What is Cabometyx?

Cabometyx is used to treat certain types of kidney cancer (renal cell carcinoma), liver cancer (hepatocellular carcinoma), differentiated thyroid cancer, and pancreatic and extra-pancreatic neuroendocrine tumors. It is an oral tablet taken once daily.

Cabometyx (cabozantinib) gained FDA approval on November 29, 2012. There is no generic.

FDA Approvals and Uses

Cabometyx (cabozantinib) is an oral kinase inhibitor approved to treat:

• Advanced renal cell carcinoma (RCC that has spread), as monotherapy
• Advanced RCC as first-line treatment in combination with nivolumab
• Hepatocellular carcinoma in patients previously treated with sorafenib
• Locally advanced or metastatic differentiated thyroid cancer (DTC) in adults and children 12 years and older that has progressed following VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.
• Previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) or extra-pancreatic neuroendocrine tumors (epNET) in adults and children 12 years and older

It is not known if Cabometyx is safe and effective in children younger than 12 years of age.

Side Effects

Common Side Effects

The most common side effects of Cabometyx are:

• Tiredness
• Nausea and vomiting
• Constipation
• Decreased appetite
• Weight decreased.

The most common side effects of Cabometyx when used in combination with nivolumab are:

• Tiredness
• Mouth sores
• Rash
• Low thyroid hormone levels (hypothyroidism)
• Pain in muscles, bones, and joints
• Decreased appetite
• Nausea
• Changes in the way things taste
• Stomach-area (abdominal) pain
• Cough
• Upper respiratory tract infection.

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

Serious side effects and warnings

Cabometyx may cause the following serious side effects.

Bleeding (hemorrhage)

Cabometyx can cause severe bleeding that may lead to death. Tell your healthcare provider right away if you get any signs of bleeding during treatment with Cabometyx, including:

• Coughing up blood or blood clots
• Vomiting blood, or if your vomit looks like coffee grounds
• Red or black (looks like tar) stools
• Menstrual bleeding that is heavier than normal
• Any unusual or heavy bleeding

Perforations and fistulas

Cabometyx can cause a tear in your stomach or intestinal wall (perforation) or an abnormal connection between 2 parts of your body (fistula). Tell your healthcare provider right away if you get tenderness or pain in your stomacharea (abdomen) that is severe, or that does not go away.

Blood clots, stroke, heart attack, and chest pain

Cabometyx may affect the way your blood clots and increase the risk of blood clots, a stroke, heart attack, or chest pain. Get emergency help right away if you get:

• Swelling or pain in your arms or legs
• Shortness of breath
• Feel lightheaded or faint
• Sweating more than usual
• Numbness or weakness of your face, arm or leg, especially on one side of your body
• Sudden confusion, trouble speaking, or understanding
• Sudden trouble seeing in one or both eyes
• Sudden trouble walking
• Dizziness, loss of balance, or coordination
• A sudden severe headache.

High blood pressure (hypertension)

Hypertension is common with Cabometyx and sometimes can be severe. Your healthcare provider will check your blood pressure before starting Cabometyx and regularly during treatment. If needed, your healthcare provider may prescribe medicine to treat your high blood pressure. Tell your healthcare provider if you develop severe headaches, nose bleeds, tiredness or confusion, vision changes, chest pain, trouble breathing, irregular heartbeat, or blood in your urine.

Heart problems

Cabometyx can cause heart failure that may lead to death. Your healthcare provider may check your heart function before and during treatment with Cabometyx. Tell your healthcare provider right away if you get any of the following signs and symptoms:

• Feeling like your heart is pounding, racing, or beating irregularly
• Swelling of your ankles or feet
• Feeling lightheaded
• Shortness of breath
• Tiredness

Diarrhea

Diarrhea is common with Cabometyx and can be severe. If needed, your healthcare provider may prescribe medicine to treat your diarrhea. Tell your healthcare provider right away if you have frequent loose, watery bowel movements.

Hand-foot skin reaction

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

Liver problems

Liver problems may happen during treatment with Cabometyx. When Cabometyx is taken in combination with nivolumab, severe changes in liver function tests may happen more often than if you take Cabometyx alone. Your healthcare provider will do blood tests to check your liver function before and during treatment with Cabometyx. Tell your healthcare provider right away if you develop symptoms of liver problems, including yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine, bleeding, or bruising more easily than normal.

