Nilotinib

Nilotinib is a prescription medication used to treat adults with certain types of leukemia (cancer of the white blood cells). Nilotinib belongs to a group of drugs called kinase inhibitors, which stop or slow the spread of cancer cells.

This medication comes in capsule form and is taken twice a day, without food.

Common side effects include low blood count, rash, nausea, fever, and headache.

Nilotinib is a prescription medicine used to treat: 

• adults and children who have been newly diagnosed with a certain type of leukemia called Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase
• adults with chronic phase or accelerated phase who:
  • are no longer benefiting from other treatments, including imatinib (Gleevec), or
  • have taken other treatments, including imatinib (Gleevec), and cannot tolerate them
• children with chronic phase who:
  • are no longer benefiting from treatment with a tyrosine-kinase inhibitor medicine, or
  • have taken a tyrosine-kinase inhibitor medicine and cannot tolerate it

It is not known if nilotinib is safe and effective in children younger than 1 year of age with newly diagnosed, resistant, or intolerant Ph+ CML in chronic phase.

The long-term effects of treating children with nilotinib for a long period of time are not known. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Nilotinib may be found in some form under the following brand names:

• Tasigna

Nilotinib may cause serious side effects. See the “Nilotinib Drug Precautions” section.

The most common side effects of nilotinib include:

• low blood count 
• rash
• nausea 
• fever
• headache
• itching
• tiredness
• stomach (abdominal) pain
• diarrhea
• constipation
• muscle and joint pain
• back pain
• muscle spasms
• weakness
• hair loss
• runny or stuffy nose, sneezing, sore throat
• cough

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all of the possible side effects of nilotinib. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Nilotinib can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that use the enzyme CYP3A4 such as budesonide (Entocort), astemizole (Hismanal), cisapride (Propulsid), cyclosporine (Neoral, Gengraf, Sandimmune), darifenacin (Enablex), dihydroergotamine (Migranal), fentanyl (Abstral, Fentora, Onsolis, Actiq), pimozide (Orap), quinidine (Cardioquin, Duraquin, Quinact), sirolimus (Rapamune), tacrolimus (Prograf), terfenadine (Seldane), fluticasone (Flovent HFA, Flonase), eletriptan (Relpax), lovastatin (Mevacor), quetiapine (Seroquel), sildenafil (Viagra, Revatio), and simvastatin (Zocor)
• medications that use an enzyme CYP2C8 such as amiodarone (Cordarone), cabazitaxel (Jevtana), carbamazepine (Tegretol), chloroquine (Aralen), diclofenac (Voltaren), ibuprofen (Advil), paclitaxel (Taxol), rosiglitazone (Avandia), repaglinide (Prandin), treprostinil (Tyvaso)
• medications that use the enzyme CYP2D6 such as desipramine, dextromethorphan, atomoxetine
• medications that use the enzyme CYP2C9 such as warfarin (Coumadin, Jantoven), and phenytoin (Dilantin)c
• medications that use the UGT1A1 enzyme such as carvedilol (Coreg) and levothyroxine (Synthroid)
• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
• medications that can cause an arrhythmia called Torsades des Point such as
  • certain anti-arrhythmia medications including procainamide, sotalol (Betapace), quinidine, dofetilide (Tikosyn), amiodarone (Nexterone, Pacerone, Cordarone), ibutilide (Corvert)
  • certain fluoroquinolone antibiotics including levofloxacin (Levaquin), ciprofloxacin (Cipro), gatifloxacin (Zymar), moxifloxacin (Avelox)
  • certain macrolide antibiotics including clarithromycin (Biaxin), erythromycin (EES, others)
  • certain azole antifungals including ketoconazole (Nizoral), itraconazole (Sporanox, Onmel)
  • certain antidepressants including amitriptyline, desipramine (Norpramin), imipramine (Tofranil), doxepin (Silenor), fluoxetine (Prozac, Sarafem), sertraline (Zoloft), venlafaxine (Effexor XR)
  • certain antipsychotics including haloperidol (Haldol), droperidol (Inapsine), quetiapine (Seroquel XR), thioridazine, ziprasidone (Geodon)
  • and other medications including cisapride, sumatriptan (Treximet, Imitrex, Alsuma, Zecuity), zolmitriptan (Zomig), arsenic trioxide (Trisenox), dolasetron (Anzemet), and methadone (Methadone, Dolophine)
• medications that block the p-glycoprotein transporter such as amiodarone (Cordarone, Pacerone), azithromycin (Zithromax, Zmax), captopril (Capoten), carvedilol (Coreg), clarithromycin (Biaxin), conivaptan (Vaprisol), cyclosporine (Neoral, Sandimmune, Gengraf), diltiazem (Cardizem), dronedarone (Multaq), erythromycin (EES, Ery-Tab), felodipine (Plendil),  itraconazole (Sporanox, Onmel), ketoconazole (Nizoral), lopinavir and ritonavir (Kaletra), quinidine (Cardioquine, Quinact, Duraquin), ranolazine (Ranexa), verapamil (Calan, Isoptin, Covera, Verelan)
• medications that use the p-glycoprotein transporter such as digoxin (Lanoxin), loperamide (Imodium), quinidine (Cardioquine, Quinact, Duraquin), vinblastine (Velban), fexofenadine (Allegra), indinavir (Crixivan), colchicine (Colcrys), topotecan (Hycamtin), and paclitaxel (Abraxane, Onxol, Taxol)
• medications that affect gastric acid such as proton pump inhibitors: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), dexlansoprazole (Kapidex) and  histamine 2 (H2) blockers: cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid)

