Gleostine Drug Information

Brain Tumors Gleostine is indicated for the treatment of patients with primary and metastatic brain tumors following appropriate surgical and/or radiotherapeutic procedures.

Hodgkin's Lymphoma 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.

Important Prescribing and Dispensing Information PRESCRIBE ONLY ONE DOSE FOR EACH TREATMENT CYCLE. DO NOT DISPENSE ENTIRE CONTAINER. Dispense only a sufficient number of capsules for one dose.

Confirm the total dose prescribed by the physician and the appropriate combination of capsule strengths. Dispense only the appropriate number of Gleostine capsules required for the administration of a single dose. The prescribed dose may consist of two or more different strengths and colors of capsules.

Instruct patients that Gleostine is taken as a single oral dose and will not be repeated for at least 6 weeks. Taking more than the recommended dose causes toxicities, including fatal outcomes. 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.

Recommended Dose

The recommended dose of Gleostine in adult and pediatric patients is 130 mg/m 2 taken as a single oral dose every 6 weeks. Round doses to the nearest 10 mg. Give as a single oral dose and do not repeat for at least 6 weeks.

Reduce dose to 100 mg/m 2 every 6 weeks in patients with compromised bone marrow function. Also reduce dose accordingly when using with other myelosuppressive drugs.

Dose Modifications

Perform weekly complete blood counts and withhold each subsequent dose for more than 6 weeks if needed until platelet counts recover to 100,000/mm 3 or greater and leukocytes recover to 4000/mm 3 or greater. Modify each dose of Gleostine according to the hematologic response of the preceding dose as described in Table 1: Table 1. Dose Modifications for Gleostine

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Delayed myelosuppression Risks of overdosage Pulmonary toxicity Secondary malignancies Hepatotoxicity Nephrotoxicity The following adverse reactions associated with the use of Gleostine were identified in clinical trials or postmarketing reports. Because these reactions were reported from a population of uncertain size, it is not possible to estimate their frequency, reliability, or establish a causal relationship to drug exposure. Gastrointestinal disorders: nausea, vomiting, and stomatitis Ocular disorders: optic atrophy, visual disturbances, and blindness Neurologic disorders: disorientation, lethargy, ataxia, and dysarthria Other: alopecia Common adverse reactions include delayed myelosupression, nausea, vomiting, stomatitis, and alopecia.

To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy Risk Summary Based on animal data and its mechanism of action, Gleostine can cause fetal harm when administered to a pregnant woman. There are no available data on Gleostine exposure in pregnant women. 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 mg/kg. 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.

Pediatric Use Pediatric use, including dose, is not based on adequate and well-controlled clinical studies.

Overdosage with Gleostine has occurred, including fatal cases. Overdosage causes severe myelosuppression, as well as abdominal pain, diarrhea, vomiting, anorexia, lethargy, dizziness, abnormal hepatic function, cough, and shortness of breath. No antidotes exist for Gleostine overdosage.