RADIOGARDASE(Heyl Chem.-pharm. Fabrik GmbH & Co. KG)(五)
f FertilityStudies with Prussian blue insoluble to eva luate 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 137 Cs, 2 – 8 years later had either oligospermia or azospermia.
Pregnancy Category CComprehensive animal reproductive studies have not been conducted with Prussian blue insoluble. Since Prussian blue insoluble 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 Prussian blue insoluble for internal contamination with 137 Cs (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 137 Cs during her 4th month of pregnancy. She was not treated with Prussian blue insoluble. At birth the concentration of 137 Cs 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 Prussian blue insoluble.
Nursing MothersStudies to determine if Prussian blue insoluble is excreted in human milk have not been conducted. Since Prussian blue insoluble 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 UseThe safety and efficacy of Prussian blue insoluble and its dosing for the pediatric population was extrapolated from adult data and supported by pediatric patients who were internally contaminated with 137 Cs and treated with Prussian blue insoluble in the Goiânia accident.
Overall, 27 pediatric patients received Prussian blue insoluble in the range of 3 – 10 grams per day in divided doses. Prussian blue insoluble treatment reduced the whole body effective half-life of 137 Cs 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 Prussian blue insoluble on an immature gastrointestinal tract are not known. Dosing in infants and neonates has not been established.
Adverse Reactions to Radiogardase
Deaths or serious or severe adverse events attributed to Prussian blue insoluble have not been reported. Constipation was reported in 10/42 (24%) patients in the Goiânia accident treated with Pruss |
