation:Combination treatment
Melanoma
Melanoma
Monotherapy or in combination with dabrafenib in adults with unresectable or metastatic melanoma with a confirmed BRAF V600 mutation.
Adjuvant treatment of melanoma
In combination with dabrafenib in adults for the adjuvant treatment of adult patients with stage III melanoma with a BRAF V600 mutation, following complete resection.
Non-small cell lung cancer
In combination with dabrafenib in adults with advanced non-small cell lung cancer with a confirmed BRAF V600 mutation.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Patients should continue treatment until disease progression or unacceptable toxicity. In the adjuvant treatment of melanoma, patients should be treated for 12 months unless there is disease recurrence or unacceptable toxicity.
When trametinib is given in combination with dabrafenib, dabrafenib product information must be consulted prior to initiation of treatment.
Adults
2mg once a day.
Additional Dosage Information
Dose level reductions
1st reduction: 1.5mg once a day.
2nd reduction: 1mg once a day.
Reductions below 1mg are not recommended.
When used in combination with dabrafenib, consult dabrafenib product information for dabrafenib dose reductions.
Re-escalation
Once adverse reactions are under control, dose re-escalation following the same dosing steps as reduction may be considered.
CTC-AE toxicity modification schedule for adverse reactions (excluding pyrexia)
Grade 1 or Grade 2 (tolerable) toxicities: Continue treatment and monitor as clinically indicated.
Grade 2 (intolerable) or grade 3 toxicities: Suspend treatment until symptoms have resolved to grade 1 or lower. Reduce dose by one dose level when resuming treatment.
Grade 4 toxicities: Permanently discontinue or suspend treatment until symptoms resolve to grade 1 or lower, reduce dose by one dose level when resuming treatment.
Pyrexia
Interrupt treatment if the patient's temperature is greater than or equal to 38 degrees celsius. Treatment with anti-pyretics such as ibuprofen or paracetamol should be initiated. In cases where anti-pyretics are insufficient, oral corticosteroids should be considered. Patients should be evaluated for signs and symptoms of infection. If the patient is symptom free for at least 24 hours, trametinib should be restarted at the same dose level or reduced by one dose level if pyrexia is recurrent and/or accompanied by other severe symptoms including dehydration, hypotension or renal failure.
Retinal pigment epithelial detachment (RPED)
Grade 1 RPED: Continue treatment carrying out monthly retinal examinations until resolution.
Grade 2 or 3 RPED: Withhold treatment for up to 3 weeks.
Grade 2 or 3 RPED that improves to grade 1 or lower within 3 weeks: Resume treatment at a lower dose (0.5mg reduction) or discontinue trametinib in patients taking 1mg daily.
Grade 2 or 3 RPED that does not improve to at least grade 1 within 3 weeks: Discontinue permanently.
Left ventricular ejection fraction (LVEF) reduction
Interruption of treatment should occur in patients with asymptomatic absolute decrease of greater than 10% in LVEF compared to baseline and the ejection fraction is below the institution's lower limit of normal (LLN).
If LVEF recovers, treatment can be restarted but dose reduced by one dose level with careful monitoring should be performed.
Grade 3 or 4 left ventricular dysfunction (LVD) or clinically significant reduction in LVEF which does not recover within 4 weeks: Permanently discontinue treatment.
When used in combination both treatments should be modified simultaneously unless stated as an exception, see manufacturers information for further details.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Retinal blood vessel occlusion
Precautions and Warnings
Predisposition to gastrointestinal perforation
Predisposition to retinal detachment
Predisposition to retinal vein occlusion
Pyrexia
Intraocular hypertension
Left ventricular dysfunction
Moderate hepatic impairment
New York Heart Association class II failure
New York Heart Association class III failure
New York Heart Association class IV failure
Serious cardiac arrhythmias
Severe renal impairment
Thrombocytopenia
Uncontrolled diabetes mellitus
Uncontrolled glaucoma
Uncontrolled hypertension
Within 6 months of an acute coronary syndrome episode
Advise ability to drive/operate machinery may be affected by side effects
Confirm BRAF V600 mutation status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Assess LVEF before treatment, 1 month after starting, then every 3 months
Monitor blood pressure pre-treatment and periodically thereafter
Advise patient to stop and contact Dr if severe/persistent abdominal pain
Consider myocarditis if new or worsening cardiac signs or symptoms occur
If visual disturbances occur, perform ophthalmic evaluation
Monitor closely for signs and sypmtoms of Stevens-Johnson syndrome
Monitor for signs and symptoms of infection after treatment
Monitor for signs and symptoms of pneumonitis
Monitor hepatic function every 4 weeks for 6 months, or as indicated
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report any blurred vision or any other eye symptoms
Discontinue or suspend treatment if grade 4 toxicities occur
Discontinue treatment if interstitial lung disease develops
Suspend treatment if DRESS is suspected
Suspend treatment if pneumonitis is suspected
Suspend treatment if Stevens-Johnson syndrome is suspected
Consider discontinuation if symptoms of severe rhabdomyolysis occur
Discontinue if pulmonary embolism occurs
Discontinue if retinal vein occlusion occurs
Discontinue if treatment related pneumonitis is diagnosed
Discontinue treatment and/or reduce dose in grade 2 or greater RPED
Interrupt treatment if patients temperature is 38 degrees C or more
Suspend treatment if grade 3 or intolerable grade 2 toxicities
Suspend treatment if interstitial lung disease is suspected
Suspend treatment if LVEF decrease of 10% below baseline
May cause impaired fertility
Female: Barrier or non-hormonal contraception advised during treatment
Female: Contraception required during and for 4 months after treatment
Advise patient of risk of bleeding
Haemorrhagic events have occurred in patients taking trametinib, if such events occur patients should be treated as clinically indicated. The potential for these events in patients with low platelets (less than 75,000) is not established.
