busulfan

n.
An alkylating agent, C₆H₁₄O₆S₂, that is used as an antineoplastic drug in the treatment of chronic myelocytic leukemia.

[BU(TANE) + alteration of SULFON(ATE).]

Key Terms: Anemia, Bone marrow transplant, Cataract, Chemotherapy, Food and Drug Administration, Gout, Hemoglobin, Intravenous, Metastatic, Neutropenia, Polycythemia vera.

Definition

Busulfan (also known by the brand name Myleran) is a chemotherapy medicine used to treat cancer by destroying cancerous cells.

Purpose

Busulfan is approved by the Food and Drug Administration (FDA) to treat chronic myelogenous leukemia (also called chronic myelocytic leukemia). It has also been less commonly used for other acute leukemias and a blood disease known as polycythemia vera, in which there are too many red blood cells. Busulfan is also used in combination with other chemotherapy drugs for a procedure known as bone marrow transplantation.

Description

Busulfan a member of the group of chemotherapy drugs known as alkylating agents. Alkylating agents interfere with the genetic material (DNA) inside the cancer cells and prevent them from further dividing and producing more cancer cells. Busulfan is taken orally and comes in tablet form.

Recommended Dosage

Busulfan can be taken following several different dosing schedules, depending on the disease. Busulfan is a 2mg oral tablet, and patients may need to take more than one tablet at a time depending on the dose. The induction or starting dose is 4mg up to 12mg per day. This may then be decreased to 1mg to 3mg per day as a maintenance dose. The dose of busulfan for use in combination with other chemotherapy drugs before a bone marrow transplant is much larger than leukemia dosing. Busulfan, when used for bone marrow transplants, is dosed by patient body weight. Busulfan is usually given at a dose of 4mg per kilogram of body weight each day for 4 days before a bone marrow transplant.

Precautions

Blood counts are monitored regularly while on busulfan therapy. During a certain period of time after receiving busulfan, there is an increased risk of contracting infections. Caution should be taken to avoid unnecessary exposure to bacteria and viruses. All patients should increase their daily fluid intake while receiving this drug.

Patients who are pregnant or are trying to become pregnant should notify their physician before taking busulfan (or any chemotherapy medication). Busulfan causes a high incidence of sterility in males, and has been known to cause sterility in females as well.

Patients with a known previous allergic reaction to chemotherapy drugs, or who suffer from gout, thalassemia, or seizure problems, should notify their physician before beginning treatment. The physician should also be consulted before receiving live virus vaccines while on chemotherapy.

Side Effects

The most common side effect expected from taking busulfan is low blood counts, referred to as myelosuppression. Lowering of the white count, or neutropenia, is common and lasts for some time before the white count returns to normal levels. When the white blood cell count is low, patients are at an increased risk of developing a fever and infections. The platelet blood count can also be decreased due to busulfan administration. Platelets are blood cells in the body that cause clots to form; the purpose of these clots is to control bleeding. When the platelet count is low, patients are at an increased risk for both bruising and bleeding. If the platelet count remains too low, a platelet blood transfusion may be an option for treatment. Busulfan also causes low red blood cell counts, or anemia. Low red counts make patients feel tired, dizzy, and fatigued. Erythropoietin is a drug that can be used to increase red blood cell count.

In bone marrow transplant patients, the dose of busulfan that is given in combination with other chemotherapy drugs is intended to cause complete bone marrow destruction prior to bone marrow transplant.

Nausea, vomiting, loss of appetite, mouth sores, and diarrhea are rare side effects from busulfan at normal doses, but are common at the higher doses used for bone marrow transplant. If nausea and vomiting are a problem, patients can be given medications known as antiemetics before receiving busulfan to help prevent or decrease these side effects. Taking busulfan on an empty stomach may also decrease nausea and vomiting.

Damage to nerves and nervous system tissues is uncommon with standard busulfan therapy. However, at high doses, some reports do exist of seizures, dizziness, confusion, and visual disturbances.

Busulfan can also cause severe lung problems known as "busulfan lung". Symptoms include a nonstop cough, shortness of breath, fever, and difficulty breathing.

Less common side effects caused by busulfan include skin rashes or reactions (including darkening of the skin), dryness of the skin, itching, and hair loss (alopecia).

Although it is uncommon, severe liver problems may occur due to busulfan administration at higher doses. Rare reactions to busulfan include: lung problems, cataracts, fatigue, heart problems, low blood pressure, development of another type of cancer or leukemia, enlarged breast tissue (referred to as gynecomastia), and increased uric acid levels (which can lead to kidney problems and gout).

Any side effects experienced by a patient should be reported to his or her physician.

Interactions

Busulfan used for transplant purposes, when given in high doses with the chemotherapy drug cyclophosphamide, caused an increase in serious heart problems.

