DOCSLIB.ORG

Article a Randomized Multicenter Trial of Paricalcitol Versus Calcitriol For

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Article a Randomized Multicenter Trial of Paricalcitol Versus Calcitriol For CJASN ePress. Published on June 26, 2014 as doi: 10.2215/CJN.10661013 Article A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD Daniel W. Coyne,* Seth Goldberg,* Mark Faber,† Cybele Ghossein,‡ and Stuart M. Sprague§ Abstract Background and objectives Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. *Renal Division, School of Medicine, Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but Washington head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these University, St. Louis, agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and Missouri; †Division of hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia Nephrology and – Hypertension, Henry between calcitriol and paricalcitol, while suppressing PTH 40% 60%. Ford Hospital, Detroit, Michigan; ‡Divison of Design, setting, participants, & measurements Patients with stages 3–4CKD(n=110) with a PTH level .120 pg/ml Nephrology, Feinberg were recruited and randomized to 0.25 mg/d of calcitriol or 1 mg/d of paricalcitol between April 2009 and School of Medicine, July 2011. Subsequent dose adjustments were by protocol to achieve 40%–60% PTH suppression below Northwestern fi . University, Chicago, baseline. The primary endpoint was the rate of con rmed hypercalcemia of 10.5 mg/dl between groups. Illinois; and §Division of nephrology and Results Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH Hypertension, effectively (252% with paricalcitol and 246% with calcitriol; P=0.17), although the paricalcitol group reached a Northshore University Health System, 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; University of Chicago P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hy- Pritzker School of percalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly Medicine, Evanston, different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3–0.4 mg/dl in each Illinois electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups. Correspondence: Dr.DanielW.Coyne, School of Medicine, Conclusions These results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline Washington phosphatase suppression in stages 3–4 CKD, with small effects on serum calcium and phosphorus and a low University in St. Louis, incidence of hypercalcemia. 660 S. Euclid Avenue, Clin J Am Soc Nephrol ccc–ccc Campus Box 8129, St. 9: , 2014. doi: 10.2215/CJN.10661013 Louis, MO 63110. Email: DCoyne@dom. wustl.edu Introduction In addition to activating the vitamin D receptors Secondary hyperparathyroidism (SHPT) is common in (VDRs) in the parathyroid gland, calcitriol also activates patients with CKD, and is characterized by a progressive the VDR in other tissues, including intestine and bone increase in parathyroid hormone (PTH) and growth of (9). Administration of calcitriol or its analogs requires the parathyroid glands (1,2). A major factor in the de- regular monitoring of serum calcium and phosphorus velopment and progression of SHPT is the steady de- levels (9). Induction of hypercalcemia or hyperphospha- cline in serum calcitriol levels, the active form of temia can limit the dose of VDRA administered, thereby vitamin D (1). The incidence and severity of SHPT in- limiting its efficacy for PTH suppression. creases as renal function worsens, with 35% of patients In preclinical studies, at comparable PTH-suppressing with stage 3 CKD and 70% of patients with stage 4 doses, paricalcitol causes a significantly smaller increase CKD carrying this diagnosis (1). in serum calcium and phosphorus levels than calcitriol Exogenous administration of vitamin D receptor (10,11). Crossover trials of these agents in hemodialysis activators (VDRAs), such as calcitriol or the analogs patients have also demonstrated less intestinal calcium paricalcitol, doxercalciferol, and alfacalcidol, suppres- absorption and less stimulation of bone resorption with ses PTH levels but can increase serum calcium and paricalcitol compared with calcitriol (12,13). These dif- phosphorus (3–5). Major renal guidelines recommend ferences are thought to be the result of less activation of use of active vitamin D for SHPT in stages 3–4 CKD, the intestinal and bone VDRs by paricalcitol. Two ran- but comparison of different VDRAs in this population domized trials comparing calcitriol with paricalcitol in has been limited (6–8). hemodialysis patients have shown mixed results, with www.cjasn.org Vol 9 September, 2014 Copyright © 2014 by the American Society of Nephrology 1 2 Clinical Journal of the American Society of Nephrology one trial reporting significantly less hypercalcemia and eleva- random sequence was computer generated and site specific tion of calcium–phosphate product with paricalcitol despite without stratification. Sequentially numbered opaque sealed somewhat superior PTH suppression, whereas a smaller envelopes were provided to each site, with the next available study showed no significant differences between agents (3,4). envelope opened after the patient was confirmed to meet all In three placebo-controlled trials in patients with stages inclusion and exclusion criteria. Patients each had their own 3–4 CKD with SHPT, paricalcitol suppressed PTH by 42% PTH target goal of 40%–60% below their baseline PTH mea- at 6 months and caused hypercalcemia in 2% versus 0% of surement. Dose adjustments were based on laboratory patients who received placebo (14). A small trial of calci- results at each visit (weeks 4, 8, 12, and 