Avutometinib & Defactinib (Avmapki™ Fakzynja™)

How to take Avutometinib & Defactinib

Avutometinib is a capsule taken by mouth. If you miss a dose of Avutometinib by more than 24 hours, skip the missed dose and take the next scheduled dose as prescribed. Defactinib is a tablet taken by mouth. If you miss a dose of Defactinib by more than 6 hours, skip the missed dose and take the next scheduled dose as prescribed. Both of these medications should be taken whole and with food. You should not open, crush, break, or chew these medications. Do not take two doses to make up for a missed dose. If you vomit after taking your dose, do not take another dose. Take the next dose at its normally scheduled time. Consult with your pharmacist or provider if you are having trouble swallowing the medication.

It is important to make sure you are taking the correct amount of medication every time. Before every dose, check that what you are taking matches what you have been prescribed.

The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include: grapefruit, grapefruit juice, verapamil, ketoconazole, rifampin, phenytoin, St. John’s wort, and modafinil. This medication can also impact Coumadin/Warfarin (blood thinner) levels.

If possible, you should not take this medication at the same time as antacid medications (Tums, Rolaids), as these may affect how the medication is absorbed. If you are taking Coumadin, your doctor will likely switch you to a different blood thinner, as these two medications should not be taken together. Be sure to tell your healthcare provider about all medications and supplements you take.

Storage and Handling

Store your medications in the original, labeled containers in the refrigerator at 36°F to 46°F (2°C to 8°C). This medication should not be stored in a pillbox. Keep containers out of reach of children and pets.

If a caregiver prepares your dose for you, they should consider wearing gloves or pour the pills directly from their container into the cap, a small cup, or directly into your hand. They should avoid touching the pills. They should always wash their hands before and after giving you the medication. Pregnant or nursing women should not prepare the dose for you. Ask your oncology team where to return any unused medication for disposal. Do not flush down the toilet or throw in the trash.

Where do I get this medication?

Certain cancer medications are only available through specialty pharmacies. If you need to get this medication through a specialty pharmacy, your provider will help you start this process. Where you can fill your prescriptions may also be influenced by your prescription insurance plan. Ask your provider or pharmacist for assistance in identifying where you can get this medication.

Insurance Information

This medication may be covered under your prescription drug plan. Patient assistance may be available to qualifying individuals depending on prescription drug coverage. Co-pay cards, which reduce your co-pay responsibility for eligible commercially (non-government sponsored) insured patients, may also be available. Your provider can help you find these resources if they are available.

Possible Side Effects of Avutometinib & Defactinib

There are a number of things you can do to manage the side effects of avutometinib and defactinib. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Increased Creatine Phosphokinase (CPK) & Rhabdomyolysis

This medication can lead to an elevated level of the enzyme creatine phosphokinase (CPK) in your blood. In rare cases, very high CPK levels can indicate a serious condition called rhabdomyolysis which is when damaged muscle tissue releases proteins and electrolytes into the blood causing serious muscle weakness and pain. Your provider will monitor your creatine phosphokinase levels to monitor you for this side effect.

Symptoms of Rhabdomyolysis are:

• New or worsening muscle pain or tenderness.
• Muscle weakness.
• Dark, reddish-brown urine (like tea or cola).
• Feeling very tired.

Tell your healthcare provider right away if you have any of these symptoms.

Rash/Itching/Dry Skin

Some patients may develop a rash, scaly skin, or red itchy bumps. Use an alcohol free moisturizer on your skin and lips; avoid moisturizers with perfumes or scents. Your oncology care team can recommend a topical medication if itching is bothersome. If your skin does crack or bleed, be sure to keep the area clean to avoid infection. Be sure to notify your oncology care team of any rash that develops, as this can be a reaction. They can give you more tips on caring for your skin.

In rare cases, this medication can also lead to Severe cutaneous adverse reactions (SCARs). These are rare but serious allergic reactions that affect the skin and mucous membranes. These skin reactions often start as a rash or painful blister and can progress (get worse) to serious damage to the skin and, in some cases, death. If you notice a new rash, have a fever and flu-like symptoms, lesions on mucuous membranes, or swollen lymph nodes, call your care team right away.

