Usual Adult Dose for Malignant Disease

IV:

• When used alone, the initial dose for patients with no hematologic deficiency is 40 to 50 mg/kg IV in divided doses over 2 to 5 days
• Alternative dose: 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV 2 times a week

• Dosage should be individualized.
• During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis to reduce the risk of urinary tract toxicity; therefore, administration should be in the morning.
• Many other regimens of IV and oral administration of this drug have been reported. Dosages should be adjusted in accord with evidence of antitumor activity and/or leukopenia. The local protocol should be consulted.
• When this drug is included in combined cytotoxic regimens, it may be necessary to reduce the dose of this drug as well as that of the other drugs.

• 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 blast crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (this drug given IV during remission is effective in prolonging its duration)
• Mycosis fungoides (advanced disease)
• Neuroblastoma (disseminated disease)
• Adenocarcinoma of the ovary
• Retinoblastoma
• Breast cancer

Usual Pediatric Dose for Malignant Disease

The doses below can be regarded as general guidelines:

IV:

• When used alone, the initial dose for patients with no hematologic deficiency is 40 to 50 mg/kg IV in divided doses over 2 to 5 days
• Alternative dose: 10 to 15 mg/kg IV every 7 to 10 days OR 3 to 5 mg/kg IV 2 times a week

• Dosage should be individualized.
• The dosing recommendations provided here are guidelines. Many other regimens of IV and oral administration of this drug have been reported. Dosages should be adjusted in accord with evidence of antitumor activity and/or leukopenia. The local protocol should be consulted.
• During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis to reduce the risk of urinary tract toxicity; therefore, administration should be in the morning.
• When this drug is included in combined cytotoxic regimens, it may be necessary to reduce the dose of this drug as well as that of the other drugs.

• 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 blast crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (this drug given IV during remission is effective in prolonging its duration)
• Mycosis fungoides (advanced disease)
• Neuroblastoma (disseminated disease)
• Adenocarcinoma of the ovary
• Retinoblastoma
• Breast cancer

Usual Pediatric Dose for Nephrotic Syndrome

The doses below can be regarded as general guidelines:
2 mg/kg orally daily for 8 to 12 weeks (maximum cumulative dose 168 mg/kg); treatment beyond 90 days increases the probability of sterility in males

Comments:

• Dosage should be individualized.
• The dosing recommendations provided here are guidelines. Many other regimens of IV and oral administration of this drug have been reported. Dosages should be adjusted in accord with evidence of antitumor activity and/or leukopenia. The local protocol should be consulted.
• During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis to reduce the risk of urinary tract toxicity; therefore, administration should be in the morning.
• When this drug is included in combined cytotoxic regimens, it may be necessary to reduce the dose of this drug as well as that of the other drugs.

Renal Dose Adjustments

• Mild to moderate renal impairment: No adjustment recommended.
• Severe renal impairment (CrCl 10 to 24 mL/min): Monitor these patients for toxicity. In patients with this level of renal impairment, decreased renal excretion may result in increased plasma levels of this drug and its metabolites. This may result in increased toxicity.

Liver Dose Adjustments

• Mild to moderate hepatic impairment: No adjustment recommended.
• Severe hepatic impairment: Patients with this level of hepatic impairment have reduced conversion of this drug to the active 4-hydroxyl metabolite, potentially reducing efficacy.

Dose Adjustments

Perform regular leukocyte and platelet counts during therapy with this drug. The dose should be adjusted, if required, if myelosuppression becomes evident:

• This drug should not be administered to patients with neutrophils 1,500/mm3 or less and platelets less than 50,000/mm3.
• Therapy may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. G-CSF may be administered to reduce the risks of neutropenia complications. Primary and secondary prophylaxis with G-CSF should be considered in patients considered to be at increased risk for neutropenia complications. The nadirs of the reduction in leukocyte count and thrombocyte count are usually reached in weeks 1 and 2 of therapy. Peripheral blood cell counts are expected to normalize after approximately 20 days. Bone marrow failure has been reported. Severe myelosuppression may be expected particularly in patients pretreated with and/or receiving concomitant chemotherapy and/or radiation therapy.

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Urinary outflow obstruction

Dialysis

This drug and its metabolites are dialyzable although there are probably quantitative differences depending upon the dialysis system being used. In patients requiring dialysis, use of a consistent interval between administration of this drug and dialysis should be considered.

Other Comments

Administration advice:

• The oral formulation of this drug should be swallowed whole, early in the day, and preferably on an empty stomach; however, if gastric irritation is intolerable, it may be administered with food.
• To avoid cystitis, a urinary output of at least 100 mL/hr should be maintained during therapy. Hydration and frequent bladder emptying is recommended; however, if the patient is receiving mesna, frequent bladder emptying should be avoided.

• Store unused drug at controlled room temperature.

• The manufacturer product information should be consulted.

• Compatible with 0.9% Sodium Chloride Injection.

• This drug is an antineoplastic product. Follow special handling and disposal

• Dosages of this drug may depend upon the specific indication for its use and whether other medications are coadministered. Reference to specific protocols is recommended.
• This drug is frequently used in combination with other cytotoxic drugs as part of a chemotherapy regimen.
• In elderly patients, monitoring for toxicities and the need for dose adjustment should reflect the higher frequency of decreased hepatic, renal, cardiac, or other organ function, and concomitant diseases or other drug therapy in this population.

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