18). Albumin-corrected triol using doses of #0.5 mg/d reported that eight of 15 calcium (cCa) was calculated as follows: {serum calcium+[(4– patients with CKD became hypercalcemic at least once serum albumin)30.8]} if albumin was ,4.0 g/dl. The dose during an 8-month treatment period (15). was titrated up at any visit if PTH was suppressed ,40% Given the limited comparative data in patients with CKD from baseline and cCa was ,10.5 mg/dl. Dose increases with these agents, we performed a multicenter, open-label were conducted in the following manner: one capsule alter- randomized trial to compare the incidence of hypercalce- nating with two capsules daily, then two capsules daily, then mia in patients treated with paricalcitol and calcitriol for three capsules daily, and then four capsules daily. Maximum SHPT. The clinical goal was to suppress and maintain PTH possible doses were 4 mg/d paricalcitol or 1 mg/d calcitriol. concentrations at 40%–60% below the mean pretreatment Dosing was reduced one step if the PTH was suppressed by PTH value, and the primary endpoint was the difference in .60% from baseline; if the patient was already on the initial the incidence of hypercalcemia in each arm. step of one capsule daily, the dose was reduced to one cap- sule every other day. If the cCa was $10.5 mg/dl, a confir- matory test was obtained as soon as possible but at least Materials and Methods 1 day later; if hypercalcemia was verified, the dose was re- Study Design and Oversight duced by one step. Consistent with clinical practice, the use of The Paricalcitol and Calcitriol Endpoints study (Clinical- dietary phosphorus restriction or phosphorus binders were Trials.gov registry number NCT00823303) is an open-label, encouraged if hyperphosphatemia (.4.6 mg/dl) developed. active comparator, multicenter, parallel group, phase 4 study Study participation was over a 24-week period with active of paricalcitol versus calcitriol for suppression of PTH in medication, with a 1-week follow-up. stages 3–4 CKD. The trial was conducted at four sites in the United States and was approved by each institutional re- Endpoints view board. The trial design was investigator-initiated and The primary endpoint was the difference in the percentage was funded by Abbott, now AbbVie (Abbott Park, IL). Ab- of patients in each group developing a confirmed hypercal- bott was not involved in the design or conduct of the trial, cemic event ($10.5 mg/dl). The prespecified secondary ob- but was able to review the manuscript before submission. jectives were to evaluate the differences between treatment The four trial sites were Washington University in St. Louis groups in changes in serum calcium, incidence of hyper- (St. Louis, MO), Henry Ford Hospital (Detroit, MI), North- phosphatemia, change in serum phosphorus, change in al- western University (Chicago, IL), and the Northshore Uni- kaline phosphatase, percentage of patients achieving .40% versity Health System (Evanston, IL). PTH suppression, and mean PTH suppression. The primary – Eligible patients had stages 3 4 CKD and known or sus- endpoint was also the primary safety endpoint. Adverse . pected SHPT. Inclusion criteria were aged 18 years, a stable events were also evaluated. dose of phosphate binder (if receiving a binder), eGFR of 15– 2 fi 59 ml/min per 1.73 m using the abbreviated Modi cation Statistical Analyses . of Diet in Renal Disease equation, PTH 120 pg/ml, albumin- The primary predefined analysis was based on an intention- . , corrected calcium 8.5 mg/dl and 10.0 mg/dl, and phos- to-treat analysis, which includes participants who received at , phorus 4.6 mg/dl. Exclusion criteria were history of least one study treatment and had at least one postbaseline . primary hyperparathyroidism, prednisone use for 30 calcium determination. Secondary endpoints were also asses- days within the previous 6 months, administration of bi- sed on an intention-to-treat basis. On the basis of prior pub- sphosphonates or calcitonin within the previous 12 months, lished reports, we estimated a 5% rate of hypercalcemia with recent hospitalization, an expected need for dialysis or paricalcitol and a 30% rate with calcitriol (15,16).
Load more

Recommended publications
  • Vitamin D and Its Analogues Decrease Amyloid- (A) Formation
    International Journal of Molecular Sciences Article Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation Marcus O. W. Grimm 1,2,3,*,† ID , Andrea Thiel 1,† ID , Anna A. Lauer 1 ID , Jakob Winkler 1, Johannes Lehmann 1,4, Liesa Regner 1, Christopher Nelke 1, Daniel Janitschke 1,Céline Benoist 1, Olga Streidenberger 1, Hannah Stötzel 1, Kristina Endres 5, Christian Herr 6 ID , Christoph Beisswenger 6, Heike S. Grimm 1 ID , Robert Bals 6, Frank Lammert 4 and Tobias Hartmann 1,2,3 1 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany; [email protected] (A.T.); [email protected] (A.A.L.); [email protected] (J.W.); [email protected] (J.L.); [email protected] (L.R.); [email protected] (C.N.); [email protected] (D.J.); [email protected] (C.B.); [email protected] (O.S.); [email protected] (H.S.); [email protected] (H.S.G.); [email protected] (T.H.) 2 Neurodegeneration and Neurobiology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany 3 Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany 4 Department of Internal Medicine II–Gastroenterology, Saarland University Hospital, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany; [email protected] 5 Department of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany; [email protected] 6 Department of Internal Medicine V–Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str.
