Radiogardase

1 INDICATIONS AND USAGE Radiogardase is indicated for treatment of patients with known or suspected internal contamination with radioactive cesium and/or radioactive or non-radioactive thallium, in order to increase their rates of elimination. Radiogardase is indicated for treatment of patients with known or suspected internal contamination with radioactive cesium and/or radioactive or non-radioactive thallium to increase their rates of elimination. ( 1 )

2 DOSAGE AND ADMINISTRATION Adults and Adolescents: 3 grams orally three times a day ( 2.3 ) Pediatrics (2 – 12 years): 1 gram orally three times a day ( 2.3 ) Administer as soon as possible after internal contamination with cesium or thallium is suspected ( 2.1 ) 2.1 Important Administration Instructions Obtain quantitative baseline of the internalized contamination by radioactive cesium (137Cs) and/or thallium by appropriate whole-body counting and/or by bioassay (e.g., biodosimetry), or feces/urine samples, whenever possible prior to Radiogardase treatment. Initiate treatment with Radiogardase as soon as possible after contamination is suspected. Even when delayed, treatment with Radiogardase is effective and should not be withheld. Take Radiogardase capsules with food to stimulate excretion of cesium or thallium. In patients who cannot tolerate swallowing large numbers of capsules, open the capsules and mix with bland food or liquids. 2.2 Decontamination Procedures for Radioactive Cesium or Thallium Contamination Prior to initiating treatment with Radiogardase, follow radioactive decontamination safety procedures including: Use appropriate radiation protective attire and closely monitor personnel and treatment area for radiation levels using radiation detection, indication, and computation devices (RADIAC) or thermal luminescent devices (TLD). Control spread of radiation contamination through the establishment of a patient decontamination area and a contaminated material disposal site (with proper labeling, handling, and disposal of contaminated material). 2.3 Recommended Dosage Adults and Adolescents : 3 grams (6 capsules) taken orally three times a day (a total daily dose of 9 grams) Pediatric Patients (2 – 12 years) : 1 gram (2 capsules) taken orally three times a day (a total daily dose of 3 grams) 2.4 Treatment of Radioactive Cesium Contamination Anticipate that treatment with Radiogardase may last 30 days or longer. Base duration of Radiogardase treatment on weekly measurements of radioactivity in urine and fecal samples to monitor cesium elimination rate. Obtain weekly laboratory evaluations (complete blood count, serum chemistry and electrolytes). 2.5 Treatment of Radioactive and Non-radioactive Thallium Contamination Anticipate that treatment with Radiogardase may last 30 days or longer. For radioactive thallium: Base duration of Radiogardase treatment on weekly measurements of radioactivity inurine and fecal samples to monitor thallium elimination rate. Continue Radiogardase treatment until a 24-hour urine thallium test is normal (less than 5 micrograms per liter) and radiation level is acceptable. For non-radioactive thallium: Continue Radiogardase treatment until a 24-hour urine thallium test is normal (less than 5 micrograms per liter). Obtain weekly laboratory evaluations (complete blood count, serum chemistry and electrolytes). In cases of severe thallium intoxication, additional types of treatment may be necessary, such as: Induced emesis, followed by gastric intubation and lavage Forced diuresis until urinary thallium excretion is less than 1 mg/24 hours Charcoal hemoperfusion may be useful during the first 48 hours after thallium ingestion (biodistribution phase). Hemodialysis has also been reported to be effective in thallium intoxication.

4 CONTRAINDICATIONS None None ( 4 )

5 WARNINGS AND PRECAUTIONS Increased radiation absorbed dose to gastrointestinal mucosa : Monitor for decreased gastrointestinal motility ( 5.1 ) Constipation : Monitor and treat ( 5.2 ) Electrolyte abnormalities : Monitor serum electrolytes during treatment ( 5.3 ) Blue discoloration of stool, oral mucosa and dentition ( 5.4 ) 5.1 Increased Radiation Absorbed Dose to Gastrointestinal Mucosa Radiogardase can decrease gastrointestinal motility, thus slowing the transit time of radioactivity in the gastrointestinal tract. The slowed transit time can increase the radiation absorbed dose to the gastrointestinal mucosa. 5.2 Constipation Radiogardase can cause constipation. Monitor and treat for signs and symptoms of constipation. Patients with disorders associated with decreased gastrointestinal motility are at higher risk. 5.3 Electrolyte Abnormalities Radiogardase may bind to electrolytes found in the gastrointestinal tract. Hypokalemia, with serum potassium values of 2.5 – 2.9 (normal 3.5 – 5.0), was reported in 3 (7%) of 42 patients during treatement with Radiogardase. Monitor serum electrolytes during Radiogardase treatment, particularly when treating patients with pre-existing cardiac arrhythmias or electrolyte imbalances. 5.4 Blue Discoloration of Feces, Oral Mucosa, and Dentition Radiogardase is excreted primarily in feces and turns stools blue. When Radiogardase capsules are opened and the contents eaten with food, the oral mucosa and dentition may also be colored blue.

7 DRUG INTERACTIONS Based on animal data, co-administration of Radiogardase with other decorporation agents does not affect the efficacy of Radiogardase for treatment of internal contamination with radioactive cesium and/or radioactive or non-radioactive thallium.

6 ADVERSE REACTIONS Constipation was reported in 10 (24%) of 42 patients treated with Radiogardase. Severity of constipation was mild in 7 patients and moderate in 3 patients [see Warnings and Precautions (5.2) ]. Most common adverse reaction (incidence >24%) was constipation ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact info@heyl-berlin.de, Fax +49 30 817 4049 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Pregnancy Category C It is not known whether Radiogardase can cause fetal harm when administered to a pregnant woman or if it can affect reproduction capacity. Animal reproduction studies have not been conducted with prussian blue insoluble. However, since Radiogardase is not absorbed from the gastrointestinal tract, effects on the fetus are not expected. Radioactive cesium ( 137 Cs) crosses the human placenta. One patient, contaminated with 0.005 mCi 137 Cs during her 4 th month of pregnancy, was not treated with Radiogardase. At birth, the concentration of 137 Cs was the same in the mother and the infant. Thallium crosses the human placenta. Reported fetal effects include failure to thrive and death. The toxicity from untreated radioactive cesium or thallium exposure is greater than the potential reproductive toxicity of Radiogardase.