Ziftomenib (Komzifti™)

How to Take Ziftomenib

This medication comes in tablet form that you take by mouth once a day, at about the same time each day. This medication should be taken on an empty stomach (at least 1 hour before or 2 hours after a meal). Take the tablets whole with a glass of water. Do not open, break, or chew the tablets.

If a dose is missed or not taken at the usual time, take the dose as soon as you remember, but at least 12 hours before the next scheduled dose. Return to the normal schedule on the next day. Do not take 2 doses within 12 hours.

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, Seville oranges (often used in marmalade), St. John's Wort, itraconazole, erythromycin, fluconazole, rifampin, and diltiazem, among others. Be sure to tell your healthcare provider about all medications and supplements you take.

Tell your provider if you are taking other medications that can prolong your heart’s QT interval. These medications can be antiarrhythmics (like amiodarone, sotalol, quinidine), antipsychotics (like haloperidol, quetiapine), antibiotics (like macrolides and fluoroquinolones), and certain antidepressants. You may need an ECG before, during, and after treatment with ziftomenib to track your QT interval.

You should not take certain "heartburn" medications called proton pump inhibitors while being treated with ziftomenib, as these may affect how this medication is absorbed. Some proton pump inhibitors are Prilosec (omeprazole), Nexium (esomeprazole), and Protonix (pantoprazole). Do not take ziftomenib at the same time as other heartburn medications:

• Take ziftomenib 2 hours before or 10 hours after taking an H2 receptor antagonist like Pepcid (famotidine) and cimetidine (Tagamet HB).
• Take ziftomenib 2 hours before or 2 hours after taking antacids, such as Tums (calcium-carbonate) and Rolaids (Calcium Carbonate and Magnesium Hydroxide).

If needed, please ask your provider what the best “heartburn” medication is to use and when to take it.

Storage and Handling

Store your medication in the original, labeled container at room temperature and in a dry location (unless otherwise directed by your provider or pharmacist). 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?

Ziftomenib is available through select specialty pharmacies. Your oncology team will work with your prescription drug plan to identify an in-network specialty pharmacy for distribution of this medication and shipment directly to your home.

Insurance Information

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

Possible Side Effects of Ziftomenib

There are a number of things you can do to manage the side effects of ziftomenib. Talk to your provider 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:

Infection and Low White Blood Cell Count (Neutropenia)

This medication can cause life-threatening infections, with or without a decrease in white blood cell counts. Your provider may prescribe medications to prevent certain infections that can develop with this treatment.

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.

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 including 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 oncology care team before scheduling dental appointments or procedures.
• Ask your oncology care team before you, or someone you live with has any vaccinations.

Differentiation Syndrome

Differentiation syndrome is caused by the changes that ziftomenib makes to blood cell production in patients with leukemia. Symptoms of differentiation syndrome are fever (temperature higher than100.4°F or 38°C), sudden weight gain, bone or joint pain, and fluid build-up around the heart, lungs, and/or chest, causing shortness of breath or having a hard time breathing. This syndrome is treated with high doses of steroids (like dexamethasone or prednisone) and diuretics (fluid pills). Your provider will monitor for these signs or symptoms, but it is also important for you to tell your provider right away if you have any of these symptoms.

Hemorrhage/Bleeding

You may have minor bleeding, such as a nosebleed. Serious bleeding has also occurred in patients treated with this medication, including coughing up blood, bleeding into the stomach, blood in stool, vomiting blood, bleeding in the brain (stroke), nosebleeds, blood in the urine, and more. People who have had serious bleeding should not take this medication. Tell your provider right away if you notice bleeding of any kind.

Diarrhea

Your provider 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 to 10 glasses of non-alcoholic, un-caffeinated fluid a day to prevent dehydration.

Nausea and/or Vomiting

Talk to your provider 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 provider 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.

Peripheral Edema

Peripheral edema is swelling of the extremities caused by retention of fluid. It can cause swelling of the hands, arms, legs, ankles and feet. The swelling can become uncomfortable. Tell your provider if you have any new or worsening swelling.

Muscle or Joint Pain/Aches

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

Pruritus (Itching)

This medication can make you feel itchy. You may be given skin care instructions to lessen the itch. Skin care can also prevent infection due to scratching.

Some ways to lessen itching may be to:

• Limit baths and use the shower instead. Avoid hot water when washing or bathing. Wash only with gentle, soap-free cleansers.
• After washing, gently dry your skin. Pat the area dry (don't rub) with a soft towel.
• Use lotions and moisturizers daily if your provider says it is okay to do so. Choose gentle lotions without perfumes or dyes.
• Wear natural fibers like cotton or linen clothing. Choose loose clothing that doesn't rub against your skin.
• Drink 6 to 8 eight-ounce glasses of non-alcoholic fluids each day. Keeping hydrated can keep your skin moist and less itchy.
• Keep your fingernails short to prevent scratching yourself.
• If you are feeling itchy, placing lotion or a cool washcloth on the area may lessen the urge to scratch.

Medications, such as antihistamines, sedatives, or antidepressants may be prescribed to help with the itchiness.

Liver Toxicity

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

Electrolyte Changes

This medication can affect the normal levels of electrolytes (sodium, potassium, etc.) in your body. Your levels will be monitored using blood tests. If your levels become too low, your provider may prescribe certain electrolytes to be given by IV or taken by mouth. Do not take any supplements without first consulting with your provider.

Important but Less Common Side Effects

• QT prolongation: This medication can cause slow or abnormal heartbeats or an abnormal heart rhythm called QT prolongation. Your provider may ask you to have an EKG before you start treatment and during treatment. Tell your provider right away if you feel abnormal heartbeats or if you feel dizzy or faint.

Sexual & 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. For females, effective birth control is necessary during treatment and for 6 months after your last dose, even if your menstrual cycle stops. For males, effective birth control is necessary during treatment and for 3 months after your last dose, even if you believe you are not producing sperm. You may want to consider sperm banking or egg harvesting if you might wish to have a child in the future. Talk about these options with your provider. You should not breastfeed while taking this medication and for 2 weeks after your last dose.