Bosutinib (Oral)

Overview

Leukemia is a type of cancer where the body makes abnormal white blood cells. Bosutinib is in a category of drugs called kinase inhibitors. It is an antineoplastic (cancer) medication that works by hampering the activity of an abnormal protein that signals the multiplication of cancer cells. This helps prevent the spread of cancer cells. Bosutinib is usually prescribed to patients after other medications for CML have been used without success.

Since bosutinib may also affect the growth of normal cells, the patient is likely to experience other side effects. Some of these effects could be serious and should be reported to the doctor immediately. Before beginning treatment, have a discussion with your doctor about the benefits of this medication as well as the potential risks of using it. Bosutinib is available only with a doctor's prescription.

Conditions treated:

• Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML)

Type of medicine:

• Kinase inhibitor

Side Effects

Besides the desired effects, Bosutinib may be responsible for certain unwanted effects. Keep in mind that your doctor will prescribe this medication after weighing its potential benefits against the risks of taking it. Stop taking the medication and seek emergency medical attention if you experience any of these side effects:

More common:

• Chills
• Cough
• Black, tarry stools
• Bleeding gums
• Blood in stool or urine
• Fever
• Lower back or side pain
• Pale skin
• Pinpoint red spots on the skin
• Swollen face, lower legs, or feet
• Sore throat
• Ulcers, sore, or white spots in the mouth or lips
• Painful/difficult urination
• Troubled breathing with exertion
• Unusual weakness or fatigue
• Tightness in the chest
• Unusual bleeding or bruising

Less common:

• Stomach or abdominal pain or tenderness
• Increased thirst
• Cough with mucus
• Dark urine
• Increased sweating
• Confusion
• Dry mouth
• Loss of appetite
• Agitation
• Chest pain or discomfort
• Depression
• Diarrhea
• Hoarseness
• Irritation
• Hostility
• Shivering
• Dizziness
• Fainting
• Faster or irregular heartbeat
• General feeling illness or discomfort
• Headache
• Lightheadedness
• Hives, skin rash or itching
• Joint pain, swelling or stiffness
• Muscle aches, pains, or twitching
• Sneezing
• Numbness or tingling in the lips, hands, or feet
• Fast breathing
• Rapid weight gain
• Nausea or vomiting
• Runny nose
• Seizures
• Clay-colored stools
• Decreased urination
• Decreased appetite
• Difficulty swallowing
• Wrinkled skin
• Redness of the skin
• Sunken eyes
• Swollen of the eyelid, face, hands, or feet
• Thirst
• Weakness/heaviness of the legs
• Trouble sleeping

Rare:

• Blue lips, skin or fingernails
• Blistering, loosening or peeling of the skin
• Chest pain, possibly shifting to the left arm, shoulder or neck
• Coughing that may sometimes produce a pink, frothy sputum
• Bloating
• Indigestion
• Constipation
• Irregular, slow or fast, or shallow breathing
• Yellowing or skin or eyes
• Red, irritated eyes
• Difficult and noisy breathing, with occasional wheezing
• Pains in stomach, abdomen or side, possibly spreading to the back
• Puffiness/swelling of the eyelids or around the eyes, face, lips or tongue
• Vomiting blood or a substance that looks like coffee grounds

Some of the side effects of bosutinib may not require medical attention. These side effects will likely go away in the course of treatment, as your system adjusts itself to the medicine. Ask for advice from your doctor on the various ways to reduce or prevent these side effects. Be sure to check with your doctor if the side effects below persist, or if you need further clarification about them:

More common:

• Back pain
• Lack or loss of strength
• Muscle stiffness
• Stuffy nose
• Difficulty with movement

Less common:

• Change in taste
• Loss of taste
• Burning feeling in the stomach or chest
• Stomach upset
• Tenderness in stomach area
• Blemishes on skin
• Hearing loss
• Pimples
• Muscle cramping
• Buzzing, ringing or other unusual noise in the ears that persists

Rare :

• Peeling and falling off of the skin

Severe allergic reactions to Bosutinib are rare. However seek medical attention immediately if you notice any of these symptoms of an allergic reaction: rash, itching, swelling, dizziness and labored/difficult breathing.

Note that bosutinib sometimes causes a mild rash that is typically not serious. You might however not be able to distinguish it from a rare rash that may be a sign of a serious allergic reaction. If you develop any rash, therefore, seek medical help immediately.

Medical or lab tests (e.g. liver/kidney function, and complete blood count) should be performed from time to time to keep track of your progress and monitor side effects. Ask your healthcare professional for more details. Some other side effects not listed here may also occur in some patients. It is advisable to check with your doctor as soon as possible if you experience any other side effects.

