Radiogardase

Generic Name: Prussian Blue
Class: Other Ion-removing Agents
VA Class: AD900
Chemical Name: Ferric hexacyanoferrate (II)
Molecular Formula: Fe4[Fe(CN)6]3
CAS Number: 14038-43-8

Introduction

A crystal lattice of ferric hexacyanoferrate (II); an ion-exchange medium with high affinity for cesium and thallium, including radioactive isotopes of these metals.1 3

Uses for Radiogardase

Poisoning and Radioactive Exposure

Treatment of known or suspected internal contamination with radioactive cesium and/or radioactive or nonradioactive thallium following accidental exposure and/or intentional exposure from radioactive terrorism or warfare.1 2 3 4 5 6 Reduces the risk of death and major morbidity following exposure to these metals.2 4

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Treatment of radioactive exposures when the nature of the radioactive contamination is unknown.1 2

For severe thallium intoxication, may need to employ additional measures (e.g., induction of emesis followed by gastric intubation and lavage, forced diuresis, charcoal hemoperfusion, hemodialysis) to enhance thallium elimination.1 7

Radiogardase Dosage and Administration

General

  • Initiate therapy as soon as possible after contamination is suspected.1

  • Cesium poisoning: Determine baseline internalized137Cs contamination (by whole-body counting, bioassay, or urine/feces sampling) if possible.1 Measure radioactivity counts in urine and feces weekly to monitor137Cs elimination rate.1 Assess whole-body radioactivity after 30 days of therapy.1

  • Thallium poisoning: Determine baseline internalized thallium contamination (by whole-body counting and/or bioassay) if possible.1 Monitor CBC and serum chemistry and electrolytes weekly during therapy.1

Administration

Oral Administration

Administer orally with food to stimulate excretion of cesium or thallium.1

If patients cannot tolerate swallowing large numbers of capsules, open the capsules and mix the contents with bland food or liquids.1

Use with appropriate measures (i.e., oral fiber-based laxatives and/or a high-fiber diet) to promote regular fecal elimination.1

Can be given with 15% mannitol to prevent constipation.3 7 8

Dosage

Pediatric Patients

Poisoning and Radioactive Exposure
Cesium Poisoning
Oral

Children 2–12 years of age: 1 g 3 times daily.1

Children ≥13 years of age: 3 g 3 times daily.1 Once internal radiation has decreased substantially, reduce dosage to 1 or 2 g 3 times daily (to improve GI tolerance).1

Continue for a minimum of 30 days.1 Duration of therapy based on level of contamination and clinical judgment.1

Thallium Poisoning
Oral

Children 2–12 years of age: 1 g 3 times daily.1

Children ≥13 years of age: 3 g 3 times daily.1

Duration of therapy based on level of contamination and clinical judgment.1

Adults

Poisoning and Radioactive Exposure
Cesium Poisoning
Oral

3 g 3 times daily.1 Once internal radiation has decreased substantially, reduce dosage to 1 or 2 g 3 times daily (to improve GI tolerance).1

Continue for a minimum of 30 days.1 Duration of therapy based on level of contamination and clinical judgment.1

Thallium Poisoning
Oral

3 g 3 times daily.1

Duration of therapy based on level of contamination and clinical judgment.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for Radiogardase

Contraindications

  • No contraindications according to manufacturer.1

Warnings/Precautions

Warnings

Radiation Exposure

Effective only in decreasing radiation exposure; does not treat complications of such exposure.1 Provide supportive treatment for radiation toxicity (e.g., for severe neutropenia and thrombocytopenia) in conjunction with prussian blue therapy.1

In radiologic emergencies, the type of elemental exposure may not be known.1 Prussian blue may not bind to all radioactive elements; therefore, may need to use other radioprotectants (e.g., potassium iodide, edetate calcium disodium, sodium alginate) in addition to prussian blue in patients contaminated with unknown or multiple radioactive elements.1 2

Major Toxicities

GI Effects

Constipation reported frequently; constipation responds to oral administration of fiber (i.e., fiber-based laxatives and/or a high-fiber diet).1 3 4

Decreased GI motility will slow the GI transit time of the prussian blue-metal complex (i.e., prussian blue-137Cs, prussian blue-thallium) and may increase exposure to the metal.1 Caution in individuals with conditions associated with decreased GI motility.1

