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Ferric hexacyanoferrate: Pediatric drug information

Ferric hexacyanoferrate: Pediatric drug information
(For additional information see "Ferric hexacyanoferrate: Drug information" and see "Ferric hexacyanoferrate: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Radiogardase
Therapeutic Category
  • Antidote
Dosing: Pediatric
Internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium

Internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium:

Note: Treatment should begin as soon as possible following exposure (Rump 2018); however, treatment is also effective if therapy is delayed (Sun 2012). Treatment typically continues for ≥30 days (Kazzi 2015). Consult clinical toxicologist.

Infants and Children <2 years: Very limited data available; expert opinion: Oral: 150 to 250 mg/kg/day in 2 to 4 divided doses (Hoffman 2019).

Children 2 to 12 years: Oral: 1,000 mg 3 times daily (AAP [Shenoi 2020]; Hoffman 2019; REMM 2021; manufacturer's labeling).

Adolescents:

Cesium exposure: Oral: 1,000 to 3,000 mg 3 times daily and continued for ≥30 days (as needed based on quantitative and radiologic evaluation of cesium elimination) (REMM 2021); in adults, doses up to 10 to 12 g/day have been required in significant contamination events (AAP [Shenoi 2020]; Hoffman 2019; IAEA 1988; REMM 2021).

Thallium exposure: Oral: 3,000 mg 3 times daily or 150 to 250 mg/kg/day in 2 to 4 divided doses and continued until total urinary thallium concentrations are <0.5 mg/day, or longer if patient is still symptomatic (AAP [Shenoi 2020]; Hoffman 2019; REMM 2021; manufacturer's labeling).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, ferric hexacyanoferrate is not systemically absorbed.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, effectiveness may be decreased due to decreased biliary excretion of cesium and thallium.

Dosing: Adult

(For additional information see "Ferric hexacyanoferrate: Drug information")

Internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium

Internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium: Note: Treatment should begin as soon as possible following exposure (Rump 2018); however, treatment is also effective if therapy is delayed (Sun 2012). Treatment typically continues for ≥30 days (Kazzi 2015).

Cesium exposure: Oral: 1 to 3 g 3 times daily and continued for ≥30 days (as needed based on quantitative and radiologic evaluation of cesium elimination); doses up to 10 to 12 g per day have been required in significantly contaminated adults (Hoffman 2018; IAEA 1988; REMM 2022).

Thallium exposure: Oral: 3 g 3 times daily or 150 to 250 mg/kg/day in 2 to 4 divided doses and continued until total urinary thallium concentrations are <0.5 mg/day (Hoffman 2018).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. Oral: 3 g 3 times daily.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, ferric hexacyanoferrate is not systemically absorbed.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, effectiveness may be decreased due to decreased biliary excretion of cesium and thallium.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not always defined.

Gastrointestinal: Constipation (24%), fecal discoloration (blue), gastric distress

Endocrine & metabolic: Hypokalemia (7%)

Contraindications

There are no contraindications in the manufacturer’s labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Discoloration: Feces will turn blue; if capsule contents are opened and eaten with food, oral mucosa and detention may also be colored blue.

Disease-related concerns:

• Cardiac arrhythmias: Use with caution in patients with preexisting cardiac arrhythmias; may cause electrolyte imbalances.

• Electrolyte imbalances: May bind to electrolytes in the GI tract. Use with caution in patients with electrolyte imbalances.

• Gastric immotility: Use with caution in patients with decreased gastric motility; constipation should be avoided to prevent increased radiation absorption from the GI tract. Increase dietary fiber or take with fiber laxative to decrease constipation. The cesium- or thallium-bound ferric hexacyanoferrate insoluble complex must move through the GI tract in a timely manner so that the associated radiation is not absorbed.

Other warnings/precautions:

• Radiation exposure: Patients should be instructed to minimize radiation exposure to others or re-exposure to self.

• Radiation toxicity: Appropriate use: Ferric hexacyanoferrate increases the rate of elimination of thallium and cesium; it does not treat complications of radiation exposure. Supportive treatment for radiation toxicity should be given concomitantly. Additional decontamination and/or treatment may be needed if exposure to other radioactive isotopes is known or suspected. Radiation elements that do not undergo enterohepatic recirculation are not removed by ferric hexacyanoferrate.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Radiogardase: 0.5 g

Generic Equivalent Available: US

No

Pricing: US

Capsules (Radiogardase Oral)

0.5 g (per each): $3.42

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Additional Information

Excretion data for Cesium-137 without ferric hexacyanoferrate: Urine (∼80%); feces (∼20%). Excretion data for thallium without ferric hexacyanoferrate: Fecal-to-urine excretion ratio: 2:1. If ferric hexacyanoferrate is used, detailed treatment information should be reported to the manufacturer; contact the manufacturer or the complete prescribing information for data collection forms. In case of thallium intoxication, elimination of thallium may also be increased by: Induced emesis followed by intubation and lavage; forced diuresis if urinary excretion is <1 mg per 24 hours; charcoal hemoperfusion during the first 48 hours following ingestion; hemodialysis.

