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Treatment Name: Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®)

Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®) is a Chemotherapy Regimen for Melanoma

How does vemurafenib + cobimetinib work?
Each of the medications in vemurafenib + cobimetinib are designed to not only kill melanoma cells, but prevent the development of new skin cancers. They work by shutting off signals within the cancer cell that constantly tells the cell to grow and divide. These signals are known as “RAF” and “MEK” signals.

Goals of therapy:
If melanoma has spread to multiple areas in the body or is metastatic, vemurafenib + cobimetinib are taken to shrink melanoma cells and decrease symptoms from melanoma. The combination of vemurafenib + cobimetinib is not commonly given with the goal of cure.


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Usual starting doses:

  • Vemurafenib 960 mg (four 240 mg tablets) by mouth TWICE Daily (continuously, no rest period)
  • Cobimetinib 60 mg (three 20 mg tablets) by mouth ONCE Daily for 21 days, followed by 7 days of rest (no medication taken during the last week)

*It is important to note, one of these medications (vemurafenib) is taken TWICE daily, while the other (cobimetinib) is taken ONCE daily. Cobimetinib may be taken at the same time as vemurafenib

Information on FDA-approved tests for specific mutations, such as BRAF V600E, can be found here.

Vemurafenib + cobimetinib are usually taken at home. Vemurafenib is taken twice daily continuously for 28 days straight, while cobimetinib is taken for 21 days straight, then NOT taken for 7 days. This is known as one Cycle. Each cycle is 28 days (4 weeks) and may be repeated until it is no longer working or until unacceptable side effects are seen. The first day of Cycle 2 can also be thought of as Day 29.

Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported side effects with vemurafenib + cobimetinib are shown here:

  • Diarrhea (57%)
  • Nausea (39%)
  • Rash (39%)
  • Joint pain (33%)
  • Fatigue (32%)
  • Increased muscle breakdown [creatine kinase increase] (31%)
  • Skin sensitivity (28%)
  • Fever (26%)
  • Liver dysfunction (up to 24%)
  • Vomiting (21%)
  • Hair loss (15%)
  • Eye problems (up to 13%)
  • Decrease in heart pumping ability (8%)
  • Altered heart rhythm (4%)
  • New squamous cell carcinoma skin cancer (3%)
  • Bleeding (13%), Severe bleeding (1%)

Of the side effects listed above, most were mild or moderate. Up to 6% were noted to be severe side effects. Roughly 13% of patients discontinued treatment due to unacceptable side effects.

Side effect videos Side Effect Videos
DiarrheaDiarrheaNausea and VomitingNausea and VomitingPainPainFatigue Fatigue Hair LossHair Loss


How often is monitoring needed?
Labs (blood tests) may be checked before treatment, weekly during the 1st month, then as needed until stable. Labs often include: a blood test called “BRAF V600E mutation” test, which helps predict the chance of responding to these medications, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Creatine Phosphokinase (CPK), Lactate Dehydrogenase, Magnesium, Phosphorous, plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment, then up to every 8 weeks while receiving therapy. Imaging may include: x-rays, computerized tomography (CT scan), magnetic resonance imaging (MRI scan).

How might blood test results/imaging affect treatment?
It is recommended that treatment with vemurafenib NOT begin if the time to make a heart beat is too long when using an ECG to measure the heart beat duration.

It is recommended that treatment with cobimetinib NOT begin if the strength of each heart beat is too weak when using an echocardiogram (“Echo”) to measure this. An Echo should be performed before therapy, 1 month after starting, and every 3 months while receiving treatment.

Tests obtained from the CMP used to evaluate kidney and liver function, such as SCr, AST, ALT, often increase in patients taking vemurafenib + cobimetinib. Your doctor will monitor the SCr, AST, and ALT (using the CMP blood test) to determine if it is safe to continue

Depending upon the results, your doctor may advise to continue Vemurafenib + cobimetinib as planned, reduce either or both of their doses, delay, or switch therapy.

