Mekinist Adverse Reactions

Summary of the safety profile: Unresectable or metastatic melanoma: Mekinist monotherapy: he safety of Mekinist monotherapy was evaluated in an integrated population of 329 patients with BRAF V600 mutant unresectable or metastatic melanoma treated with Mekinist 2 mg orally once daily. Of these patients, 211 patients were treated with Mekinist for BRAF V600 mutant melanoma in a randomized open-label study (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The most common adverse events (≥ 20 %) for Mekinist were rash, diarrhea, fatigue, edema peripheral, nausea, and dermatitis acneiform. In clinical trials with Mekinist, adverse events of diarrhea and rash were managed with appropriate supportive care (see Dosage & Administration).
Mekinist and dabrafenib combination therapy: The safety of Mekinist and dabrafenib combination therapy was evaluated in two randomized Phase III studies of patients with BRAF V600 mutant unresectable or metastatic melanoma treated with Mekinist 2 mg orally once daily and dabrafenib 150 mg orally twice daily (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). The most common adverse events (≥20%) for Mekinist and dabrafenib combination therapy were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, arthralgia, hypertension, vomiting, peripheral edema and cough.
Tabulated summary of adverse events from clinical trials in unresectable metastatic melanoma: Adverse events from clinical trials in patients with unresectable or metastatic melanoma are listed by MedDRA system organ class in Table 8 and Table 9 for Mekinist monotherapy and Mekinist in combination with Tafinlar, respectively. Within each system organ class, the adverse events are ranked by frequency, with the most frequent adverse events first. In addition, the corresponding frequency category for each adverse event is based on the following convention (CIOMS III): Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). (See Table 8.)

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Table 9 lists adverse events when Mekinist was used in combination with dabrafenib from the randomized double-blind Phase III study MEK115306 (N=209), and integrated safety data from MEK115306 (N=209) and from the randomized open-label Phase III study MEK 116513 (N=350). (See Table 9a and 9b.)

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Adjuvant treatment of melanoma: Mekinist in combination with Tafinlar: The safety of Mekinist in combination with Tafinlar was evaluated in a Phase III, randomized, double-blind study of Mekinist in combination with Tafinlar versus two placebos in the adjuvant treatment of Stage III BRAF V600 mutation-positive melanoma after surgical resection (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
In the Mekinist 2 mg once daily and Tafinlar 150 mg twice daily arm, the most common adverse reactions (≥20%) were pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia.
Table 10 lists the adverse drug reactions in study BRF115532 (COMBI-AD) occurring at an incidence ≥10% for all grade adverse reactions or at an incidence ≥2% for Grade 3 and Grade 4 adverse drugs reactions or adverse events that are medically significant in the Mekinist in combination with Tafinlar arm.
Adverse drug reactions are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent adverse drug reactions first. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). (See Table 10.)

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Advanced non-small cell lung cancer (NSCLC): Mekinist in combination with dabrafenib: The safety of Mekinist in combination with dabrafenib was evaluated in a Phase II, multicenter, multi-cohort, non-randomized, open label study of patients with BRAF V600E mutation positive metastatic NSCLC (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
In the Mekinist 2 mg orally once daily and dabrafenib 150 mg orally twice daily arms (Cohorts B and C) the most common adverse events (≥20%) reported for Mekinist and dabrafenib combination therapy were pyrexia, nausea, vomiting, peripheral edema, diarrhea, decreased appetite, asthenia, dry skin, chills, cough, fatigue, rash and dyspnea.
Table 11 lists the adverse drug reactions for Mekinist in combination with dabrafenib occurring at an incidence ≥10% for all adverse drug reactions or at an incidence ≥2% for Grade 3 and Grade 4 adverse drug reactions or events which are medically significant in Cohorts B and C of study BRF113928.
Adverse drug reactions are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent adverse drug reactions first. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). (See Table 11.)

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