Adrenal gland problems

Your healthcare provider will monitor you for this problem. Your healthcare provider may prescribe hormone replacement therapy or corticosteroid medicines if needed. Tell your healthcare provider right away if you develop any of the following signs or symptoms: extreme tiredness, dizziness or fainting, weakness, nausea, or vomiting.

Protein in your urine and possible kidney problems

Symptoms may include swelling in your hands, arms, legs, or feet. Your healthcare provider will check you for this problem during treatment with Cabometyx.  

Severe jawbone problems (osteonecrosis)

Your healthcare provider should examine your mouth before you start and during treatment with Cabometyx. Tell your dentist that you are taking Cabometyx. It is important for you to practice good mouth care during treatment with Cabometyx. Tell your healthcare provider right away if you develop any symptoms of jaw problems, including: jaw pain, toothache, or sores on your gums.

Wound healing problems

Wound healing problems have happened in people who take Cabometyx. Tell your healthcare provider if you plan to have any surgery before or during treatment with Cabometyx.

• You should stop taking Cabometyx at least 3 weeks before planned surgery.
• Your healthcare provider should tell you when you may start taking Cabometyx again after surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

A condition called reversible posterior leukoencephalopathy syndrome can happen during treatment with Cabometyx. Tell your healthcare provider right away if you have headaches, seizures, confusion, changes in vision, or problems thinking.

Change in thyroid function

Cabometyx can cause changes in your thyroid function, including changes to thyroid hormone levels in your blood. Your healthcare provider will do blood tests to check your thyroid function before and during treatment with Cabometyx.

Decreased calcium level in your blood (hypocalcemia)

Cabometyx can cause you to have a decreased amount of calcium in your blood. Your healthcare provider will do blood tests to check you for this problem and give you calcium if needed. Tell your healthcare provider right away if you get any of the following signs or symptoms:

• Muscle stiffness or muscle spasms
• Sudden weight gain
• Numbness or tingling in your fingers, toes, or around your mouth
• Swelling of your arms, hands, legs, and ankles
• Seizures.

Notes:

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Cabometyx if you have certain side effects.

These are not all of the possible side effects of Cabometyx. Call your doctor for medical advice about side effects.

How does Cabometyx work?

Cabometyx (cabozantinib) works by blocking multiple tyrosine kinase enzymes, including MET, VEGFR, AXL, RET, and others. These enzymes regulate normal cell functions but also drive cancer-related processes like tumor growth, spread, blood vessel formation, drug resistance, and tumor microenvironment maintenance.

Cabometyx (cabozantinib) belongs to the drug class called multikinase inhibitors. It may also be called a VEGF/VEGFR inhibitor.

Before taking this medicine

Before you take Cabometyx, tell your healthcare provider about all of your medical conditions, including if you:

• Have had a liver problem other than liver cancer
• Have a recent history of bleeding, including coughing up or vomiting blood, or black tarry stools.
• Have an open or healing wound
• Have high blood pressure
• Have heart problems
• Have a low calcium level in your blood (hypocalcemia)
• Plan to have any surgery, dental procedure, or have had a recent surgery. You should stop taking Cabometyx at least 3 weeks before planned surgery
• Are pregnant, or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Cabometyx can harm your unborn baby.

• If you can become pregnant, your healthcare provider will check your pregnancy status before you start treatment with Cabometyx.
• Females who can become pregnant should use effective birth control (contraception) during treatment and for 4 months after their last dose of Cabometyx.
• Talk to your healthcare provider about birth control methods that may be right for you.
• If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Cabometyx passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of Cabometyx.

How should I take Cabometyx?

• Take Cabometyx exactly as your healthcare provider tells you to take it.
• Do not take Cabometyx with food. Take Cabometyx on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Swallow Cabometyx tablets whole.
• Do not crush, chew, or split Cabometyx tablets.

What happens if I miss a dose?

If you miss a dose and your next scheduled dose is in less than 12 hours, take your next dose at the normal time. Do not make up the missed dose.

