Cyclophosphamide

What is Cyclophosphamide?

• Cyclophosphamide is an alkylating drug used for treatment of lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis, and following organ transplant, among other conditions.

Error creating thumbnail:

Cyclophosphamide

Error creating thumbnail:

Cyclophosphamide-3D-balls

What are the uses of this medicine?

Cyclophosphamide is used for the treatment of:

• Malignant Diseases: malignant lymphomas: Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma
• Minimal Change Nephrotic Syndrome in Pediatric Patients: biopsy proven minimal change nephrotic syndrome patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy

Limitations of Use: The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established.

How does this medicine work?

• The mechanism of action is thought to involve cross-linking of tumor cell DNA.
• The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard.
• This metabolite is only formed in cells that have low levels of ALDH.
• Phosphoramide mustard forms DNA crosslinks both between and within DNA strands at guanine N-7 positions (known as interstrand and intrastrand crosslinkages, respectively).
• This is irreversible and leads to cell apoptosis.

Cyclophosphamide induces beneficial immunomodulatory effects in adaptive immunotherapy. Suggested mechanisms include:

• Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
• Induction of T cell growth factors, such as type I IFNs, and/or
• Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space niche.
• Thus, cyclophosphamide preconditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor immunity.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who have:

• Hypersensitivity to cyclophosphamide
• Urinary outflow obstruction

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following:

• allopurinol (Zyloprim®)
• cortisone acetate
• doxorubicin (Adriamycin®, Doxil®)
• hydrocortisone (Cortef®)
• phenobarbital (Luminal® Sodium)

Is this medicine FDA approved?

• Cyclophosphamide was approved for medical use in the United States in 1959.

How should this medicine be used?

Recommended dosage: Malignant Diseases:

• Adult and Pediatric Patients

Intravenous: Initial course for patients with no hematologic deficiency: 40 mg per kg to 50 mg per kg in divided doses over 2 to 5 days.

• Other regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

Oral: Usually 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Minimal Change Nephrotic Syndrome in Pediatric Patients: Recommended oral dose:

• 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg).
• Treatment beyond 90 days increases the probability of sterility in males.

Administration:

• Cyclophosphamide injection comes as a powder to be added to fluid and injected intravenously (into a vein) by a doctor or nurse in a medical office or hospital outpatient clinic. It may also be injected intramuscularly (into a muscle), intraperitoneally (into the abdominal cavity), or intrapleurally (into the chest cavity).
• Cyclophosphamide comes as a tablet to take by mouth once a day.
• The length of treatment depends on the types of drugs you are taking, how well your body responds to them, and the type of cancer or condition you have. Take cyclophosphamide at around the same time every day.
• Swallow the tablets whole; do not split, chew, or crush them.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection, sterile white powder: 500 mg, 1 g, and 2 g
• Injection: 200 mg/mL (500 mg/2.5 mL, 1 g/5 mL and 2 g/10 mL) in a multiple-dose vial
• Tablet for oral administration contains cyclophosphamide USP (calculated as anhydrous) 25 or 50 mg.

This medicine is available in fallowing brand namesː

• Cytoxan; Cytoxan Injection; Neosar Injection

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• vomiting
• loss of appetite or weight
• abdominal pain
• diarrhea
• hair loss
• sores on the mouth or tongue
• changes in skin color
• changes in color or growth of finger or toe nails

What special precautions should I follow?

• Cyclophosphamide can cause myelosuppression (leukopenia, neutropenia, thrombocytopenia and anemia), bone marrow failure, and severe immunosuppression which may lead to serious and sometimes fatal infections, including sepsis and septic shock. Close hematological monitoring is required.
• Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Exclude or correct any urinary tract obstructions prior to treatment.
• Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy. Monitor patients, especially those with risk factors for cardiotoxicity or pre-existing cardiac disease.
• Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Monitor patients for signs and symptoms of pulmonary toxicity.
• Secondary malignancies (urinary tract cancer, myelodysplasia, acute leukemias, lymphomas, thyroid cancer, and sarcomas) have been reported in patients treated with cyclophosphamide-containing regimens. The risk of bladder cancer may be reduced by prevention of hemorrhagic cystitis.
• Veno-occlusive liver disease (VOD) including fatal outcome has been reported in patients receiving cyclophosphamide-containing regimens.
• Cyclophosphamide can cause fetal harm when administered to a pregnant woman. Advise female patients of reproductive potential to avoid becoming pregnant and to use highly effective contraception during treatment and for up to 1 year after completion of therapy.
• Male and female reproductive function and fertility may be impaired in patients being treated with cyclophosphamide. Advise patients on the potential risks for infertility.
• Cyclophosphamide may interfere with normal wound healing.
• Hyponatremia associated with increased total body water, acute water intoxication, and a syndrome resembling SIADH (syndrome of inappropriate secretion of antidiuretic hormone), which may be fatal, has been reported.

What to do in case of emergency/overdose?

Symptoms of overdosage may:

• myelosuppression, urotoxicity, cardiotoxicity (including cardiac failure), veno-occlusive hepatic disease, and stomatitis.

Treatment of overdosage:

• No specific antidote for cyclophosphamide is known.
• Overdosage should be managed with supportive measures.
• Patients who received an overdose should be closely monitored for the development of toxicities, and hematologic toxicity in particular.
• Cyclophosphamide and its metabolites are dialyzable.
• Therefore, rapid hemodialysis is indicated when treating any suicidal or accidental overdose or intoxication.
• Cystitis prophylaxis with mesna may be helpful for urotoxic effects.

Can this medicine be used in pregnancy?

• Cyclophosphamide can cause fetal harm when administered to a pregnant woman based on its mechanism of action and published reports of effects in pregnant patients or animals.

Can this medicine be used in children?

• Cyclophosphamide is not recommended to use in Pre-pubescent girls and boys.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• CYCLOPHOSPHAMIDE

Inactive ingredients:

• none

Who manufactures and distributes this medicine?

Manufactured for Intalere Choice by:

• Baxter Healthcare Corporation
• Deerfield, IL USA
• Product Made in Germany

What should I know about storage and disposal of this medication?

• Store vials at or below 25°C (77°F).
• During transport or storage of cyclophosphamide vials, temperature influences can lead to melting of the active ingredient, cyclophosphamide.
• Cyclophosphamide is an antineoplastic product.
• Follow special handling and disposal procedures.

• Dailymed label info on Cyclophosphamide
• FDA Cyclophosphamide

Cyclophosphamide Resources
Latest articles Most recent articles Ongoing trials	Wikipedia