Omcazio

Omcazio (cabozantinib) is a prescription medicine used to treat certain types of kidney cancer, liver cancer, and neuroendocrine tumors. It contains the active ingredient cabozantinib, a kinase inhibitor (a targeted cancer medicine that blocks signals cancer cells use to grow).

Omcazio capsules are taken once daily, with or without food.

How is Omcazio different from other cabozantinib medicines?

Omcazio is a different salt form of cabozantinib, called the laurylsulfate salt. This changes how the drug is absorbed, so Omcazio can be taken with or without food and comes in different strengths than other cabozantinib products.

Omcazio is used to treat advanced kidney cancer, liver cancer that has already been treated with sorafenib, and certain neuroendocrine tumors. It is approved for:

• adults with advanced kidney cancer (renal cell carcinoma, or RCC), used on its own
• adults with advanced RCC, used as a first treatment in combination with nivolumab
• adults with liver cancer (hepatocellular carcinoma, or HCC) who have already been treated with sorafenib
• adults and children 12 years and older with extra-pancreatic neuroendocrine tumors (epNET, a tumor that starts in hormone-producing cells outside the pancreas). This use applies when the tumor has already been treated, cannot be removed with surgery, and is locally advanced or has spread

Omcazio has not been shown to be safe and effective for epNET in children younger than 12 years, or in children with kidney cancer or liver cancer.

If your healthcare provider prescribes Omcazio with nivolumab, also read the Medication Guide that comes with nivolumab.

Take Omcazio exactly as your healthcare provider tells you to, once a day.

• Capsules can be taken with or without food
• Swallow the capsules whole with water
• Do not crush, chew, or open the capsules
• Do not switch from Omcazio to another cabozantinib medicine without talking to your healthcare provider
• Check that you or your child received the correct product and strength each time the prescription is filled

What if I miss a dose?

Take the missed dose as soon as you can. If more than 12 hours have passed since your usual dose time, skip it and take your next dose at the normal time. Do not take two doses at once to make up for a missed dose.

Surgery and dental work

Stop taking Omcazio at least 3 weeks before any scheduled surgery, including dental surgery. This lowers the risk of bleeding and wound healing problems. After major surgery, Omcazio is not restarted for at least 2 weeks, and not until the wound has healed properly. Your healthcare provider will tell you when to start again.

What if I take too much?

Call your healthcare provider or the Poison Help line at 1-800-222-1222, or go to the nearest hospital emergency room right away. In one reported case with another form of cabozantinib, a person who took double the intended dose for 9 days developed memory and thinking problems and weight loss.

Tell your healthcare provider about all of your medical conditions before you start Omcazio, including if you:

• have had a liver problem other than liver cancer
• have had recent bleeding, including coughing up or vomiting blood, or black tarry stools. Omcazio is not given to people who have bled recently
• have an open or healing wound
• have high blood pressure
• have heart problems
• plan to have surgery or a dental procedure, or have had surgery recently

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Pregnancy

Omcazio can harm an unborn baby. Animal studies showed the loss of pregnancies and birth defects at doses lower than those used in people. Tell your healthcare provider if you are pregnant or plan to become pregnant.

If you are able to become pregnant, your healthcare provider will check whether you are pregnant before you start. Use effective birth control during treatment and for 4 months after your last dose. Talk to your provider about which methods are right for you, and tell your provider right away if you become pregnant or think you may be.

Fertility

Omcazio may make it harder to have children later. In animal studies, cabozantinib reduced fertility in both males and females. Males had lower sperm counts and smaller reproductive organs, and females had fewer live embryos and more lost pregnancies.

There are no studies of how Omcazio affects fertility in people, so the size of the risk is not known. If you may want children in the future, raise this with your healthcare provider before you start treatment.

Breastfeeding

It is not known whether cabozantinib passes into breast milk. Because of the risk of serious side effects in a breastfed baby, do not breastfeed during treatment or for 4 months after your last dose.

Children

Omcazio is approved for epNET in children aged 12 years and older. Widening of the growth plates has been seen in children whose bones are still growing, so your child's healthcare provider should monitor growth during treatment. The dose for children aged 12 and older depends on body weight.

