Insoluble Prussian blue is administered to decrease radiation exposure. It does not treat the complications of radiation exposure. Patients contaminated with high doses of ¹³⁷Cs may develop radiation toxicity including bone marrow suppression with severe neutropenia and thrombocytopenia. Supportive treatment for radiation toxicity symptoms should be given concomitantly with insoluble Prussian blue treatment.

In radiological emergencies, the type of elemental exposure may not be known. Insoluble Prussian blue may not bind to all radioactive elements and some radioactive elements may not undergo enterohepatic circulation which is needed for insoluble Prussian blue binding and elimination. Patients contaminated with unknown or multiple radioactive elements may require treatment with other agents in addition to insoluble Prussian blue.

Gastrointestinal : Insoluble Prussian blue can cause constipation. Decreased gastrointestinal motility will slow the transit time of ¹³⁷Cs bound to insoluble Prussian blue in the gastrointestinal tract, and may increase the radiation absorbed dose to the gastrointestinal mucosa. Constipation occurring during insoluble Prussian blue treatment may be treated with a fiber based laxative and/or a high fiber diet. Insoluble Prussian blue should be used with caution in patients with disorders associated with decreased gastrointestinal motility.

Cesium-137 is excreted in the urine and feces. Appropriate safety measures should be taken to minimize radiation exposure to others. When possible, a toilet should be used instead of a urinal, and it should be flushed several times after each use. Spilled urine or feces should be cleaned up completely and patients should wash their hands thoroughly. If blood or urine gets onto clothing, such clothing should be washed separately.

Parents and child-care givers should take extra precaution in handling the urine and feces of pediatric patients. Care is intended to prevent re-exposure to the adult and pediatric patient.

In patients with constipation, a fiber based laxative and/or high fiber diet is recommended during treatment with insoluble Prussian blue.

Patients taking insoluble Prussian blue should be informed that their stools might be blue-colored.

In patients who cannot swallow capsules, when the capsules are opened and the contents are mixed with food and eaten, the mouth and teeth might be colored blue.

Insoluble Prussian blue may bind electrolytes found in the gastrointestinal tract. Asymptomatic hypokalemia, with serum potassium values of 2.5-2.9 (normal 3.5-5.0), was reported in 3/42 (7%) of patients on treatment with insoluble Prussian blue. Serum electrolytes should be closely monitored during insoluble Prussian blue treatment. Caution should be exercised when treating patients with pre-existing cardiac arrhythmias or electrolyte imbalances.

Insoluble Prussian blue may bind some orally administered therapeutic drugs. As appropriate, blood levels or clinical response to oral medications should be monitored.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with insoluble Prussian blue to evaluate carcinogenesis, mutagenesis and impairment of fertility have not been performed.

All males who received a whole body radiation absorbed dose greater than 1 Gy of ¹³⁷Cs, 2-8 years later had either oligospermia or azospermia.

Pregnancy Category C

Comprehensive animal reproductive studies have not been conducted with insoluble Prussian blue. Since insoluble Prussian blue is not absorbed from the gastrointestinal tract, effects on the fetus are not expected. In one patient that became pregnant 3 years and 8 months after being treated with insoluble Prussian blue for internal contamination with ¹³⁷Cs (8 mCi), complications or birth defects were not identified in the literature report.

Cesium-137 is known to cross the human placenta. One patient, in Goiânia, was contaminated with 0.005 mCi ¹³⁷Cs during her 4^th month of pregnancy. She was not treated with insoluble Prussian blue. At birth the concentration of ¹³⁷Cs was the same in the mother and the infant. Thallium crosses the human placenta. Reported fetal effects in the reviewed literature include fetal death, failure to thrive, alopecia, or in some instances outwardly normal development. The risk of toxicity from untreated radioactive cesium or thallium exposure is expected to be greater than the reproductive toxicity risk of insoluble Prussian blue.

Nursing Mothers

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

Pediatric Use

The safety and efficacy of insoluble Prussian blue and its dosing for the pediatric population was extrapolated from adult data and supported by pediatric patients who were internally contaminated with ¹³⁷Cs and treated with insoluble Prussian blue in the Goiânia accident.

Overall, 27 pediatric patients received insoluble Prussian blue in the range of 3 - 10 grams per day in divided doses. Insoluble Prussian blue 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 TID and in pediatric patients treated with 1 gram TID. (See CLINICAL PHARMACOLOGY, Clinical Trials, Table 2.) By body weight, the dose ranged from 0.32 gram/kg in the 12-year old patient (10 gram Prussian blue daily dose, 31 kg weight) to 0.21 gram/kg in the 4-year old patient (3 gram Prussian blue daily dose, 14 kg weight).

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

There are variations in the developmental maturity of the biliary system and gastrointestinal tract of neonates and infants (0-2 years). The dose-related adverse effects of insoluble Prussian blue on an immature gastrointestinal tract are not known. Dosing in infants and neonates has not been established.

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