ChemoExperts Tips

  • As many as 1 in 5 patients who take vemurafenib alone may develop a second type of skin cancer known as “squamous cell carcinoma.” These new skin cancers usually develop in the first 2 – 3 months of therapy with vemurafenib, unless other medications such as cobimetinib, are taken to prevent them from developing. Additional surgical procedures may be needed to remove these cancers and therapy with vemurafenib may usually continue
  • Of the patients that experienced any hair loss, it was usually not obvious from a distance and could be seen only on close inspection. For a few patients, a different hair style may help cover up hair loss. A wig or hair piece to camouflage hair loss is almost never required for patients receiving this regimen
  • Sun sensitivity may occur with vemurafenib. When outside, patients should wear protective clothing, suncscreen with SPF 30 or greater, and use a chapstick with SPF of 30 or greater
  • Skin rash, when it occurs, begins most commonly 11 days after therapy with cobimetinib is started, but may range from 3 days to 3 months. It can be mild, moderate, or severe, although severe rash is seen in 3%. After stopping therapy, patients with moderate or severe rash often need 21 days for the rash to completely go away, however it can take longer
  • An eye problem known as “uveitis” can develop in about 2% of patients taking vemurafenib. Uveitis may cause it difficult to tolerate any light as well as blurred vision. Treatment may consist of steroid eye drops with or without a medication to dilate the pupils
  • If vemurafenib is taken with a high-fat-containing meal, absorption of the medication may increase by 200% or more leading to additional, or more severe side effects. Consider taking vemurafenib on an empty stomach with a large glass of water if possible
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • If you are hospitalized, bring your vemurafenib and cobimetinib with you as most hospitals will need to use the patient’s own supply
  • Clinical trials may exist for melanoma. Ask your doctor if any studies are currently enrolling in your area. If not, go to to search for other centers offering study medications.

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®). Depending upon your income, they may be able to help cover the cost of:

  • Vemurafenib
  • Cobimeti­nib

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with Vemurafenib (Zelboraf®) + Cobimetinib (Cotellic®)

Individual Drug Label Information

Vemurafenib (Zelboraf®)

  • Vemurafenib is a tablet available in a 240 mg strength only  
  • A specific test, approved by FDA, known as the “BRAF V600E mutation,” is recommended before starting vemurafenib therapy to determine the chance that the medication will kill melanoma cells. If the mutation is NOT detected, then the chance of vemurafenib working may be low 
  • New, non-melanoma skin cancers can occur. Skin evaluations are recommended every 2 months while receiving vemurafenib therapy and for 6 months after the last dose. If a new non-melanoma skin cancer occurs, it can often be removed, without having to stop vemurafenib therapy 
  • Hypersensitivity reactions are rare, but may include a generalized rash, redness, low blood pressure, or a more serious reaction with systemic symptoms 
  • Vemurafenib may slow the time it takes to make a heart beat. If it slows too much, an abnormal rhythm called an “arrhythmia” may develop. A simple test known as an electrocardiogram (ECG or “EKG”) is recommended before starting therapy to make sure the heart is healthy enough for treatment 
  • In clinical trials, vemurafenib was given without regard to food. Therefore, vemurafenib can be taken with or without food, swallowed whole with a large glass of water. Importantly, when taken with a high fat meal, vemurafenib absorption may increase to as much as 500%, thereby increasing the risk of side effects. 
  • Each dose of vemurafenib should be taken roughly 12 hours apart. If a dose is missed, it can be taken up to 4 hours before the next dose. 
  • Vemurafenib should be stored at room temperature and in the original container. If any doses go unused, call your local police or fire department for advice on disposing it rather than throwing it in the garbage or flushing it down the toilet 
  • Vemurafenib may increase side effects from many common medications, such as dextromethorphan found in Delsym® or Robitussin® cough syrups. Lower doses of these medications may need to be taken to avoid side effects.  
  • May increase sensitivity to warfarin and increase bruising or bleeding risk. Lower doses of warfarin may be needed when starting vemurafenib therapy 
  • May cause fetal harm, avoid this drug during pregnancy. Women of childbearing potential along with men should use appropriate birth control measures during vemurafenib and for at least 2 months the last dose of vemurafenib 
General Vemurafenib (Zelboraf) Side Effects 
  • Rash and sun-sensitivity are common. Patients taking vemurafenib should avoid direct and prolonged sun exposure and use sun screen when outside to prevent sunburn 
  • Eye problems may occur. Seek an eye doctor if you notice any change in vision or eye pain 
  • Bone pain 
  • Fatigue 
  • Hair loss 
  • Nausea 
  • Diarrhea 
  • Itching 
  • Headache 
  • Taste alteration or decreased appetite 
  • Swelling in legs or feet 
  • Fever 
  • Sensitivity to areas that have received radiation therapy 
  • Liver problems, which may require dose reduction or stopping therapy 
  • Click on the vemurafenib (Zelboraf) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPain

See DailyMed package insert.

