"The cystic fibrosis (CF) drug Orkambi (Vertex Pharmaceuticals) has received a green light from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).
Orkambi is a fixed-dose oral combination "...
Ca-DTPA (pentetate calcium trisodium inj) 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 (pentetate calcium trisodium inj) is recommended. After the initial single dose of Ca-DTPA (pentetate calcium trisodium inj) , 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 (pentetate calcium trisodium inj) but mineral supplements containing zinc should be given concomitantly, as appropriate.
Ca-DTPA (pentetate calcium trisodium inj) 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)
Serum electrolytes and essential metals should be closely monitored during Ca-DTPA (pentetate calcium trisodium inj) treatment. Mineral or vitamin plus mineral supplements that contain zinc should be given as appropriate. (See WARNINGS)
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies with Ca-DTPA (pentetate calcium trisodium inj) to evaluate carcinogenesis, mutagenesis, and impairment of fertility have not been performed. Data for Ca-DTPA (pentetate calcium trisodium inj) 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 (pentetate calcium trisodium inj) exposure on fetal development. Ca-DTPA (pentetate calcium trisodium inj) 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 (pentetate calcium trisodium inj) . Based on its mechanism of action, the likelihood that a single dose or multiple doses of Ca-DTPA (pentetate calcium trisodium inj) is teratogenic in humans cannot be ruled out. In mice, Ca-DTPA (pentetate calcium trisodium inj) has been shown to be teratogenic and embryocidal following five daily injections of 720-2880 Ámol Ca-DTPA (pentetate calcium trisodium inj) /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 Ámol Ca-DTPA (pentetate calcium trisodium inj) /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 Ámol Ca-DTPA (pentetate calcium trisodium inj) /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 (pentetate calcium trisodium inj) 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 (pentetate calcium trisodium inj) toxicity. Also, because Ca-DTPA (pentetate calcium trisodium inj) 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 (pentetate calcium trisodium inj) with vitamin or mineral supplements that contain zinc as the initial treatment.
Studies to determine if Ca-DTPA (pentetate calcium trisodium inj) 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)
The safety and effectiveness of Ca-DTPA (pentetate calcium trisodium inj) 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.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/7/2009
Additional Ca-DTPA Information
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