Medication

INDICATIONS AND USAGE CHEMET is indicated for the treatment of lead poisoning in pediatric patients with blood lead levels above 45 mcg/dL. CHEMET is not indicated for prophylaxis of lead poisoning in a lead-containing environment; the use of CHEMET should always be accompanied by identification and removal of the source of the lead exposure.

DOSAGE AND ADMINISTRATION Start dosage at 10 mg/kg or 350 mg/m 2 every eight hours for five days. Initiation of therapy at higher doses is not recommended. (See Table II for Dosing chart and number of capsules.) Reduce frequency of administration to 10 mg/kg or 350 mg/m 2 every 12 hours (two-thirds of initial daily dosage) for an additional two weeks of therapy. A course of treatment lasts 19 days. Repeated courses may be necessary if indicated by weekly monitoring of blood lead concentration. A minimum of two weeks between courses is recommended unless blood lead levels indicate the need for more prompt treatment. TABLE II CHEMET (SUCCIMER) PEDIATRIC DOSING CHART * To be administered every 8 hours for 5 days, followed by dosing every 12 hours for 14 days. LBS KG DOSE (MG)* Number of CAPSULES* 18-35 8-15 100 1 36-55 16-23 200 2 56-75 24-34 300 3 76-100 35-44 400 4 > 100 > 45 500 5 In young pediatric patients who cannot swallow capsules, CHEMET can be administered by separating the capsule and sprinkling the medicated beads on a small amount of soft food or putting them in a spoon and following with fruit drink. Identification of the source of lead in the pediatric patient's environment and its abatement are critical to a successful therapy outcome. Chelation therapy is not a substitute for preventing further exposure to lead and should not be used to permit continued exposure to lead. Patients who have received CaNa 2 EDTA with or without BAL may use CHEMET for subsequent treatment after an interval of four weeks. Data on the concomitant use of CHEMET with CaNa 2 EDTA with or without BAL are not available, and such use is not recommended.

ADVERSE REACTIONS Clinical experience with CHEMET has been limited. Consequently, the full spectrum and incidence of adverse reactions including the possibility of hypersensitivity or idiosyncratic reactions have not been determined. The most common events attributable to succimer, i.e., gastrointestinal symptoms or increases in serum transaminases, have been observed in about 10% of patients (see PRECAUTIONS ). Rashes, some necessitating discontinuation of therapy, have been reported in about 4% of patients. If rash occurs, other causes (e.g. measles) should be considered before ascribing the reaction to succimer. Rechallenge with succimer may be considered if lead levels are high enough to warrant retreatment. One allergic mucocutaneous reaction has been reported on repeated administration of the drug (see PRECAUTIONS ). Mild to moderate neutropenia has been observed in some patients receiving succimer (see WARNINGS ). Table I presents adverse events reported with the administration of succimer for the treatment of lead and other heavy metal intoxication. TABLE I INCIDENCE OF ADVERSE EVENTS IN DOMESTIC STUDIES REGARDLESS OF ATTRIBUTION OR SUCCIMER DOSAGE * Does not include neutropenia - see WARNINGS . Pediatric Patients (191) Adults (134) % (n) % (n) Digestive: 12.0 23 20.9 28 Nausea, vomiting, diarrhea, appetite loss, hemorrhoidal symptoms, loose stools, metallic taste in mouth. Body as a Whole: 5.2 10 15.7 21 Back pain, abdominal cramps, stomach pains, head pain, rib pain, chills, flank pain, fever, flu-like symptoms, heavy head/tired, head cold, headache, moniliasis. Metabolic: 4.2 8 10.4 14 Elevated SGPT, SGOT, alkaline phosphatase, elevated serum cholesterol. Nervous: 1.0 2 12.7 17 Drowsiness, dizziness, sensorimotor neuropathy, sleepiness, paresthesia. Skin and Appendages: 2.6 5 11.2 15 Papular rash, herpetic rash, rash, mucocutaneous eruptions, pruritus. Special Senses: 1.0 2 3.7 5 Cloudy film in eye, ears plugged, otitis media, eyes watery. Respiratory 3.7 7 0.7 1 Throat sore, rhinorrhea, nasal congestion, cough. Urogenital: 0.0 - 3.7 5 Decreased urination, voiding difficulty, proteinuria increased. Cardiovascular: 0.0 - 1.8 2 Arrhythmia Heme/Lymphatic: 0.5* 1 1.5* 2 Mild to moderate neutropenia, increased platelet count, intermittent eosinophilia. Musculoskeletal: 0.0 - 3.0 4 Kneecap pain, leg pains. To report SUSPECTED ADVERSE REACTIONS, contact Lundbeck at 1-800-455-1141 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interaction: CHEMET is not known to interact with other drugs including iron supplements; interactions have not been systematically studied. Concomitant administration of CHEMET with other chelation therapy, such as CaNa 2 EDTA is not recommended.