Drug information of Cyclophosphamide

Mechanism of effect

Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells.
The mechanism of action is thought to involve cross-linking of tumor cell DNA

Pharmacodynamic

Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer.
Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells.
They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA.
This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific.
Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

Pharmacokinetics

After oral administration, peak concentrations occur at one hour.
Volume of distribution: 30-50 L. 20% of cyclophosphamide is protein bound with no dose dependent changes.
Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms. Cyclophosphamide is eliminated primarily in the form of metabolites.
10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. Half life: 3-12 hours Clearance: Total body clearance = 63 ± 7.6 L/kg.

Drug indications

Ovary cancer , Malignant Diseases , Nephrotic Syndrome in Children

Dosage

Usual Adult Dose for Malignant Disease Intravenous:
When used alone, the initial dose for patients with no hematologic deficiency is 40 to 50 mg/kg usually in divided doses over 2 to 5 days.
Alternatively, 10 to 15 mg/kg may be administered every 7 to 10 days or 3 to 5 mg/kg twice a week. Oral: Usual Range: 1 to 8 mg/kg/day for initial and maintenance dosing.
Usual Adult Dose for Ovarian Cancer For use in the treatment of epithelial ovarian cancer:
600 mg/m2 intravenously on day one in combination with carboplatin or cisplatin Repeat cycle every 28 days.
Usual Pediatric Dose for Malignant Disease Intravenous:
When used alone, the initial dose for patients with no hematologic deficiency is 40 to 50 mg/kg usually in divided doses over 2 to 5 days.
Alternatively, 10 to 15 mg/kg may be administered every 7 to 10 days or 3 to 5 mg/kg twice a week.
Oral: Usual Range: 1 to 8 mg/kg/day for initial and maintenance dosing
. Usual Pediatric Dose for Nephrotic Syndrome When use for biopsy proven
"minimal change" nephrotic syndrome in children, a dose of 2.5 to 3 mg/kg/day orally for 60 to 90 days is recommended.

Drug contraindications

hypersensitivity to drug or its components. , severely depressed bone marrow function.

Side effects

nausea , vomiting , Diarrhea , asthenia , thrombocytopenia , neutropenia , leukopenia , anemia , Stevens-Johnson syndrome , Alopecia , anorexia , malaise , Pain , renal tubular necrosis , Hemorrhagic ureteritis , hemorrhagic colitis

Interactions

Trastuzumab , Dactinomycin , Succinylcholine , Phenobarbital , Chloramphenicol , Clozapine , thiotepa , Adenovirus types 4 and 7 live, oral , Lorlatinib , Cannabidiol , Meningococcal conjugate vaccine

Alerts

1-Carcinogenesis, Mutagenesis, and Impairment of Fertility may develop in patients treated with Cyclophosphamide
2- Hemorrhagic cystitis may develop in patients treated with Cyclophosphamide
3- Although a few instances of cardiac dysfunction have been reported following use of recommended doses of Cyclophosphamide. Cyclophosphamide has been reported to potentiate doxorubicin-induced cardiotoxicity
4- Treatment with Cyclophosphamide may cause significant suppression of immune responses. Serious, sometimes fatal, infections may develop in severely immunosuppressed patients.
Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop viral, bacterial, fungal, protozoan, or helminthic infections
5- Anaphylactic reactions have been reported; death has also been reported in association with this event. Possible cross-sensitivity with other alkylating agents has been reported.

Points of recommendation

1- Special attention to the possible development of toxicity should be exercised in patients being treated with Cyclophosphamide if any of the following conditions are present:
1. Leukopenia
2. Thrombocytopenia
3 . Tumor cell infiltration of bone marrow
4. Previous X-ray therapy
5. Previous therapy with other cytotoxic agents
6. Impaired hepatic function
7. Impaired renal function

2- During treatment, the patient’s hematologic profile (particularly neutrophils and platelets) should be monitored regularly to determine the degree of hematopoietic suppression.
Urine should also be examined regularly for red cells which may precede hemorrhagic cystitis

Pregnancy level

D

Related drugs

Ifosfamide , Lomustine , Melphalan , Chlorambucil , Treosulfan , thiotepa , Bendamustine , Niraparib