GENERIC NAME Cyclophosphamide Tablets

• The original designation that the drug was given when the drug company applied for the
approval process

Pronounciation (sye kloe FOS fah mide)

BRAND NAME Cytoxan OR Neozar

• Also known as Trade Name

• Given by the manufacturer

FDA categorize cyclophosphamide as PREGNANCY CATEGORY D

 Human fetal risk studies = there is evidence

Has acceptable benefits versus the risk of use

 There is positive evidence of human fetal risk based dun sa adverse reaction data from
investigational or marketing experience or studies, but pwede pa rin naman gamitin tong drug in
pregnant women/ buntis despite potential risks.
 Use is contraindicated.
 -This drug can cause fetal harm when administered to a pregnant woman.
 -Advise female patients of reproductive potential to avoid becoming pregnant and to use
effective contraception during treatment and for up to 1 year after completion of therapy.
 -Kasi pag ginamit to during pregnancy, or naging pregnant yung patient habang tinitake yung
drug, dapat alam niya yung potential harm ng drug dun sa fetus.
 -Maaari din tong mag cause ng sterility both males and females. meaning or hirap sa
pagbubuntis or makabuo in one year.
 Malformations of the skeleton, palate, limbs, and eyes and maaring makunan pag after
maexpose dun sa drug during the first trimester. Fetal growth retardation or slow development
ng newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and
gastroenteritis
 US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience or studies in humans, but potential
benefits may warrant use of the drug in pregnant women despite potential risks.

DRUG CLASS (Therapeutic Drug Class) Nitrogen Mustard Analogue

types of alkylating agents

which is A chemotherapy agent used to treat lymphomas, myelomas, leukemia, mycosis fungoides,
neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma.
THERAPEUTIC ACTIONS Alkylating agent; has activity as both an antineoplastic and
immunosuppressant

for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and
immune-mediated diseases.

now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in
haplo-identical unmanipulated bone marrow after transplantation.

Combination of cyclophosphamide with other immunomodulatory agents could be a promising

approach to treat different forms of advanced cancer.

Cyclophosphamide has immunosuppressive as well as immunomodulatory properties.

Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour
vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated
bone marrow after transplantation. The schedule of administration is of special importance for the
immunological effect: while Cyclophosphamide can be used in high-dose therapy for the complete
eradication of haematopoietic cells, lower doses of cyclophosphamide are relatively selective for T cells.
Of special interest is the fact that a single administration of low-dose cyclophosphamide is able to
selectively suppress regulatory T cells (Tregs). This effect can be used to counteract immunosuppression
in cancer. However, cyclophosphamide can also increase the number of myeloid-derived suppressor
cells.

INDICATIONS

• Used for the treatment of a variety of solid tumors, NHL cancer of the lymph tissue , Hodgkin
lymphoma cancer of lymphatic system, and ALL acute lymphoblastic leukemia immature white blood
cell bone marrow; oral cyclophosphamide used for nephrotic syndrome(kidney disorder too much
protein in urine) in pediatric patients.

Contraindications and Cautions

• Contraindicated in patients hypersensitive to drug and in those with severe bone marrow
suppression. Treatment using cyclophosphamide maaring mauwi sa severe bone marrow suppression
and immunosuppression. This may predispose the patient to serious and sometimes fatal bacterial, viral
and fungal infections. Patients who are receiving cyclophosphamide should be closely monitored.

• Use cautiously in patients with impaired renal or hepatic function, leukopenia,

thrombocytopenia, or malignant cell infiltration of bone marrow and in those who have recently
undergone radiation therapy or chemotherapy. those receiving concurrent radiation therapy and
cyclophosphamide chemotherapy bone marrow failure may occur, leading to prolonged cytopenia and
risk of infections and transfusion requirements.
Available Forms

Injection: 100-mg, 200-mg, 500-mg, 1-g, 2-g vials

Tablets: 25 mg, 50 mg

Dosages

Breast, head, neck, lung, and ovarian carcinoma; Hodgkin’s disease; myelocytic and acute lymphoblastic
leukemia; neuroblastoma; retinoblastoma; malignant lymphomas; multiple myeloma; mycosis
fungoides; sarcomas; severe rheumatoid disorders. Adults: 40 to 50 mg/kg I.V. in divided doses over 2
to 5 days. Oral dosing for initial and maintenance dosage is 1 to 5 mg/kg P.O. daily.

Nephrotic syndrome(too much protein in urine) in children. Children: 2.5 to 3 mg/kg P.O. daily for 60 to
90 days.

Pharmacokinetics

Cyclophosphamide is administered orally and intravenously

Sa iv 2-4 hours

Sa oral route the median time to peak pasma concentration is 1 hour

Distribution: Distributed throughout the body, although only minimal amounts have been found in
saliva, sweat, and synovial fluid. The level in CSF is too low for treatment of meningeal leukemia. The
active metabolites are about 50% bound to plasma proteins.

Metabolism: Metabolized to its active form by hepatic microsomal enzymes. The activity of these
metabolites is terminated by metabolism. to inactive forms.

Excretion: Eliminated primarily in urine, with 15% to 30% excreted as unchanged drug. The elimination
half-life ranges from 3 to 12 hours.

Preparation: Wear protective gloves. Care should be taken to avoid splashing material into the eyes. The
material should not be handled by women who are pregnant or who are breast-feeding.

Infusion: IV infusion, (containing cyclophosphamide) is reconstituted by adding sterile water for injection
or 0.9% sterile sodium chloride solution.

Incompatibility: Benzyl alcohol increases the degradation rate of cyclophosphamide.

Adverse Effect

• CV: cardiotoxicity (with very high doses and with doxorubicin).

• GI: anorexia, nausea, vomiting (within 6 hours), abdominal pain, stomatitis, mucositis.

• GU: hemorrhagic cystitis, fertility impairment.

• Hematologic: leukopenia (nadir between days 8 to 15, recovery in 17 to 28 days),

thrombocytopenia, anemia.
• Hepatic: hepatotoxicity.

• Metabolic: increased serum uric acid levels.

• Respiratory: pulmonary fibrosis (with high doses).

• Skin: reversible alopecia.

• Other: secondary malignant disease, anaphylaxis, hypersensitivity reactions.

Interactions

• Drug-drug. Allopurinol, chloramphenicol, chloroquine, imipramine, phenothiazines, potassium

iodide, vitamin A: May inhibit cyclophosphamide metabolism. Monitor patient closely.