What Binimetinib Is Used For

• Binimetinib is used in combination with encorafenib (Braftovi) to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed with surgery and that has specific BRAF gene mutations.
• Important note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Binimetinib Is Given

• Binimetinib is a tablet, taken by mouth two times a day, about 12 hours apart.
• Binimetinib may be taken with or without food.
• Take binimentinib exactly as your healthcare provider tells you to take it. Do not change you dose or stop taking binimetinib unless your healthcare provider tells you to.
• If you miss a dose of binimetinib, take it as soon as you remember. If it is within 6 hours of your next scheduled dose, take you next dose at your regular time. Do not make up for the missed dose.
• Do not take an extra dose if you vomit after taking your scheduled dose. Take your next dose at your regular time.
• The amount of binimetinib that you will receive depends on many factors, including your liver function, your general health or other health problems, and the type of cancer or condition you have. Your doctor will determine your exact dosage and schedule.

Side Effects

Important things to remember about the side effects of binimetinib (when administered with encorafenib):

Most people will not experience all of the binimetinib side effects. Side effects are often predictable in terms of their onset, duration, and severity. Side effects are almost always reversible and will go away after treatment is complete. Side effects may be quite manageable. There are many options to minimize or prevent the side effects of binimetinib.

The following side effects are common (occurring in greater than 30%) for patients taking binimetinib with encorafenib:

• Fatigue
• Nausea and vomiting
• Diarrhea
• Increased serum creatinine 

These are less common side effects (occurring in 10-29%) for patients receiving binimetinib with encorafenib:

• Abdominal pain
• Fever
• Edema (swelling)
• Constipation
• Rash
• Dizziness
• Visual impairment
• Bleeding problems
• High blood pressure
• Elevated liver enzymes

Not all side effects are listed above. Side effects that are very rare -- occurring in less than about 10 percent of patients -- are not listed here. But you should always inform your health care provider if you experience any unusual symptoms.

When to Contact Your Doctor or Health Care Provider

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Shortness of breath, wheezing, difficulty breathing, closing up of the throat, swelling of facial features, hives (possible allergic reaction).

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Shortness of breath, wheezing, difficulty breathing, closing up of the throat, swelling of facial features, hives (possible allergic reaction).

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Nausea (interferes with ability to eat and unrelieved with prescribed medication)
• Vomiting (vomiting more than 4-5 times in a 24-hour period)
• Diarrhea (4-6 episodes in a 24-hour period)
• Unusual bleeding or bruising
• Black or tarry stools, or blood in your stools
• Coughing up or vomiting blood
• Blood in the urine
• Extreme fatigue (unable to carry on self-care activities)
• Lightheadedness or dizziness
• Heart pounding or racing
• Any sudden change in eyesight (blurred or distorted vision, halos, partly missing vision)
• Stomach pain
• Sudden shortness of breath or trouble breathing
• Pain in legs with or without swelling
• Swelling in arms or legs that occurs in one leg or arm, but not the other

Always inform your health care provider if you experience any unusual symptoms.

Precautions

• Before starting binimetinib treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.).
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Binimetinib may cause harm to the fetus when given to a pregnant woman.

For women: Use contraceptives, and do not conceive a child (get pregnant) while taking binimetinib and for up to 30 days after last dose of binimetinib. Barrier methods of contraception, such as condoms, are recommended.

Do not breastfeed while taking binimetinib or for up to three days after the final dose of binimetinib.

Self-Care Tips

• If you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals. Sucking on lozenges and chewing gum may also help.
• Drink plenty of water.
• Follow regimen of anti-diarrhea medication as prescribed by your health care professional.
• Eat foods that may help reduce diarrhoea.
• Get plenty of rest.
• Maintain good nutrition.
• Remain active as you are able. Gentle exercise is encouraged, such as a daily walk.
• Binimetinib can cause visual changes, dizziness and tiredness. If you have any of these symptoms, use caution when driving a car, using machinery, or anything that requires you to be alert and make sure your provider is aware.
• If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing While Taking Binimetinib

• You will be checked regularly by your health care professional while you are taking binimetinib to monitor side effects and check your response to therapy. You will have regular tests to assess your heart, eye, and liver health. You may have blood work done as well.

How Binimetinib Works

• Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells. To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that they divide rapidly. Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects.
• Targeted therapy is about identifying other features of cancer cells. Scientists look for specific differences in the cancer cells and the normal cells. This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects. Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells.
• There are different types of targeted therapies, defined in three broad categories. Some targeted therapies focus on the internal components and function of the cancer cell. The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. There are several types of targeted therapy that focus on the inner parts of the cells. Other targeted therapies target receptors that are on the outside of the cell. Therapies that target receptors are also known as monoclonal antibodies. Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.
• Binimetinib is a targeted therapy that targets the MEK 1 and MEK 2 protein (kinase) within the cancer cell. It is usually given in combination with the BRAF kinase inhibitor encorafenib.
• The BRAF gene plays an important role in both normal and cancer cells. This gene leads to the production of BRAF protein. This protein is normally part of a chain of molecules that relay a signal that tells cells how to grow and divide. A change in the BRAF gene (called a mutation) can alter the way that BRAF protein works. Instead of waiting for its turn to signal a cell to divide or grow, the BRAF protein is out of control and signals all of the time, this out of control BRAF signaling may drive the uncontrolled growth of cancer cells. MEK 1-2 are proteins further down the chain of molecules in this pathway. Binimetinib interferes with the signal at the MEK 1-2 part of the chain, this interference may cause a slowdown in the growth of cancer.

References:

http://chemocare.com/chemotherapy/drug-info/binimetinib.aspx

https://www.medicines.org.uk/emc/product/9501/smpc#POSOLOGY

https://reference.medscape.com/drug/mektovi-binimetinib-1000139

https://en.wikipedia.org/wiki/Binimetinib

https://pubchem.ncbi.nlm.nih.gov/compound/Binimetinib#section=3D-Conformer

https://www.ema.europa.eu/en/documents/product-information/mektovi-epar-product-information_en.pdf

https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/binimetinib

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf

https://go.drugbank.com/drugs/DB11967