Cyphos

Contents: Cyclophosphamide

Indication/Uses: Malignant Diseases. Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs. The following malignancies are often susceptible to cyclophosphamide treatment:

  • Malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin’s disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma.
  • Multiple myeloma..
  • Leukemias: Chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia in children (cyclophosphamide given during remission is effective in prolonging its duration).
  • Mycosis fungoides (advanced disease).
  • Neuroblastoma (disseminated disease).
  • Adenocarcinoma of the ovary.
  • Retinoblastoma.
  • Carcinoma of the breast.

Dosage/Direction for Use: Adult : PO Low dose regimen: 2-6 mg/kg/wk in divided dose. Alternatively, 100-300 mg/day in divided doses or 50-250 mg/m2/day, or 80-300 mg/m2/day in divided doses. IV Low dose regimen: 2-6 mg/kg/wk as a single dose; moderate dose regimen: 10-15 mg/kg/wk as a single dose; high dose regimen: 20-40 mg/kg as a single dose every 10-20 days. Alternatively, 80-300 mg/m2/day as a single dose, or 300-600 mg/m2/wk as a single dose, or 600-1,500 mg/m2 as a single dose or short infusion at 10- to 20-day intervals.

Dosage Details: 

Intravenous
Malignancies
Adult: Low dose regimen: 2-6 mg/kg wkly as a single dose; moderate dose regimen: 10-15 mg/kg wkly as a single dose; high dose regimen: 20-40 mg/kg as a single dose every 10-20 days. Alternatively, 80-300 mg/m2 daily as a single dose, or 300-600 mg/m2 wkly as a single dose, or 600-1,500 mg/m2 as a single dose or short infusion at 10- to 20-day intervals.

Oral
Nephrotic syndrome
Child: 2 mg/kg daily for 8-12 wk. Max cumulative dose: 168 mg/kg. Max duration: 90 days.

Oral
Malignancies
Adult: Low dose regimen: 2-6 mg/kg wkly in divided dose. Alternatively, 100-300 mg daily in divided doses, or 50-250 mg/m2 daily or 80-300 mg/m2 daily in divided doses.

Administration: Should be taken on an empty stomach. Preferably taken on an empty stomach, but may be taken w/ meals to minimise GI irritation. Ensure adequate fluid intake. Swallow whole.

Reconstitution: 

Intravenous:
Reconstitute w/ 25 mL for a 500 mg vial, 50 mL for a 1,000 mg vial or 100 mL for a 2,000 mg vial to a concentration of 20 mg/mL using NaCl 0.9% for direct IV push, or NaCl 0.9% or sterile water for inj for IV infusion. Gently swirl to mix. For IV infusion, dilute further w/ dextrose 5% in water, NaCl 0.45% or dextrose 5% and NaCl 0.9% inj to a minimum concentration of 2 mg/mL.

Incompatibility
Y-site: Incompatible w/ amphotericin B cholesteryl sulfate complex.

Contraindications: Patient w/ bone marrow aplasia, urinary outflow obstruction, UTI, acute infection, drug- or radiation-induced urothelial toxicity. Pregnancy.

Special Precaution: Patient w/ DM, severe immunosuppression, acute porphyria, pre-existing CV disease or those at risk for cardiotoxicity. Renal and hepatic impairment. Lactation.

Adverse Reaction: Alopecia, skin and nails hyperpigmentation, nausea and vomiting, mucositis, inappropriate antidiuretic hormone secretion, carbohydrate metabolism disturbances, gonadal suppression, interstitial pulmonary fibrosis.
Potentially Fatal: Anaphylactic reactions, bone marrow failure, severe immunosuppression, urotoxicity, cardiotoxicity, hyponatraemia, haemorrhagic cystitis.

Drug Interaction: Increased risk of cardiotoxicity w/ doxorubicin or other cardiotoxic drugs. May increase incidence of mucositis w/ protease inhibitors. May increase haematotoxicity and/or immunosuppression w/ ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine. May increase pulmonary toxicity w/ amiodarone. May increase nephrotoxicity w/ amphotericin B. May result to acute water intoxication w/ indometacin. May increase risk of hepatotoxicity w/ azathioprine. May increase incidence of hepatic veno-occlusive disease and mucositis w/ busulfan. May increase risk of haemorrhagic cystitis w/ previous or concomitant radiotherapy. May result to acute encephalopathy w/ metronidazole. May increase risk of thromboembolic complications. May alter the effect of warfarin. May increase immunosuppressive effect of ciclosporin. May result to prolonged apnoea w/ depolarising muscle relaxants (e.g. suxamethonium).

Pharmacokinetics: Absorption: Well absorbed from the GI tract. Bioavailability: >75%. 
Time to peak plasma concentration: Approx 1 hr (oral); 2-3 hr (IV as metabolites).
Distribution: Widely distributed in the tissues, crosses the blood-brain barrier and placenta; enters breast milk. Volume of distribution: 30-50 L. Plasma protein binding: Approx 20%; >60% (some metabolites).
Metabolism: Undergoes hepatic metabolism and converted to active metabolites acrolein, 4-aldophosphamide, 4-hydroperoxycyclophosphamide and nor-nitrogen mustard.
Excretion: Via urine (10-20% as unchanged drug); faeces (4%). Mean half-life: 4-8 hr.

Storage: Store at or below 25°C.

.