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MEKINIST is a brand name for Trametinib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: and 7 General). MEKINIST (trametinib) Page 61 of 113 Unresectable or Metastatic Melanoma – MEKINIST in Combination with Dabrafenib Table 25 Summary of Patient Demographics for Clinical Trials in Unresectable or Metastatic Melanoma - MEKINIST in Combination with Dabrafenib Study # Study design Dosage, route of…
Verbatim from this product's HC label. Tap a section to expand.
) for dose modifications of MEKINIST in patients who have serious non-infectious febrile events while on the combination therapy. Interrupt therapy (MEKINIST when used in monotherapy, or both MEKINIST and dabrafenib when used in combination) if patient’s temperature is ≥ 38oC.
In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia. Initiate treatment with anti-pyretics and evaluate patients for signs and symptoms of infection. The use of oral corticosteroids should be considered in those instances in which anti-pyretics are insufficient.
0 °C) for at least 24 hours. Reduce the dose if recurrent pyrexia cannot be managed with interruption or corticosteroids. 0°C or fevers associated with other severe signs or symptoms, and a decision is made to restart therapy (MEKINIST when used in monotherapy or both MEKINIST and dabrafenib when used in combination), the dose should be reduced according to dose modification protocols See Table 3 (4 DOSAGE AND ADMINISTRATION).
Brain Metastases:
The safety and efficacy of the combination of MEKINIST and dabrafenib has not been evaluated in patients with a BRAF V600 mutation-positive melanoma which has MEKINIST (trametinib) Page 16 of 113 metastasized to the brain. Three patients who developed brain metastases while on treatment with MEKINIST in combination with dabrafenib in phase III trials experienced fatal cerebral hemorrhage (see 7 Hematologic).
Gender:
When administered as a monotherapy in adult patients, female patients with lower body weights had higher systemic exposure of trametinib compared to male patients (see 10 Sex/Weight). 2 Clinical Trial Adverse Reactions). Carcinogenesis and Mutagenesis Carcinogenicity studies have not been performed with trametinib.
There was no indication for a genotoxic potential of trametinib after testing in standard in vitro assays and in vivo in rats (see 16 General Toxicology). Secondary malignancies have occurred in patients receiving combination therapy with dabrafenib and MEKINIST.
Cardiovascular Left Ventricular Dysfunction:
MEKINIST has been reported to decrease left ventricular ejection fraction (LVEF) (see 8 ADVERSE REACTIONS). In clinical trials with patients treated with MEKINIST at the recommended dose, patients with abnormal left ventricular ejection fraction were excluded.
). In clinical trials with patients treated with MEKINIST at the recommended dose, patients with abnormal left ventricular ejection fraction were excluded. In the randomized clinical study in patients with unresectable or metastatic melanoma, cardiac adverse events including decreased LVEF, left ventricular dysfunction, and cardiac failure were reported in 8% patients treated with MEKINIST monotherapy whereas none was reported in patients in the chemotherapy arm.
5 (range: 16-526) days. In a phase III clinical study of MEKINIST in combination with dabrafenib compared to dabrafenib monotherapy in unresectable or metastatic melanoma, cardiac-related events (LVEF reduction and/or cardiac failure) were reported in 6% (12/209) of patients treated with combination therapy.
2 Clinical Trial Adverse Reactions). The median time to onset of the first occurrence of left ventricular dysfunction, cardiac failure and LVEF decrease in patients treated with MEKINIST in combination with dabrafenib was 157 (range: 28-758) days.
In a phase III trial in the adjuvant treatment of melanoma, cardiac-related events (LVEF reduction and/or cardiac failure) were reported in 5% (22/435) of patients treated with MEKINIST in combination with dabrafenib and in 2% (7/432) of patients who received placebo.
The median time to onset of cardiac-related events was 81 days in the combination arm compared to 168 days in the placebo arm. 7% (9/93) of patients treated with MEKINIST in combination with dabrafenib. 2) months. MEKINIST (trametinib) Page 17 of 113 Across clinical trials in adult patients, cardiac-related events were reported in 6% (43/737) of patients receiving combination therapy.
In a pooled safety population of pediatric patients receiving MEKINIST in combination with dabrafenib (n=171), cardiac related events were reported in 6% of patients. LVEF should be evaluated in all patients prior to initiation of treatment with MEKINIST with a recommendation of periodic follow-up within 8 weeks of initiating therapy.
and 10 Renal Insufficiency).
