Version May 2024
Internal contamination with plutonium, americium, or curium; internal contamination with californium, cobalt, iridium, thorium, or yttrium (off-label use): Note: Calcium diethylene triamine penta-acetic acid (Ca-DTPA) is the preferred initial agent if used within 24 hours of internal contamination; sequential administration of Ca-DTPA then zinc diethylene triamine penta-acetic acid (Zn-DTPA) is recommended.
IV, inhalation:
Initial: Ca-DTPA: 1 g/day. Note: In pregnant women, Zn-DTPA should be used for the initial dose except in cases of high internal contamination.
Maintenance: Zn-DTPA: 1 g/day; length of therapy depends on patient response and degree of contamination. Note: An equivalent dose of Ca-DTPA should be used for maintenance therapy only if Zn-DTPA is not available.
No dosage adjustment necessary; however, dialysis may be used to increase the rate of elimination after the initial dose. If calcium diethylene triamine penta-acetic acid (Ca-DTPA) is not available, substitute zinc diethylene triamine penta-acetic acid (Zn-DTPA) as initial therapy.
Refer to adult dosing.
(For additional information see "Diethylene triamine penta-acetic acid: Pediatric drug information")
Internal contamination with plutonium, americium, curium, californium, cobalt, iridium, thorium, or yttrium: Limited data available with californium, cobalt, iridium, thorium, or yttrium internal contamination (Rella 2018; REMM 2021):
Note: Diethylene triamine penta-acetic acid (DTPA) is available as 2 different salts: Calcium diethylene triamine penta-acetic acid (Ca-DTPA) and zinc diethylene triamine penta-acetic acid (Zn-DTPA). Ca-DTPA is the preferred initial agent if used within 24 hours of internal contamination as it is more effective in the first 24 hours; after 24 hours the salts are equally effective; sequential administration of Ca-DTPA then Zn-DTPA is recommended as it has a lower risk of depleting essential minerals (eg, zinc, manganese, magnesium). Dosing below has both Ca-DTPA and Zn-DTPA recommendations; although not preferred, salts may be substituted for each other on an equivalent mg:mg basis if one is not available; if done, monitor electrolytes closely (eg, zinc, manganese, magnesium) (AAP [Shenoi 2020]; REMM 2021; manufacturer's labeling).
Children <12 years:
Initial (day 1): Ca-DTPA: IV: 14 mg/kg once; maximum dose: 1,000 mg/dose (AAP [Shenoi 2020]; Rella 2018; REMM 2021).
Maintenance (day 2): Zn-DTPA: IV: 14 mg/kg/day once daily; maximum daily dose: 1,000 mg/day; begin next day after the first dose administered; length of therapy depends on patient response and degree of contamination (AAP [Shenoi 2020]; Rella 2018; REMM 2021).
Children ≥12 years and Adolescents:
Initial (day 1): Ca-DTPA: IV: 1,000 mg once (AAP [Shenoi 2020]; Rella 2018; REMM 2021).
Maintenance (day 2): Zn-DTPA: IV: 1,000 mg once daily; begin next day after the first dose administered; length of therapy depends on patient response and degree of contamination (AAP [Shenoi 2020]; Rella 2018; REMM 2021).
No dosage adjustment necessary; however, dialysis may be used to increase the rate of elimination after the initial dose.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Chest pain
Central nervous system: Chills, dizziness, headache, metallic taste
Dermatologic: Dermatitis, pruritus
Gastrointestinal: Diarrhea, nausea, vomiting
Genitourinary: Pelvic pain
Hypersensitivity: Hypersensitivity reaction
Local: Injection site reaction
Neuromuscular & skeletal: Muscle cramps
Respiratory: Cough (nebulization in patients with asthma), wheezing (nebulization in patients with asthma)
Miscellaneous: Fever
There are no contraindications listed in the manufacturer’s labeling.
Disease-related concerns:
• Asthma: Administer via nebulization with caution in patients with asthma; may result in asthma exacerbations.
• Hemochromatosis: Calcium diethylene triamine penta-acetic acid (Ca-DTPA) should be used with caution in patients with hemochromatosis.
• Neptunium, radioactive iodine, or uranium exposure: Treatment with DTPA is not effective for neptunium, radioactive iodine, or uranium exposure.
• Renal impairment: Radioactive materials chelated to diethylene triamine penta-acetic acid (DTPA) are excreted renally; dialysis may be considered in patients with renal impairment to increase the rate of excretion.
Dosage form specific issues:
• Ca-DTPA: Use is associated with the depletion of endogenous trace metals (zinc, magnesium, manganese). The amount of depletion is dependent upon the length of therapy; vitamin and mineral supplements containing zinc should be provided. The initial treatment dose should be with Ca-DTPA; if additional doses are needed, zinc DTPA (Zn-DTPA) should be used if available due to safety concerns.