Dosage

Take this medication exactly as prescribed by your doctor. Before taking bosutinib, it is also vital that you read through the Patient Information Leaflet provided by your pharmacist. Should you have any questions, or require more information, consult your pharmacist or doctor.

Take bosutinib by mouth with food as directed by your health caregiver, usually once a day. The usual dosage for leukemia treatment is 500 mg once a day (adults). Swallow the tablet whole. Do not crush, break or chew the tablets. Avoid touching or handling broken tablets.

To get the most benefit from this medicine, take it at about the same time every day.

Medicines that block or reduce stomach acid (such as H2 blockers, antacids and proton pump inhibitors/PPIs) could lower the absorption of bosutinib, making it less effective. Avoid taking proton pump inhibitors such as lansoprazole and omeprazole while using bosutinib. If you use H2 blockers or antacids (such as ranitidine and famotidine), take them at least two hours before or after taking this medication.

While using this medication, do not eat grapefruit or drink grapefruit juice unless your pharmacist or doctor says it is safe to do so. Grapefruit may increase the risk of side effects with this medication. Ask your health care giver for more details.

Because this medication can be absorbed through the lungs and skin and could harm an unborn baby, pregnant women or those who may become pregnant should not handle the drug or inhale the dust from the tablets.

Missed dose:

In case of a missed dose, be sure take it the moment you remember. However, you can go back to your regular dosing schedule if it's almost time to take the next dose. Do not make up for the missed dose by double dosing.

Overdose:

Contact your local poison control center as soon as you suspect overdosing. For US residents, the national poison hotline is 1-800-222-1222. If you are in Canada, call your local poison center directly.

Symptoms of an overdose may include:

• Lightheadedness
• Blurred vision
• Nausea
• Dizziness
• Fainting

Major Drug Interactions

Drug interactions could affect the functioning of the medication in the body, or heighten the risk of serious side effects occurring. Although some medications should not be used together, there may be cases where they may be prescribed together even if an interaction could occur. In such cases, your doctor may alter the dosage, or advise you to take certain precautions. When taking bosutinib, it is absolutely important to let your doctor know whether you are also using any of the drugs listed below.

It is not recommended to use bosutinib with any of the following medications. In some instances, your doctor may decide against prescribing this medication or they may change the dosing for the other drugs you are taking:

• Varicella Virus Vaccine
• Measles Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rubella Virus Vaccine, Live

Using bosutinib with any of the medicines highlighted below is usually not advisable, but may be necessary in some cases. If your pharmacist or doctor prescribes both medicines together, they may decide to change the dose or the frequency of using one or both of the medications:

• Amprenavir
• Conivaptan
• Aprepitant
• Bacillus of Calmette and Guerin Vaccine, Live
• Carbamazepine
• Adenovirus Vaccine
• Ceritinib
• Ketoconazole
• Cholera Vaccine, Live
• Lansoprazole
• Esomeprazole
• Clarithromycin
• Cobicistat
• Boceprevir
• Bosentan
• Delavirdine
• Darunavir
• Fosamprenavir
• Verapamil
• Fosphenytoin
• Diltiazem
• Dexamethasone
• Fosaprepitant
• Dexlansoprazole
• Voriconazole
• Dronedarone
• Efavirenz
• Atazanavir
• Enzalutamide
• Erythromycin
• Fluconazole
• Idelalisib
• Poliovirus Vaccine, Live
• Imatinib
• Indinavir
• Lopinavir
• Mibefradil
• Ritonavir
• Smallpox Vaccine
• Mifepristone
• Mitotane
• Etravirine
• Modafinil
• Nefazodone
• Omeprazole
• Oxcarbazepine
• Pantoprazole
• Phenytoin
• Posaconazole
• Nelfinavir
• Influenza Virus Vaccine, Live
• Prednisone
• Ciprofloxacin
• Primidone
• Phenobarbital
• Rabeprazole
• Telaprevir
• Telithromycin
• Rifabutin
• Nevirapine
• Itraconazole
• Rifampin
• St John's Wort
• Typhoid Vaccine
• Yellow Fever Vaccine
• Saquinavir

This is not necessarily an exhaustive list of all the possible drug interactions with bosutinib. It is advisable to keep a list of all products you use, including prescription and non-prescription medicines, diet supplements and herbal products. This information is important to your doctor as they prepare your prescription.

Food/alcohol/tobacco:

To avoid interactions from occurring, it may be necessary to stop consuming certain foods, as well as alcohol and tobacco. When using bosutinib, avoid drinking grapefruit juice as it could heighten the risk of side effects. Have a talk with your doctor about the use of alcohol, or tobacco with your medicine.

