Gleostine

• Brain and Spinal Cord Tumors in Adults (Symptoms, Signs, Causes, Treatment Options, Life Expectancy)
• Brain Tumor (Symptoms, Signs, Types, Causes, Survival Rates)
• Hodgkin's Disease

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of lomustine can be fatal.

Overdose symptoms may include stomach pain, vomiting, diarrhea, loss of appetite, dizziness, cough, feeling short of breath, or signs of infection.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using lomustine, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies on the relationship of age to the effects of lomustine have not been performed in the pediatric population. However, pediatric-specific problems that would limit the usefulness of this medicine in children are not expected.

Geriatric

No information is available on the relationship of age to the effects of lomustine in geriatric patients. However, elderly patients are more likely to have age-related kidney problems, which may require an adjustment in the dose for patients receiving lomustine.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine
• Bacillus of Calmette and Guerin Vaccine, Live
• Cholera Vaccine, Live
• Influenza Virus Vaccine, Live
• Poliovirus Vaccine, Live
• Smallpox Vaccine
• Typhoid Vaccine
• Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia (low red cells in the blood) or
• Bone marrow problems or
• Leukopenia (low white cells in the blood) or
• Lung disease or
• Thrombocytopenia (low platelets in the blood)—May make these conditions worse.

• Chickenpox, including recent exposure, or
• Herpes zoster (shingles) or
• Infection—May decrease the ability to fight an infection.

• Kidney disease—Effects may be increased because of slower removal from the body.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Check with your doctor right away if you have any of the following symptoms: fever, chills, dry cough, sore throat, confusion, shortness of breath, swelling of the feet or lower legs, unusual bleeding or bruising, or yellow eyes or skin.

While you are being treated with lomustine, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Lomustine may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have recently taken oral polio vaccine. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Lomustine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

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 [see Warnings and Precautions ( 5.2) and Overdosage ( 10)] .

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 5 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 3or greater [see Warnings and Precautions ( 5.1)] .

Modify each dose of Gleostine according to the hematologic response of the preceding dose as described in Table 1:

None.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Delayed myelosuppression [see Warnings and Precautions ( 5.1)]
• Risks of overdosage [see Warnings and Precautions ( 5.2)]
• Pulmonary toxicity [see Warnings and Precautions ( 5.3)]
• Secondary malignancies [see Warnings and Precautions ( 5.4)]
• Hepatotoxicity [see Warnings and Precautions ( 5.5)]
• Nephrotoxicity [see Warnings and Precautions ( 5.6)]

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 establishment 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

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lomustine is carcinogenic in rats and mice, producing a marked increase in tumor incidence in doses lower than those employed clinically.

In female rats, daily intraperitoneal treatment with lomustine for 2 weeks prior to mating with untreated males resulted in dose dependent decreases in number of corpora lutea and resorption rates with no live births at a dose of 3 mg/kg (approximately 0.14 times the recommended clinical dose of 130 mg/m 2 based on body surface area (BSA), or approximately twice the total clinical dose of lomustine over 6 weeks) and decreased pup survival during the first 4 postnatal days at doses greater than or equal to 1.5 mg/kg (a daily dose of approximately 0.06 times the recommended clinical dose of 130 mg/m 2 based on BSA or approximately equal to the total clinical dose of lomustine over 6 weeks). Gleostine may also result in decreased male fertility. Intraperitoneal injection of lomustine resulted in decreased fertility in male rats mated to untreated females based on decreased implantations and decreased fetal body weight at weekly doses greater than or equal to 5 mg/kg (approximately 0.23 times the single clinical dose of 130 mg/m 2 based on BSA, or approximately equal to the total clinical dose of lomustine over 6 weeks), and increased resorptions at doses greater than or equal to

2.5 mg/kg/week.