Cytoxan: Potent Alkylating Chemotherapy for Malignant and Autoimmune Conditions
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Synonyms | |||
Cytoxan (cyclophosphamide) is a cornerstone alkylating chemotherapeutic and immunosuppressive agent, widely utilized in the management of various malignancies and severe autoimmune disorders. Its prodrug design allows for selective activation, enabling targeted cytotoxic effects against rapidly dividing cells. This medication represents a critical component of many combination chemotherapy regimens and immunosuppressive protocols, offering clinicians a versatile tool for managing complex diseases. Proper understanding of its pharmacology, administration, and safety profile is essential for optimizing therapeutic outcomes.
Features
- Prodrug requiring hepatic activation to active metabolites 4-hydroxycyclophosphamide and phosphoramide mustard
- Broad-spectrum antineoplastic activity against numerous solid tumors and hematologic malignancies
- Dual mechanism: cytotoxic alkylation of DNA and immunosuppressive effects on B and T lymphocytes
- Available in oral tablet and intravenous formulations for flexible administration
- Demonstrated efficacy in both neoplastic conditions and severe autoimmune diseases
- Extensive clinical experience with well-characterized pharmacokinetic profile
Benefits
- Provides potent cytotoxic activity against a wide range of malignant cell types
- Enables effective immunosuppression for autoimmune conditions unresponsive to conventional therapies
- Offers flexible administration routes suitable for various clinical settings
- Demonstrates synergistic effects when combined with other chemotherapeutic agents
- Supported by decades of clinical evidence establishing efficacy and safety profiles
- Allows for dose adjustment based on individual patient tolerance and response
Common use
Cytoxan is indicated for the treatment of multiple malignant conditions including Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, leukemia, neuroblastoma, retinoblastoma, breast cancer, and ovarian carcinoma. In autoimmune contexts, it is employed for severe cases of rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis, microscopic polyangiitis, and other vasculitides where conventional immunosuppressants have proven inadequate. The medication may be used as monotherapy or more commonly as part of combination chemotherapy regimens, particularly in hematologic malignancies where it forms the backbone of many established protocols.
Dosage and direction
Dosage varies significantly based on indication, patient status, and treatment protocol. For neoplastic diseases, intravenous doses typically range from 40-50 mg/kg divided over 2-5 days, or 500-1500 mg/m² every 2-4 weeks. Oral maintenance therapy generally involves 1-5 mg/kg daily. For autoimmune conditions, typical regimens involve 1-2 mg/kg orally daily or pulse intravenous therapy at 500-1000 mg/m² monthly. Administration requires careful hydration with at least 2 liters of fluid daily to prevent hemorrhagic cystitis. Intravenous administration should be performed slowly with adequate hydration before, during, and after infusion. Dose adjustments are necessary for renal impairment, hepatic dysfunction, bone marrow suppression, or advanced age.
Precautions
Rigorous monitoring is essential throughout therapy. Complete blood counts should be obtained weekly during treatment and for at least three weeks following discontinuation. Renal and hepatic function must be assessed regularly. Patients should be monitored for signs of infection, bleeding, or anemia. Urinalysis should be performed regularly to detect hemorrhagic cystitis. Fertility preservation discussions are mandatory before initiation due to high risk of gonadal toxicity. Secondary malignancy risk requires long-term surveillance. Vaccination with live vaccines is contraindicated during treatment. Pregnancy must be excluded before initiation due to teratogenic effects.
Contraindications
Absolute contraindications include severe bone marrow suppression (unless disease-related), demonstrated hypersensitivity to cyclophosphamide or any component, active urinary tract infection, or urinary outflow obstruction. Relative contraindications include severe renal impairment (creatinine clearance <10 mL/min), significant hepatic dysfunction, pre-existing hemorrhagic cystitis, recent radiation therapy, compromised bone marrow reserve, and pregnancy. The medication should not be administered to breastfeeding women due to secretion in breast milk.
Possible side effect
- Hematologic: myelosuppression (neutropenia, thrombocytopenia, anemia), leukopenia
- Genitourinary: hemorrhagic cystitis, bladder fibrosis, renal tubular necrosis
- Gastrointestinal: nausea, vomiting, mucositis, diarrhea, anorexia
- Dermatologic: alopecia, skin pigmentation changes, nail changes
- Reproductive: amenorrhea, azoospermia, infertility, teratogenicity
- Other: cardiotoxicity, pulmonary fibrosis, secondary malignancies, syndrome of inappropriate antidiuretic hormone secretion
- Immunologic: increased susceptibility to infections, reactivation of latent viruses
Drug interaction
Cytoxan demonstrates significant interactions with multiple medication classes. Allopurinol may increase myelosuppression and should be used cautiously. CYP450 inducers (phenobarbital, rifampin) may enhance metabolism to active metabolites, potentially increasing toxicity. Succinylcholine may exhibit prolonged apnea due to inhibited pseudocholinesterase activity. Concurrent cardiotoxic agents (anthracyclines) increase risk of myocardial damage. Live vaccines are contraindicated due to immunosuppression. Warfarin effect may be potentiated. Nephrotoxic agents may enhance renal toxicity.
Missed dose
If a dose is missed, patients should contact their oncology team immediately rather than doubling the next dose. For oral administration, if remembered within a few hours, the dose may be taken. If nearly time for the next dose, skip the missed dose and resume regular schedule. Intravenous doses are typically administered in clinical settings where missed doses are managed by the treatment team according to protocol specifications. Dose adjustments may be necessary based on the timing of the missed dose and current hematologic parameters.
Overdose
Overdose manifests as exaggerated pharmacological effects, particularly severe myelosuppression with pancytopenia, hemorrhagic cystitis with potential bladder necrosis, cardiotoxicity, and neurotoxicity. Management requires immediate medical attention with supportive care including transfusion support, granulocyte colony-stimulating factors, vigorous hydration with bladder irrigation, and monitoring for infections. Hemodialysis may remove some circulating drug but is not routinely recommended. Treatment is primarily supportive with management of specific toxicities as they arise.
Storage
Store at controlled room temperature (20-25°C or 68-77°F). Protect from light and moisture. Keep in original container with tight closure. Oral tablets should not be removed from blister packaging until administration. Intravenous solution should be protected from light during preparation and administration. Reconstituted solutions are stable for 24 hours at room temperature or 6 days under refrigeration. Discard any unused portion appropriately according to institutional guidelines for cytotoxic medications.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by qualified healthcare professionals based on individual patient circumstances. Dosage and administration may vary based on specific protocols and patient factors. Patients should consult their healthcare provider for personalized medical advice and report any adverse effects promptly. The information presented reflects current knowledge but may not encompass all recent developments or individual variations.
Reviews
Clinical experience with Cytoxan spans decades, establishing its position as a fundamental chemotherapeutic agent. Oncology specialists appreciate its broad efficacy spectrum and predictable toxicity profile when managed appropriately. Rheumatologists value its potency in severe autoimmune conditions refractory to other treatments. The predictable myelosuppression requires careful monitoring but is generally manageable with supportive care. The risk of hemorrhagic cystitis has been significantly reduced with adequate hydration protocols. Long-term concerns regarding fertility impact and secondary malignancies remain important considerations in treatment planning. Overall, Cytoxan continues to serve as an essential tool in the management of complex malignant and autoimmune conditions.