General Precautions

Hypokalemia

Hypokalemia (serum potassium concentrations of 2.5–2.9 mEq/L) reported.1 3 Closely monitor serum electrolytes.1

Use with caution in individuals with preexisting cardiac arrhythmias or electrolyte imbalances.1

Specific Populations

Pregnancy

Category C.1

Lactation

Prussian blue is unlikely to distribute into breast milk.1

Cesium and thallium are distributed into human breast milk; women contaminated with these metals should not breast-feed.1

Pediatric Use

Safety and efficacy and dosage recommendations in pediatric patients ≥2 years of age extrapolated from adult data and supported by experience in pediatric patients (4–12 years of age).1

Dosing recommendations not established for pediatric patients <2 years of age.1

Hepatic Impairment

Use not contraindicated; however, may be less effective in these patients due to decreased excretion of cesium and/or thallium in the bile.1

Renal Impairment

Use not contraindicated.1

Common Adverse Effects

Constipation,1 3 4 GI distress,1 4 blue discoloration of sweat and tears (long-term administration).7

Interactions for Radiogardase

Orally Administered Drugs and Nutrients

Possible pharmacokinetic interaction (binding of prussian blue to drug and/or essential nutrient).1 Monitor serum concentrations and/or clinical response in patients receiving clinically important drugs.1

Specific Drugs

Drug

Interaction

Comments

Radioprotectants

Pharmacologic interaction unlikely; not expected to affect efficacy of prussian blue in the management of137Cs poisoning1

 

Tetracycline, oral

Possible pharmacokinetic interaction (decreased bioavailability of tetracycline)1

Monitor serum concentrations of and/or clinical response to tetracycline1

Radiogardase Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed through intact GI wall.1 7

Elimination

Elimination Route

Eliminated unchanged in feces.1 Clearance depends on GI transit time.1 7

Stability

Storage

Oral

Capsules

In the dark at 25°C (may be exposed to 15–30°C).1

Actions

  • An ion-exchange medium with high affinity for cesium and thallium, including radioactive isotopes of these metals.1

  • Binds cesium and/or thallium in the GI tract, thus preventing absorption or reabsorption of these metals and increasing the rate of their elimination as insoluble complexes in feces.1

  • Reduces whole-body effective half-life of cesium and mean serum biologic half-life of thallium.1 4

  • May bind other elements (e.g., potassium).1 (See Hypokalemia under Cautions.)

Advice to Patients

  • Importance of taking prussian blue with food; importance of taking appropriate measures (i.e., oral fiber-based laxatives and/or a high-fiber diet) to promote regular fecal elimination.1

  • Importance of instructing patients on safety measures that should be used to minimize radiation exposure to others, including appropriate disposal of urine and feces.1 Clothing contaminated with blood or urine should be washed separately.1

  • Advise patients of possible bluish appearance of their stools.1

  • Advise patients who are unable to swallow capsules that their mouth and teeth might be colored blue if prussian blue capsules are opened and the contents mixed with food or liquid.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Prussian Blue (Insoluble)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

500 mg

Radiogardase

Heyl Chemisch-pharmazeutische

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Heyl Chemisch-pharmazeutische. Radiogardase (insoluble Prussian blue) capsules prescribing information. From the FDA web site (). (Accessed 7 Oct 2003).

2. US Food and Drug Administration. Questions and answers on Prussian Blue. From the FDA web site (). (Accessed 2003 Oct 7.)

3. Thompson DF, Church CO. Prussian blue for treatment of radiocesium poisoning. Pharmacotherapy. 2001; 21:1364-7. [IDIS 472544] [PubMed 11714209]

4. US Food and Drug Administration. Guidance for industry on Prussian blue for treatment of internal contamination with thallium or radioactive cesium; availability. [Docket No. 03D-0023.] Fed Regist. 2003; 68:5645-8.

5. US Food and Drug Administration Center for Drug Evaluation and Research. Guidance for industry: Prussian blue drug products—submitting a new drug application. Rockville, MD: FDA; 2003 Jan.

6. American Academy of Pediatrics. Radiation disasters and children: policy statement. Pediatrics. 2003; 111:1455-66. [PubMed 12777572]

7. Hoffman RS. Thallium toxicity and the role of Prussian blue in therapy. Toxicol Rev. 2003; 22:29-40. [IDIS 511730] [PubMed 14579545]

8. Reviewers’ comments (personal observations).

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