    [Show full text]
  • A Clinical Update on Vitamin D Deficiency and Secondary
    References 1. Mehrotra R, Kermah D, Budoff M, et al. Hypovitaminosis D in chronic 17. Ennis JL, Worcester EM, Coe FL, Sprague SM. Current recommended 32. Thimachai P, Supasyndh O, Chaiprasert A, Satirapoj B. Efficacy of High 38. Kramer H, Berns JS, Choi MJ, et al. 25-Hydroxyvitamin D testing and kidney disease. Clin J Am Soc Nephrol. 2008;3:1144-1151. 25-hydroxyvitamin D targets for chronic kidney disease management vs. Conventional Ergocalciferol Dose for Increasing 25-Hydroxyvitamin supplementation in CKD: an NKF-KDOQI controversies report. Am J may be too low. J Nephrol. 2016;29:63-70. D and Suppressing Parathyroid Hormone Levels in Stage III-IV CKD Kidney Dis. 2014;64:499-509. 2. Hollick MF. Vitamin D: importance in the prevention of cancers, type 1 with Vitamin D Deficiency/Insufficiency: A Randomized Controlled Trial. diabetes, heart disease, and osteoporosis. Am J Clin Nutr 18. OPKO. OPKO diagnostics point-of-care system. Available at: http:// J Med Assoc Thai. 2015;98:643-648. 39. Jetter A, Egli A, Dawson-Hughes B, et al. Pharmacokinetics of oral 2004;79:362-371. www.opko.com/products/point-of-care-diagnostics/. Accessed vitamin D(3) and calcifediol. Bone. 2014;59:14-19. September 2 2015. 33. Kovesdy CP, Lu JL, Malakauskas SM, et al. Paricalcitol versus 3. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors ergocalciferol for secondary hyperparathyroidism in CKD stages 3 and 40. Petkovich M, Melnick J, White J, et al. Modified-release oral calcifediol of vitamin D status and cancer incidence and mortality in men.
    [Show full text]
  • Vitamin D and Anemia: Insights Into an Emerging Association Vin Tangpricha, Emory University Ellen M
    Vitamin D and anemia: insights into an emerging association Vin Tangpricha, Emory University Ellen M. Smith, Emory University Journal Title: Current Opinion in Endocrinology, Diabetes and Obesity Volume: Volume 22, Number 6 Publisher: Lippincott, Williams & Wilkins | 2015-12-01, Pages 432-438 Type of Work: Article | Post-print: After Peer Review Publisher DOI: 10.1097/MED.0000000000000199 Permanent URL: https://pid.emory.edu/ark:/25593/rtnx3 Final published version: http://dx.doi.org/10.1097/MED.0000000000000199 Copyright information: © 2015 Wolters Kluwer Health, Inc. All rights reserved. Accessed September 30, 2021 7:39 AM EDT HHS Public Access Author manuscript Author Manuscript Author ManuscriptCurr Opin Author Manuscript Endocrinol Diabetes Author Manuscript Obes. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: Curr Opin Endocrinol Diabetes Obes. 2015 December ; 22(6): 432–438. doi:10.1097/MED. 0000000000000199. Vitamin D and Anemia: Insights into an Emerging Association Ellen M. Smith1 and Vin Tangpricha1,2,3 1Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA 2Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA 3Atlanta VA Medical Center, Decatur, GA, USA Abstract Purpose of review—This review highlights recent findings in the emerging association between vitamin D and anemia through discussion of mechanistic studies, epidemiologic studies, and clinical trials. Recent findings—Vitamin D has previously been found to be associated with anemia in various healthy and diseased populations. Recent studies indicate that the association may differ between race and ethnic groups and is likely specific to anemia of inflammation.
    [Show full text]
  • Paricalcitol | Memorial Sloan Kettering Cancer Center
    PATIENT & CAREGIVER EDUCATION Paricalcitol This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. Brand Names: US Zemplar Brand Names: Canada Zemplar What is this drug used for? It is used to treat high parathyroid hormone levels in certain patients. What do I need to tell my doctor BEFORE I take this drug? If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you have any of these health problems: High calcium levels or high vitamin D levels. This is not a list of all drugs or health problems that interact with this drug. Paricalcitol 1/8 Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor. What are some things I need to know or do while I take this drug? All products: Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. Have blood work checked as you have been told by the doctor. Talk with the doctor. If you are taking other sources of vitamin D, talk with your doctor.