• Zn-DTPA: Long-term use may be associated with the depletion of magnesium and manganese; vitamin and mineral supplements should be provided.
Other warnings/precautions:
• Administration: For IV administration; avoid oral administration as this route may increase the absorption of the radionuclides (Rella 2018). In adult patients whose contamination is via inhalation within the last 24 hours only, DTPA may be administered via nebulization.
• Appropriate use: Treatment is most effective if initiated within 24 hours but should be started as soon as available; efficacy decreases with time following exposure as the radiocontaminants become sequestered in liver and bone. When given within the first day after internal contamination, Ca-DTPA is approximately 10 times more effective than Zn-DTPA at chelating plutonium, americium, and curium. After 24 hours have passed, both are equally efficacious (CDC 2006). Patients should maintain adequate hydration and urinate frequently to minimize radiation exposure directly to the bladder. Appropriate safety measures should be taken to minimize contamination of others. DTPA is not recommended or approved for treating patients contaminated with uranium or neptunium (Rella 2018).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Combination:
Generic: 200 mg/mL (5 mL)
Solution, Combination [preservative free]:
Generic: 200 mg/mL (5 mL)
Yes
Solution (Pentetate Calcium Trisodium Combination)
200 mg/mL (per mL): $45.36
Solution (Pentetate Zinc Trisodium Combination)
200 mg/mL (per mL): $45.36
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.
Dose should be administered once daily.
Infusion: Administer over 30 minutes.
IV push: Administer over 3-4 minutes.
Nebulization: Patients should be instructed not to swallow any expectorant.
Parenteral: Calcium diethylene triamine penta-acetic acid (Ca-DTPA), zinc diethylene triamine penta-acetic acid (Zn-DTPA):
IV infusion: Administer as a diluted solution over 30 minutes.
IV push: Administer undiluted over 3 to 4 minutes.
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during IV administration. NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration of a powder or solution for inhalation or an aerosol treatment; if there is potential for inhalation, respiratory protections is recommended (NIOSH 2016).
Internal contamination with plutonium, americium, or curium: Treatment of known or suspected internal contamination with plutonium, americium, or curium
Note: DTPA is not recommended or approved for treating patients contaminated with uranium or neptunium (Rella 2018).
Internal contamination with californium, cobalt, iridium, thorium, or yttrium
None known.
There are no known significant interactions.
Teratogenic effects have been reported with calcium diethylene triamine penta-acetic acid (Ca-DTPA) in animal studies. Multiple doses during pregnancy may increase adverse effects to the fetus due to zinc depletion. Reproduction studies with zinc diethylene triamine penta-acetic acid (Zn-DTPA) did not show teratogenic effects in animals; there are no well-controlled studies in pregnant women. Except in cases of high internal contamination, treatment should be initiated and maintained with Zn-DTPA during pregnancy.
Radiocontaminants such as plutonium, americium, or curium can be found in breast milk; excretion of calcium diethylene triamine penta-acetic acid (Ca-DTPA) or zinc diethylene triamine penta-acetic acid (Zn-DTPA) is unknown. Women suspected of internal contamination, regardless of treatment, should not breast feed and precautions should be taken when discarding breast milk.
Fluids should be consumed liberally to promote dilution and excretion of radioactive chelate and minimize radiation exposure to bladder. Supplemental zinc or other vitamins and minerals may be needed.
CBC with differential, BUN, urinalysis, blood and urine radioassays (baseline and throughout therapy); blood, urine, and fecal radioactivity (weekly); serum essential metals (eg, magnesium, manganese, zinc)
Calcium diethylene triamine penta-acetic acid (Ca-DTPA) and zinc diethylene triamine penta-acetic acid (Zn-DTPA) form chelates with some metal ions by exchanging calcium or zinc for a metal of greater binding capacity. The radioactive chelates are then excreted in the urine. Treatment is most effective when radiocontaminants are in circulation or interstitial fluids. Radiocontaminants eventually sequester in liver and bone; therefore, the efficacy of treatment decreases with time after the exposure.
Absorption:
Calcium diethylene triamine penta-acetic acid (Ca-DTPA): Oral: Poor (~5%); Inhalation: 20%
Zinc diethylene triamine penta-acetic acid (Zn-DTPA): Oral: Poor (~5%)
Distribution: Ca-DTPA, Zn-DTPA: Distributed throughout extracellular fluid; not found to accumulate in organs
Metabolism: Ca-DTPA, Zn-DTPA: Minimal
Half-life elimination: Ca-DTPA, Zn-DTPA: May be increased by renal impairment
Excretion: Ca-DTPA, Zn-DTPA: Urine; Rate of excretion may be decreased by renal impairment Ca-DTPA provides a 10-fold higher rate of radioactivity elimination than Zn-DTPA within the first 24 hours; after 24 hours rate of radioactivity elimination is comparable.
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