|
Cyclophosphamide - Alkylating
Antineoplastic
 |
| Action |
| A
pro-drug which has to be activated in the body to active
metabolites. Acts on cells at any stage of the cell cycle
but the cycle is blocked at G2 (premitotic) stage. This
arrest of cell division is brought about by alkylation
of the DNA in a dose-dependent manner. Also exerts immunosuppressive
effects possibly due to a cytotoxic effect on lymphocytes.
|
| Indication |
| Leukaemias, lymphogranulomatosis,
lymphosarcoma, reticulum cell sarcoma. Hodgkin's disease,
multiple myeloma, retinoblastoma, carcinoma of the breast,
adenocarcinoma of the ovary. Inoperable solid malignancies.
Combination with surgery, radiation and other therapeutic
measures. Minimal change nephrotic syndrome in children.
|
| Pharmaco-Kinetics |
| After oral administration
it is well absorbed. It is metabolised in liver to active
metabolites. |
| Contraindication |
| Bladder haemorrhage, acute
urinary tract infection, myelosuppression |
| Adverse-Effects |
| Nausea, vomiting, visual blurring, facial
burning with I.V. administration, teratogenic effect,
haemorrhagic cystitis, bone marrow depression, hyponatraemia,
sterility, inappropriate secretion of ADH. Alopecia and
increased skin pigmentation.
|
| Special Precaution |
| Diabetes,
elderly, hepatic, cardiac or renal impairment, acute systemic
or urinary infections. to stop the drug if leucocyte count
is less than 3000/cu.mm. Carcinogenic potential, infection,
adequate contraception, previous X-Ray or cytotoxic therapy.
|
| Interactions |
Chloramphenicaol
|
Decreased
efficacy of cyclophosphamide due to increase in half-life
and
decrease in metabolite concenteration, increased risk
of bone marrow toxicity. |
Thiazide
Diuretics
|
Increased
efficacy, anti-neoplastic induced leukopenia may be prolonged. |
Anticoagulants
|
Increase
in anti-coagulant effect. |
Digoxin
|
Decreased
serum levels of digoxin. |
Doxorubicin
|
Doxorubicin
induced cardiac toxicity potentiated. |
Succinyl
choline
|
Neuromuscular
blockade prolonged. |
Allopurinol
|
Increased
risk of bone marrow toxicity. |
Phenobarbitone
|
Increased
metabolism and leukopenic activity. |
| Myelotoxic
drugs, radiotherapy |
Serious toxicity. |
| Dosage |
Malignancy I.V
|
40-50mg /
kg in div. doses over 2-5 days or 10-15mg/kg every 7-10
days or 3-5mg / kg twice weekly. |
|
Oral
|
Dose ranges
from 1-5mg / kg per day. |
| Minimal change
nephrotic syndrome |
2.5-3mg
/ kg daily orally.
|
| Onset
of action |
| Maximal beneficial
effects not felt for upto 6 weeks. |
| Duration
of action |
| upto several
weeks. |
| Strength
& Packing |
250mg, 500mg,
1g Injection (single vial per box),
50mg tablet (10 tablets per box). |
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|
