Cyclophosphamide (Page 5 of 5)
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Cyclophosphamide administered by different routes, including intravenous, subcutaneous or intraperitoneal injection, or in drinking water, caused tumors in both mice and rats. In addition to leukemia and lymphoma, benign and malignant tumors were found at various tissue sites, including urinary bladder, mammary gland, lung, liver, and injection site [see Warnings and Precautions (5.5)].
Cyclophosphamide was mutagenic and clastogenic in multiple in vitro and in vivo genetic toxicology studies.
Cyclophosphamide is genotoxic in male and female germ cells. Animal data indicate that exposure of oocytes to cyclophosphamide during follicular development may result in a decreased rate of implantations and viable pregnancies, and in an increased risk of malformations. Male mice and rats treated with cyclophosphamide show alterations in male reproductive organs (e.g., decreased weights, atrophy, changes in spermatogenesis), and decreases in reproductive potential (e.g., decreased implantations and increased post-implantation loss) and increases in fetal malformations when mated with untreated females [see Use in Specific Populations (8.3)].
15 REFERENCES
1. OSHA Hazardous Drug. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.
16 HOW SUPPLIED/STORAGE AND HANDLING
Cyclophosphamide Capsules, USP
25 mg, supplied as a blue/blue opaque capsule with “54 006” printed in black ink on the cap and body, containing a white to off-white powder.
NDC 0054-0382-13: Bottle of 30 Capsules
NDC 0054-0382-25: Bottle of 100 Capsules
50 mg, supplied as a blue/blue opaque capsule with “54 881” printed in black ink on the cap and body, containing a white to off-white powder.
NDC 0054-0383-13: Bottle of 30 Capsules
NDC 0054-0383-25: Bottle of 100 Capsules
Storage
Store at 20°C to 25°C (68°F to 77°F); with excursions permitted between 15ºC to 30ºC (59°F to 86°F). [See USP Controlled Room Temperature.]
Cyclophosphamide is an antineoplastic product. Follow special handling and disposal procedures.1
17 PATIENT COUNSELING INFORMATION
Advise the patient of the following:
Myelosuppression, Immunosuppression, and Infections
- •
- Inform patients of the possibility of myelosuppression, immunosuppression, and infections. Explain the need for routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever [see Warnings and Precautions (5.1)].
Urinary Tract and Renal Toxicity
- •
- Advise the patient to report urinary symptoms (patients should report if their urine has turned a pink or red color) and the need for increasing fluid intake and frequent voiding [see Warnings and Precautions (5.2)].
Cardiotoxicity
- •
- Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Warnings and Precautions (5.3)].
Pulmonary Toxicity
- •
- Warn patients of the possibility of developing non-infectious pneumonitis. Advise patients to report promptly any new or worsening respiratory symptoms [see Warnings and Precautions (5.4)].
Embryo-Fetal Toxicity
- •
- Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1)].
- •
- Advise females of reproductive potential to use effective contraception during treatment and for up to 1 year after completion of therapy [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1, 8.3)]. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1, 8.3)].
Lactation
- •
- Advise lactating women not to breastfeed during treatment and for 1 week after the last dose of Cyclophosphamide Capsules [see Use in Specific Populations (8.2)].
Infertility
- •
- Cyclophosphamide Capsules may impair fertility in males and females of reproductive potential [see Warnings and Precautions (5.8) and Use in Specific Populations (8.3, 8.4)].
Common Adverse Reactions
- •
- Explain to patients that side effects such as nausea, vomiting, stomatitis, impaired wound healing, amenorrhea, premature menopause, sterility and hair loss may be associated with cyclophosphamide administration. Other undesirable effects (including, e.g., dizziness, blurred vision, visual impairment) could affect the ability to drive or use machines [see Adverse Reactions (6.1, 6.2)].
Hydration and Important Administration Instructions
- •
- Advise the patient that during or immediately after the administration, adequate amounts of fluid are required to reduce the risk of urinary tract toxicity [see Dosage And Administration (2.1)].
- •
- Instruct the patient to swallow cyclophosphamide capsules whole. Do not open, chew, or crush capsules [see Dosage And Administration (2.1)].
- •
- Advise caregivers to wear gloves when handling cyclophosphamide containers and capsules and to avoid exposure to broken capsules. If contact with broken capsules occurs, wash hands immediately and thoroughly [see Dosage And Administration (2.1)].
Distributed by: Hikma
Pharmaceuticals USA Inc.
Berkeley Heights, NJ 07922
C50000459/01
Revised July 2023
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
CYCLOPHOSPHAMIDE cyclophosphamide capsule | ||||||||||||||||||||||||||||
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CYCLOPHOSPHAMIDE cyclophosphamide capsule | ||||||||||||||||||||||||||||
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Labeler — Hikma Pharmaceuticals USA Inc. (080189610) |
Establishment | |||
Name | Address | ID/FEI | Operations |
West-Ward Columbus Inc. | 058839929 | MANUFACTURE (0054-0382), MANUFACTURE (0054-0383) |
Revised: 07/2023 Hikma Pharmaceuticals USA Inc.
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