What should I avoid while taking Cabometyx?

Avoid drinking grapefruit juice, eating grapefruit, or taking supplements that contain grapefruit or St. John’s wort during treatment with Cabometyx.

What other drugs will affect Cabometyx?

Tell your healthcare provider about all the medicines you take, including prescription or over-the-counter medicines, vitamins, and herbal supplements. Cabometyx and certain other medicines may affect each other, causing side effects.

Do NOT substitute Cabometyx tablets with cabozantinib capsules. 

Dosing information

• Administer on an empty stomach at least 1 hour before or at least 2 hours after eating.
• Stop treatment with Cabometyx at least 3 weeks before scheduled surgery, including dental surgery.

Adult Dose of Cabometyx for RCC

• Monotherapy: 60 mg orally once daily
• Combination therapy: 40 mg orally once daily with:
  • nivolumab 240 mg by intravenous infusion every 2 weeks

OR

• • nivolumab 480 mg by intravenous infusion every 4 weeks

OR

• • nivolumab 600 mg and hyaluronidase 10,000 units subcutaneously every 2 weeks

OR

• • nivolumab 1,200 mg and hyaluronidase 20,000 units subcutaneously every 4 weeks

Adult Dose of Cabometyx for HCC

• 60 mg orally once daily

Adult and Pediatric 12+ Dose of Cabometyx for DTC, pNET, epNET

• ≥40 kg: 60 mg orally once daily
• <40 kg: 40 mg orally once daily.

Storage

Store Cabometyx at room temperature between 68°F to 77°F (20°C to 25°C).

Keep out of the reach of children.

What are the ingredients in Cabometyx?

Active ingredient: cabozantinib

Inactive ingredients: microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. The film coating contains hypromellose, titanium dioxide, triacetin, and iron oxide yellow.

Available as 20 mg, 40 mg, 60 mg, oral tablets.

Company

Cabometyx is manufactured for Exelixis, Inc. Alameda, CA 94502.

Bevacizumab injection is a targeted cancer drug used to treat types of colon and rectal cancer, non-small cell lung cancer (NSCLC), glioblastoma, renal cell cancer (RCC), cervical cancer, ovarian cancer, fallopian tube cancer, or peritoneal cancer. Avastin is also used to treat types of hepatocellular carcinoma (HCC).

Bevacizumab belongs to a class of medications called antiangiogenic agents. Bevacizumab works by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors.

Avastin was the first brand of bevacizumab to be approved by the FDA on February 26, 2004, and is called the reference product.  Biosimilars of Avastin are Alymsys, Jobevne, Mvasi, Vegzelma, and Zirabev.
Bevacizumab is used together with other chemotherapy medications.

Bevacizumab side effects

Common bevacizumab side effects may include increased blood pressure, headache, back pain, dry or watery eyes, dry or flaky skin, stuffy nose, runny nose, sneezing, or altered sense of taste.

Serious bevacizumab side effects 

Get emergency medical help if you have signs of an allergic reaction to bevacizumab, including hives, difficulty breathing, and swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your medical caregiver right away if you feel dizzy, nauseated, light-headed, itchy, sweaty, or have a headache, chest tightness, back pain, trouble breathing, or swelling in your face.

Bevacizumab can cause a serious but rare neurologic disorder that affects the brain. Symptoms may occur within hours of your first dose or may not appear for up to a year after your treatment started. Call your doctor at once if you have extreme weakness or tiredness, headache, confusion, vision problems, fainting, or seizures (blackout or convulsions).

Bevacizumab can cause you to bleed more easily. Call your doctor or seek emergency medical attention if you have:

• easy bruising, unusual bleeding, or any bleeding that will not stop;
• signs of bleeding in your digestive tract – severe stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or
• signs of bleeding in the brain – sudden numbness or weakness, slurred speech, severe headache, problems with vision or balance.

Some people taking bevacizumab have developed a perforation (a hole or tear) or a fistula (an abnormal passageway) in the stomach, intestines, throat, lungs, gallbladder, kidney, bladder, or vagina. Call your doctor if you have severe stomach pain or if you feel like you are choking when you eat or drink.

