Cyclophosphamide


Concise Prescribing Info
Indications/Uses
Malignancies.
Dosage/Direction for Use
Adult : PO Low dose regimen: 2-6 mg/kg/wk in divided dose. Alternatively, 100-300 mg/day in divided doses or 50-250 mg/m2/day, or 80-300 mg/m2/day in divided doses. IV Low dose regimen: 2-6 mg/kg/wk as a single dose; moderate dose regimen: 10-15 mg/kg/wk as a single dose; high dose regimen: 20-40 mg/kg as a single dose every 10-20 days. Alternatively, 80-300 mg/m2/day as a single dose, or 300-600 mg/m2/wk as a single dose, or 600-1,500 mg/m2 as a single dose or short infusion at 10- to 20-day intervals.
Dosage Details
Intravenous
Malignancies
Adult: Low dose regimen: 2-6 mg/kg wkly as a single dose; moderate dose regimen: 10-15 mg/kg wkly as a single dose; high dose regimen: 20-40 mg/kg as a single dose every 10-20 days. Alternatively, 80-300 mg/m2 daily as a single dose, or 300-600 mg/m2 wkly as a single dose, or 600-1,500 mg/m2 as a single dose or short infusion at 10- to 20-day intervals.

Oral
Nephrotic syndrome
Child: 2 mg/kg daily for 8-12 wk. Max cumulative dose: 168 mg/kg. Max duration: 90 days.

Oral
Malignancies
Adult: Low dose regimen: 2-6 mg/kg wkly in divided dose. Alternatively, 100-300 mg daily in divided doses, or 50-250 mg/m2 daily or 80-300 mg/m2 daily in divided doses.
Administration
Should be taken on an empty stomach. Preferably taken on an empty stomach, but may be taken w/ meals to minimise GI irritation. Ensure adequate fluid intake. Swallow whole.
Reconstitution
Intravenous:
Reconstitute w/ 25 mL for a 500 mg vial, 50 mL for a 1,000 mg vial or 100 mL for a 2,000 mg vial to a concentration of 20 mg/mL using NaCl 0.9% for direct IV push, or NaCl 0.9% or sterile water for inj for IV infusion. Gently swirl to mix. For IV infusion, dilute further w/ dextrose 5% in water, NaCl 0.45% or dextrose 5% and NaCl 0.9% inj to a minimum concentration of 2 mg/mL.
Incompatibility
Y-site: Incompatible w/ amphotericin B cholesteryl sulfate complex.
Contraindications
Patient w/ bone marrow aplasia, urinary outflow obstruction, UTI, acute infection, drug- or radiation-induced urothelial toxicity. Pregnancy.
Special Precautions
Patient w/ DM, severe immunosuppression, acute porphyria, pre-existing CV disease or those at risk for cardiotoxicity. Renal and hepatic impairment. Lactation.
Adverse Reactions
Alopecia, skin and nails hyperpigmentation, nausea and vomiting, mucositis, inappropriate antidiuretic hormone secretion, carbohydrate metabolism disturbances, gonadal suppression, interstitial pulmonary fibrosis.
Potentially Fatal: Anaphylactic reactions, bone marrow failure, severe immunosuppression, urotoxicity, cardiotoxicity, hyponatraemia, haemorrhagic cystitis.
IM/Intraperitoneal/Intrapleural/IV/Parenteral/PO: D
Patient Counseling Information
This drug may cause visual impairment and dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC w/ differential and platelets, serum electrolytes and creatinine, BUN, urinalysis. Monitor for signs/symptoms of haemorrhagic cystitis or other urinary/renal toxicity, cardiac, pulmonary and/or hepatic toxicity.
Overdosage
Symptoms: Urotoxicity, myelosuppression, cardiotoxicity (including cardiac failure), stomatitis, veno-occlusive hepatic disease. Management: Supportive treatment. May consider haemodialysis. Cystitis prophylaxis w/ mesna may be useful for urotoxicity.
Drug Interactions
Increased risk of cardiotoxicity w/ doxorubicin or other cardiotoxic drugs. May increase incidence of mucositis w/ protease inhibitors. May increase haematotoxicity and/or immunosuppression w/ ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine. May increase pulmonary toxicity w/ amiodarone. May increase nephrotoxicity w/ amphotericin B. May result to acute water intoxication w/ indometacin. May increase risk of hepatotoxicity w/ azathioprine. May increase incidence of hepatic veno-occlusive disease and mucositis w/ busulfan. May increase risk of haemorrhagic cystitis w/ previous or concomitant radiotherapy. May result to acute encephalopathy w/ metronidazole. May increase risk of thromboembolic complications. May alter the effect of warfarin. May increase immunosuppressive effect of ciclosporin. May result to prolonged apnoea w/ depolarising muscle relaxants (e.g. suxamethonium).
Action
Description: Cyclophosphamide is a prodrug which is converted in the body to the active metabolites. It acts at any stage of the cell cycle. It prevents cell division by cross-linking deoxyribonucleic acid (DNA) strands and reducing DNA synthesis. It also exerts a potent immunosuppressive effect.
Pharmacokinetics:
Absorption: Well absorbed from the GI tract. Bioavailability: >75%. Time to peak plasma concentration: Approx 1 hr (oral); 2-3 hr (IV as metabolites).
Distribution: Widely distributed in the tissues, crosses the blood-brain barrier and placenta; enters breast milk. Volume of distribution: 30-50 L. Plasma protein binding: Approx 20%; >60% (some metabolites).
Metabolism: Undergoes hepatic metabolism and converted to active metabolites acrolein, 4-aldophosphamide, 4-hydroperoxycyclophosphamide and nor-nitrogen mustard.
Excretion: Via urine (10-20% as unchanged drug); faeces (4%). Mean half-life: 4-8 hr.
Chemical Structure

Chemical Structure Image
Cyclophosphamide

Source: National Center for Biotechnology Information. PubChem Database. Cyclophosphamide, CID=2907, https://pubchem.ncbi.nlm.nih.gov/compound/Cyclophosphamide (accessed on Jan. 22, 2020)

Storage
Store at or below 25°C.
ATC Classification
L01AA01 - cyclophosphamide ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
References
Anon. Cyclophosphamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 12/01/2016.

Buckingham R (ed). Cyclophosphamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/01/2016.

Cyclophosphamide Capsule (Roxane Laboratories, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/01/2016.

Cyclophosphamide Injection, Powder for Solution (Sandoz Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 12/01/2016.

Joint Formulary Committee. Cyclophosphamide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 12/01/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Cyclophosphamide. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 12/01/2016.

Disclaimer: This information is independently developed by MIMS based on Cyclophosphamide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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