RADIOGARDASE Capsule Ref.[27566] Active ingredients: Prussian blue

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.

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)].

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.

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 (¹³⁷Cs) crosses the human placenta. One patient, contaminated with 0.005 mCi ¹³⁷Cs during her 4^th month of pregnancy, was not treated with Radiogardase. At birth, the concentration of ¹³⁷Cs 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.

Studies to determine if Radiogardase is excreted in human milk have not been conducted. Since Radiogardase is not absorbed from the gastrointestinal tract, its excretion in milk is unlikely. However, cesium and thallium are transmitted from mother to infant in breast milk. Women internally contaminated with cesium or thallium should not breastfeed.

Radioactive Cesium Contamination

The safety and efficacy of Radiogardase in the treatment of ¹³⁷Cs in pediatric patients ages, 2 to 18 years old, was established from data from Radiogardase-treated pediatric patients exposed to ¹³⁷Cs in the Goiânia, Brazil, contamination incident and from Radiogardase-treated adults exposed to ¹³⁷Cs [see Clinical Studies (14.1)].

Overall, 27 pediatric patients received Radiogardase in the range of 3 to 10 grams per day in divided doses (the maximum recommended adolescent dosage is 9 grams per day). Radiogardase treatment reduced the whole body effective half-life of ¹³⁷Cs by 46% in adolescents and by 43% in children aged 4 to 12 years of age. In 12 patients for whom the rate of radiation elimination data are available, the rate was similar to that in adults treated with 3 grams three times daily and in pediatric patients treated with 1 gram three times daily. By body weight, the dose ranged from

0.32 gram/kg in the 12-year old patient (10 gram Radiogardase daily dose, 31 kg weight) to

0.21 gram/kg in the 4 year old patient (3 gram Radiogardase daily dose, 14 kg weight) [see Clinical Studies (14.1)].

Pediatric patients aged 2 up to 4 years are expected to have biliary and gastrointestinal function that is comparable to that of a 4-year old.

The safety and efficacy of Radiogardase has not been established in the treatment of ¹³⁷Cs contamination in pediatric patients 0 to 2 years old. There are differences in the developmental maturity of the biliary system and gastrointestinal tract of neonates and infants (0–2 years). The dosage-related adverse reactions of Radiogardase on an immature gastrointestinal tract are not known.

Radioactive and Non-Radioactive Thallium Contamination

The safety and efficacy of Radiogardase for the treatment of radioactive and non-radioactive thallium contamination in pediatric patients has not been established.

The safety and efficacy of Radiogardase in patients aged 65 and over have not been evaluated, to determine whether they respond differently from younger subjects.. In general, elderly patients should be monitored closely, reflecting the greater frequency of decreased cardiac function and of concomitant disease or other drug therapy.

Radiogardase is not systemically bioavailable and does not rely on hepatic metabolism for activation or inactivation. However, Radiogardase may be less effective in patients with hepatic impairment, due to decreased excretion of cesium and thallium in the bile.