Also call your doctor if you have:

• slow wound healing;
• skin infection or open sores;
• missed menstrual periods;
• kidney problems – swelling, urinating less, feeling tired or short of breath;
• signs of a blood clot – chest pain, sudden cough or shortness of breath, dizziness, coughing up blood, pain, swelling, or warmth in one leg;
• heart problems – chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating, swelling, rapid weight gain, feeling short of breath; or
• low white blood cell counts – fever, mouth sores, skin sores, sore throat, cough.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

Bevacizumab can make it easier for you to bleed. Seek emergency medical attention if you have any bleeding that will not stop. You may also have bleeding on the inside of your body.

Call your doctor if you have: signs of bleeding in your digestive tract–feeling very weak or dizzy, severe stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or signs of bleeding in the brain–sudden numbness or weakness, slurred speech, severe headache, problems with vision or balance.

Bevacizumab can also cause problems with wound healing, which could result in bleeding or infection. Do not use bevacizumab within 28 days before or after a planned surgery.

Bevacizumab can cause a rare but serious neurologic disorder affecting the brain. Symptoms include headache, confusion, vision problems, feeling very weak or tired, fainting, and seizure (blackout or convulsions). These rare symptoms may occur within hours of your first dose of bevacizumab, or they may not appear for up to a year after your treatment started. Call your doctor at once if you have any of these side effects.

Some people receiving a bevacizumab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your medical caregiver right away if you feel dizzy, nauseated, light-headed, sweaty, itchy, or have a fast heartbeat, chills, wheezing, or chest pain during the injection.

Before taking this medicine

You may not be able to use bevacizumab if you are being treating with other cancer medicines such as doxorubicin, daunorubicin, or if you have or ever had:

• ovarian cancer with symptoms such as severe stomach pain or pelvic pain;
• slow healing of a skin wound or surgical incision;
• surgery within the past 4 weeks (28 days);
• you plan to have surgery within the next 4 weeks (28 days); or
• coughing up blood or vomit that looks like coffee grounds.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• diabetes;
• heart problems such as a heart attack, stroke, blood clot or blood clotting disorder;
• high blood pressure;
• bleeding problems or a perforation (a hole or tear) in your esophagus, stomach, or intestines; or
• kidney disease.

Pregnancy

Bevacizumab may harm an unborn baby. Do not use if you are pregnant. You may need a pregnancy test to make sure you are not pregnant. Use effective birth control while using bevacizumab and for at least 6 months after your last dose. Tell your doctor at once if you become pregnant.

This medicine may cause a woman’s ovaries to stop working correctly. Symptoms of ovarian failure include 3 or more missed menstrual periods in a row. It may be harder for you to get pregnant while you are using this medicine and after this treatment. Talk to your doctor about your individual risk.

Breastfeeding

Do not breastfeed while using bevacizumab and for at least 6 months after your last dose.

How is bevacizumab given?

Bevacizumab is given as an infusion into a vein. A healthcare provider will give you this injection.

Tell your caregivers right away if you feel dizzy, nauseated, light-headed, sweaty, or have a headache, shortness of breath, or chest pain during the injection.

Bevacizumab is usually given once every 2 or 3 weeks.

Doses are based on weight. Your dose may change if you gain or lose weight.

You may need frequent medical tests and your cancer treatments may be delayed based on the results.

For detailed bevacizumab dosing information, click the link below.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your bevacizumab injection.

What happens if I overdose?

In a medical setting, an overdose would be treated quickly.

What should I avoid while receiving bevacizumab?

Avoid activities that may increase your risk of bleeding or injury. Use extra care while shaving or brushing your teeth.

What other drugs will affect bevacizumab?

Tell your doctor about all other cancer treatments you are receiving.

Other drugs may interact with bevacizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Ingredients and manufacturer

Active ingredient: bevacizumab

Avastin (bevacizumab)
Inactive ingredients: a,a-trehalose dihydrate, polysorbate 20, sodium phosphate dibasic (anhydrous), sodium phosphate monobasic (monohydrate), and Water for Injection, USP.
Manufacturer: Genentech, Inc, 1 DNA Way South San Francisco, CA 94080, USA.