Nausea and/or Vomiting

Talk to your oncology care team so they can prescribe medications to help you manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try saltines or ginger ale to lessen symptoms.

Call your oncology care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your provider for helpful tips on dealing with this side effect.

Liver Toxicity

This medication can cause liver toxicity, which your oncology care team may monitor for using blood tests called liver function tests. Notify your healthcare provider if you notice yellowing of the skin or eyes, your urine appears dark or brown, or you have pain in your abdomen, as these can be signs of liver toxicity.

Ocular Toxicities (Eye Problems)

This medication can cause problems with your eyes, including keratitis and retinal pigment epithelial detachment. Tell your care team about any new or worsening vision or eye symptoms, such as blurry vision, redness, eye pain, excess tears or discharge from your eye, sensitivity to light, or a feeling that something is in your eye. You may need to see an ophthalmologist for treatment.

Diarrhea

Your oncology care team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals and seeds. Soluble fiber is found in some foods and absorbs fluid, which can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange sections, boiled potatoes, white rice, products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses on non-alcoholic, un-caffeinated fluid a day to prevent dehydration.

Muscle or Joint Pain

Your healthcare provider can recommend medications and other strategies to help relieve pain.

Swelling (Edema)

This medication can cause a buildup of fluid and swelling (edema) in the face, especially around the eyes, and extremities (arms and legs). It may also cause a buildup of fluid and swelling in the lower abdomen (belly). This can be a sign of other problems, so be sure to report any abnormal swelling to your healthcare team for further testing.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your doctor or nurse know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4°F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal. The most common infection related to this medication is a urinary tract infection. Symptoms of urinary tract infection include frequency, urgency, and burning with urination.

Tips to preventing infection:

• Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e. those who have a cold, fever or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing like long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your care team before scheduling dental appointments or procedures.
• Ask your care team before you, or someone you live with, has any vaccinations.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your doctor or nurse know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin®, Aleve®, Advil®, etc. as these can all increase the risk of bleeding. Unless your healthcare team tells you otherwise, you may take acetaminophen (Tylenol).
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

Mouth Ulcers (Mucositis/Stomatitis)

Some who receive this medication may have sores or soreness in their mouth and/or throat. Notify your oncology care team if your mouth, tongue, inside of your cheek, or throat becomes white, ulcerated, or painful. Performing regular mouth care can help prevent or manage mouth sores. If mouth sores become painful, your doctor or nurse can recommend a pain reliever.

• Brush with a soft-bristle toothbrush or cotton swab twice a day.
• Avoid mouthwashes that contain alcohol. A baking soda and/or salt with warm water mouth rinse (2 level teaspoons of baking soda or 1 level teaspoon of salt in an eight-ounce glass of warm water) is recommended 4 times daily.
• If your mouth becomes dry, eat moist foods, drink plenty of fluids (6-8 glasses), and suck on sugarless hard candy.
• Avoid smoking and chewing tobacco, drinking alcoholic beverages, and citrus juices.

Increased Triglycerides

This medication can increase the blood levels of triglycerides. Your healthcare team may monitor your blood levels and treat the elevated levels as needed.

Constipation                                   

There are several things you can do to prevent or relieve constipation. Include fiber in your diet (fruits and vegetables), drink 8-10 glasses of non-alcoholic fluids a day, and keep active. A stool softener once or twice a day may prevent constipation. If you do not have a bowel movement for 2 to 3 days, you should contact your healthcare team for suggestions to relieve the constipation.

Abdominal (Belly) Pain

This medication can cause belly pain, with or without diarrhea. Tell your provider if you have belly pain.

Kidney Toxicity

This medication can cause kidney toxicity, which your oncology team will monitor for using blood tests to check your creatinine level. Notify your care team if you notice decreased urine output, dark colored urine, blood in the urine, or swelling in the ankles.

Reproductive Concerns                                     

Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. Effective birth control is necessary during and after treatment for 1 month after your last dose for females and 1 month after last dose for males. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should not breastfeed while taking this medication and for 2 week after the final dose.