INDICATIONS
Malignant Diseases
CYTOXAN, although effective alone in susceptible malignancies,
is more frequently used concurrently or sequentially with
other antineoplastic drugs. The following malignancies
are often susceptible to CYTOXAN treatment:
1. 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.
2. Multiple myeloma.
3. 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 (CYTOXAN given during
remission is effective in prolonging its duration).
4. Mycosis fungoides (advanced disease).
5. Neuroblastoma (disseminated disease).
6. Adenocarcinoma of the ovary.
7. Retinoblastoma.
8. Carcinoma of the breast.
Nonmalignant Disease
Biopsy Proven “MinimalChange”
Nephrotic Syndrome in Children
CYTOXAN is useful in carefully selected cases of biopsy
proven “minimal change” nephrotic syndrome in
children but should not be used as primary therapy. In children
whose disease fails to respond adequately to appropriate
adrenocorticosteroid therapy or in whom the adrenocorticosteroid
therapy produces or threatens to produce intolerable side
effects, CYTOXAN may induce a remission. CYTOXAN is not
indicated for the nephrotic syndrome in adults or for any
other renal disease.
DOSAGE AND ADMINISTRATION
Treatment of Malignant Diseases
Adults and Children
When used as the only oncolytic drug therapy, the initial
course of CYTOXAN for patients with no hematologic deficiency
usually consists of 40 to 50 mg/kg given intravenously
in divided doses over a period of 2 to 5 days. Other intravenous
regimens include 10 to 15 mg/kg given every 7 to 10 days
or 3 to 5 mg/kg twice weekly.
Oral CYTOXAN dosing is usually in the range of 1 to 5
mg/kg/day for both initial and maintenance dosing.
Many other regimens of intravenous and oral CYTOXAN have
been reported. Dosages must be adjusted in accord with
evidence of anti-tumor activity and/or leukopenia. The
total leukocyte count is a good, objective guide for regulating
dosage. Transient decreases in the total white blood cell
count to 2000 cells/mm3 (following short courses) or more
persistent reduction to 3000 cells/mm3 (with continuing
therapy) are tolerated without serious risk of infection
if there is no marked granulocytopenia.
When CYTOXAN is included in combined cytotoxic regimens,
it may be necessary to reduce the dose of CYTOXAN as well
as that of the other drugs.
CYTOXAN and its metabolites are dialyzable although there
are probably quantitative differences depending upon the
dialysis system being used. Patients with compromised
renal function may wshow some measurable changes in pharmacokinetic
parameters of CYTOXAN metabolism, but there is no consistent
evidence indicating a need for CYTOXAN dosage modification
in patients with renal function impairment.
Treatment of Nonmalignant Diseases
Biopsy Proven“ MinimalChange” Nephrotic
Syndrome in Children
An oral dose of 2.5 to 3 mg/kg daily for a period of
60 to 90 days is recommended. In males, the incidence
of oligospermia and azoospermia increases if the duration
of CYTOXAN treatment exceeds 60 days. Treatment beyond
90 days increases the probability of sterility. Adrenocorticosteroid
therapy may be tapered and discontinued during the course
of CYTOXAN therapy. See PRECAUTIONS section concerning
hematologic monitoring.
Preparation and Handling of Solutions
Parenteral drug products should be inspected visually
for particulate matter and discoloration prior to administration,
whenever solution and container permit.
Lyophilized CYTOXAN should be prepared for parenteral use
by adding Sterile Water for Injection, USP, to the vial
and shaking to dissolve. Use the quantity of diluent shown
below to reconstitute the product.
| Lyophilized
CYTOXAN |
| Dosage Strength |
Quantity
of Diluent |
| 100 mg |
5 mL |
| 200 mg |
10 mL |
| 500 mg |
20—25 mL |
| 1g |
50 mL |
| 2g |
80—100 mL
|
Solutions of Lyophilized CYTOXAN may be injected intravenously,
intramuscularly, intraperitoneally, or intrapleurally or
they may be infused intravenously in the following:
- Dextrose Injection, USP (5% dextrose)
- Dextrose and Sodium Chloride Injection, USP (5% dextrose
and 0.9% sodium chloride)
- 5% Dextrose and Ringer’s Injection
- Lactated Ringer’s Injection, USP
- Sodium Chloride Injection, USP (0.45% sodium chloride)
- Sodium Lactate Injection, USP (1/6 molar sodium lactate)
Reconstituted Lyophilized CYTOXAN are chemically and physically
stable for 24 hours at room temperature or for six days
in the refrigerator; it does not contain any antimicrobial
preservative and thus care must be taken to assure the sterility
of prepared solutions.