Alymsys (bevacizumab-maly)
inactive ingredients: dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 20, trehalose, and Water for Injection, USP.
Manufacturer: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Product of Spain 

Mvasi (bevacizumab-awwb)
Inactive ingredients: α,α-trehalose dihydrate, polysorbate 20, sodium phosphate dibasic, anhydrous, sodium phosphate monobasic, monohydrate, and Water for Injection, USP.
Manufacturer: Amgen, Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 

Vegzelma (bevacizumab-adcd)
Inactive ingredients: dibasic sodium phosphate, monobasic sodium phosphate, polysorbate 20, trehalose, and Water for Injection, USP.
Manufacturer: CELLTRION, Inc. 20, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea. 

Zirabev (bevacizumab-bvzr)
Inactive ingredients: edetate disodium dihydrate, polysorbate 80, succinic acid, sucrose, and Water for Injection, USP. Sodium hydroxide is added to adjust the pH.
Manufacturer: Pfizer Inc. NY, NY 10017.

Bevacizumab Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for bevacizumab.Avastin (bevacizumab) – Genentech, Inc.

What is Iclusig?

Iclusig is an oral kinase inhibitor that may be used to treat adults with:

• Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in those who cannot receive any other kinase inhibitor medicines or have a specific type of abnormal gene (T315I-positive Ph+ ALL)
• Newly diagnosed Ph+ ALL in combination with chemotherapy (this approval is under the accelerated approval designation and is based on minimal residual disease (MRD)-negative complete remission (CR) at the end of induction)
• Chronic phase chronic myeloid leukemia (CML) who did not tolerate or no longer benefit from treatment with at least 2 prior kinase inhibitor medicines
• T315I-positive CML (chronic phase, accelerated phase, or blast phase).

Iclusig is not for use to treat people with newly diagnosed chronic phase CML.

It is not known if Iclusig is safe and effective in children.

Warnings

Iclusig may cause heart or blood vessel problems that could lead to heart attack, stroke, or death.

Call your doctor or get emergency medical help if you have: chest pain spreading to your jaw or shoulder, shortness of breath, dizziness, severe stomach pain, swelling in your legs, sudden numbness or weakness, headache, or problems with vision or speech.

Iclusig may also harm your liver. Call your doctor right away if you have upper stomach pain with loss of appetite, dark urine, bruising, or yellowing of your skin or eyes.

Before taking this medicine

You should not use Iclusig if you are allergic to ponatinib.

To make sure Iclusig is safe for you, tell your doctor if you have ever had:

• heart failure, high blood pressure, heart rhythm problems;
• long QT syndrome (in you or a family member);
• a stroke or blood clot;
• diabetes;
• high cholesterol;
• liver disease;
• bleeding problems;
• lactose intolerance (tablets may contain lactose);
• pancreatitis; or
• if you’ve had surgery within the past 2 weeks.

You may need to have a negative pregnancy test before starting this treatment.

Ponatinib may harm an unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 3 weeks after your last dose.

This medicine may affect fertility (ability to have children) in women. However, it is important to use birth control to prevent pregnancy because Iclusig can harm an unborn baby.

You should not breastfeed while using Iclusig and for at least 6 days after your last dose.

How should I take Iclusig?

Take Iclusig exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Iclusig is usually taken once daily, with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

You may need frequent medical tests to be sure this medicine is not causing harmful effects. Your cancer treatments may be delayed based on the results.

If you need surgery, tell the surgeon ahead of time that you are using Iclusig. You may need to stop using the medicine at least 1 week before surgery.

Do not stop taking Iclusig or change your medication dose without your doctor’s advice.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Chronic Myelogenous Leukemia:

Chronic phase chronic myeloid leukemia (CP-CML):
-Initial Dose: 45 mg orally once a day
-Upon achievement of 1% BCR-ABL1 or less (standardized according to International Scale): 15 mg orally once a day
-For loss of response: Re-escalate to a previously tolerated dosage of 30 mg or 45 mg orally once a day

Accelerated phase chronic myeloid leukemia (AP-CML), blast phase chronic myeloid leukemia (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL):
-Initial dose: 45 mg orally once a day