Patients who have taken busulfan with the drug thioguanine over long periods of time have shown an increase in enlarged veins in the esophagus and liver problems.

—Nancy J. Beaulieu, RPh., BCOP

n

trade name: Myleran; drug class: antineoplastic; action: changes essential cellular ions to covalent bonding with resultant alkylation, which interferes with biologic function of deoxyribonucleic acid; uses: treatment of chronic myelocytic leukemia.

Brand names: Busulfex®, Myleran®

Chemical formula:

Drug Forms:
• Busulfan tablets (below)
• Busulfan injection

Español:
• Tabletas de busulfán
• Inyección de busulfán

Busulfan tablets

What are busulfan tablets?

BUSULFAN (Myleran®) is a type of chemotherapy used for treating chronic myelogenous leukemia. It may also be used as part of the chemotherapy given before bone marrow transplantation. Busulfan may be used in combination with other cancer chemotherapy agents. Generic busulfan tablets are not yet available.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
• blood disorders
• bleeding problems
• dental disease
• gout
• infection (especially virus infection such as chickenpox or herpes)
• liver disease
• previous radiation therapy
• previous cancer chemotherapy
• seizures
• an unusual or allergic reaction to busulfan, other chemotherapy agents, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take busulfan tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Finish the full course prescribed by your doctor or health care professional even if the tablets make you feel unwell. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What drug(s) may interact with busulfan?

• bosentan
• digoxin
• imatinib, STI-571
• itraconazole
• medicines used to suppress the immune system (such as cyclosporine)
• other chemotherapy medicines
• phenytoin
• strontium-89 chloride
• thioguanine
• vaccines

Talk to your prescriber or health care professional before taking any of these medicines:
• acetaminophen
• aspirin
• blood thinners such as warfarin (Coumadin®)
• clopidogrel
• ibuprofen
• naproxen
• ticlopidine

Tell your prescriber or health care professional about all other medicines that you are taking, including nonprescription medicines, nutritional supplements, or herbal products. Also, tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking busulfan?

Visit your prescriber or health care professional for checks on your progress. You will need to have regular blood checks. The side effects of busulfan can continue after you finish your treatment; report side effects promptly.

Busulfan may make you feel generally unwell. This is not uncommon because busulfan affects good cells as well as cancer cells. Report any side effects as above, but continue your course of medicine even though you feel ill, unless your prescriber or health care professional tells you to stop.

Busulfan will decrease your body's ability to fight infections. Call your prescriber or health care professional if you have a fever, chills, sore throat or other symptoms of a cold or flu. Do not treat these symptoms yourself. Try to avoid being around people who are sick. Busulfan may increase your risk to bruise or bleed. Call your prescriber or health care professional if you notice any unusual bleeding. Be careful not to cut, bruise or injure yourself because you may get an infection and bleed more than usual.

Avoid taking aspirin, acetaminophen (Tylenol®), ibuprofen (Advil®) or naproxen (Aleve®) products as these may mask a fever, unless instructed to by your prescriber or health care professional.

Be careful brushing and flossing your teeth or using a toothpick while receiving busulfan because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are taking busulfan.

Do not have any vaccinations without your prescriber's approval and avoid anyone who has recently had oral polio vaccine.

Call your prescriber or health care professional for advice if you get a fever, chills or sore throat, do not treat yourself.

Men and women of childbearing age should use effective birth control methods during and after busulfan treatment. There is a risk of birth defects if a women becomes pregnant and either partner is being treated with busulfan. Women should not become pregnant while being treated with busulfan. Talk to your prescriber or health care professional about how this medicine can affect your ability to have normal babies.

Drink several glasses of water a day. This will help to reduce possible kidney problems.

Busulfan can discolor your skin and nails, especially if you have a dark complexion.

What side effects may I notice from taking busulfan?

The side effects you may experience with busulfan therapy depend upon the dose, other types of chemotherapy or radiation therapy given, and the disease being treated. Not all of these effects occur in all patients. Discuss any concerns or questions with your prescriber or health care professional.

Side effects that you should report to your prescriber or health care professional as soon as possible:
• low blood counts - busulfan will decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
• signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
• signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
• signs of decreased red blood cells - unusual weakness or tiredness, fainting spells, lightheadedness
• blurred vision
• difficulty breathing
• lower back pain
• rash
• seizures (convulsions)
• sores in mouth or throat
• vomiting
• yellowing of eyes or skin

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• changes in color of nails and/or skin
• diarrhea
• dry mouth
• missed or irregular menstrual periods
• nausea
• stomach pains or cramps
• weight loss

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 25 degrees C (59 and 77 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

An alkylating antineoplastic agent used in the treatment of chronic granulocytic leukemia.

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