Cobimetinib

What is Cobimetinib?

• Cobimetinib (Cotellic) is a kinase inhibitor indicated used in combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can’t be removed by surgery, and that has a certain type of abnormal gene (BRAF V600E or V600K mutation).

What are the uses of this medicine?

This medicine is used with the medicine vemurafenib, to treat a type of skin cancer called melanoma:

• that has spread to other parts of the body or cannot be removed by surgery, and
• that has a certain type of abnormal "BRAF" gene

How does this medicine work?

• Cobimetinib (koe" bi me' ti nib) is a small molecule tyrosine kinase receptor inhibitor with potent activity against the mitogen-activated extracellular regulated kinase (MEK), which is an important component of the kinase cascade in the mitogen activated protein kinase (MAPK) pathway (RAS-RAF-MEK-ERK).
• Components of the MAPK pathways are frequently mutated in patients with malignant melanoma, particularly the RAF isoform BRAF.
• BRAF-mutations cause a constitutive activation of the MAPK pathways, resulting in unregulated cell growth and proliferation.
• Inhibition of MEK has been found to be synergistic when combined with specific BRAF inhibitors as therapy of BRAF-mutated cancers.
• Clinical trials have shown that the addition of cobimetinib with vemurafenib (a specific BRAF-kinase inhibitor) results in improvements in survival in patients with melanoma who harbor the V600 BRAF mutation.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Avoid concomitant administration of Cotellic with strong (eg: itraconazole, ketoconazole, clarithromycin) or moderate CYP3A inhibitors (eg: Amprenavir, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil, and grapefruit juice) .
• Avoid concurrent use of Cotellic and strong or moderate CYP3A inducers including but not limited to carbamazepine, efavirenz, phenytoin, rifampin, and St. John's Wort.

Is this medicine FDA approved?

• It was approved for use in the United States in 2015.

How should this medicine be used?

• Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with Cotellic with vemurafenib.

Recommended Dosage:

• The recommended dosage regimen of Cotellic is 60 mg (three 20 mg tablets) orally taken once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.

Concurrent CYP3A Inhibitors

• Do not take strong or moderate CYP3A inhibitors while taking Cotellic.
• If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking Cotellic 60 mg, reduce Cotellic dose to 20 mg.

Administration

• Take Cotellic exactly as your healthcare provider tells you. Do not change your dose or stop taking Cotellic unless your healthcare provider tells you to.
• Take Cotellic one time a day for 21 days, followed by 7 days off treatment, to complete a 28-day treatment cycle.
• Take Cotellic with or without food.
• If you miss a dose of Cotellic or vomit after taking your dose, take your next dose as scheduled.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 20 mg

This medicine is available in fallowing brand namesː

• Cotellic

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• nausea
• fever
• vomiting

Cotellic may cause serious side effects, including:

• Risk of new skin cancers
• Bleeding problems
• Heart problems
• Severe rash
• Eye problems
• Liver problems
• Muscle problems (rhabdomyolysis)
• Skin Sensitivity to sunlight (photosensitivity)

What special precautions should I follow?

• Avoid sunlight during treatment with Cotellic. Cotellic can make your skin sensitive to sunlight. You may burn more easily and get severe sunburns. To help protect against sunburn:
• When you go outside, wear clothes that protect your skin, including your head, face, hands, arms, and legs.
• Use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.
• New primary malignancies, cutaneous and non-cutaneous, can occur with Cotellic. Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and for up to 6 months following the last dose of Cotellic.
• Major hemorrhagic events can occur with Cotellic. Monitor for signs and symptoms of bleeding.
• The risk of cardiomyopathy is increased in patients receiving Cotellic with vemurafenib compared with vemurafenib as a single agent. The safety of Cotellic has not been established in patients with decreased left ventricular ejection fraction (LVEF). Evaluate LVEF before treatment, after one month of treatment, then every 3 months thereafter during treatment with Cotellic.
• Severe rash and other skin reactions can occur with Cotellic. Monitor for severe skin rashes. Interrupt, reduce, or discontinue Cotellic.
• Ocular toxicities can occur with Cotellic, including serous retinopathy (fluid accumulation under layers of the retina). Perform an ophthalmological evaluation at regular intervals and for any visual disturbances. Permanently discontinue Cotellic for retinal vein occlusion (RVO).
• Hepatotoxicity can occur with Cotellic. Monitor liver laboratory tests during treatment and as clinically indicated.
• Rhabdomyolysis can occur with Cotellic. Monitor creatine phosphokinase periodically and as clinically indicated for signs and symptoms of rhabdomyolysis.
• Cotellic Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

• There is no information on overdosage of Cotellic.

Can this medicine be used in pregnancy?

• Cotellic can cause fetal harm when administered to a pregnant woman.
• There are no available data on the use of Cotellic during pregnancy.

Can this medicine be used in children?

• The safety and effectiveness of Cotellic have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: cobimetinib fumarate
• Inactive ingredients:

Tablet Core: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate Coating: polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc

Who manufactures and distributes this medicine?

• Distributed by: Genentech USA, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco,

What should I know about storage and disposal of this medication?

• Store Cotellic at room temperature below 30°C (86°F).
• Ask your healthcare provider or pharmacist how to safely throw away (dispose of) any unused or expired Cotellic.

• Dailymed label info on Cobimetinib
• FDA Cobimetinib

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