binimetinib

High Alert

Metastatic/unresectable melanoma in patients with the BRAF V600E or V600K mutation (in combination with encorafenib).
Metastatic non-small cell lung cancer (NSCLC) in patients with the BRAF V600E mutation (in combination with encorafenib).

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Left ventricular ejection fraction (LVEF) <50%;
History of retinal vein occlusion;
Uncontrolled glaucoma or history of hypercoagulability (↑ risk of retinal vein occlusion);
Moderate or severe hepatic impairment (↓ dose);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: cardiomyopathy, hypertension, peripheral edema, DEEP VENOUS THROMBOSIS (DVT)

Derm: rash, photosensitivity

EENT: retinopathy, visual impairment, macular edema, retinal detachment, retinal vein occlusion (RVO), uveitis

F and E: hyponatremia

GI: ↑liver enzymes, abdominal pain, constipation, diarrhea, nausea, vomiting, colitis, HEPATOTOXICITY

GU: ↑serum creatinine

Hemat: anemia, hemorrhage, leukopenia, lymphopenia, neutropenia

MS: ↑CK, RHABDOMYOLYSIS

Neuro: dizziness, fatigue

Resp: INTERSTITIAL LUNG DISEASE (ILD), PULMONARY EMBOLISM (PE)

Misc: fever, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

None reported.

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

PO (Adults ): 45 mg twice daily; continue until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 30 mg twice daily; continue until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

Decreased progression of melanoma and improved survival.
Decreased progression of NSCLC.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: At least 50% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: 97%.

Metabolism/Excretion: Mostly metabolized by the liver via glucuronidation. 62% excreted in feces (32% as unchanged drug); 31% excreted in urine (6.5% as unchanged drug).

Half-Life: 3.5 hr.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.6 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise to read Patient Information before starting therapy.
Instruct patient to take missed dose as soon as remembered, but no closer than 6 hr to next dose. If patient vomits after dose, omit and take next scheduled dose.
Advise patient to notify health care professional promptly if signs and symptoms of HF, venous thromboembolism (sudden onset of difficulty breathing, leg pain, swelling), changes in vision, ILD (new or worsening cough or dyspnea), hepatotoxicity (jaundice, dark urine, nausea, vomiting, loss of appetite, fatigue, bruising, bleeding), rhabdomyolysis (unusual or new onset weakness, myalgia, darkened urine), hemorrhage, or abnormal skin changes (mole color/shape changes, new wart, unhealed skin sores) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for ≥30 days after last dose and to avoid breastfeeding for 3 days after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected.

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Indications ⬇