Introduction

Cycloph 500 mg (Cyclophosphamide) is a potent antineoplastic medication widely recognized for its effectiveness in treating various malignancies and select non-malignant conditions. As a cornerstone in cytotoxic chemotherapy, this high-dose formulation provides oncologists with a powerful tool in combating aggressive cancers. Manufactured by Eskayef Pharmaceuticals Ltd., a premier pharmaceutical company with over three decades of excellence, and distributed by Orio Pharma, Cycloph 500 mg represents the gold standard in quality and efficacy for cancer treatment.

Therapeutic Applications

Malignant Conditions

Cycloph 500 mg demonstrates significant efficacy against numerous malignancies, including:

• Malignant Lymphomas (Stages III and IV per Ann Arbor staging): Hodgkin’s disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, and Burkitt’s lymphoma
• Multiple Myeloma
• Leukemias: Chronic lymphocytic leukemia, chronic granulocytic leukemia (note: usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, and acute lymphoblastic leukemia in children
• Advanced Mycosis Fungoides
• Neuroblastoma (disseminated disease)
• Ovarian Adenocarcinoma
• Retinoblastoma
• Breast Carcinoma

While effective as monotherapy in susceptible malignancies, Cycloph 500 mg is most frequently administered concurrently or sequentially with other antineoplastic agents to maximize therapeutic outcomes.

Non-Malignant Conditions

In carefully selected cases, Cycloph may be prescribed for biopsy-proven “minimal change” nephrotic syndrome in children. This application is reserved for patients who have not responded adequately to appropriate adrenocorticosteroid therapy or who experience intolerable side effects from such treatment. It should not be used as primary therapy and is not indicated for nephrotic syndrome in adults or other renal diseases.

Mechanism of Action

Cyclophosphamide is a prodrug that undergoes biotransformation primarily in the liver via a mixed function microsomal oxidase system, converting it to active alkylating metabolites. These metabolites interfere with DNA replication in rapidly dividing malignant cells through DNA cross-linking, thereby inhibiting cellular division and promoting cell death.

The medication demonstrates excellent bioavailability exceeding 75% when administered orally, with an elimination half-life ranging from 3 to 12 hours. While primarily eliminated as metabolites, approximately 5-25% is excreted unchanged in urine. Metabolite concentrations typically peak in plasma 2-3 hours following intravenous administration.

While plasma protein binding of the unchanged drug is minimal, some metabolites may bind to plasma proteins at rates exceeding 60%. Research has not definitively identified any single metabolite as solely responsible for either therapeutic benefits or toxic effects of cyclophosphamide.

Dosage and Administration

For Malignant Diseases:

• Initial course (adults and children with no hematologic deficiency): 40-50 mg/kg administered intravenously in divided doses over 2-5 days
• Alternative intravenous regimens: 10-15 mg/kg every 7-10 days or 3-5 mg/kg twice weekly
• Oral dosing: 1-5 mg/kg/day for both initial and maintenance therapy

Dosage adjustments should be guided by evidence of antitumor activity and/or leukopenia. The total leukocyte count serves as an objective guide for regulating dosage. Transient decreases to 2000 cells/mm³ following short courses or more persistent reduction to 3000 cells/mm³ with continuing therapy are generally tolerated without serious infection risk in the absence of marked granulocytopenia.

When used in combination therapy with other cytotoxic agents, dose reduction may be necessary for both cyclophosphamide and the other medications in the regimen.

For patients undergoing dialysis, cyclophosphamide and its metabolites are dialyzable, though quantitative differences may exist depending on the dialysis system. While patients with compromised renal function may show measurable changes in pharmacokinetic parameters, there is no consistent evidence indicating a need for cyclophosphamide dosage modification in such patients.

For Non-Malignant Diseases:

• Minimal Change Nephrotic Syndrome in Children: 2.5-3 mg/kg orally daily for 60-90 days

In male patients, prolonged treatment increases the risk of reproductive effects. The incidence of oligospermia and azoospermia increases when treatment exceeds 60 days, and treatment beyond 90 days significantly increases the probability of sterility. Adrenocorticosteroid therapy may be tapered and discontinued during cyclophosphamide treatment.

Drug Interactions

Healthcare providers should be vigilant regarding potential interactions:

• Phenobarbital: Chronic administration of high doses may increase metabolism and leukopenic activity of Cycloph
• Succinylcholine chloride: Cycloph treatment causes marked and persistent inhibition of cholinesterase activity, potentiating the effect of succinylcholine chloride
• Anesthesia: Anesthesiologists should be alerted if a patient has received Cycloph within 10 days of general anesthesia
• Other cytotoxic drugs: Monitor for combined actions, both beneficial and adverse

Contraindications

Cycloph is contraindicated in:

• Patients with severely depressed bone marrow function
• Patients with previous hypersensitivity to cyclophosphamide

Adverse Effects

Digestive System:

• Common: Nausea, vomiting, anorexia
• Less frequent: Abdominal discomfort, pain, diarrhea
• Rare: Hemorrhagic colitis, oral mucosal ulceration, jaundice

Skin and Associated Structures:

• Common: Alopecia (hair typically regrows, possibly with different texture/color)
• Occasional: Skin rash
• Rare: Pigmentation changes, nail changes, Stevens-Johnson syndrome, toxic epidermal necrolysis

Hematopoietic System:

• Common: Leukopenia (dose-related)
• Occasional: Thrombocytopenia, anemia
• Other: Fever without documented infection in neutropenic patients

Urinary System:

• Hemorrhagic ureteritis
• Renal tubular necrosis

Respiratory System:

• Interstitial pneumonitis
• Pulmonary fibrosis (with high doses over prolonged periods)

Other:

• Anaphylactic reactions (including fatalities)
• Cross-sensitivity with other alkylating agents
• SIADH (syndrome of inappropriate ADH secretion)
• Malaise and asthenia

Most adverse effects generally resolve following cessation of therapy. Recovery from leukopenia typically begins 7-10 days after stopping treatment.

Special Populations

Pregnancy and Lactation:

• Pregnancy Category D: Potential for serious fetal harm exists
• Breastfeeding: Cyclophosphamide is excreted in breast milk; either nursing or medication should be discontinued based on the importance of the drug to the mother

Pediatric Use:

• Safety profile similar to adult population

Geriatric Use:

• Elderly patients may be more susceptible to Cycloph toxicities
• Cautious dosing recommended, starting at lower end of dosing range with adjustments based on response

Precautions

Special monitoring recommended for patients with:

• Leukopenia
• Thrombocytopenia
• Tumor cell infiltration of bone marrow
• Previous X-ray therapy
• Previous therapy with other cytotoxic agents
• Impaired hepatic function
• Impaired renal function

Overdose Management

No specific antidote exists for Cycloph. Treatment involves supportive measures, including appropriate management of infections, myelosuppression, and cardiac toxicity if they occur.

Storage Conditions

Store at temperatures not exceeding 25°C in a dry place. Protect from light and moisture. Do not freeze.

Conclusion

Cycloph 500 mg (Cyclophosphamide) Injection represents a vital component in modern oncology practice, offering healthcare providers a potent therapeutic option for treating various malignancies. The higher dosage formulation provides flexibility in treatment protocols, particularly for patients requiring intensified therapy.

Manufactured by Eskayef Pharmaceuticals Ltd., a company renowned for quality since 1990, and supplied by Orio Pharma, a dedicated oncology medicine supplier committed to compassionate care, Cycloph 500 mg ensures patients receive treatment that meets the highest standards. With worldwide delivery available within 3-7 working days, healthcare providers can rely on timely access to this essential medication for their patients battling cancer.