Hepatic impairment:
No dosage adjustment is required in patients with mild hepatic impairment. There are no clinical data in patients with moderate or severe hepatic impairment; the need for starting dose adjustment is unknown (see 7 WARNINGS AND PRECAUTIONS and 10 Hepatic Insufficiency).
3 Pharmacokinetics). When MEKINIST and dabrafenib are taken in combination, the once-daily dose of MEKINIST should be taken at the same time each day with either the morning dose or the evening dose of dabrafenib. Health professionals should regularly monitor the weight of pediatric patients to ensure that they are receiving the appropriate dose, and confirm that patients or caregiver(s) understand how to administer the correct daily dose.
Tablets MEKINIST tablets should be taken with a full glass of water. Powder for Oral Solution To prepare MEKINIST for oral solution, tap the bottle until powder flows freely. Add 90 mL distilled or purified water to the powder in the bottle and invert or gently shake the bottle with re-attached cap for up to 5 minutes until powder is fully dissolved yielding a clear solution.
Separate the dosing adapter from the oral syringe. Insert dosing adapter into bottle neck after reconstitution of the solution. Write the discard-after date. Once reconstituted, MEKINIST oral solution can be used for 35 days. Administer MEKINIST for oral solution from oral dosing syringe or feeding tube.
After reconstitution, store in original bottle below 25°C and do not freeze. MEKINIST (trametinib) Page 13 of 113 When using MEKINIST powder for oral solution, health professionals should review and discuss with the patient or caregiver(s) the Patient Medication Information and instructions for administering MEKINIST.
A complete illustrated set of instructions for administration of the prepared solution is in the Patient Medication Information section. 5 Missed Dose If a dose of MEKINIST is missed, it should not be taken if it is less than 12 hours until the next dose.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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In the randomized clinical study in patients with unresectable or metastatic melanoma, cardiac adverse events including decreased LVEF, left ventricular dysfunction, and cardiac failure were reported in 8% patients treated with MEKINIST monotherapy whereas none was reported in patients in the chemotherapy arm.
5 (range: 16-526) days. In a phase III clinical study of MEKINIST in combination with dabrafenib compared to dabrafenib monotherapy in unresectable or metastatic melanoma, cardiac-related events (LVEF reduction and/or cardiac failure) were reported in 6% (12/209) of patients treated with combination therapy.
2 Clinical Trial Adverse Reactions). The median time to onset of the first occurrence of left ventricular dysfunction, cardiac failure and LVEF decrease in patients treated with MEKINIST in combination with dabrafenib was 157 (range: 28-758) days.
In a phase III trial in the adjuvant treatment of melanoma, cardiac-related events (LVEF reduction and/or cardiac failure) were reported in 5% (22/435) of patients treated with MEKINIST in combination with dabrafenib and in 2% (7/432) of patients who received placebo.
The median time to onset of cardiac-related events was 81 days in the combination arm compared to 168 days in the placebo arm. 7% (9/93) of patients treated with MEKINIST in combination with dabrafenib. 2) months. MEKINIST (trametinib) Page 17 of 113 Across clinical trials in adult patients, cardiac-related events were reported in 6% (43/737) of patients receiving combination therapy.
In a pooled safety population of pediatric patients receiving MEKINIST in combination with dabrafenib (n=171), cardiac related events were reported in 6% of patients. LVEF should be evaluated in all patients prior to initiation of treatment with MEKINIST with a recommendation of periodic follow-up within 8 weeks of initiating therapy.
LVEF should continue to be evaluated during treatment with MEKINIST as clinically appropriate. MEKINIST is not recommended in patients with decreased LVEF at baseline. Dose modifications for managing decreased LVEF/left ventricular dysfunction are outlined in Table 3 (see 4 DOSAGE AND ADMINISTRATION).
2 Recommended Dose and Dosage Adjustment). MEKINIST should be used with caution in patients with conditions that could impair left ventricular function.
Venous Thromboembolism:
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) can occur with MEKINIST. Across clinical studies in patients receiving MEKINIST monotherapy (n = 329), DVT was reported in 3 patients (1%) and PE was reported in 12 (4%) patients.
