TUNEL labeling of free 3'-OH DNA ends demonstrated that cyclophosphamide promotes outer membrane blebbing, leading to DNA fragmentation, and promoting cleavage of the caspase 3 and caspase 7 substrate PARP in 9L/P450 cells. Bcl-2 expression totally prevents activation of initiator and effector caspase 3 in cells treated with activated cyclophosphamide. Bcl-2 suppresses the cytotoxic effects but not the cytostatic effects of activated cyclophosphamide [1]. Cyclophosphamide reversibly inhibits AChE with an IC50 of 511 μM [2]. Carbon tetrachloride does not impact the direct cytotoxicity of cyclophosphamide or 4-hydroxycyclophosphamide to cultivated cells [3].

Cyclophosphamide increases the percentage of cells stained for CD3, CD4, or CD8 in the spleen and tumors when given intraperitoneally (i.p.) to SW1 tumor-bearing C3H mice (2 mg/mouse in 0.1 mL PBS) [4].

Animal/Disease Models: Six- to eightweeks old female C3H/HeN mice bearing SW1 tumors [4]
Doses: 2 mg/mouse
Route of Administration: intraperitoneal (ip) injection; 2 mg/mouse in 0.1 mL PBS; Four-day
Experimental Results: spleen and an increase in the percentage of cells staining for CD3, CD4, or CD8 in the tumor.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Cyclophosphamide appears in milk in potentially toxic amounts; additionally, highly toxic active metabolites could add to the risk to the infant. Neutropenia has been reported in 2 infants whose mothers breastfed them while receiving cyclophosphamide. Most sources consider breastfeeding to be contraindicated during maternal cytotoxic antineoplastic drug therapy, especially alkylating agents such as cyclophosphamide. Although some have suggested withholding breastfeeding for 1 to 3 days after a dose, it appears to take more than 21 days for the drug and its metabolites to be completely eliminated from breastmilk. Some authors’ data suggest that it might take 6 weeks for milk levels to drop to a safe level after a dose of cyclophosphamide 750 mg/sq. m.
Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.
◉ Effects in Breastfed Infants
In one 23-day-old infant, neutropenia, thrombocytopenia and a low hemoglobin were possibly caused by cyclophosphamide after 3 days of maternal treatment with cyclophosphamide 6 mg/kg IV daily (total dose 300 mg).
In a 4-month-old, neutropenia was probably caused by cyclophosphamide in a mother 9 days after the last of 6 weekly doses of 800 mg cyclophosphamide intravenously, 2 mg vincristine intravenously and daily doses of 30 mg of prednisolone orally. Neutropenia persisted at least 12 days and was accompanied by a brief episode of diarrhea.
A woman was diagnosed with B-cell lymphoma at 27 weeks of pregnancy. Labor was induced at 34 4/7 weeks and treatment was begun with a standard regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in unspecified doses on a 21-day cycle, starting on day 2 postpartum. She pumped and discarded her milk and fed her infant donor milk for the first 10 days of each cycle and then breastfed her infant for the remaining 10 days before the next treatment cycle. The 10-day period of breastfeeding abstinence was determined by using about 3 half-lives of vincristine. After completion of 4 cycles of chemotherapy, her infant was reportedly healthy and developing without any complications.
◉ Effects on Lactation and Breastmilk
A case of euprolactinemic galactorrhea was reported in a 55-year-old woman receiving cyclophosphamide for pemphigus vulgaris. One month after starting cyclophosphamide 50 mg daily she experienced fullness in both breasts and bilateral milky nipple discharge. No hormonal abnormalities were found. After cyclophosphamide was discontinued, her symptoms resolved completely and did not recur. Galactorrhea was probably caused by cyclophosphamide.
Telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 56 women who received a cyclophosphamide-containing regimen, 34 had breastfeeding difficulties.

[1]. Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. Mol Pharmacol. 2001 Dec;60(6):1268-1279.

[2]. Administration of cyclophosphamide changes the immune profile of tumor-bearing mice. J Immunother. 2010 Jan;33(1):53-9.

[3]. Inhibition of human acetylcholinesterase by cyclophosphamide. Toxicology. 1995 Jan 19;96(1):1-6.

[4]. Carbon tetrachloride-induced increase in the antitumor activity of cyclophosphamide in mice: a pharmacokineticstudy. Cancer Chemother Pharmacol. 1984;12(3):167-72.

Cyclophosphamide monohydrate appears as fine white crystalline powder with a slightly bitter taste. Little or no odor. (NTP, 1992)
Cyclophosphamide hydrate is the monohydrate of cyclophosphamide. It has a role as an antineoplastic agent, an immunosuppressive agent, an alkylating agent and a carcinogenic agent. It contains a cyclophosphamide.
Cyclophosphamide is a synthetic alkylating agent chemically related to the nitrogen mustards with antineoplastic and immunosuppressive activities. In the liver, cyclophosphamide is converted to the active metabolites aldophosphamide and phosphoramide mustard, which bind to DNA, thereby inhibiting DNA replication and initiating cell death.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
See also: Cyclophosphamide (annotation moved to).

C7H17CL2N2O3P

279.1012

278.035

6055-19-2

Cyclophosphamide;50-18-0;Cyclophosphamide-d8 hydrate

22420

White to off-white solid powder

336.1ºC at 760 mmHg

49-51 °C(lit.)

>230 °F

2.148

2

5

5

15

212

0

PWOQRKCAHTVFLB-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O2P.H2O/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14;/h1-7H2,(H,10,12);1H2

N,N-bis(2-chloroethyl)-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine;hydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~179.15 mM)
DMSO : ≥ 38 mg/mL (~136.15 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (89.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)