Introduction

Cycloph 1g (Cyclophosphamide) Injection represents the maximum-strength formulation of this essential antineoplastic medication, designed for the management of aggressive and advanced malignancies. This high-potency cytotoxic agent delivers concentrated therapeutic power for oncologists treating patients with complex cancer presentations and those requiring intensive chemotherapy regimens. Manufactured by Eskayef Pharmaceuticals Ltd., a leader in pharmaceutical excellence for over three decades, and distributed globally by Orio Pharma, Cycloph 1g embodies the pinnacle of quality and efficacy in cancer treatment.

Therapeutic Applications

Malignant Conditions

Cycloph 1g demonstrates remarkable efficacy in treating numerous malignancies, including:

• Advanced 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: generally ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, and acute lymphoblastic leukemia in children (particularly effective during remission to prolong duration)
• Advanced Mycosis Fungoides
• Neuroblastoma (disseminated disease)
• Ovarian Adenocarcinoma
• Retinoblastoma
• Breast Carcinoma

While Cycloph 1g can be effective as monotherapy for susceptible malignancies, it is most commonly administered as part of combination therapy protocols, used either concurrently or sequentially with other antineoplastic agents to maximize treatment outcomes and overcome resistance mechanisms.

Non-Malignant Conditions

In highly selected cases, cyclophosphamide may be prescribed for children with biopsy-proven “minimal change” nephrotic syndrome. This application is reserved for patients who have failed to respond adequately to appropriate adrenocorticosteroid therapy or who experience intolerable side effects from corticosteroid treatment. Cyclophosphamide should not be used as primary therapy for this condition and is not indicated for nephrotic syndrome in adults or any other renal disease.

Mechanism of Action

Cyclophosphamide functions as a prodrug that undergoes biotransformation primarily in the liver through a mixed function microsomal oxidase system, converting it to active alkylating metabolites. These metabolites disrupt cellular function by cross-linking tumor cell DNA, thereby preventing DNA replication and RNA transcription, ultimately leading to cell death. This mechanism is particularly effective against rapidly dividing malignant cells.

The drug 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 reach peak plasma levels 2-3 hours following intravenous administration.

Plasma protein binding of the unchanged drug is minimal, though some metabolites bind to plasma proteins at rates exceeding 60%. Research has not definitively identified any single metabolite as solely responsible for either the therapeutic benefits or toxic effects of cyclophosphamide, suggesting a complex pharmacological profile contributing to its clinical efficacy.

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

The 1g formulation allows for precise dosing in high-dose protocols and for patients with larger body mass, minimizing the need for multiple vial reconstitutions.

Dosage adjustments should be guided by clinical response, evidence of antitumor activity, and hematologic parameters, particularly leukopenia. The total leukocyte count serves as an excellent objective guide for dosage regulation. 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 other medications in the regimen to prevent excessive toxicity.

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

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 cyclophosphamide
• Succinylcholine chloride: Cyclophosphamide causes marked and persistent inhibition of cholinesterase activity, potentiating the effect of succinylcholine chloride
• Anesthesia: Anesthesiologists should be alerted if a patient has received cyclophosphamide within 10 days of general anesthesia
• Other cytotoxic drugs: Monitor for combined actions, both beneficial and adverse

Contraindications

Cycloph 1g 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 cyclophosphamide toxicities
• Cautious dosing recommended, starting at lower end of dosing range with adjustments based on response
• Clinical trials in advanced ovarian carcinoma showed 28% of patients receiving cyclophosphamide plus cisplatin were 65 years or older

Precautions

Enhanced monitoring recommended for patients with:

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

Overdose Management

No specific antidote exists for cyclophosphamide overdose. Treatment involves supportive measures, including appropriate management of infections, myelosuppression, and cardiac toxicity should 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 1g (Cyclophosphamide) Injection represents a critical high-dose treatment option in the oncologist’s arsenal against aggressive and advanced malignancies. Its maximum-strength formulation provides convenience and precision in dosing for complex treatment protocols and high-dose regimens.

Manufactured by Eskayef Pharmaceuticals Ltd., a company with a legacy of quality since 1990, and distributed by Orio Pharma, an oncology specialist dedicated to compassionate patient care, Cycloph 1g embodies excellence in cancer treatment. With worldwide delivery available within 3-7 working days, healthcare providers globally can access this vital medication with confidence, knowing they are providing their patients with a premium therapeutic option backed by decades of clinical experience and pharmaceutical expertise.