WARNINGS
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, Pharmacodynamics, Adverse Metabolic Effects). Only a single initial dose of Ca-DTPA is recommended. After the initial single dose of Ca-DTPA, if additional chelation therapy is indicated, it is recommended that therapy be continued with Zn-DTPA. (See Zn-DTPA labeling) If Zn-DTPA is not available, chelation therapy may continue with Ca-DTPA but mineral supplements containing zinc should be given concomitantly, as appropriate.
Ca-DTPA should be used with caution in individuals with severe hemochromatosis. Deaths have been reported in patients with severe hemochromatosis that received up to 4 times the recommended daily dose, for more than 1 day, by IM injection. Causal association with these events and drug has not been established. (See OVERDOSE).
Nebulized chelation therapy may be associated with exacerbation of asthma. Caution should be exercised when administering Ca-DTPA by the inhalation route. (See ADVERSE REACTIONS)
PRECAUTIONS
Information for Patients
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. Appropriate safety measures should be taken to minimize contamination of others. When possible, a toilet should be used instead of a urinal, and it should be flushed several times after each use. Spilled urine or feces should be cleaned up completely and patients should wash their hands thoroughly. If blood or urine comes in contact with clothing or linens, they should be washed separately. Patients should drink plenty of fluids and void frequently. If patients are coughing, any expectorant should be disposed of carefully. Swallowing the expectorant should be avoided if possible. Parents and child-care givers should take extra precaution in handling the urine, feces, and expectorants of children to avoid any additional exposure to either the care-giver or to the child. Nursing mothers should take extra precaution in disposing of breast milk. (See PRECAUTIONS, Nursing Mothers)
Laboratory Tests
Serum electrolytes and essential metals should be closely monitored during Ca-DTPA treatment. Mineral or vitamin plus mineral supplements that contain zinc should be given as appropriate. (See WARNINGS)
Drug-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).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies with Ca-DTPA to evaluate carcinogenesis, mutagenesis, and impairment of fertility have not been performed. Data for Ca-DTPA effects on spermatogenesis are not available.
Teratogenic Effects
Pregnancy Category C
There are no human pregnancy outcome data from which to assess the risk of Ca-DTPA exposure on fetal development. Ca-DTPA is believed to be teratogenic based on animal data and because chelation therapy results in the depletion of body stores of zinc which is known to affect DNA and RNA synthesis in humans. There are no animal or human data evaluating the teratogenic effect of the administration of a single dose of Ca-DTPA. Based on its mechanism of action, the likelihood that a single dose or multiple doses of Ca-DTPA is teratogenic in humans cannot be ruled out. In mice, Ca-DTPA has been shown to be teratogenic and embryocidal following five daily injections of 720-2880 µmol Ca-DTPA/kg [2- 8 times the recommended daily human dose of 1 gram based on body surface area (BSA) adjusted dose] given during any period of gestation. The frequency of gross malformations (e.g., exencephaly, spina bifida, and cleft palate) increased with dose, with higher susceptibility in early and mid gestation. Five daily doses of 360 µmol Ca-DTPA/kg in mice, approximately equivalent to the recommended daily human dose (based on BSA) produced no harmful effects. Studies of 2 pregnant dogs given daily injections of 30 µmol Ca-DTPA/kg (approximately half the recommended daily human dose based on BSA) from implantation until parturition showed severe teratogenic effects (especially brain damage).
Multiple doses of Ca-DTPA could result in an increased risk for adverse reproductive outcomes and thus are not recommended during pregnancy. Therefore, treatment of pregnant women should begin and continue with Zn-DTPA, if available, except in cases of high internal radioactive contamination. In these cases, the risk of immediate and delayed radiation-induced toxicity to both the mother and the fetus should be considered in comparison to the risk of Ca-DTPA toxicity. Also, because Ca-DTPA is more effective than Zn-DTPA in the first 24 hours after internal contamination, it may be appropriate to use a single dose of Ca-DTPA with vitamin or mineral supplements that contain zinc as the initial treatment.
Nursing Mothers
Studies to determine if Ca-DTPA is excreted in breast milk have not been conducted. 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 PRECAUTIONS, Information for Patients)
Pediatric Use
The safety and effectiveness of Ca-DTPA was established in the adult population and efficacy was extrapolated to the pediatric population for the intravenous route based on the comparability of pathophysiologic mechanisms. The dose is based on body size adjustment for an intravenous drug that is renally cleared. The safety and effectiveness of the nebulized route of administration has not been established in the pediatric population.
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