Comments:
-The optimal dose has not been identified for AP-CML, BP-CML, and Ph+ ALL.
-Consider dose reduction for AP-CML patients who have achieved major cytogenic response.
-Continue treatment until loss of response or unacceptable toxicity.
-Drug discontinuation should be considered if patient response has not occurred by 3 months (90 days).
-This drug is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Uses:
-For the treatment of adult patients with CP-CML with resistance or intolerance to at least two prior kinase inhibitors
-For the treatment of adult patients with AP-CML, or BP-CML or Ph+ ALL for whom no other kinase inhibitors are indicated
-For the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL

Usual Adult Dose for Acute Lymphoblastic Leukemia:

Chronic phase chronic myeloid leukemia (CP-CML):
-Initial Dose: 45 mg orally once a day
-Upon achievement of 1% BCR-ABL1 or less (standardized according to International Scale): 15 mg orally once a day
-For loss of response: Re-escalate to a previously tolerated dosage of 30 mg or 45 mg orally once a day

Accelerated phase chronic myeloid leukemia (AP-CML), blast phase chronic myeloid leukemia (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL):
-Initial dose: 45 mg orally once a day

Comments:
-The optimal dose has not been identified for AP-CML, BP-CML, and Ph+ ALL.
-Consider dose reduction for AP-CML patients who have achieved major cytogenic response.
-Continue treatment until loss of response or unacceptable toxicity.
-Drug discontinuation should be considered if patient response has not occurred by 3 months (90 days).
-This drug is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Uses:
-For the treatment of adult patients with CP-CML with resistance or intolerance to at least two prior kinase inhibitors
-For the treatment of adult patients with AP-CML, or BP-CML or Ph+ ALL for whom no other kinase inhibitors are indicated
-For the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

Grapefruit may interact with ponatinib and lead to unwanted side effects. Avoid the use of grapefruit products.

Iclusig side effects

Get emergency medical help if you have signs of an allergic reaction to Iclusig: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Iclusig may cause heart or blood vessel problems that could lead to heart attack or stroke. Call your doctor right away or get emergency medical help if you have:

• heart attack symptoms – chest pain or pressure, pain spreading to your jaw or shoulder, feeling short of breath;
• signs of a stroke – sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance; or
• signs of a blood clot – severe stomach pain, pain or swelling in your arms or legs, coughing up blood.

Call your doctor at once if you have:

• dizziness, confusion, headache, change in mental status;
• a seizure;
• swelling, rapid weight gain, feeling short of breath;
• a wound that will not heal;
• eye problems – vision problems, eye pain or swelling, bleeding in the eye, increased sensitivity to light, flashes of light or “floaters” in your vision;
• heart problems – chest pain, shortness of breath, fast or pounding heartbeats, feeling like you might pass out;
• a hole or tear in your stomach or intestine – severe pain or swelling in your stomach with a high fever;
• low blood cell counts – fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet;
• nerve problems – muscle weakness, trouble moving your eyes or other parts of your face, tingling, burning pain, numbness in your hands and feet;
• severe bleeding – nosebleeds, bloody or tarry stools, pink or brown urine, heavy menstrual periods, coughing up blood or vomit that is bloody or looks like coffee grounds; or
• signs of liver or pancreas problems – loss of appetite, upper stomach pain (that may spread to your back), nausea or vomiting, fast heart rate, dark urine, jaundice (yellowing of the skin or eyes).

Common Iclusig side effects include:

• dry skin, rash;
• stomach pain, nausea, vomiting, diarrhea, constipation;
• headache, muscle or joint pain;
• pain in your arms, hands, legs, or feet;
• increased blood pressure; or
• fever, tired feeling.

What is Inlyta?

Inlyta is a prescription medicine that interferes with the growth of some cancer cells.

Inlyta is used to treat advanced kidney cancer (advanced renal cell carcinoma).

Inlyta is sometimes given after at least one other cancer treatment did not work or has stopped working.

It is not known if Inlyta is safe and effective in children.

Warnings

Do not use Inlyta if you are pregnant. It could harm the unborn baby. Use birth control to prevent pregnancy while you are receiving this medicine, whether you are a man or a woman. Inlyta use by either parent may cause birth defects or miscarriage.

