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Cobimetinib Dosage

Applies to the following strength(s): 20 mg

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Melanoma - Metastatic

60 mg orally once a day for first 21 days of each 28-day cycle

Duration of therapy: Until disease progression or unacceptable toxicity

Comments: The presence of BRAF V600E or V600K mutation in tumor specimens should be confirmed with an FDA-approved test prior to treatment initiation; information on FDA-approved tests available at http://www.fda.gov/CompanionDiagnostics.

Use: In combination with vemurafenib, indicated for treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.

Renal Dose Adjustments

-Mild (CrCl 60 to 89 mL/min) to Moderate (CrCl 30 to 59 mL/min) Renal Impairment: No adjustment recommended.
-Severe (CrCl less than 30 mL/min) Renal Impairment or End-Stage Renal Disease: Data not available; no recommended dose.

Liver Dose Adjustments

-Mild (Child-Pugh A), Moderate (Child-Pugh B), and Severe (Child-Pugh C) Hepatic Impairment: No adjustment in the starting dose recommended.

Liver Laboratory Abnormalities and Hepatotoxicity Occur During Treatment:
First Occurrence Grade 4:
-Withhold treatment for up to 4 weeks.
-Resume at next lower dose if improved to Grade 0 or 1; permanently discontinue drug if not improved to Grade 0 or 1 within 4 weeks.
-Permanently discontinue drug for recurrent Grade 4 abnormalities/hepatotoxicity.

-First Dose Reduction: 40 mg orally once a day
-Second Dose Reduction: 20 mg orally once a day
-Permanently discontinue drug if patient unable to tolerate 20 mg orally once a day.

Dose Adjustments

Moderate or Strong CYP450 3A Inhibitors:
-Avoid concomitant use.
-If a patient is taking cobimetinib 60 mg once a day and is required to use a moderate CYP450 3A inhibitor for 14 days or less concurrently, reduce the dose of cobimetinib to 20 mg. Resume cobimetinib 60 mg dose after the moderate CYP450 3A inhibitor is discontinued.
-Use an alternative to a strong or moderate CYP450 3A inhibitor if a patient is taking a reduced dose (20 to 40 mg once a day) of cobimetinib.

Moderate or Strong CYP450 3A Inducers:
-Avoid concomitant use.

FOR THE FOLLOWING ADVERSE REACTIONS:
-First Dose Reduction: 40 mg orally once a day
-Second Dose Reduction: 20 mg orally once a day
-Permanently discontinue drug if patient unable to tolerate 20 mg orally once a day.

CARDIOMYOPATHY:
Asymptomatic, Absolute Decrease in Left Ventricular Ejection Fraction (LVEF) from Baseline of Greater than 10% AND Less than Institutional Lower Limit of Normal (LLN):
-Withhold treatment for 2 weeks; repeat LVEF.
-Resume at next lower dose if LVEF at or above LLN AND absolute decrease from baseline LVEF 10% or less.
-Permanently discontinue treatment if LVEF less than LLN OR absolute decrease from baseline LVEF is more than 10%.

Symptomatic LVEF Decrease from Baseline:
-Withhold treatment for up to 4 weeks; repeat LVEF.
-Resume at next lower dose if symptoms resolve, LVEF at or above LLN, AND absolute decrease from baseline LVEF 10% or less.
-Permanently discontinue drug if symptoms persist, LVEF less than LLN, OR absolute decrease from baseline LVEF more than 10%.

HEMORRHAGE:
Grade 3:
-Withhold treatment for up to 4 weeks.
-Resume at next lower dose if improved to Grade 0 or 1.
-Permanently discontinue drug if not improved within 4 weeks.

Grade 4:
-Permanently discontinue drug.

GRADE 4 CREATINE PHOSPHOKINASE (CPK) ELEVATION or ANY CPK ELEVATION and MYALGIA:
-Withhold treatment for up to 4 weeks.
-Resume at next lower dose if improved to Grade 3 or lower.
-Permanently discontinue drug if not improved within 4 weeks.

GRADE 2 (INTOLERABLE), 3, or 4 DERMATOLOGIC REACTIONS:
-Withhold drug or reduce dose.

GRADE 2 (INTOLERABLE), 3, or 4 PHOTOSENSITIVITY:
-Withhold drug for up to 4 weeks.
-Resume at next lower dose if improved to Grade 0 or 1.
-Permanently discontinue drug if not improved within 4 weeks.

RETINAL VEIN OCCLUSION:
-Permanently discontinue drug.

SEROUS RETINOPATHY:
-Withhold drug for up to 4 weeks.
-Resume at next lower dose if signs and symptoms improve.
-Permanently discontinue drug if not improved or symptoms recur at the lower dose within 4 weeks.

OTHER ADVERSE REACTIONS:
Grade 2 (Intolerable) or 3 Adverse Reaction:
-Withhold drug for up to 4 weeks.
-Resume at next lower dose if improved to Grade 0 or 1.
-Permanently discontinue drug if not improved within 4 weeks.

First Occurrence of Grade 4 Adverse Reaction:
-Withhold drug for up to 4 weeks.
-Resume at next lower dose OR permanently discontinue drug if improved to Grade 0 or 1.

Recurrent Grade 4 Adverse Reaction:
-Permanently discontinue drug.

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:
-This drug can be taken with or without food.
-If a dose is missed or if vomiting occurs when a dose is taken, resume dosing with the next scheduled dose.

Storage Requirements:
-This drug should be stored at room temperature below 30 degrees Celsius (86 Fahrenheit).

General:
-This drug is not indicated for patients with wild-type BRAF melanoma.
-Administration of this drug with vemurafenib results in increased apoptosis and reduced tumor growth in tumor cell lines harboring BRAF V600E mutations since these drugs target different kinases in the RAS/RAF/MEK/ERK pathway.
-This drug also prevented vemurafenib-mediated growth enhancement of a wild-type BRAF tumor cell line in an in vivo mouse implantation model.
-There is no information on overdosage with this drug.

Monitoring:
-Cardiovascular: LVEF (prior to treatment initiation, 1 month after initiation, and every 3 months thereafter until treatment discontinuation); in patients restarting treatment after a dose reduction or interruption: LVEF (at 2, 4, 10, and 16 weeks during treatment and periodically as clinically indicated); ECG and electrolytes (before treatment initiation and routinely during treatment)
-Hepatic: Liver lab tests (before treatment initiation and at least monthly during treatment)
-Musculoskeletal: Baseline serum CPK and creatinine levels (prior to treatment initiation, and periodically during treatment)
-Ocular: Ophthalmological evaluation (at regular intervals and any time a patient reports new or worsening visual disturbances)
-Oncology: Cutaneous and non-cutaneous malignancies; dermatologic evaluations (prior to treatment initiation and every 2 months during therapy up to 6 months following last dose)

Patient Advice:
-Avoid grapefruit, grapefruit juice, and St. John's Wort during treatment.
-This drug can make your skin sensitive to sunlight. Wear clothes that protect your skin, and use sunscreen and lip balm with SPF 30 or higher to help protect against sunburn.
-Use effective contraception during treatment and for 2 weeks after the last dose if you are a female patient with childbearing potential.
-Do not breastfeed during treatment and for 2 weeks after the final dose.

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