THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

(For veterinary information only)

Brand Name: Cytoxan

Available as 25 mg and 50 mg tablets

How this Medication Works

Cyclophosphamide is a serious drug used to treat very serious disease. Cyclophosphamide is used to kill cells that are causing harm, usually cancer cells or inflammatory cells.

This potent cell-killing medication is a nitrogen mustard derivative, meaning it is related to the toxic chemical weapon mustard gas (so named because of its mustard or horseradish odor) used widely in the first World War. In chemotherapy, cyclophosphamide is classified as an alkylating agent, which means it works by binding to DNA and thus interfering with normal cell function. By disrupting cellular DNA, cyclophosphamide is able to kill the cell. Cells that divide rapidly (and thus replicate their DNA rapidly) are especially targeted by cyclophosphamide. This makes cyclophosphamide especially able to kill:

• Rapidly dividing cancer cells
• Bone marrow cells such as developing blood cells
• Stimulated lymphocytes (those engaged in proliferation and antibody production)
• Fetal cells
• Hair follicle cells
• Intestinal cells

Uses of this Medication

Because of its ability to kill rapidly dividing, cyclophosphamide has been used most successfully in two situations:

• Immune mediated diseases (especially those of life-threatening nature such as immune-mediated hemolytic anemia )
• Cancer chemotherapy (especially for bone marrow or blood cell cancers such as lymphoma)

Side Effects

There are several important side effects to consider when using cyclophosphamide:

• Bone Marrow Suppression
  White cell blood lines show suppression (i.e. counts will drop) approximately 1 to 2 weeks following a dose of cyclophosphamide. This time period makes the patient especially vulnerable to infection. Many oncologists like to monitor white blood cell count and withhold cyclophosphamide if the white blood cell count is not greater than a certain minimum number. Other oncologists do not like to reduce the cyclophosphamide dose without evidence of infection as reducing the cyclophosphamide dose will give the tumor an advantage and possibly jeopardize the remission.
  
• Hair Loss
  While human chemotherapy patients commonly lose their hair, animal patients almost never do. The exceptions are wavy coated dogs such as poodles and Old English Sheepdogs). Cats undergoing chemotherapy commonly lose their whiskers. Hair texture on pets in general tends to get softer on chemotherapy.
  
• Upset Stomach
  Despite the image most people have of nausea associated with chemotherapy, this is actually a surprisingly uncommon problem in dogs and cats. When it occurs, it is generally readily controllable with antinausea medications.
  
• Development of Hemorrhagic Cystitis
  Up to 30% of dogs (depending on the study) receiving cyclophosphamide for over 2 months develop bloody urine caused by excretion of irritating cyclophosphamide metabolites. This condition may represent pre-cancer in itself and must be distinguished from a bladder infection. This is a serious side effect of cyclophosphamide use and any sign of bloody urine should be reported to the veterinarian at once.

Interactions with other Drugs

Cyclophosphamide should be avoided in patients taking other bone marrow suppressing agents such as azathioprine or methimazole. The effect of two marrow suppressors is additive.

Phenobarbital will increase the rate of excretion of cyclophosphamide (i.e. cyclophosphamide will be more rapidly removed from the body). This will increase the toxicity potential of the cyclophosphamide.

Diuretics of the thiazide class may increase the bone marrow suppression side effects of cyclophosphamide.

In the treatment of immune-mediated disease, it is common and usual to use cyclophosphamide in conjunction with corticosteroids such as prednisone or dexamethasone.

Concerns and Cautions

Obviously it is not prudent to suppress the immune system in the face of a known infection.

Cyclophosphamide is toxic to the unborn fetus and should not be used in pregnancy.

The majority of cyclophosphamide is excreted in urine and a dose is still detectable in urine some 72 hours after administration.

Due to the unique manufacture of cyclophosphamide tablets, these tablets cannot be accurately dosed after being cut. It is best to use tablets whole.

If cyclophosphamide is administered at home, it is important to wear gloves when handling it.

It is our policy not to give dosing information over the Internet.

Date Published: 4/28/2003 11:13:00 AM
Date Reviewed/Revised: 06/05/2008