COLONYSTIMULATING FACTORS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Neupogen ¹
• Leukine ²

In Canada?

• Neupogen ¹

Other commonly used names are:

• Granulocyte colony stimulating factor (G-CSF)
• Granulocyte-macrophage colony stimulatingfactor (GM-CSF)

Category

• Antineutropenic?Filgrastim; Sargramostim
• Hematopoietic stimulant?Filgrastim; Sargramostim

Description

Filgrastim and sargramostimare synthetic (man-made) versions of substances naturally produced in yourbody. These substances, called colony stimulating factors, help the bone marrowto make new white blood cells.

When certain cancer medicines fight your cancer cells, they also affectthose white blood cells that fight infection. To help prevent infections whenthese cancer medicines are used, colony stimulating factors may be given.Colony stimulating factors also may be used to help the bone marrow recoverafter bone marrow transplantation and stem cell transplantation.

Colony stimulating factors are available only with your doctor's prescription,in the following dosage form:

Parenteral
• Filgrastim
  • Injection (U.S. and Canada)
• Sargramostim
  • Injection (U.S.)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For colony stimulatingfactors, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to the colony stimulating factor. Also tell your healthcare professional if you are allergic to any other substances, such as foods,preservatives, or dyes.

Pregnancy?Colony stimulating factors have not been studiedin pregnant women. Before you take a colony stimulating factor, make sureyour doctor knows if you are pregnant of if you may become pregnant.

• Filgrastim?In studies in rabbits,filgrastim did not cause birth defects but did cause internal defects, a decreasein average weight, and death of the fetus at high doses.
• Sargramostim?Studies on birth defectshave not been done in animals.

Breast-feeding?It is not known whether colony stimulating factorspass into human breast milk. However, these medicines have not been reportedto cause problems in nursing babies. Mothers who are taking a colony stimulatingfactor and who wish to breast-feed should discuss this with their doctor.

Children?Although there is no specific information comparinguse of colony stimulating factors in children with use in other age groups,this medicine is not expected to cause different side effects or problemsin children than it does in adults. In Canada, data from clinical trials inchildren indicate that the safety of filgrastim is similar in both adultsand children receiving certain cancer medicines. Sargramostim may containbenzyl alcohol and should not be given to infants because it could cause seriousadverse effects.

Older adults?Many medicines have not been studiedspecifically in older people. Therefore, it may not be known whether theywork exactly the same way they do in younger adults. Although there is nospecific information comparing use of colony stimulating factors in the elderlywith use in other age groups, this medicine has been used in many elderlypatients and is not expected to cause different side effects or problems inolder people than it does in younger adults.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takinga colony stimulating factor, it is especially important that your health careprofessional knows if you are taking any of the following:

• Chemotherapy or
• Radiation therapy?You should not use filgrastim close to thetime you are undergoing chemotherapy or radiation therapy for cancer treatment.

Other medical problems?The presence of other medicalproblems may affect the use of colony stimulating factors. Make sure you tellyour doctor if you have any other medical problems, especially:

• Conditions caused by inflammation or immune system problems?Thereis a chance these may be worsened by colony stimulating factor

• Heart disease?Risk of some unwanted effects (heart rhythm problems,retaining water) may be increased

• Kidney disease or
• Liver disease?May sometimes be worsened by colony stimulatingfactor

• Leukemia (cancer of the blood-forming organs)?May make conditionworse

• Lung disease?Colony stimulating factor may cause shortnessof breath

• Sickle cell disease (condition that affects the cells in your blood)?Maymake condition worse

Proper Use of This Medicine

If you areinjecting this medicine yourself, use it exactly as directedby your doctor. Do not use more or less of it, and do not use it moreoften than your doctor ordered. The exact amount of medicine you need hasbeen carefully worked out. Using too much will increase the risk of side effects,while using too little may not improve your condition.

If you are injecting this medicine yourself, each packageof colony stimulating factor will contain a patient instruction sheet. Readthis sheet carefully and make sure you understand:

• How to prepare the injection.
• Proper use of disposable syringes.
• How to give the injection.
• How long the injection is stable.

If you have any questions about any of this, check with your health careprofessional.

Dosing?The dose of colony stimulating factors willbe different for different patients. The dose that is used may depend on anumber of things, including what the medicine is being used for, the patient'sbody weight or size, and whether or not other medicines are also being taken. If you are receiving colony stimulating factors at home,follow your doctor's orders or the directions on the label. If youhave any questions about the proper dose of colony stimulating factors, askyour doctor.

Missed dose?If you miss a dose of this medicine, check withyour doctor.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store in the refrigerator.
• Keep the medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Ask yourhealth care professional how you should dispose of any medicine you do notuse. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It is very important that your doctor check your progress atregular visits to make sure that this medicine is working properlyand to check for unwanted effects.

Colony stimulating factors are used to prevent or reduce the risk of infectionwhile you are being treated with cancer medicines. Because your body's abilityto fight infection is reduced, it is very important thatyou call your doctor at the first sign of any infection (for example,if you get a fever or chills) so you can start antibiotic treatment rightaway.

Contact your doctor if you develop shortness of breath, tightness in chest.troubled breathing, or wheezing. These could be symptoms of a serious lungcondition called adult respiratory distress syndrome (ARDS).

If you experience left upper abdominal or shouldertip pain, contact your doctor right away. These could be symptoms of an enlargedor ruptured spleen.

Colony stimulating factors commonly cause mild bone pain, usually in thelower back or pelvis, about the time the white blood cells start to come backin your bone marrow. The pain is usually mild and lasts only a few days. Yourdoctor will probably prescribe a mild analgesic (painkiller) for you to takeduring that time. If you find that the analgesic is not strong enough, talkwith your doctor about using something that will make you more comfortable.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

The side effects listed below include only those that might be caused bycolony stimulating factors. To find out about other side effects that maybe caused by the cancer medicines you are also receiving, look under the informationabout those specific medicines.

Check with your doctor as soon as possible if any of the following sideeffects occur:

For filgrastim

Less common

Redness or pain at the site of subcutaneous (under the skin)injection

Rare

Fever; rapid or irregular heartbeat; sores on skin; wheezing

For sargramostim

Less common

Fever; redness or pain at the site ofsubcutaneous (under the skin) injection; shortnessof breath; swelling of feet or lower legs; weight gain (sudden)

Rare

Chest pain; rapid or irregular heartbeat; sores on skin; wheezing

Other side effects may occur that usually do not need medicalattention. These side effects may go away during treatment as your body adjuststo the medicine. However, check with your doctor if any of the following sideeffects continue or are bothersome:

For both filgrastim and sargramostim

More common

Headache; pain in arms or legs; pain in joints or muscles; pain in lowerback or pelvis; skin rash or itching

For sargramostin only (in addition to the above)

Less common or rare

Dizziness or faintness after first dose of medicine; flushing of face after first dose of medicine; weakness

Other side effects not listed above may also occur in some patients. Ifyou notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it also is usefulfor other medical problems. Although not specifically included in the productlabeling, colony stimulating factors are used in certain patients with thefollowing medical conditions:

• Failure or delay of myeloid engraftment after hemapoietic stem celltransplantation
• Myelodysplastic syndromes
• Neutropenia, AIDS-associated
• Neutropenia, drug-induced

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.