Pentetate Zinc Trisodium

Description

11 DESCRIPTION Pentetate zinc trisodium injection contains the sodium salt of zinc diethylenetriaminepentaacetate. Pentetate zinc trisodium is also known as trisodium zinc diethylenetriaminepentaacetate and is commonly referred to as Zn-DTPA. It has a molecular formula of Na 3 ZnC 14 H 18 N 3 O 10 and a molecular weight of 522.7 Daltons. It is represented by the following structural formula: Zn-DTPA is supplied as a clear, colorless, hyperosmolar (1260 mOsmol/kg) solution in a colorless ampoule containing 5 mL. The ampoule contents are sterile, non-pyrogenic and suitable for intravenous administration. Each mL of solution contains the equivalent of 200 mg pentetate zinc trisodium (obtained from 150.51 mg pentetic acid, 31.14 mg zinc oxide and NaOH) and water for injection, USP. The pH of the solution is adjusted with NaOH and is between 6.5-7.5. Chemical Structure

What Is Pentetate Zinc Trisodium Used For?

1 INDICATIONS AND USAGE Zn-DTPA is indicated for treatment of individuals with known or suspected internal contamination with plutonium, americium, or curium to increase the rates of elimination. Pentetate zinc trisodium injection is a radiomitigation chelator indicated for treatment of individuals with known or suspected internal contamination with plutonium, americium, or curium to increase the rates of elimination. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Chelation treatment is most effective if administered within the first 24 hours. Administer Ca-DTPA, if available, as the initial dose. ( 2.1 , 2.2 ) If Ca-DTPA is not available during the first 24 hours, in adults and adolescents, administer intravenously a single 1.0 gram Zn-DTPA initial dose. ( 2.1 ) in children less than 12 years of age, administer intravenously a single 14 mg/kg Zn-DTPA initial dose, not to exceed 1.0 gram. ( 2.1 ) After the first 24 hours, continue chelation therapy with Zn-DTPA: in adults and adolescents, administer intravenously 1.0 gram Zn-DTPA once daily. ( 2.1 ) in children less than 12 years of age, administer intravenously 14 mg/kg Zn-DTPA once daily, not to exceed 1.0 gram daily. ( 2.1 ) See Full Prescribing Information for dose ( 2.1 ) and nebulized chelation therapy. ( 2.3 ) 2.1 Dose Administer Ca-DTPA as the initial dose during the first 24 hours after internal contamination. Ca-DTPA is more effective than Zn-DTPA during this time period (see Ca-DTPA labeling). If Ca-DTPA is not available, use Zn-DTPA as initial therapy. On the next day, if additional chelation therapy is indicated, begin daily treatment with Zn-DTPA. If Zn-DTPA is not available, chelation therapy may continue with Ca-DTPA and concomitant mineral supplements containing zinc should be given (see Ca-DTPA labeling). Do not administer more than one dose per 24 hour period. If Ca-DTPA is not available during the first 24 hours: in adults and adolescents, administer intravenously a single 1.0 gram initial dose of Zn-DTPA. in children less than 12 years of age, administer intravenously a single 14 mg/kg initial dose of Zn-DTPA, not to exceed 1.0 gram. After the first 24 hours, continue chelation therapy with Zn-DTPA: in adults and adolescents, administer intravenously 1.0 gram Zn-DTPA once daily. in children less than 12 years of age, administer intravenously 14 mg/kg Zn-DTPA once daily, not to exceed 1.0 gram daily. Renally Impaired Patients No dose adjustment is needed. However, renal impairment may reduce the rate at which chelators remove radiocontaminants from the body. In heavily contaminated patients with renal impairment, dialysis may be used to increase the rate of elimination. High efficiency high flux dialysis is recommended. Because dialysis fluid will become radioactive, radiation precautions must be taken to protect personnel, other patients, and the general public. 2.2 General Chelation treatment is most effective if administered within the first 24 hours after internal contamination. Start chelation treatment as soon as possible after suspected or known internal contamination. When treatment cannot be started right away, give chelation treatment as soon as it becomes available. Chelation treatment is still effective even after time has elapsed following internal contamination. The chelating effects of Zn-DTPA are greatest when the radiocontaminants are still circulating or are in interstitial fluids. The...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS In the U.S. Registry, a total of 646 individuals received at least one dose of either Ca-DTPA or Zn-DTPA. Of these, 62 received Zn-DTPA by one or more routes of administration. Forty-eight individuals were dosed by intravenous administration, 18 by inhalation and 8 by other or unknown routes of administration. Of the individuals that received Zn-DTPA, 23/62 (37%) received one dose and 8 (13%) received two doses. The remaining 31 individuals received three or more doses. The largest number of Zn-DTPA doses to a single individual was 574 doses delivered over 3.5 years. Overall, the presence or absence of adverse events was recorded in 310/646 individuals. Of these 19 (6.1%) individuals reported at least one adverse event. The total number of recorded adverse events was 20. Of the 20 adverse events, 1 individual treated with Zn-DTPA reported headache, lightheadedness, and pelvic pain. Two individuals experienced cough and/or wheezing with nebulized Ca-DTPA therapy however there was no report of such events with nebulized Zn-DTPA. There is limited experience with Zn-DTPA. Nebulized chelation therapy may be associated with exacerbation of asthma. Headache, light headedness, and pelvic pain have been reported. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact the hameln Pharmacovigilance Department at +44 (0) 7706 210 133 or [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

7 DRUG INTERACTIONS Adequate and well-controlled drug-drug interaction studies in humans were not identified in the literature. When an individual is contaminated with multiple radiocontaminants, or when the radiocontaminants are unknown, additional therapies may be needed (e.g., Prussian blue, potassium iodide). Adequate and well-controlled drug-drug interaction studies in humans were not identified in the literature. ( 7 )

Contraindications

4 CONTRAINDICATIONS None. None ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Category B Risk Summary There are no adequate and well-controlled studies of Zn-DTPA use in pregnant women. Chelation treatment of pregnant women should begin and continue with Zn-DTPA. Reproduction studies have been performed in pregnant mice at doses up to 31 times (11.5 mmol/kg) the recommended daily human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Zn-DTPA. There was a slight reduction in the average birth weight. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

8.3 Nursing mothers It is not known whether Zn-DTPA is excreted in human milk. Radiocontaminants are known to be excreted in breast milk. Women with known or suspected internal contamination with radiocontaminants should not breast feed, whether or not they are receiving chelation therapy. Precautions should be taken when discarding breast milk. [See Warnings and Precautions (5.3) ]

Overdosage

10 OVERDOSAGE Overdose with Zn-DTPA has not been reported.

How Supplied

16 HOW SUPPLIED Zn-DTPA is supplied as a sterile solution in 5 mL single-use clear glass ampoules at a concentration of 200 mg/mL for intravenous use. Each ampoule contains the equivalent of 1000 mg of pentetate zinc trisodium. NDC 70651-002-03: 5 mL single-dose ampoules, package of 10 16.2 Storage Store between 15-30°C (59-86°F). 16.3 Handling Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The product may be filtered using a sterile filter if particles are seen subsequent to opening of the ampoule. OPC ampoule: to open, turn so that the point faces upward and break off the neck with a downward movement. Figure