This is not a complete list of nilotinib drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with nilotinib including the following:

• Low blood counts. Low blood counts are common with nilotinib. Your doctor will check your blood counts regularly during treatment with nilotinib. Symptoms of low blood counts include:
        ○  unexplained bleeding or bruising 
        ○  blood in urine or stool 
        ○  unexplained weakness
• Liver problems. Nilotinib can increase your risk of liver problems. People who have had liver problems in the past may be at risk for getting liver problems with nilotinib. Call your healthcare provider or get medical help right away if you develop any symptoms of liver problems including stomach area pain, yellow skin and eyes, and dark-colored urine. 
• Pancreas inflammation (pancreatitis). Symptoms include sudden stomach area pain with nausea and vomiting.
• Bleeding in the brain. Symptoms include sudden headache, changes in your eyesight, not being aware of what is going on around you and becoming unconscious.
• Tumor Lysis Syndrome (TLS). TLS is caused by a fast breakdown of cancer cells. TLS can cause you to have:
  • kidney failure and the need for dialysis treatment
  • an abnormal heart beat
  • Your doctor may do blood tests to check you for TLS.

• Harm to your unborn baby. Your healthcare provider should do a pregnancy test before you start treatment with nilotinib. If you are able to become pregnant, you should use effective birth control during treatment with Tasigna and for at least 14 days after the last dose.
• Abnormal growth or development in children. Effects on growth and development in children being treated for chronic phase CML is possible. The long term effects of prolonged treatment with Nilotinib on growth and development in children are unknown.
• Heart problems called QTc prolongation. Nilotinib can cause a possible life-threatening heart problem called QTc prolongation. QTc prolongation causes an irregular heartbeat, which may lead to sudden death.

Your doctor should check the electrical activity of your heart with a test called an electrocardiogram (ECG):

• before starting nilotinib
• 7 days after starting nilotinib
• with any dose changes
• regularly during nilotinib treatment

You may lower your chances of having QTc prolongation with nilotinib if you take nilotinib:

• On an empty stomach. Do not take nilotinib with food.
  • at least 2 hours after eating any food, and 
  • wait at least 1 hour before eating any food
• Avoid grapefruit, grapefruit juice, and any supplement containing grapefruit extract while taking nilotinib. Food and grapefruit products increase the amount of nilotinib in your body. 
• Avoid taking other medicines or supplements with nilotinib that can also cause QTc prolongation.
• Nilotinib can interact with many medicines and supplements and increase your chance for serious and life-threatening side effects.
• Do not take any other medicine while taking nilotinib unless your doctor tells you it is okay to do so.
• If you cannot swallow nilotinib capsules whole, you may open the nilotinib capsule and sprinkle the contents of each capsule in 1 teaspoon of applesauce (puréed apple). Swallow the mixture right away (within 15 minutes). 

Call your doctor right away if you feel lightheaded, faint or have an irregular heartbeat while taking nilotinib. These can be symptoms of QTc prolongation.

