Trametinib dimethyl sulfoxide

Permanently discontinue MEKINIST for patients diagnosed with treatment-related ILD or pneumonitis [see Dosage and Administration] . 5.8 Serious Febrile Reactions Serious febrile reactions and fever of any severity accompanied by hypotension, rigors or chills, dehydration, or renal failure, can occur when MEKINIST is administered with dabrafenib.

MEKINIST Administered with Dabrafenib (Adult) : In the pooled safety population [see Adverse Reactions] , fever occurred in 58% of patients. Serious febrile reactions and fever of any severity complicated by hypotension, rigors or chills, dehydration or renal failure occurred in 5% of patients. Fever was complicated by hypotension in 4%, dehydration in 3%, syncope in 2%, renal failure in 1%, and severe chills/rigors in < 1% of patients.

Fever may be complicated by hypotension, rigors or chills, dehydration, or renal failure. Evaluate for signs and symptoms of infection and monitor serum creatinine and other evidence of renal function during and following severe pyrexia. If appropriate, MEKINIST, or both MEKINIST and dabrafenib when used in combination, may be restarted if the patient has recovered from the febrile reaction for at least 24 hours, either at same or lower dose [see Dosage and Administration] .

Administer antipyretics as secondary prophylaxis when resuming MEKINIST if patient had a prior episode of severe febrile reaction or fever associated with complications. Administer corticosteroids (e.g., prednisone 10 mg daily) for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications, such as dehydration, hypotension, renal failure, or severe chills/rigors, and there is no evidence of active infection. 5.9 Serious Skin Toxicities Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with MEKINIST administered with dabrafenib [see Adverse Reactions] .

Hepatic Impairment No dose adjustment is recommended in patients with mild (bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or bilirubin > 1x to 1.5x ULN and any AST) hepatic impairment. A recommended dosage of MEKINIST has not been established for patients with moderate (bilirubin > 1.5x to 3x ULN and any AST) or severe (bilirubin > 3x to 10x ULN and any AST) hepatic impairment.

Consider the risk-benefit profile of MEKINIST related to dosing prior to determining whether to administer MEKINIST to patients with moderate or severe hepatic impairment. In patients with moderate hepatic impairment, 3 patients who received a starting dose of 1.5 mg orally once daily and two patients who received a starting dose of 2 mg orally once daily did not experience dose limiting toxicities (DLTs) during the first cycle of therapy.

In patients with severe hepatic impairment, 3 patients who received a starting dose of 1 mg orally once daily did not experience DLTs during the first cycle; one patient who received a starting dose of 1.5 mg orally once daily experienced a DLT (grade 3 acneiform rash). Compared to patients with normal hepatic function, there was no increase in exposure of trametinib in patients with moderate or severe hepatic impairment [see Clinical Pharmacology] .

Administration Take MEKINIST at the same time each day, approximately 24 hours apart. Do not take a missed dose of MEKINIST within 12 hours of the next dose of MEKINIST. If vomiting occurs after MEKINIST administration, do not take an additional dose. Take the next dose at its scheduled time. MEKINIST Tablets Take MEKINIST tablets on an empty stomach (at least 1 hour before or 2 hours after a meal) [see Clinical Pharmacology] .

Do not crush or break MEKINIST tablets. MEKINIST for Oral Solution MEKINIST powder for oral solution must be reconstituted by a pharmacist or other healthcare provider prior to dispensing to the patient. MEKINIST for oral solution is intended for administration by a caregiver. Prior to use of the oral solution, ensure caregivers receive training on proper dosing and administration of MEKINIST for oral solution.

When administering MEKINIST for oral solution as a single agent, take the oral solution with a low-fat meal or on an empty stomach [see Clinical Pharmacology] . When coadministering with dabrafenib, take the MEKINIST oral solution on an empty stomach (at least 1 hour before or 2 hours after a meal). Breastfeeding and/or baby formula may be given on demand if a pediatric patient is unable to tolerate the fasting conditions [see Clinical Pharmacology] .

Preparation and Administration 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 bottle adapter from the oral syringe.

Insert bottle adapter into bottle neck after reconstitution of the solution. Write the discard after date. Once reconstituted, MEKINIST for oral solution can be used for 35 days. The final concentration of the solution is 0.05 mg/mL. Administer MEKINIST for oral solution from an oral syringe or feeding tube (4 French gauge or larger).

After reconstitution, store in original bottle below 25°C (77°F) and do not freeze.