Cobimeti­nib (Cotellic®)

  • Cobimetinib is a tablet available in a 20 mg strength only 
  • A specific test, approved by FDA, known as the “BRAF V600E” or BRAF V600K” mutation, is recommended before starting cobimetinib therapy to determine the chance that the medication will kill melanoma cells. If the mutation is NOT detected, then the chance of cobimetinib working may be low  
  • New skin cancers can occur. Skin evaluations are recommended before starting, every 2 months while receiving cobimetinib therapy, and for 6 months after the last dose. If a new non-melanoma skin cancer occurs, it can often be removed, without having to stop cobimetinib therapy 
  • Major bleeding can occur. Watch out for signs or symptoms of bruising or bleeding. 
  • May cause heart problems. An echocardiogram (“Echo”) is recommended before beginning therapy with cobimetinib to ensure that the heart is healthy enough for treatment 
  • Severe skin rash may require a dose reduction, stopping therapy for a brief time, or stopping altogether, 
  • Food does NOT affect the absorption of cobimetinib. Therefore, cobimetinib may be taken with or without food, swallowed whole with a large glass of water. 
  • May cause eye problems, requiring drug discontinuation. It is recommended that an eye doctor evaluate any trouble with vision 
  • Tell you doctor if you experience any muscle pain as this may be a sign of a serious condition known as rhabdomyolysis 
  • If you miss a dose, or vomit up a dose, resume therapy with the next scheduled dose. Do not take an extra dose to make up for a missed dose 
  • Cobimetinib should be stored at room temperature. If any doses go unused, call your local police or fire department for advice on disposing it rather than throwing it in the garbage or flushing it down the toilet 
  • Dosage adjustments may be required liver, kidney, heart, skin, or eye problems 
  • May interact with ciprofloxacin or other antibiotics, certain anti-seizure medications, and some oral antifungal medications such as fluconazole, as well as over-the-counter herbal products. Avoidance of these products or a dose reduction of cobimetinib is usually advised
  • May cause fetal harm, avoid this drug during pregnancy. Women of childbearing potential along with men should use appropriate birth control measures during cobimetinib and for at least 2 months the last dose of cobimetinib 
General Cobimetinib (Cotellic) Side Effects 
  • Diarrhea 
  • Sun-sensitivity is common. Patients taking cobimetinib should avoid direct and prolonged sun exposure and use sun screen when outside to prevent sunburn 
  • Nausea 
  • Fever 
  • High blood pressure 
  • Vision problems 
  • Vomiting 
  • Mouth sores 
  • Bleeding 
  • Click on the cobimetinib (Cotellic) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaBleedingBleeding

See DailyMed package insert.

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Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867-1876.

Created: March 30, 2016 Updated: October 3, 2018

What is Melanoma?

A disease of the melanocytes found in the skin. Melanoma is a rare diagnosed condition. The risk of melanoma may increase with increased exposure to UV light. Melanoma may be hereditary. Melanoma may occur in areas that do not receive much sun light, such as the bottom of a foot. It may also occur in places other than skin, such as the eye. The stage of melanoma can vary at diagnosis and throughout treatment. Stages of melanoma include Stage I, II, III, and IV. The effectiveness of the treatment may depend upon the stage at diagnosis.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

FDA-approved mutation tests

Note: You may have to scroll to bottom and click on page "2" or page "3," as this document has several pages:

FDA-approved mutation tests

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

14) Serum calcium

What is a CPK?

Creatine phosphokinase is a muscle breakdown product and can increase in the blood if the either muscle is rapidly breaking down, the kidneys are not working well, or both. An elevation well above the normal range, may suggest muscle damage

What if the QTc interval is too long?

If the “QTc” interval, which measures the time to make one heart beat, is greater than 500 milliseconds, it recommended to fix any electrolyte problems and discontinue any medications associated with increasing the QTc interval if they are not needed. It is also recommended that treatment with cobimentinib NOT begin until the QTc interval has been corrected.

How strong must the heart pump to receive treatment?

The Left ventricular ejection fraction, better known as the “LVEF” measures the strength of the heart beat and should be above 50% prior to starting therapy.

Time to develop additional skin cancer

  • When vemurafenib and cobimetinib are taken together, the new cancers most commonly appear after 4 months of therapy, but can range from as few as 27 days to as long as 13 months
  • Combination therapy reduces squamous cell carcinoma skin cancer from 20% to 6%, compared to vemurafenib alone
  • Combination therapy reduces basal cell carcinoma skin cancer from 4.5% to 2.4%, compared to vemurafenib alone

Check to see if you are taking these medications:

Blood thinners such as warfarin, oral anticoagulants, or injectable anticoagulants should be used with caution as vemurafenib + cobimetinib therapy can increase the risk of serious bleeding

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.