Do not take if you:

• are allergic to nilotinib or to any of its ingredients
• have low levels of potassium or magnesium in your blood
• have long QTc syndrome 

Grapefruit and grapefruit juice may interact with nilotinib and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before taking nilotinib, tell your doctor about all of your medical conditions, including if you have:

• heart problems
• irregular heartbeat
• QTc prolongation or a family history of it
• liver problems
• had pancreatitis
• low blood levels of potassium or magnesium in your blood
• a severe problem with lactose (milk sugar) or other sugars. The nilotinib capsules contain lactose. Most patients who have mild or moderate lactose intolerance can take nilotinib.
• had a surgical procedure involving the removal of the entire stomach (total gastrectomy)
• are pregnant or plan to become pregnant. Nilotinib may harm your unborn baby. If you are able to become pregnant, you should use effective birth control during treatment with nilotinib and for at least 14 days after the last dose. Talk to your doctor about the best birth control methods to prevent pregnancy while you are taking nilotinib.
• are breastfeeding or plan to breastfeed. It is not known if nilotinib passes into your breast milk. You and your doctor should decide if you will take nilotinib or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant. Nilotinib may harm your unborn baby.

Your healthcare provider should do a pregnancy test before you start treatment with nilotinib.

If you are able to become pregnant, you should use effective birth control during treatment with nilotinib and for at least 14 days after the last dose. Talk to your doctor about the best birth control methods to prevent pregnancy while you are taking nilotinib.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if nilotinib passes into your breast milk. You and your doctor should decide if you will take nilotinib or breastfeed. You should not do both.

Do not breastfeed during treatment and for at least 14 days after your last dose of nilotinib.

Take nilotinib exactly as your doctor tells you to take it.

Do not change your dose or stop taking nilotinib unless your doctor tells you. Nilotinib is a long-term treatment.

Your healthcare provider will tell you how many nilotinib capsules to take and when to take them.

If your child takes nilotinib, your healthcare provider will change the dose as your child grows.

Take nilotinib on an empty stomach. 

• Avoid eating food for at least 2 hours before the dose is taken, and
• Avoid eating food for at least 1 hour after the dose is taken.

Swallow nilotinib capsules whole with water. If you cannot swallow nilotinib capsules whole, tell your doctor.

If you cannot swallow nilotinib capsules whole, open the nilotinib capsules and sprinkle the contents in 1 teaspoon of applesauce (puréed apple).

• Only use applesauce. Do not sprinkle nilotinib onto other foods.
• Do not use more than 1 teaspoon of applesauce.
• Swallow the mixture right away (within 15 minutes).

If you miss a dose, just take your next dose as scheduled. Do not take 2 doses at the same time to make up for a missed dose.

During treatment with nilotinib your doctor will do tests to check for side effects and to see how well nilotinib is working for you. The tests will check your:

• heart
• blood cells (white blood cells, red blood cells, and platelets). Your blood cells should be checked every two weeks for the first two months and then monthly.
• electrolytes (potassium, magnesium)
• pancreas and liver function
• bone marrow samples

Your doctor may change your dose. Your doctor may have you stop nilotinib for some time or lower your dose if you have side effects with it.

Your healthcare provider will monitor your chronic myeloid leukemia (CML) during treatment with Tasigna to see if you are in a remission.

• After at least 3 years of treatment with nilotinib, your healthcare provider may do certain tests to determine if you continue to be in remission.
• Based on your test results, your healthcare provider may decide if you may be eligible to try stopping treatment with nilotinib. This is called Treatment Free Remission (TFR).

Your healthcare provider will carefully monitor your leukemia during and after you stop taking nilotinib. Based you your test results, your healthcare provider may need to re-start your nilotinib if your leukemia is no longer in remission.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your liver function

Adults:

• For newly diagnosed leukemia, the recommended dose is 300 mg by mouth twice daily.
• For resistant or intolerant leukemia, the recommended dose is 400 mg by mouth twice daily.

Children:

• For newly diagnosed leukemia and resistant or intolerant leukemia, the recommended dose is 230 mg/m2 orally twice daily, rounded to the nearest 50 mg dose (to a maximum single dose of 400 mg). 

If you take too much nilotinib, call your doctor or poison control center right away. Symptoms may include vomiting and drowsiness.

• Store nilotinib at room temperature, 59° to 86°F (15° to 30°C).
• Safely throw away medicine that is out of date or no longer needed.
• Keep nilotinib and all medicines out of the reach of children.

WARNING: QT PROLONGATION AND SUDDEN DEATHS

• Nilotinib prolongs the QT interval. Prior to nilotinib administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, and follow any dose adjustments. 
• Sudden deaths have been reported in patients receiving nilotinib. Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. 
• Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. 
• Patients should avoid food 2 hours before and 1 hour after taking dose.