Axitinib can increase your risk of serious bleeding. Stop using Inlyta and call your doctor at once if you have severe stomach pain, bloody or tarry stools, coughing up blood, or any heavy or unusual bleeding.

Some people taking this medicine have developed a perforation (a hole or tear) or a fistula (an abnormal passageway) within the stomach or intestines. Call your doctor if you have severe stomach pain, or if you feel like you are choking and gagging when you eat or drink.

Inlyta is usually taken once every 12 hours. It should be taken at evenly spaced intervals. Follow your doctor’s instructions.

To be sure this medication is not causing harmful effects, your kidney, thyroid, and liver function will need to be tested. Your blood pressure will also need to be checked often. Visit your doctor regularly.

Before taking this medicine

You should not use Inlyta if you are allergic to axitinib.

To make sure Inlyta is safe for you, tell your doctor if you have:

• a perforation (a hole or tear) in your stomach or intestines;
• bleeding problems, or a wound that has not healed;
• a heart attack, heart failure, stroke, or blood clot;
• high blood pressure;
• liver disease; or
• a thyroid disorder.

You may need to have a negative pregnancy test before starting this treatment.

Both men and women using this medicine should use effective birth control to prevent pregnancy. Axitinib can cause harm an unborn baby if the mother or father is using this medicine.

Keep using birth control for at least 1 week after your last dose. Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Inlyta.

This medicine may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because axitinib can harm an unborn baby.

It is not safe to breast-feed a baby while you are using this medicine. Also do not breast-feed for at least 2 weeks after your last dose.

How should I take Inlyta?

Take Inlyta exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Inlyta should be taken at evenly spaced intervals, usually once every 12 hours.

Take this medicine with a full glass of water. You may take this medicine with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

If you vomit shortly after taking Inlyta, do not take another dose. Wait until your next scheduled dose time to take the medicine again.

Your blood pressure will need to be checked often. You may also need frequent medical tests.

If you need surgery, tell your surgeon you currently use Inlyta. You will need to stop using the medicine at least 24 hours before a planned surgery.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Renal Cell Carcinoma:

Initial dose: 5 mg orally twice a day
Maintenance dose: Increase or decrease dose based on individual safety and tolerability
Dose range: 2 to 10 mg twice a day

Comments: Doses should be taken approximately 12 hours apart.

Use: For the treatment of advanced renal cell carcinoma after the failure of 1 prior systemic therapy.

What happens if I miss a dose?

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What to avoid

Grapefruit may interact with axitinib and lead to unwanted side effects. Avoid the use of grapefruit products.

Inlyta side effects

Get emergency medical help if you have signs of an allergic reaction to Inlyta: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some people taking Inlyta have developed a perforation (a hole or tear) or a fistula (an abnormal passageway) within the stomach or intestines. Call your doctor if you have severe stomach pain, or if you feel like you are choking and gagging when you eat or drink.

Also call your doctor at once if you have:

• chest pain or pressure, pain spreading to your jaw or shoulder, trouble breathing;
• sudden numbness or weakness, problems with vision or speech;
• headache, confusion, thinking problems, seizure (convulsions);
• a light-headed feeling, like you might pass out;
• easy bruising, unusual bleeding, purple or red spots under your skin;
• heavy menstrual bleeding;
• any bleeding that will not stop;
• liver problems – severe nausea or vomiting, right-sided upper stomach pain, loss of appetite, dark urine, clay- colored stools, jaundice (yellowing of the skin or eyes);
• heart problems – swelling, rapid weight gain, feeling short of breath;
• signs of stomach bleeding – bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or
• signs of a thyroid problem – sudden weight gain or loss, feeling very weak or tired, muscle pain, feeling hot or cold, hair loss, hoarse or deepened voice.

Common Inlyta side effects may include:

• liver problems;
• stomach pain;
• muscle and bone pain;
• abnormal blood tests;
• mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina;
• cough, shortness of breath;
• headache;
• nausea, vomiting, diarrhea, constipation;
• rash, itching, redness, and peeling skin on your hands or feet;
• feeling weak or tired;
• increased blood pressure;
• decreased appetite, weight loss; or
• hoarse voice.