• Metastatic/unresectable melanoma with the BRAF V600E or V600K mutation (in combination with vemurafenib).
• Histiocytic neoplasms.

Contraindicated in:

• Concurrent use of strong or moderate CYP3A4 inhibitors or inducers
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Left ventricular ejection fraction <50%
• Severe renal impairment (CCr <30 mL/min)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: cardiomyopathy, hypertension.

Derm: alopecia, erythema, photosensitivity, rash.

EENT: retinopathy.

F and E: hyperkalemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia.

GI: diarrhea, hypoalbuminemia, nausea, stomatitis, vomiting, HEPATOTOXICITY.

GU: ↑serum creatinine, ↓ fertility.

Hemat: anemia, hemorrhage, lymphopenia, thrombocytopenia.

MS: ↑creatine kinase, RHABDOMYOLYSIS.
Misc: fever, MALIGNANCY.

Drug-Drug:

• Strong or moderate CYP3A4 inhibitors, including itraconazole, may ↑ levels; avoid concurrent use
• Strong or moderate CYP3A4 inducers, including carbamazepine, efavirenz, phenytoin, and rifampin, may ↓ levels; avoid concurrent use.

Drug-Natural Products:

• St. John's wort may ↓ levels; avoid concurrent use.

• Tablets: 20 mg;

• PO (Adults): 60 mg once daily for days 1–21 of each 28-day cycle; continue until disease progression or unacceptable toxicity; Concurrent short-term use of moderate CYP3A4 inhibitor: 20 mg once daily; resume 60 mg once daily once 3A4 inhibitor discontinued (avoid use of strong or moderate CYP3A4 inhibitor if patient already taking reduced dose of 20–40 mg once daily).

Cotellic

• Inhibits the activity of mitogen-activated extracellular kinase (MEK) 1 and 2, which are enzymes that normally promote cellular proliferation.

• Decreased progression of melanoma and histiocytic neoplasms.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: 46% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: 95%.

Metabolism/Excretion: Mostly metabolized by the liver (via CYP3A4 enzyme system and glucuronidation). 6.6% excreted in feces unchanged; 20% excreted in urine (mostly as metabolites).

Half-life: 44 hr.

(blood levels)

• Instruct patient to take cobimetinib as directed. If dose is missed or vomiting occurs after dose, do not repeat, take next dose as scheduled.
• Advise patient to notify health care professional immediately if skin changes (new wart, skin sore that bleeds or does not heal, change in size or color of mole), signs and symptoms of bleeding (blood in urine, red or black stools, unusual or excessive vaginal bleeding, bleeding of gums, abdominal pain, headache, dizziness, feeling weak), cardiomyopathy (persistent coughing or wheezing, tiredness, shortness of breath, increased heart rate, swelling of ankles and feet), eye problems (blurred vision, halos, distorted vision, other vision changes, partly missing vision), liver injury (yellowing of skin or white of eyes, feeling tired or weak, dark or brown [tea color] urine, loss of appetite, nausea or vomiting), rhabdomyolysis (muscle aches, dark, reddish urine, muscle spasms, weakness), or rash occur.
• Advise patient to avoid sun exposure, wear protective clothing and use a broad-spectrum UVA/UVB sunscreen and lip balm (SPF 30) when outdoors. May require dose reduction or discontinuation.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• May cause fetal harm. Advise patient use effective contraception and avoid breastfeeding during and for at least 2 wk following therapy. May reduce fertility in females and males of reproductive potential.

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