Fatal venous thromboembolism events have occurred when MEKINIST was used in combination with dabrafenib. In clinical trials in adult […]
LVEF should continue to be evaluated during treatment with MEKINIST as clinically appropriate. MEKINIST is not recommended in patients with decreased LVEF at baseline. Dose modifications for managing decreased LVEF/left ventricular dysfunction are outlined in Table 3 (see 4 DOSAGE AND ADMINISTRATION).
2 Recommended Dose and Dosage Adjustment). MEKINIST should be used with caution in patients with conditions that could impair left ventricular function.
Venous Thromboembolism:
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) can occur with MEKINIST. Across clinical studies in patients receiving MEKINIST monotherapy (n = 329), DVT was reported in 3 patients (1%) and PE was reported in 12 (4%) patients.
Fatal venous thromboembolism events have occurred when MEKINIST was used in combination with dabrafenib. In clinical trials in adult patients receiving MEKINIST in combination with dabrafenib, DVT and/or PE were reported in 3% (29/941) of patients, including 2 fatalities (<1%).
In a pooled safety population of pediatric patients receiving MEKINIST in combination with dabrafenib, one case of embolism was reported (1/171 patients; < 1%). If patients develop symptoms of PE or DVT such as shortness of breath, chest pain, or arm or leg swelling, they should immediately seek medical care.
Electrocardiography:
MEKINIST was associated with a concentration-dependent prolongation of the PR interval in a phase I study. 2 Pharmacodynamics). 5 Post-Market Adverse Reactions). Caution should be observed in patients with pre-existing conduction system disease or a history of syncope of unknown etiology.
There are no data regarding concomitant use of MEKINIST with medications that result in PR interval prolongation. Nonetheless, these medications should be used with caution with MEKINIST (see
5 Overdose Symptoms and Signs There were no cases of MEKINIST dosed above 4 mg once daily reported from the clinical trials. Doses of up to 4 mg orally once daily or loading doses of up to 10 mg on two consecutive days, have been administered to limited numbers of patients in a clinical study.
Doses above the recommended 2 mg orally once daily regimen were associated with increased toxicities including retinal pigment epithelial detachment. Treatment There is no specific antidote for overdosage of MEKINIST. In case of suspected overdose, MEKINIST should be withheld and supportive care instituted.
Patients who develop adverse reactions should receive appropriate symptomatic treatment. Haemodialysis is not expected to enhance the elimination as trametinib is highly bound to plasma proteins. For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669).
5 or 2 mg of trametinib) Croscarmellose sodium, hypromellose, magnesium stearate (vegetable source), mannitol, microcrystalline cellulose, silicon dioxide (colloidal), and sodium lauryl sulphate. 5 mg tablets only), iron oxide red and polysorbate 80 (2 mg tablets only).
5 mg tablets are yellow, modified oval, biconvex, film coated tablets with ‘GS’ debossed on one face and ‘TFC’ on the opposing face. Available in bottles of 30 tablets. Bottles contain a silica gel desiccant. 5 mg tablets are yellow, ovaloid, biconvex, unscored film coated tablets with bevelled edges and with the ‘Novartis logo’ debossed on one side and ‘TT’ on the other side.
Available in bottles of 30 tablets. Bottles contain a silica gel desiccant. MEKINIST 2 mg tablets are pink, round, biconvex, film-coated tablets with ‘GS’ debossed on one face and ‘HMJ’ on the opposing face. Available in bottles of 30 tablets.
Bottles contain a silica gel desiccant. OR MEKINIST 2 mg tablets are pink, round, biconvex, unscored film-coated tablets with bevelled edges and with the ‘Novartis logo’ debossed on one side and ‘LL’ on the other side. Available in bottles of 30 tablets.
Bottles contain a silica gel desiccant. 7 mg powder for oral solution is a white or almost white powder available in a 180mL amber glass bottle. 7 Warnings and Precautions Please see 3 Serious Warnings and Precautions Box. 7 mg of trametinib.
05 mg of trametinib. Citric acid monohydrate, disodium phosphate, flavour strawberry, methyl parahydroxybenzoate, potassium sorbate sucralose, sulfobutylbetadex sodium. MEKINIST (trametinib) Page 15 of 113 secondary malignancies, non-infectious febrile events, decreased efficacy of oral contraceptives, valve abnormalities, QTc prolongation, hyperglycaemia, pancreatitis, uveitis, effects on fertility in males, renal failure, teratogenicity and use in pediatrics, geriatrics, moderate or severe hepatic impairment or severe renal impairment.
General BRAF V600 […]