Liver and kidney problems

If you have moderate liver impairment, your healthcare provider will prescribe a lower dose. Omcazio should be avoided if you have severe liver impairment, because it has not been studied in that situation.

No dose change is needed for mild or moderate kidney impairment. How Omcazio behaves in people with severe kidney impairment or on dialysis is not known.

Omcazio is not interchangeable with other cabozantinib medicines on a milligram-for-milligram basis. Taking the wrong cabozantinib product, or converting a dose incorrectly, can raise your risk of serious side effects or make your treatment less effective.

Check that the cabozantinib product, dose, and strength you are given are the ones your healthcare provider intended, every time your prescription is filled. Do not switch between Omcazio and another cabozantinib medicine unless your healthcare provider tells you to.

The most common side effects of Omcazio taken on its own are tiredness, nausea and vomiting, reduced appetite, weight loss, and constipation.

When Omcazio is taken together with nivolumab, the most common side effects are tiredness, mouth sores, rash, low thyroid hormone levels (hypothyroidism), pain in the muscles, bones, and joints, reduced appetite, nausea, changes in the way things taste, stomach-area pain, cough, and upper respiratory tract infection.

Serious side effects of Omcazio

Omcazio can cause serious side effects. Some of these can be life threatening. Tell your healthcare provider right away if you notice any of the signs below.

Bleeding (hemorrhage). Omcazio can cause severe bleeding that may lead to death. Signs include coughing up blood or blood clots, vomiting blood or vomit that looks like coffee grounds, red or black tarry stools, menstrual bleeding that is heavier than usual, or any unusual or heavy bleeding.

A tear in the stomach or intestinal wall (perforation), or an abnormal connection between two parts of the body (fistula). Tell your healthcare provider right away about tenderness or pain in your stomach area that is severe or does not go away.

Blood clots, stroke, heart attack, and chest pain. Get emergency help right away if you have swelling or pain in your arms or legs, shortness of breath, lightheadedness or faintness, sweating more than usual, numbness or weakness in your face, arm, or leg (especially on one side of the body), sudden confusion, trouble speaking or understanding, sudden trouble seeing in one or both eyes, sudden trouble walking, dizziness or loss of balance, or a sudden severe headache.

High blood pressure (hypertension). High blood pressure is common with Omcazio and can sometimes be severe. Your healthcare provider will check your blood pressure before you start and regularly during treatment, and may prescribe a medicine to treat it. Tell your provider about severe headaches, nosebleeds, tiredness or confusion, vision changes, chest pain, trouble breathing, an irregular heartbeat, or blood in your urine.

Heart problems. Omcazio can cause heart failure that may lead to death. Your healthcare provider may check how well your heart is working before and during treatment. Tell your provider right away if your heart feels like it is pounding, racing, or beating irregularly, or if you have shortness of breath, swelling in your ankles or feet, lightheadedness, or tiredness.

Diarrhea. Diarrhea is common with Omcazio and can be severe. Your healthcare provider may prescribe a medicine to treat it. Tell your provider right away if you have frequent loose, watery bowel movements.

Hand-foot skin reaction. Hand-foot skin reactions are common with Omcazio and can be severe. Tell your healthcare provider right away about rashes, redness, pain, swelling, or blisters on the palms of your hands or the soles of your feet.

Liver problems. Liver problems can happen during treatment. When Omcazio is taken together with nivolumab, severe changes in liver function tests happen more often than with Omcazio alone. Your healthcare provider will do blood tests to check your liver before and during treatment. Tell your provider right away about yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area, dark urine, or bleeding or bruising more easily than usual.

Adrenal gland problems. Your healthcare provider will monitor you for this and may prescribe hormone replacement therapy or corticosteroid medicines if needed. Tell your provider right away about extreme tiredness, dizziness or fainting, weakness, nausea, or vomiting.

Protein in the urine and possible kidney problems. Symptoms can include swelling in your hands, arms, legs, or feet. Your healthcare provider will check you for this during treatment.

Severe jaw bone problems (osteonecrosis). Your healthcare provider should examine your mouth before you start and during treatment. Tell your dentist that you are taking Omcazio, and take good care of your mouth during treatment. Tell your healthcare provider right away about jaw pain, toothache, or sores on your gums.

