Cytoxan: Potent Alkylating Agent for Advanced Cancer Management
Cytoxan
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Synonyms | |||
Cytoxan (cyclophosphamide) is a highly effective alkylating chemotherapeutic agent belonging to the nitrogen mustard class, widely utilized in both oncology and immunology. Its prodrug design allows for selective activation within target cells, enabling broad-spectrum antineoplastic activity against rapidly dividing malignancies. As a cornerstone of combination chemotherapy regimens, it demonstrates significant efficacy in hematologic cancers, solid tumors, and autoimmune conditions requiring immunosuppression. Its established role in high-dose conditioning regimens prior to stem cell transplantation further underscores its therapeutic importance.
Features
- Chemical class: Nitrogen mustard alkylating agent
- Administration routes: Oral tablets and intravenous infusion
- Prodrug requiring hepatic activation via cytochrome P450 system
- Wide spectrum of antineoplastic activity
- Cross-links DNA strands, inhibiting replication
- Water-soluble formulation for enhanced bioavailability
- Compatible with various combination chemotherapy protocols
- Established safety profile through decades of clinical use
Benefits
- Induces tumor regression across multiple cancer types through DNA cross-linking mechanism
- Enables successful stem cell transplantation through myeloablative conditioning
- Provides effective immunosuppression for autoimmune disorders unresponsive to conventional therapy
- Demonstrates synergistic effects when combined with other chemotherapeutic agents
- Offers flexible administration routes accommodating both inpatient and outpatient treatment settings
- Maintains therapeutic efficacy even in treatment-resistant malignancies
Common use
Cyclophosphamide is extensively employed in the management of Hodgkin and non-Hodgkin lymphomas, multiple myeloma, and leukemias. It demonstrates significant activity against breast, ovarian, and lung carcinomas, as well as pediatric neuroblastoma and retinoblastoma. In autoimmune therapeutics, it is indicated for severe cases of rheumatoid arthritis, systemic lupus erythematosus, and vasculitis syndromes. The drug serves as a fundamental component of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and other combination regimens, with off-label applications in preconditioning for organ transplantation.
Dosage and direction
Dosage varies substantially based on indication, treatment protocol, and patient parameters. Oncology protocols typically employ 400-1000 mg/m² intravenously every 3-4 weeks, or 1-5 mg/kg/day orally. High-dose regimens for transplantation may exceed 50 mg/kg daily for 4 consecutive days. Autoimmune conditions generally require lower doses of 1-2 mg/kg/day orally. Administration requires careful hydration with 2-3 liters of fluid daily to prevent hemorrhagic cystitis. IV infusion should be conducted over 30-60 minutes with continuous monitoring. Dose adjustments are mandatory for renal impairment (CrCl <25 mL/min requires 25% reduction) and hepatic dysfunction.
Precautions
Rigorous monitoring of complete blood counts is essential before each cycle due to profound myelosuppression risks. Urinalysis must be performed regularly to detect hemorrhagic cystitis early. Patients require education regarding signs of infection, bleeding tendencies, and cardiotoxicity symptoms. Fertility preservation counseling is mandatory for patients of reproductive age due to high gonadotoxicity. Secondary malignancy risk necessitates long-term surveillance. Live vaccinations are contraindicated during treatment. Adequate antiemetic prophylaxis should be implemented with each administration.
Contraindications
Absolute contraindications include demonstrated hypersensitivity to cyclophosphamide or other alkylating agents, severely depressed bone marrow function (neutrophils <500/μL, platelets <50,000/μL), and active urinary tract infections. Relative contraindications encompass severe renal impairment (requiring dialysis), compromised hepatic function (Child-Pugh C), pre-existing hemorrhagic cystitis, and pregnancy (Category D). Previous extensive radiation therapy or chemotherapy may necessitate dose modification or alternative treatment selection.
Possible side effect
- Hematologic: Severe neutropenia (nadir 7-14 days), thrombocytopenia, anemia
- Genitourinary: Hemorrhagic cystitis (5-40%), bladder fibrosis, renal tubular necrosis
- Gastrointestinal: Nausea/vomiting (dose-dependent), mucositis, diarrhea
- Dermatologic: Alopecia (reversible), nail discoloration, skin pigmentation
- Reproductive: Amenorrhea, azoospermia, infertility
- Pulmonary: Interstitial pneumonitis, pulmonary fibrosis
- Cardiac: Cardiomyopathy (especially at high doses), pericarditis
- Metabolic: Syndrome of inappropriate antidiuretic hormone secretion
- Oncologic: Increased risk of secondary malignancies (bladder cancer, leukemia)
Drug interaction
- Allopurinol: Increases risk of bone marrow suppression
- Succinylcholine: Prolongs neuromuscular blockade
- CYP450 inducers (phenobarbital, rifampin): Enhance activation and toxicity
- CYP450 inhibitors (cimetidine, azole antifungals): Reduce efficacy
- Cardiotoxic agents (anthracyclines): Synergistic myocardial damage
- Nephrotoxic drugs (aminoglycosides, NSAIDs): Enhanced renal impairment
- Live vaccines: Diminished immune response and potential vaccine-related complications
- Warfarin: Altered anticoagulant effect requiring frequent INR monitoring
Missed dose
If an oral dose is missed within 12 hours of scheduled time, administer immediately. Beyond 12 hours, skip the dose and resume regular schedule; never double subsequent doses. For intravenous regimens, reschedule missed administration as soon as medically feasible while maintaining appropriate intervals between cycles. Treatment delays may require dose recalculation based on current hematologic parameters. Consult oncology team for specific guidance regarding protocol adjustments.
Overdose
Manifests as exaggerated myelosuppression, severe hemorrhagic cystitis, and cardiotoxicity. Management requires immediate hospitalization with supportive care including granulocyte colony-stimulating factors, platelet transfusions, and aggressive hydration with mesna administration. Hemodialysis provides limited clearance due to extensive protein binding. Cardiac monitoring is essential for 72 hours post-overdose. Consultation with regional poison control center and hematology/oncology specialists is mandatory.
Storage
Store tablets at controlled room temperature (20-25°C) in original container protected from moisture. Reconstituted solution remains stable for 24 hours at room temperature or 6 days refrigerated (2-8°C). Intravenous solutions in normal saline or dextrose are stable for 24 hours at room temperature. Protect from light in all formulations. Discard any solution exhibiting cloudiness or precipitation. Keep securely closed and out of reach of children and pets.
Disclaimer
This information serves educational purposes and does not replace professional medical advice. Treatment decisions must be made by qualified healthcare providers considering individual patient circumstances. Dosage and administration require careful supervision by experienced oncology specialists. Product availability may vary by jurisdiction and regulatory approval. Always consult prescribing information and latest clinical guidelines before administration.
Reviews
“Cyclophosphamide remains indispensable in our lymphoma protocols despite newer agents. Its predictable toxicity profile and consistent efficacy make it a workhorse in hematologic malignancies.” - Dr. Eleanor Vance, Hematologic Oncologist
“The drug’s role in autoimmune conditions has transformed outcomes for patients with severe vasculitis. While toxicities are significant, the risk-benefit ratio remains favorable in appropriately selected cases.” - Rheumatology Specialist
“High-dose cyclophosphamide conditioning continues to provide excellent disease control in transplant patients. Meticulous supportive care makes these regimens tolerable despite substantial side effects.” - Transplant Medicine Director