Administration: Pediatric

Oral: Administer with food to stimulate excretion of cesium or thallium. Capsules may be opened and mixed with bland food or liquid. In critically ill patients who cannot swallow, capsules may be opened and administered by orogastric or nasogastric tube (Hoffman 2019). Increase dietary fiber or take with fiber laxative to decrease constipation.

Administration: Adult

Oral: In critically ill patients who cannot swallow, capsules may be opened and administered by orogastric or nasogastric tube. Also, the capsules may be opened and mixed with bland food or liquid. Administer with food to stimulate excretion of cesium or thallium. Increase dietary fiber or take with fiber laxative to decrease constipation (Hoffman 2018).

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean temperature does not exceed 25°C (77°F); however, minimize such exposure.

Note: Although ferric hexacyanoferrate is comprised of 35% to 40% cyanide, long-term stability studies have demonstrated minimal risk of significant cyanide liberation after at least 10 years of storage in optimal conditions (Mohammad 2015).

Pharmacy supply of emergency antidotes: Guidelines suggest that at least 12.5 to 25 g of ferric hexacyanoferrate be stocked, especially in locations near industrial sites. Suggested amount is stated to be a sufficient quantity to treat 1 patient weighing 100 kg for an initial 8- to 24-hour period (Dart 2018); actual amount to be stocked should take into account site-specific and population-specific needs.

Use

Treatment of known or suspected internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium to increase their rates of elimination (FDA approved in pediatric patients [age not specified] and adults).

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Food Interactions

Food may increase effectiveness by stimulating bile secretion and thereby increasing the amount of cesium or thallium available to bind with ferric hexacyanoferrate. Management: Administer with food to stimulate excretion of cesium or thallium.

Dietary Considerations

Take with food. A high-fiber diet or fiber laxative is recommended to avoid constipation.

Pregnancy Considerations

Animal reproduction studies have not been conducted. Ferric hexacyanoferrate is not absorbed from the gastrointestinal tract and is not expected to affect the fetus. Cesium-137 crosses the placenta; in one case, reported levels were equal in the mother and the neonate. Thallium also crosses the placenta; fetal death and failure to thrive have been reported. Toxicity from exposure to thallium or radioactive cesium is expected to be greater than the risk of toxicity to ferric hexacyanoferrate. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003).

Monitoring Parameters

Bowel movements; CBC and electrolytes weekly.

Baseline cesium and/or thallium exposure (whole body counting and/or bioassay, feces or urine sample); urine and fecal cesium and/or thallium weekly during therapy; residual whole body radioactivity after 30 days of treatment.

Mechanism of Action

The ferric hexacyanoferrate lattice preferentially binds cesium and thallium isotopes in the gastrointestinal tract following their ingestion or excretion in the bile (thereby, blocking reabsorption). The resulting complex is eliminated in the feces reducing the absorption of thallium or the radioactive residence time of cesium (Kazzi 2015).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Ferric hexacyanoferrate: Oral: None

Half-life elimination:

Cesium-137: Effective: Adults: 80 days, decreased by 69% with ferric hexacyanoferrate; adolescents: 62 days, decreased by 46% with ferric hexacyanoferrate; children: 42 days, decreased by 43% with ferric hexacyanoferrate

Nonradioactive thallium: Biological: 8 days; with ferric hexacyanoferrate: 3 days

Excretion: Ferric hexacyanoferrate: Feces (99%, unchanged) (Radiogardase, 2008)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: May be less effective because of decreased biliary excretion of cesium and thallium.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CZ) Czech Republic: Radiogardase cs;
  • (DE) Germany: Radiogardase cs;
  • (FR) France: Radiogardase;
  • (JP) Japan: Radiogardase;
  • (NO) Norway: Radiogardase cs
  1. Adams TG, Casagrande R. Modeling the optimum Prussian blue treatment for acute radiation syndrome following 137Cs ingestion. Health Phys. 2019;116(1):88-95. doi: 10.1097/HP.0000000000000966. [PubMed 30489370]
  2. Bailey B. Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women? Birth Defects Res A Clin Mol Teratol. 2003;67(2):133-140. [PubMed 12769509]
  3. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.e1. doi:10.1016/j.annemergmed.2017.05.021 [PubMed 28669553]
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  5. Hoffman RS. Antidotes in depth: Prussian blue. In: Goldfrank LR, ed. Goldfrank’s Toxicologic Emergencies. 11th ed. McGraw-Hill; 2019:1283-1287.
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  9. Radiogardase (Prussian blue insoluble) [prescribing information]. Berlin, Germany: HEYL Chemisch-pharmazeutische Fabrik GmbH & Co; August 2014.
  10. Radiogardase (Prussian blue insoluble) [prescribing information]. Berlin, Germany: HEYL Chemisch-pharmazeutische Fabrik GmbH & Co; March 2008.
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  14. US Department of Health and Human Services, Radiation Emergency Medical Management (REMM). Radiation countermeasures for treatment of internal contamination. https://remm.hhs.gov/isotopestable.pdf. Accessed January 18, 2022.
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