Concomitant use of antiplatelet and anticoagulant therapy may increase risk of haemorrhage.
Signs and symptoms of rhabdomyolysis should warrant clinical evaluation and appropriate treatment.
If patients present with new or progressive pulmonary symptoms including suspected interstitial lung disease (ILD) or pneumonitis, trametinib treatment should be withheld. Following diagnosis of ILD or pneumonitis, trametinib treatment should be discontinued.
LVD due to myocarditis has been reported in patients taking trametinib and dabrafenib, which fully recovered once treatment stopped. Myocarditis should be considered following any new or worsening cardiac signs or symptoms.
Sarcoidosis has been reported in patients treated with trametinib in combination with dabrafenib. In cases of a diagnosis with sarcoidosis, relevant treatment should be considered. It is important that sarcoidosis is not misinterpreted as disease progression.
Pregnancy and Lactation
Pregnancy
Trametinib is contraindicated during pregnancy.
The manufacturer recommends that trametinib should not be administered to pregnant women. At the time of writing there is limited published information regarding the use of trametinib during pregnancy in humans. Animal studies have shown reproductive toxicity including decreased foetal body weight, incomplete ossification and skeletal malformations.
Lactation
Trametinib is contraindicated during breastfeeding.
The manufacturer recommends that trametinib should not be administered to breastfeeding mothers. At the time of writing there is limited published information regarding the use of trametinib during breastfeeding. It is not known whether trametinib is excreted into human breast milk, a risk to neonates cannot be excluded.
Counselling
Tablets to be taken whole and at similar times of the day. At least 1 hour before or 2 hours after a meal.
Advise patients to seek urgent medical attention if they develop severe abdominal pain.
Advise patient if a dose is missed to take as soon as remembered only if it is more than 12 hours until the next scheduled dose. Patients should not take extra tablets to make up for the missed dose.
Males taking trametinib in combination with dabrafenib should be informed of potential risk of impaired irreversible spermatogenesis.
Advise female patients to use highly effective barrier or non-hormonal contraception during treatment and for 4 months after.
Advise patients ability to drive or operate machinery may be affected by side effects.
Advise patient to report any muscle pain, tenderness or weakness.
Advise patient to report any skin reactions, pain, erythema, pruritus.
Advise patient to report any symptoms of pulmonary embolism / deep vein thrombosis.
Advise patient to report any visual disturbances.
Side Effects
Abdominal pain
Acrochordon
Actinic keratosis
Alanine aminotransferase increased
Alopecia
Anaemia
Arthralgia
Aspartate aminotransferase increased
Asthenia
Blurred vision
Bradycardia
Cardiac failure
Cellulitis
Chills
Chorioretinopathy
Colitis
Constipation
Cough
Creatine phosphokinase increased
Cutaneous lesions
Decreased appetite
Decreased ejection fraction
Dehydration
Dermatitis
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dry skin
Dyspnoea
Erythema
Exfoliative dermatitis
Facial oedema
Fatigue
Folliculitis
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal perforation
Haemorrhage
Headache
Hyperglycaemia
Hyperhidrosis
Hyperkeratosis
Hypersensitivity reactions
Hypertension
Hyponatraemia
Hypophosphataemia
Hypotension
Impaired vision
Increase in alkaline phosphatase
Influenza-like symptoms
Interstitial lung disease
Left ventricular failure
Leukopenia
Lymphoedema
Mucosal inflammation
Muscle spasm
Myalgia
Myocarditis
Nasopharyngitis
Nausea
Nephritis
Neutropenia
Night sweats
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Panniculitis
Papilloedema
Papilloma
Paronychia
Periorbital oedema
Peripheral oedema
Photosensitivity
Pneumonitis
Primary melanoma
Pruritus
Pustular rash
Pyrexia
Rash
Renal failure
Retinal detachment
Retinal vein occlusion
Rhabdomyolysis
Sarcoidosis
Seborrhoeic keratosis
Skin fissures
Squamous cell carcinoma
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Urinary tract infections
Uveitis
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2018
Reference Sources
Summary of Product Characteristics: Mekinist 0.5 mg film-coated tablets. Novartis Pharmaceutical UK Ltd. Revised July 2022.
Summary of Product Characteristics: Mekinist 2 mg film-coated tablets. Novartis Pharmaceutical UK Ltd. Revised July 2022.
Gov.uk. Government departments. Medicines and Healthcare products Regulatory Agency. Drug Safety Updates. Trametinib (Mekinist): Risk of gastrointestinal perforation and colitis. Available at: https://www.gov.uk/ Last accessed: 15 January 2018.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.