Other medical conditions:

Suffering from certain other medical problems could affect how this medicine functions. Inform your healthcare professional if you have other medical problems, especially:

• Diarrhea
• Blood or bone marrow problems
• Edema (fluid retention or swelling)
• Anemia (low levels of red blood cells)
• Neutropenia (low levels of white blood cells)
• Thrombocytopenia (low platelets count in the blood) should be used with caution; could make the conditions worse.
• Nausea or vomiting
• Kidney disease
• Infection May decrease your body's ability to fight infection.
• Liver disease should be used with caution. The effects may increase due to slower elimination of the medication from the body.

Warnings

Before using any medicine, it's always important to consider the potential risks of using it against the benefits it has to offer. Your health caregiver should help you with making this decision. Here are some of the top factors to consider:

Allergies: let your physician know if you have had any odd or allergic reactions to bosutinib or any other medicines. In addition, tell your healthcare professional if you have some other type of allergy, such as to dyes, animals, foods, or preservatives. When buying a non-prescription product, be sure to go through the package or label ingredients carefully.

Pediatric: no appropriate studies have been performed as yet on the relationship of age to the effects of this drug in the pediatric population. The efficacy and safety of this medication have not been established.

Older adults: to date, no appropriate studies done have shown geriatric-specific issues that would limit the usefulness of bosutinib among the elderly population.

Pregnancy: Taking this medication may cause harm to the unborn baby. Use of bosutinib during pregnancy is therefore not recommended. Use a reliable form of birth control while under treatment with this medication, and for at least a month after stopping the treatment. If you think you've become pregnant while taking this medicine, inform your doctor right away.

Breastfeeding: It is not quite known if this medicine passes into breast milk. However, because of the possible risk to the infant, do not use the medication without discussing the risks with your doctor.

Bosutinib can cause dizziness, and the effect could be worse if you use it with marijuana or alcohol. Use it with caution, and avoid driving or performing other tasks that require alertness until you know how your body responds to it.

Bosutinib may temporarily lower the white blood cell count in your blood, increasing the risk of infections. It could also reduce the number of platelets, which are important for blood clotting. If this happens, there are a few precautions you can take to lower the risk of bleeding or infection:

• If possible, avoid getting close to anyone with an infection. Call your health caregiver immediately if you suspect you are catching an infection, or if you start experiencing chills, fever, hoarseness or cough, painful/difficult urination, or lower back/side pain.
• Check with your healthcare professional immediately if you experience any unusual bruising or bleeding, blood in the stools or urine, black or tarry stools, or pinpoint red spots on the skin.
• Take care when using a toothpick, toothbrush or dental floss. Your physician or dentist may recommend different ways to clean your gums and teeth. Consult your doctor before having any dental procedure.
• Avoid touching the eyes or inside of your nose without cleaning your hands first.
  Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
  Exercise caution with sharp objects such as a toenail cutter or a safety razor to avoid cutting yourself.
• Avoid aggressive activity where there's risk of injury or bruising.

Check with your doctor immediately if you have stomach pain, loss of appetite, yellow eyes or skin, dark urine, or pale stools. These may be the symptoms of a severe liver problem.

Cancer medications are known to cause diarrhea, stomach pain, nausea and vomiting, even after taking other drugs to prevent this. Ask your physician about ways to limit these side effects.

Do not take other medications unless you have discussed them with your doctor. This includes prescription and non-prescription OTC drugs, as well as vitamins or herbal supplements.

Storage

Bosutinib should be stored at room temperature and away from light, excess heat and moisture. Keep the medication tightly sealed in its original container, out of the sight and reach of children and pets.

If your healthcare professional decides that treatment with this medication is no longer necessary, dispose of any unused tablets properly to ensure that children, pets or other people cannot find them. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Ask your pharmacist about the proper disposal of any left-over medication.

Summary

Bosutinib is used in adults for the treatment of chronic myelogenous leukemia (CML) that is Philadelphia chromosome positive. It is usually prescribed after other CML medications have not been effective. It is an antineoplastic medication that works by blocking the activity of an abnormal protein that signals the multiplication of cancer cells. This helps prevent the spread of cancer cells.

Patients taking bosutinib need to observe certain precautions. For example, you should be aware that taking cancer medications like bosutinib can lower the level of the white blood cell count in the body, which increases the risk of getting infections. Be sure to avoid close contact with people with infections. If you have an allergy of any kind or some other medical problem, make sure you inform your doctor. Avoid taking grapefruit juice when using bosutinib as it may increase the risk of side effects.

It is also important to inform your doctor if you are currently taking other medicines, so they can help you avoid interactions. In particular avoid PPIs such as omeprazole, as they could interfere with the absorption of this medicine. If you use antacids or H2 antagonists, take them at least one hour before or after your bosutinib dose.