FDA label 1b3410c5-6dba-401e-8a6e-4b483e65dc48

WARNING: ASTHMA EXACERBATION WITH NEBULIZATION and DEPLETION OF TRACE METALS DURING THERAPY Nebulized Ca-DTPA may be associated with asthma exacerbation. ( 5.1 ) Ca-DTPA is associated with depletion of trace metals such as zinc. The magnitude of depletion increases with split daily dosing, with increasing dose and with increased treatment duration. Only a single dose of Ca-DTPA is recommended. Use Zn-DTPA if additional chelation therapy is indicated. Monitor serum zinc levels, serum creatinine, BUN, electrolytes, urinalysis and blood cell counts during Ca-DTPA or Zn-DTPA therapy. ( 2.4 , 5.2 ) WARNING: ASTHMA EXACERBATION WITH NEBULIZATION and DEPLETION OF TRACE METALS DURING THERAPY See full prescribing information for complete boxed warning. Nebulized Ca-DTPA may be associated with asthma exacerbation. ( 5.1 ) Ca-DTPA is associated with depletion of trace metals such as zinc. The magnitude of depletion increases with split daily dosing, with increasing dose and with increased treatment duration. Only a single dose of Ca-DTPA is recommended. Use Zn-DTPA if additional chelation therapy is indicated. Monitor serum zinc levels, serum creatinine, BUN, electrolytes, urinalysis and blood cell counts during Ca-DTPA or Zn-DTPA therapy. ( 2.4 , 5.2 )

5 WARNINGS AND PRECAUTIONS Nebulized Ca-DTPA may be associated with exacerbation of asthma. Monitor patients for signs and symptoms of asthma exacerbation when administering Ca-DTPA by the inhalation route. ( 5.1 ) Ca-DTPA is associated with depletion of endogenous trace metals (e.g., zinc, magnesium, manganese). ( 5.2 ) Take appropriate safety measures to minimize contamination of care-takers by contaminated body fluids. ( 5.3 ) Use Ca-DTPA with caution in individuals with severe hemochromatosis. ( 5.4 ) 5.1 Asthma Exacerbation Nebulized Ca-DTPA is associated with asthma exacerbation. Monitor patients for signs and symptoms of asthma exacerbation when administering Ca-DTPA by the inhalation route. [See Adverse Reactions (6) ] 5.2 Depletion of Body Trace Mineral Stores Ca-DTPA is associated with depletion of endogenous trace metals (e.g., zinc, magnesium, manganese). The magnitude of depletion increases with split daily dosing, with increasing dose, and with increased treatment duration. [See Clinical Pharmacology (12.3) ] Only a single initial dose of Ca-DTPA is recommended. Use Zn-DTPA if additional chelation therapy is indicated (See Zn-DTPA labeling). If Zn-DTPA is not available, chelation therapy may continue with Ca-DTPA but give mineral supplements containing zinc concomitantly, as appropriate. Monitor serum zinc levels, electrolytes and blood cell counts during Ca-DTPA or Zn-DTPA therapy. Give mineral or vitamin plus mineral supplements that contain zinc as appropriate. [See Dosage and Administration (2.4) ] 5.3 Risks to Care-takers Radioactive metals are known to be excreted in the urine, feces, and breast milk. In individuals with recent internal contamination with plutonium, americium, or curium, Ca-DTPA treatment increases excretion of radioactivity in the urine. Take appropriate safety measures to minimize contamination of others. [See Patient Counseling Information (17) ] 5.4 Risks for Patients with Hemochromatosis Use of only a single Ca-DTPA dose is particularly important for patients with hemochromatosis. Deaths have been reported in patients with severe hemochromatosis who received Ca-DTPA for more than 1 day, by intramuscular injection. [See Overdosage (10) ]

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, 632 received Ca-DTPA by one or more routes of administration. Three hundred and twenty-six individuals were dosed by inhalation, 293 by intravenous injection, and 60 by other or unknown routes of administration. Of the individuals that received Ca-DTPA, 393/632 (62%) received one dose and 65 (10%) received two doses. The remaining 174 individuals received three or more doses. The largest number of Ca-DTPA doses to a single individual was 338 delivered over 6.5 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, 18 adverse events occurred after treatment with Ca-DTPA. Adverse events included headache, lightheadedness, chest pain, allergic reaction, dermatitis, metallic taste, nausea and diarrhea, and injection site reactions. Cough and/or wheezing were experienced by 2 individuals receiving nebulized Ca-DTPA, one of whom had a history of asthma. In literature reports, prolonged treatment with Ca-DTPA resulted in depletion of zinc, magnesium, manganese and possibly metalloproteinases. [See Warnings and Precautions (5.2) ] There is limited experience with Ca-DTPA. Adverse events included headache, lightheadedness, chest pain, allergic reaction, dermatitis, metallic taste, nausea and diarrhea, and injection site reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact the hameln Pharmacovigilance Department at +44 (0) 7706 210 133 or drugsafety@hameln.co.uk or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.