GLEOSTINE- lomustine capsule, gelatin coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

LOMUSTINE (UNII: 7BRF0Z81KG) (LOMUSTINE - UNII:7BRF0Z81KG)

Available from:

NextSource Biotechnology, LLC

INN (International Name):

LOMUSTINE

Composition:

LOMUSTINE 40 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Gleostine is indicated for the treatment of patients with primary and metastatic brain tumors following appropriate surgical and/or radiotherapeutic procedures. Gleostine is indicated as a component of combination chemotherapy for the treatment of patients with Hodgkin's lymphoma whose disease has progressed following initial chemotherapy. None. Risk Summary Based on animal data and its mechanism of action, Gleostine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1)] . There are no available data on Gleostine exposure in pregnant women. Lomustine was teratogenic in rats and embryotoxic in rabbits at total dose levels approximately two to four times the total human dose of 130 mg/m 2 over 6 weeks (0.18 to 0.27 times the single human dose of 130 mg/m 2 ) based on BSA [see Data] . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Lomustine was administered by intraperitoneal injection daily to pregnant rats during the period of organogenesis at dose levels of 0, 2, 4, 6, and 8 mg/kg. Resorption rates and post-implantation loss occurred at doses greater than or equal to 4 mg/kg (approximately 0.18 times the clinical dose of 130 mg/m 2 based on BSA or approximately twice the total clinical dose of lomustine over 6 weeks). Malformations (omphalocele, ectopia cordis, scoliosis, syndactyly, hydrocephalus, microphthalmia, anophthalmia, anomalies of aortic arch, dextrocardia, malpositioning of the ovaries and testes, sternoschisis, and shortened/misshapen bone of the fore or hind limbs) and decreased fetal body weight occurred at all dose levels. In pregnant rabbits treated with lomustine at 3 mg/kg (approximately 0.27 times the 130 mg/m 2 clinical dose based on BSA or approximately four times the total clinical dose of lomustine over 6 weeks) during organogenesis, there were increases in abortions and decreases in surviving pup weight that persisted postnatally. Risk Summary There is no information on the presence of lomustine or its metabolites in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from Gleostine, advise women not to breastfeed during treatment with Gleostine and for 2 weeks after the final dose. Contraception Females Based on animal data and its mechanism of action, Gleostine can cause fetal harm [see Use in Specific Populations ( 8.1)] . Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the final dose. Males Based on Gleostine's mechanism of action, advise males with female partners of reproductive potential to use effective contraception during treatment with Gleostine and for 3.5 months after the final dose [see Clinical Pharmacology ( 12.1)] . Infertility Based on animal findings and its mechanism of action, Gleostine may result in reduced fertility in males and females of reproductive potential [see Nonclinical Toxicology ( 13.1)] . Pediatric use, including dose, is not based on adequate and well-controlled clinical studies. No data in the clinical studies of Gleostine are available for patients 65 years of age and over to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Lomustine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

Product summary:

Gleostine is available in three strengths, distinguishable by the color of the capsules, in individual bottles of 5 capsules each: Strength Capsule Description NDC Code 100 mg Moss green cap and body, imprinted in black ink, with "CPL" over "3032" on the cap and "100 mg" on the body of the capsule. 58181-3042-5 40 mg White cap and a moss green body, imprinted in black ink, with "CPL" over "3031" on the cap and "40 mg" on the body of the capsule. 58181-3041-5 10 mg White cap and body, imprinted in black ink, with "CPL" over "3030" on the cap and "10 mg" on the body of the capsule 58181-3040-5 Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Avoid temperatures over 40°C (104°F). Gleostine is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 To minimize the risk of dermal exposure, always wear impervious gloves when handling bottles containing Gleostine capsules. Do not break Gleostine capsules; avoid exposure to broken capsules. If dermal contact occurs, wash areas of skin contact immediately and thoroughly.

Authorization status:

New Drug Application

Summary of Product characteristics

GLEOSTINE- LOMUSTINE CAPSULE, GELATIN COATED
NEXTSOURCE BIOTECHNOLOGY, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
GLEOSTINE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR GLEOSTINE.
GLEOSTINE
(LOMUSTINE) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 1976
WARNING: DELAYED MYELOSUPPRESSION AND RISK OF OVERDOSAGE
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
DELAYED MYELOSUPPRESSION
GLEOSTINE CAUSES MYELOSUPPRESSION INCLUDING FATAL MYELOSUPPRESSION.
MYELOSUPPRESSION IS DELAYED, DOSE-RELATED, AND CUMULATIVE.
THROMBOCYTOPENIA IS GENERALLY MORE SEVERE THAN LEUKOPENIA. MONITOR
BLOOD COUNTS AND
DO NOT GIVE GLEOSTINE MORE FREQUENTLY THAN EVERY 6 WEEKS. ( 2.2, 2.3,
5.1)
RISK OF OVERDOSAGE
PRESCRIBE, DISPENSE, AND ADMINISTER ONLY ENOUGH
CAPSULES FOR ONE DOSE. FATAL TOXICITY OCCURS WITH OVERDOSAGE OF
GLEOSTINE. BOTH
PHYSICIAN AND PHARMACIST SHOULD EMPHASIZE TO PATIENT THAT ONLY ONE
DOSE OF GLEOSTINE
IS TAKEN EVERY 6 WEEKS. ( 2.1, 5.2, 10)
INDICATIONS AND USAGE
Gleostine is an alkylating drug indicated for the treatment of
patients with:
Brain tumors, primary and metastatic, following appropriate surgical
and/or radiotherapeutic
procedures. ( 1)
Hodgkin's lymphoma in combination with other chemotherapies, following
disease progression with
initial chemotherapy. ( 1)
DOSAGE AND ADMINISTRATION
Recommended dose in adult and pediatric patients is 130 mg/m
orally every 6 weeks. ( 2.1)
Round dose to nearest 10 mg.
Give as a single oral dose and do not repeat for at least 6 weeks.
DOSAGE FORMS AND STRENGTHS
Capsules: 10 mg, 40 mg, and 100 mg ( 3)
WARNINGS AND PRECAUTIONS
Pulmonary toxicity: Pulmonary infiltrates and/or fibrosis occurs with
Gleostine. Perform pulmonary
function tests prior to treatment and repeat frequently. Permanently
discontinue Gleostine in patients
diagnosed with pulmonary fibrosis. ( 5.3)
Secondary malignancies: Acute leukemia and myelodysplasia can occur
with long-term use. ( 5.4)
Hepatotoxicity: Increase