The osmolarities of solutions of Lyophilized CYTOXAN and
normal saline are found in the following table:
| Lyophilized
CYTOXAN |
mOsm/L |
| 4 mL diluent
per 100 mg cyclophosphamide |
219 |
| 5 mL diluent
per 100 mg cyclophosphamide |
172 |
Lyophilized CYTOXAN is slightly hypotonic.
Extemporaneous liquid preparations of CYTOXAN for oral
administration may be prepared by dissolving Lyophilized
CYTOXAN in Aromatic Elixir, N.F.Such preparations should
be stored under refrigeration in glass containers and
used within 14 days.
HOW SUPPLIED
Lyophilized CYTOXAN® contains 75 mg of mannitol per
100 mg of cyclophosphamide (anhydrous) and is supplied
in vials for single dose use.
Lyophilized CYTOXAN(cyclophoaphamide for injection, USP).
U.S. Patent No. 4,537,883
| NDC
0015-0539-41 |
100
mg vials, carton of 12, case of 1 carton |
| NDC
0015-0546-41 |
200
mg vials, carton of 12, case of 1 carton |
| NDC
0015-0547-41 |
500
mg vials, carton of 12, case of 1 carton |
| NDC
0015-0548-41 |
1.0
g vials, carton of 6 |
| NDC
0015-0549-41 |
2.0
g vials, carton of 6 |
CYTOXAN®Tablets, 25 mg and CYTOXAN Tablets, 50 mg,
are white tablets with blue flecks containing 25 mg and
50 mg cyclophosphamide (anhydrous), respectively.
CYTOXAN Tablets (cyclophosphamide tablets, USP).
| NDC
0015- 0503-01 |
50
mg, bottles of 100 |
| NDC
0015-0503 02 |
50
mg, bottles of 1000 |
| NDC
0015- 0504-01 |
25
mg, bottles of 100 |
Storage at or below 77°F(25°C) is recommended; this
product will withstand brief exposure to temperatures up
to 86°F(30°C) but should be protected from temperatures
above 86°F(30°C).
Procedures for proper handling and disposal of
anticancer drugs should be considered. Several guidelines
on this subject have been published. There is no general
agreement that all of the procedures recommended in the
guidelines are necessary or appropriate.
REFERENCES
1. Recommendations for the Safe Handling of Parenteral
Antineoplastic Drugs, NIH Publication No 83-2621. For
sale by the Superintendent of Documents, US Government
Printing Office, Washington, DC 20402.
2. AMA Council Report. Guidelines for Handling Parenteral
Antineoplastics. JAMA 1985; 253 (11): 1590-1592.
3. National Study Commission on Cytotoxic Exposure—
Recommendations for Handling Cytotoxic Agents. Available
from Louis P.Jeffrey, Sc. D.,Chairman, National Study
Commission on Cytotoxic Exposure, Massachusetts College
of Pharmacy and Allied Health Sciences, 179 Longwood Avenue,
Boston, Massachusetts 02115.
4. Clinical Oncological Society of Australia. Guidelines
and Recommendations for Safe Handling of Antineoplastic
Agents.Med J Australia 1983; 1:426-428.
5. Jones RB, et al: Safe Handling of chemotherapeutic
agents: A Report from the Mount Sinai Medical Center.
CA A Cancer Journal for Clinicians 1983; (Sept/Oct)258-263.
6. American Society of Hospital Pharmacists Technical
Assistance Bulletin on Handling Cytotoxic and Hazardous
Drugs. Am J Hosp Pharm 1990; 47: 1033-1049.
7. Controlling Occupational Exposure to Hazardous Drugs.(OSHA
WORK-PRACTICE GUIDELINES). Am J Health-Syst Pharm 1996;
53: 1669-1685.
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