Endoxana

Action

Unclear. Thought to prevent cell division by cross-linking DNA strands, thereby interfering with growth of susceptible cancer cells.

Availability

Powder for injection: 500 mg, 1 g, 2 g

Tablets: 25 mg, 50 mg

Indications and dosages

➣ Hodgkin's disease; malignant lymphoma; multiple myeloma; leukemia; advanced mycosis fungoides; neuroblastoma; ovarian cancer; breast cancer; and certain other tumors

Adults: Initially, 40 to 50 mg/kg I.V. in divided doses over 2 to 5 days, or 10 to 15 mg/kg I.V. q 10 days, or 3 to 5 mg/kg I.V. twice weekly.

Children: Initially, 2 to 8 mg/kg or 60 to 250 mg/m² P.O. or I.V. daily in divided doses for 6 or more days.

Maintenance dosage is 2 to 5 mg/kg or 50 to 150 mg/m² P.O. twice weekly.

➣ Biopsy-proven nephrotic syndrome in children

Children: 2.5 to 3 mg/kg/day P.O. for 60 to 90 days

Off-label uses

• Severe rheumatologic conditions

• Selected cases of severe progressive rheumatoid arthritis and systemic lupus erythematosus

Contraindications

• Hypersensitivity to drug

• Severe bone marrow depression

Precautions

Use cautiously in:

• renal or hepatic impairment, adrenalectomy, mild to moderate bone marrow depression, other chronic debilitating illnesses

• females of childbearing age

• pregnant patients

• breastfeeding patients (use not recommended).

Administration

• Verify that patient isn't pregnant before administering.

• Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic drugs.

• Administer tablets on empty stomach. If drug causes severe GI upset, give with food.

• Don't cut or crush tablets.

• Know that dosage may need to be decreased if drug is given with other antineoplastics.

• Dilute each 100 mg of powder with 5 ml of sterile water for injection, to yield 20 mg/ml. Further dilute with compatible fluid, such as 5% dextrose injection, 5% dextrose and normal saline solution for injection, 5% dextrose and Ringer's injection, lactated Ringer's injection, or half-normal saline solution for injection.

• For I.V. injection, give each 100 mg over at least 1 minute. When giving dosages above 500 mg diluted in 100 to 250 ml of compatible solution, administer over 20 to 60 minutes.

• Use solution prepared with bacteriostatic water for injection within 24 hours if stored at room temperature or within 6 days if refrigerated.

• To minimize bladder toxicity, increase patient's fluid intake during therapy and for 1 to 2 days afterward. Most adults require fluid intake of at least 2 L/day.

Adverse reactions

CV: cardiotoxicity

GI: nausea, vomiting, diarrhea, abdominal pain or discomfort, stomatitis, oral mucosal ulcers, anorexia, hemorrhagic colitis

GU: urinary bladder fibrosis, hematuria, amenorrhea, decreased sperm count, sterility, acute hemorrhagic cystitis, renal tubular necrosis, hemorrhagic ureteral inflammation

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression, neutropenia

Hepatic: jaundice

Metabolic: hyperuricemia

Respiratory: interstitial pulmonary fibrosis

Skin: nail and pigmentation changes, alopecia

Other: poor wound healing, infections, allergic reactions including anaphylaxis, secondary cancer

Interactions

Drug-drug. Allopurinol, thiazide diuretics: increased risk of leukopenia

Digoxin: decreased digoxin blood level

Cardiotoxic drugs (such as cytarabine, daunorubicin, doxorubicin): additive cardiotoxicity

Chloramphenicol: prolonged cyclophosphamide half-life

Phenobarbital: increased risk of cyclophosphamide toxicity

Quinolones: decreased antimicrobial effect

Succinylcholine: prolonged neuromuscular blockade

Warfarin: increased anticoagulant effect

Drug-diagnostic tests. Hemoglobin, platelets, pseudocholinesterase, red blood cells (RBCs), white blood cells: decreased values

Uric acid: increased level

Patient monitoring

• Assess infusion site for signs of extravasation.

• Monitor hematologic profile to determine degree of hematopoietic suppression. Be aware that leukopenia is an expected drug effect and is used to help determine dosage.

• Monitor urine regularly for RBCs, which may precede hemorrhagic cystitis.

Patient teaching

• Tell patient to take tablets on empty stomach. However, if GI upset occurs, instruct him to take them with food.

See Advise patient to promptly report unusual bleeding or bruising, fever, chills, sore throat, cough, shortness of breath, seizures, lack of menstrual flow, unusual lumps or masses, flank or stomach pain, joint pain, mouth or lip sores, or yellowing of skin or eyes.

• Instruct patient to drink 2 to 3 L of fluids daily (unless prescriber has told him to restrict fluids).

• Tell patient that drug may cause hair loss, but that hair usually grows back after treatment ends.

• Advise female patient to use barrier contraception during therapy and for 1 month afterward.

• Advise breastfeeding women not to breastfeed while taking this drug.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.