Wound healing problems. Wounds may heal poorly in people taking Omcazio. Tell your healthcare provider if you plan to have surgery before or during treatment. You should stop taking Omcazio at least 3 weeks before any planned surgery. Your provider will tell you when you can start taking it again.

Reversible posterior leukoencephalopathy syndrome (RPLS). This is a rare brain condition. Tell your healthcare provider right away about new or worsening headaches, seizures, confusion, vision changes, or problems thinking.

Changes in thyroid function. Omcazio can change your thyroid hormone levels. Your healthcare provider will do blood tests to check your thyroid before and during treatment.

Your healthcare provider may change your dose, pause your treatment, or stop it permanently if you have certain side effects.

Omcazio may cause fertility problems in both females and males, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of Omcazio. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The usual Omcazio dose is 34.5 mg once daily, though the dose depends on which cancer is being treated and whether Omcazio is used with nivolumab. Treatment continues until the cancer progresses or the side effects become unacceptable.

Omcazio dose reductions

If you have side effects, your healthcare provider may pause treatment and then restart at a lower dose. A 34.5 mg dose is usually reduced to 23 mg, then to 11.5 mg. A 23 mg dose is usually reduced to 11.5 mg, then to 11.5 mg every other day.

Switching from Cabometyx to Omcazio

Omcazio doses do not match Cabometyx doses milligram for milligram. If you are switching, your healthcare provider will stop Cabometyx and use the conversions below. Only a healthcare provider should make this change.

What should I avoid while taking Omcazio?

Avoid grapefruit while taking Omcazio, including grapefruit juice, whole grapefruit, and supplements containing grapefruit. Also avoid St. John's wort.

Cabozantinib is broken down in the body by an enzyme called CYP3A, so medicines that block or speed up that enzyme can change how much drug is in your system.

Medicines that block CYP3A (strong CYP3A inhibitors) raise cabozantinib levels and can increase side effects. These should be avoided. If one cannot be avoided, your healthcare provider will lower your Omcazio dose while you take it.

Medicines that speed up CYP3A (strong or moderate CYP3A inducers) lower cabozantinib levels and can make Omcazio less effective. These should be avoided too. If one cannot be avoided, your healthcare provider will raise your Omcazio dose, up to a maximum of 46 mg a day.

Grapefruit blocks CYP3A, and St. John's wort speeds it up, which is why both are avoided during treatment.

Tell your healthcare provider about every medicine, vitamin, and herbal product you take, and check before starting anything new.

Cabozantinib blocks a group of proteins called receptor tyrosine kinases, which act as switches that tell cells to grow and divide. The kinases it blocks include MET, VEGFR-1, VEGFR-2, VEGFR-3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2.

These proteins are involved in tumor growth, the spread of cancer to other parts of the body, and the growth of new blood vessels that feed a tumor. Blocking them slows tumor growth and cuts off part of the tumor's blood supply.

Cabozantinib has a half-life of about 3.7 days, which is the time it takes for blood levels to fall by half. Levels build up over the first couple of weeks of daily dosing and reach a steady point by about day 15. Peak levels occur around 3 hours after a dose.

Store Omcazio at room temperature, between 68°F and 77°F (20°C to 25°C). Brief periods between 59°F and 86°F (15°C to 30°C) are acceptable. Keep Omcazio and all medicines out of the reach of children.

Omcazio comes in 30-count bottles. The capsules are marked as follows:

• 34.5 mg: opaque white capsules printed "CZB 34.5"
• 23 mg: capsules with an opaque blue cap and opaque white body, printed "CZB 23"
• 11.5 mg: opaque blue capsules printed "CZB 11.5"

Active ingredient: cabozantinib. Each capsule contains 11.5 mg, 23 mg, or 34.5 mg of cabozantinib, which is equivalent to 17.6 mg, 35.2 mg, or 52.8 mg of cabozantinib laurylsulfate.

Inactive ingredients: ammonia solution, ascorbic palmitate, black iron oxide, FD&C Blue #1, gelatin, polyoxyl 32 stearate, potassium hydroxide, propylene glycol, shellac, titanium dioxide, and tocopherol.

Manufactured for Handa Oncology, LLC, San Jose, CA 95110. For more information, go to www.OMCAZIO.com or call 1-844-204-8384.