CYCLOPHOSPHAMIDE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CYCLOPHOSPHAMIDE (UNII: 8N3DW7272P) (CYCLOPHOSPHAMIDE ANHYDROUS - UNII:6UXW23996M)

Available from:

STI Pharma LLC

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Cyclophosphamide 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 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, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs. Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatric 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. - Hypersensitivity Cyclophosphamide is contraindicated in patients who have a history of severe hypersensitivity reactions to it, any of its metabolites, or to other components of the product. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur. - Urinary Outflow Obstruction Cyclophosphamide is contraindicated in patients with urinary outflow obstruction [see WARNINGS AND PRECAUTIONS ( 5.2)] . Pregnancy Category D Cyclophosphamide can cause fetal harm when administered to a pregnant woman based on its mechanism of action and published reports of effects in pregnant patients or animals. Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn. Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Malformations of the skeleton, palate, limbs and eyes as well as miscarriage have been reported after exposure to cyclophosphamide in the first trimester. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide. Administration of cyclophosphamide to pregnant mice, rats, rabbits and monkeys during the period of organogenesis at doses at or below the dose in patients based on body surface area resulted in various malformations, which included neural tube defects, limb and digit defects and other skeletal anomalies, cleft lip and palate, and reduced skeletal ossification. Cyclophosphamide is present in breast milk. Neutropenia, thrombocytopenia, low hemoglobin, and diarrhea have been reported in infants breast fed by women treated with cyclophosphamide. Because of the potential for serious adverse reactions in nursing infants from cyclophosphamide, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pre-pubescent girls treated with cyclophosphamide generally develop secondary sexual characteristics normally and have regular menses. Ovarian fibrosis with apparently complete loss of germ cells after prolonged cyclophosphamide treatment in late pre-pubescence has been reported. Girls treated with cyclophosphamide who have retained ovarian function after completing treatment are at increased risk of developing premature menopause. Pre-pubescent boys treated with cyclophosphamide develop secondary sexual characteristics normally, but may have oligospermia or azoospermia and increased gonadotropin secretion. Some degree of testicular atrophy may occur. Cyclophosphamide-induced azoospermia is reversible in some patients, though the reversibility may not occur for several years after cessation of therapy. There is insufficient data from clinical studies of cyclophosphamide available for patients 65 years of age and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac functioning, and of concomitant disease or other drug therapy. Pregnancy should be avoided during treatment with cyclophosphamide because of the risk of fetal harm [see USE IN SPECIFIC POPULATIONS ( 8.1)]. Female patients of reproductive potential should use highly effective contraception during and for up to 1 year after completion of treatment. Male patients who are sexually active with female partners who are or may become pregnant should use a condom during and for at least 4 months after treatment. Females Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide. Affected patients generally resume regular menses within a few months after cessation of therapy. The risk of premature menopause with cyclophosphamide increases with age. Oligomenorrhea has also been reported in association with cyclophosphamide treatment. Animal data suggest an increased risk of failed pregnancy and malformations may persist after discontinuation of cyclophosphamide as long as oocytes/follicles exist that were exposed to cyclophosphamide during any of their maturation phases. The exact duration of follicular development in humans is not known, but may be longer than 12 months [see NONCLINICAL TOXICOLOGY ( 13.1)] . Men treated with cyclophosphamide may develop oligospermia or azoospermia which are normally associated with increased gonadotropin but normal testosterone secretion. In patients with severe renal impairment, decreased renal excretion may result in increased plasma levels of cyclophosphamide and its metabolites. This may result in increased toxicity [see CLINICAL PHARMACOLOGY ( 12.3)] . Monitor patients with severe renal impairment (CrCl =10 mL/min to 24 mL/min) for signs and symptoms of toxicity. Cyclophosphamide 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 cyclophosphamide administration and dialysis should be considered. Patients with severe hepatic impairment have reduced conversion of cyclophosphamide to the active 4-hydroxyl metabolite, potentially reducing efficacy [see CLINICAL PHARMACOLOGY ( 12.3)] .

Product summary:

Cyclophosphamide Capsules 25 mg, blue opaque capsules with STI 021 printed on the capsule in black ink, containing white to off-white powder. NDC 54879-021-01: Bottle of 100 Capsules 50 mg, blue opaque capsules with STI 022 printed on the capsule in black ink, containing white to off-white powder. NDC 54879-022-01: Bottle of 100 Capsules Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). [see USP Controlled Room Temperature] Cyclophosphamide is an antineoplastic product. Follow special handling and disposal procedures. 1

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CYCLOPHOSPHAMIDE- CYCLOPHOSPHAMIDE CAPSULE
STI PHARMA LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
"THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CYCLOPHOSPHAMIDE
CAPSULES SAFELY AND EFFECTIVELY". "SEE FULL PRESCRIBING INFORMATION
FOR
CYCLOPHOSPHAMIDE CAPSULES."
"CYCLOPHOSPHAMIDE CAPSULES"
"INITIAL U.S. APPROVAL: 1959"
INDICATIONS AND USAGE
Cyclophosphamide is an alkylating drug indicated for treatment of:
MALIGNANT DISEASES: malignant lymphomas: Hodgkin’s disease,
lymphocytic lymphoma, mixed-cell
type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple
myeloma, leukemias, mycosis
fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma,
breast carcinoma ( 1.1)
MINIMAL CHANGE NEPHROTIC SYNDROME IN PEDIATRIC PATIENTS: biopsy proven
minimal change
nephrotic syndrome in pediatric patients who failed to adequately
respond to or are unable to tolerate
adrenocorticosteroid therapy ( 1.2)
Limitations of Use: The safety and effectiveness for the treatment of
nephrotic syndrome in adults or other
renal disease has not been established.
DOSAGE AND ADMINISTRATION
MALIGNANT DISEASES: ADULT AND PEDIATRIC PATIENTS ( 2.1)
Oral: Usually 1 mg per kg per day to 5 mg per kg per day for both
initial and maintenance dosing.
MINIMAL CHANGE NEPHROTIC SYNDROME IN PEDIATRIC PATIENTS ( 2.2)
Recommended oral dose: 2 mg per kg daily for 8 to 12 weeks (maximum
cumulative dose 168 mg per
kg). Treatment beyond 90 days increases the probability of sterility
in males.
DOSAGE FORMS AND STRENGTHS
Capsules: 25 mg and 50 mg ( 3)
CONTRAINDICATIONS
Hypersensitivity to cyclophosphamide ( 4)
Urinary outflow obstruction ( 4)
WARNINGS AND PRECAUTIONS
Myelosuppression, Immunosuppression, Bone Marrow Failure and
Infections – Severe
immunosuppression may lead to serious and sometimes fatal infections.
Close hematological
monitoring is required. ( 5.1)
Urinary Tract and Renal Toxicity – Hemorrhagic cystitis, pyelitis,
ureteritis, and hematuria can occur.
Exclude or correct any urinary tract obstructions pr