Cyclophosphamide

CYCLOPHOSPHAMIDE- cyclophosphamide injection, powder, for solution
Amneal Pharmaceuticals LLC

1 INDICATIONS AND USAGE

1.1 Malignant Diseases

Cyclophosphamide for injection is indicated for the treatment of:

  • 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 (cyclophosphamide for injection 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

Cyclophosphamide for injection, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs.

1.2 Minimal Change Nephrotic Syndrome in Pediatric Patients

Cyclophosphamide for injection is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatrics patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy.

Limitations of Use:

The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established.

2 DOSAGE AND ADMINISTRATION

During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide for injection should be administered in the morning.

2.1 Dosing for Malignant Diseases

Adults and Pediatric Patients

Intravenous

When used as the only oncolytic drug therapy, the initial course of cyclophosphamide for injection for patients with no hematologic deficiency usually consists of 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly.

Oral

Oral cyclophosphamide dosing is usually in the range of 1 mg per kg per day to 5 mg per kg per day for both initial and maintenance dosing.

Many other regimens of intravenous and oral cyclophosphamide have been reported. Dosages must be adjusted in accord with evidence of antitumor activity and/or leukopenia. The total leukocyte count is a good, objective guide for regulating dosage.

When cyclophosphamide for injection is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide for injection as well as that of the other drugs.

2.2 Dosing for Minimal Change Nephrotic Syndrome in Pediatric Patients

An oral dose of 2 mg per kg daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg) is recommended. Treatment beyond 90 days increases the probability of sterility in males [see Use in Specific Populations (8.4)].

2.3 Preparation, Handling and Administration

Handle and dispose of cyclophosphamide for injection in a manner consistent with other cytotoxic drugs.1 Caution should be exercised when handling and preparing cyclophosphamide for injection. To minimize the risk of dermal exposure, always wear gloves when handling vials containing cyclophosphamide for injection.

Cyclophosphamide for Injection

Intravenous Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use cyclophosphamide for injection vials if there are signs of melting. Melted cyclophosphamide for injection is a clear or yellowish viscous liquid usually found as a connected phase or in droplets in the affected vials.

Cyclophosphamide for injection does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique.

For Direct Intravenous Injection

Reconstitute Cyclophosphamide for Injection with 0.9% Sodium Chloride Injection, USP only, using the volumes listed below in Table 1. Gently swirl the vial to dissolve the drug completely. Do not use Sterile Water for Injection, USP because it results in a hypotonic solution and should not be injected directly.

Table 1: Reconstitution for Direct Intravenous Injection

Strength

Volume of

0.9% Sodium Chloride

Cyclophosphamide for Injection

Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

For Intravenous Infusion

Reconstitution of Cyclophosphamide for Injection:

Reconstitute Cyclophosphamide for Injection using 0.9% Sodium Chloride Injection, USP or Sterile Water for Injection, USP with the volume of diluent listed below in Table 2. Add the diluent to the vial and gently swirl to dissolve the drug completely.

Table 2: Reconstitution in preparation for Intravenous Infusion

Strength

Volume of

Diluent

Cyclophosphamide for Injection

Concentration

500 mg

25 mL

20 mg per mL

1 g

50 mL

2 g

100 mL

Dilution of Reconstituted Cyclophosphamide for Injection:

Further dilute the reconstituted cyclophosphamide for injection solution to a minimum concentration of 2 mg per mL with any of the following diluents:

  • 5% Dextrose Injection, USP
  • 5% Dextrose and 0.9% Sodium Chloride Injection, USP
  • 0.45% Sodium Chloride Injection, USP

To reduce the likelihood of adverse reactions that appear to be administration rate-dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), cyclophosphamide for injection should be injected or infused very slowly. Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused.

Storage of Reconstituted and Diluted Cyclophosphamide for Injection Solution:

If not used immediately, for microbiological integrity, cyclophosphamide for injection solutions should be stored as described in Table 3.

Table 3: Storage of Cyclophosphamide for Injection Solutions

Diluent

Storage

Room Temperature

Refrigerated

Reconstituted Solution (Without Further Dilution)

0.9% Sodium Chloride Injection, USP

up to 24 hrs

Up to 6 days

Sterile Water for Injection, USP

Do not store; use immediately

Diluted Solutionsa

0.45% Sodium Chloride Injection, USP

up to 24 hrs

up to 6 days

5% Dextrose Injection, USP

up to 24 hrs

up to 36 hrs

5% Dextrose and 0.9% Sodium Chloride Injection, USP

up to 24 hrs

up to 36 hrs

a Storage time is the total time cyclophosphamide for injection is in solution including the time it is reconstituted in 0.9% Sterile Sodium Chloride Injection, USP or Sterile Water for Injection, USP.

Use of Reconstituted Solution for Oral Administration

Liquid preparations of cyclophosphamide for oral administration may be prepared by dissolving cyclophosphamide for injection in Aromatic Elixir, National Formulary (NF). Such preparations should be stored under refrigeration in glass containers and used within 14 days.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.