Cobimetinib

Class

Targeted therapy

Subclass

MEK inhibitors

Substance name

Cobimetinib

Brand names

Cotellic®

Common formulations

Film-coated tablet

Dosage and administration

Adults patients

Treatment

Histiocytic neoplasm

•

60 mg PO daily for 21 days out of a 28-day treatment cycle, with cycles repeated until disease progression or until unacceptable toxicity

Adjunctive treatment

Adjunctive treatment for melanoma in patients with BRAF V600E or V600K mutation • Unresectable or metastatic

•

60 mg PO daily for 21 days out of a 28-day treatment cycle, with cycles repeated until disease progression or until unacceptable toxicity

Administered in combination with vemurafenib.

Indications for use

Labeled indications

Adults

•

Treatment of histiocytic neoplasm

•

Adjunctive treatment for melanoma in patients with BRAF V600E or V600K mutation (unresectable or metastatic)

Safety risks

Boxed warnings

Cardiomyopathy

•

Use extreme caution with risk factors for LVEF.

Coagulopathy

•

Use extreme caution with a known risk of bleeding.

Contraindications

Treated with cobimetinib plus vemurafenib

Warnings and precautions

Malignancies

•

Use caution with risk factors for new primary malignancies.

Photosensitivity of skin

•

Use caution with excessive sunlight exposure.

Retinal detachment

•

Use caution with pre-existing ocular disease.

Rhabdomyolysis

•

Use caution with elevated levels of serum creatine phosphokinase.

Specific populations

Renal impairment

eGFR 30-50 mL/min/1.73 m²

•

Use acceptable. No dose adjustment required.

eGFR 10-30 mL/min/1.73 m²

•

Use with caution. Treatment-Related Nephrotoxicity Intolerable grade 2, or any grade 3: Hold cobimetinib therapy. If improved to grade 0 or 1 within 4 weeks, resume treatment at the next lower dose level (1st dose reduction, 40 mg PO once daily; 2nd dose reduction, 20 mg PO once daily). If not improved within 4 weeks, or if the patient is unable to tolerate 20 mg once daily, permanently discontinue therapy. Grade 4, first occurrence: Hold cobimetinib therapy. When it has improved to grade 0 or 1, resume treatment at the next lower dose level (1st dose reduction, 40 mg PO once daily; 2nd dose reduction, 20 mg PO once daily). Alternatively, permanently discontinue cobimetinib therapy. If the patient is unable to tolerate 20 mg once daily, permanently discontinue therapy. Grade 4, recurrent: Permanently discontinue cobimetinib therapy.

eGFR < 10 mL/min/1.73 m²

•

Use with caution. Treatment-Related Nephrotoxicity Intolerable grade 2, or any grade 3: Hold cobimetinib therapy. If improved to grade 0 or 1 within 4 weeks, resume treatment at the next lower dose level (1st dose reduction, 40 mg PO once daily; 2nd dose reduction, 20 mg PO once daily). If not improved within 4 weeks, or if the patient is unable to tolerate 20 mg once daily, permanently discontinue therapy. Grade 4, first occurrence: Hold cobimetinib therapy. When it has improved to grade 0 or 1, resume treatment at the next lower dose level (1st dose reduction, 40 mg PO once daily; 2nd dose reduction, 20 mg PO once daily). Alternatively, permanently discontinue cobimetinib therapy. If the patient is unable to tolerate 20 mg once daily, permanently discontinue therapy. Grade 4, recurrent: Permanently discontinue cobimetinib therapy.

Renal replacement therapy

Continuous renal replacement

•

Use with caution. Dose as in eGFR 10-30 mL/min/1.73 m².

Intermittent hemodialysis

•

Use with caution. Dose as in eGFR < 10 mL/min/1.73 m².

Peritoneal dialysis

•

Use with caution. Dose as in eGFR < 10 mL/min/1.73 m².

Hepatic impairment

Child-Pugh A (mild)

•

Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c387,579e-cee0-4,334-bd1e-73f93ac1bde6.

Child-Pugh B (moderate)

•

Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c387,579e-cee0-4,334-bd1e-73f93ac1bde6.

Child-Pugh C (severe)

•

Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c387,579e-cee0-4,334-bd1e-73f93ac1bde6.

Pregnancy and breastfeeding

Pregnancy

All trimesters • Australia Category: D

•

Avoid use. Evidence of fetal harm in humans.

Breastfeeding

Little information available on breastfeeding safety.

Unknown amount excreted in breastmilk.

Unknown drug levels in breastfed infants.

Adverse reactions

Very common > 10%

•

↓ blood lymphocyte count, ↓ platelet count, ↓ serum phosphate, ↓ serum potassium, ↓ serum sodium, heart failure, ↑ liver enzymes, low oxygen levels, maculopapular rash, nephrotoxicity, blurred vision, cough, dry mouth, dysesthesia, dyspepsia, dyspnea, fatigue, headache, skin rash, retinal pathology, skin dryness

Common 1-10%

•

Acneiform lesions, ↓ WBC count, ↓ blood neutrophil count, gastrointestinal bleeding, hypertension, hypocalcemia, ↑ serum TBIL, ↑ serum potassium, photosensitivity of skin, pneumonitis, pulmonary edema, chills, diarrhea, fever, hematuria, itching, nausea, visual disturbances, vomiting, respiratory failure, retinal detachment, skin cancer, stomatitis

Uncommon < 1%

•

↓ serum albumin, ICH

Unknown frequency

•

Cardiomyopathy, ecchymosis, gastritis, gastroesophageal reflux, influenza virus infection, macular edema, menorrhagia, ocular hemorrhage, oral ulcers, peripheral edema, pharyngitis, purpura, hematemesis, hemoptysis, malaise, melena, nosebleed, vaginal bleeding, retinal hemorrhage, rhabdomyolysis

Interactions

Drug(s)

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