Prussian Blue Insoluble Capsules

Description

11 DESCRIPTION Radiogardase (prussian blue insoluble) is a decorporation agent for oral use. Radiogardase capsules contain insoluble ferric hexacyanoferrate(II), with an empirical formula of Fe 4 [Fe(CN) 6 ] 3 and a molecular weight of 859.3 Daltons. It is supplied as 0.5 gram of blue powder in gelatin capsules with 0 – 38 mg of microcrystalline cellulose. The dark blue capsule is imprinted with the light blue inscription: PB. The powder may vary from uniformly fine, dark granules to coarse light and dark-colored granules. The structural formula for prussian blue insoluble is shown below. The crystal structure of prussian blue insoluble is a cubic lattice with the Fe II and Fe III atoms occupying the corners of the cube and the cyanide groups positioned on the sides. Heyl imprint image Structural formula for Prussian blue insoluble

What Is Prussian Blue Insoluble Capsules Used For?

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 )

Dosage and Administration

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:...

Side Effects (Adverse Reactions)

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 [email protected], Fax +49 30 817 4049 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

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.

Contraindications

4 CONTRAINDICATIONS None None ( 4 )

Pregnancy and Breastfeeding

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.

8.3 Nursing Mothers 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.

Overdosage

10 OVERDOSAGE Based on reported adverse reactions and mechanism of action, possible overdosage symptoms may include constipation, obstruction, or severe decrease in electrolytes. Gastric distress was reported in 3 patients treated with 20 gram/day of Radiogardase (approximately 2.2 times the maximum recommended dosage). In these patients, the dose was reduced to 10 gram/day for continued treatment.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Radiogardase is supplied as gelatin capsules containing 0.5 grams of prussian blue insoluble for oral administration. The dark blue capsule is imprinted with the light blue inscription: PB. It is packaged in white plastic containers with a child-resistant tamper-evident closure. Each container contains 36 capsules. NDC: 58060-002-02 Storage Store at 20 °C to 25 °C (68 °F to 77 °F), excursions permitted between 15 °C and 30°C (between 59 °F and 86 °F). Brief exposure to temperatures up to 40 °C (104 °F) may be tolerated, provided the mean kinetic temperature does not exceed 25 °C (77 °F); however, minimize such exposure. [see USP Controlled Room Temperature] Heyl imprint image