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

bl-25mg-label-100s.jpg
(click image for full-size original)

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

bl-50mg-0054-0383-25-100s.jpg
(click image for full-size original)
CYCLOPHOSPHAMIDE
cyclophosphamide capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0054-0382
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CYCLOPHOSPHAMIDE (CYCLOPHOSPHAMIDE ANHYDROUS) CYCLOPHOSPHAMIDE ANHYDROUS 25 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
SODIUM STEARYL FUMARATE
FD&C BLUE NO. 1
FD&C RED NO. 40
GELATIN, UNSPECIFIED
TITANIUM DIOXIDE
AMMONIA
FERROSOFERRIC OXIDE
ISOPROPYL ALCOHOL
BUTYL ALCOHOL
PROPYLENE GLYCOL
SHELLAC
Product Characteristics
Color BLUE Score no score
Shape CAPSULE Size 8mm
Flavor Imprint Code 54;006
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0054-0382-13 30 CAPSULE in 1 BOTTLE None
2 NDC:0054-0382-25 100 CAPSULE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA203856 09/16/2013
CYCLOPHOSPHAMIDE
cyclophosphamide capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0054-0383
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CYCLOPHOSPHAMIDE (CYCLOPHOSPHAMIDE ANHYDROUS) CYCLOPHOSPHAMIDE ANHYDROUS 50 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
SODIUM STEARYL FUMARATE
FD&C BLUE NO. 1
FD&C RED NO. 40
GELATIN, UNSPECIFIED
TITANIUM DIOXIDE
AMMONIA
FERROSOFERRIC OXIDE
ISOPROPYL ALCOHOL
BUTYL ALCOHOL
PROPYLENE GLYCOL
SHELLAC
Product Characteristics
Color BLUE Score no score
Shape CAPSULE Size 10mm
Flavor Imprint Code 54;881
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0054-0383-13 30 CAPSULE in 1 BOTTLE None
2 NDC:0054-0383-25 100 CAPSULE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA203856 09/16/2013
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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