    [Show full text]
  • Specialty Guideline Management Crysvita
    Effective Date: 12/2019 Reviewed: 9/2019, 6/2020, 1/2021, 5/2021 Scope: Medicaid SPECIALTY GUIDELINE MANAGEMENT CRYSVITA (burosumab-twza) POLICY I. CRITERIA FOR INITIAL APPROVAL X-linked hypophosphatemia A 6-month authorization may be granted for treatment of X-linked hypophosphatemia (XLH) when all of the following criteria are met: 1. Diagnosis of XLH confirmed by at least one of the following: a. Serum fibroblast growth factor-23 (FGF23) level > 30 pg/mL (>230 RU/mL in children 3 months-17 years; >180 RU/mL in adults using EDTA plasma); OR b. Phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX-gene) mutations in the patient 2. Member is at least 6 months of age. 3. Member will not receive oral phosphate and/or active vitamin D analogs within 1 week prior to the start of therapy. 4. Adult patients must have had an inadequate response from oral phosphate and active vitamin D analogs. 5. For adults, dose requested is 1 mg/kg, rounded to nearest 10mg, every 4 weeks and dose does not exceed 90mg [Member’s weight must be provided]. 6. For pediatric members, dose requested is 0.8 mg/kg, rounded to nearest 10mg, every 2 weeks and dose does not exceed 90mg [Member’s weight must be provided]. 7. Baseline fasting serum phosphorus* level with current hypophosphatemia, defined as a phosphate level below the lower limit of the laboratory normal reference range (Note: serum phosphorus levels should be monitored periodically throughout therapy, required on renewal). 8. Must be prescribed by, or in consultation with, a nephrologist or endocrinologist.
    [Show full text]
  • New Roles for Vitamin D Superagonists: from COVID to Cancer
    REVIEW published: 31 March 2021 doi: 10.3389/fendo.2021.644298 New Roles for Vitamin D Superagonists: From COVID to Cancer David J. Easty 1, Christine J. Farr 2* and Bryan T. Hennessy 3,4 1 Department of Medical Oncology, Our Lady of Lourdes Hospital, Drogheda, Ireland, 2 Department of Genetics, University of Cambridge, Cambridge, United Kingdom, 3 Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland, 4 Department of Oncology, Our Lady of Lourdes Hospital, Drogheda, Ireland Vitamin D is a potent steroid hormone that induces widespread changes in gene expression and controls key biological pathways. Here we review pathophysiology of vitamin D with particular reference to COVID-19 and pancreatic cancer. Utility as a therapeutic agent is limited by hypercalcemic effects and attempts to circumvent this problem have used vitamin D superagonists, with increased efficacy and reduced calcemic effect. A further caveat is that vitamin D mediates multiple diverse effects. Some of these (anti-fibrosis) are likely beneficial in patients with COVID-19 and pancreatic cancer, whereas others (reduced immunity), may be beneficial through attenuation of the Edited by: cytokine storm in patients with advanced COVID-19, but detrimental in pancreatic cancer. Jeff M. P. Holly, University of Bristol, United Kingdom Vitamin D superagonists represent an untapped resource for development of effective Reviewed by: therapeutic agents. However, to be successful this approach will require agonists with William B. Grant, high cell-tissue specificity. Sunlight Nutrition and Health Research Center, United States Keywords: COVID-19, pancreatic cancer, pancreatic stellate cell, superagonist, vitamin D, paricalcitol Erick Legrand, Centre Hospitalier Universitaire d’Angers, France *Correspondence: INTRODUCTION Christine J.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Paricalcitol Versus Calcitriol in the Treatment of Secondary Hyperparathyroidism
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 63 (2003), pp. 1483–1490 Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism STUART M. SPRAGUE,FRANCISCO LLACH,MICHAEL AMDAHL,CAROL TACCETTA, and DANIEL BATLLE Division of Nephrology/Hypertension and Department of Medicine, Northwestern University Feinberg School of Medicine, Evanston and Chicago, Illinois; Georgetown University Medical School, Washington, D.C.; and Abbott Laboratories, North Chicago, Illinois Paricalcitol versus calcitriol in the treatment of secondary hyper- Osteitis fibrosa cystica, resulting from poorly con- parathyroidism. trolled secondary hyperparathyroidism, remains a com- Background. Management of secondary hyperparathyroid- mon manifestation of renal osteodystrophy and causes ism has included the use of active vitamin D or vitamin D ana- logs for the suppression of parathyroid hormone (PTH) secre- significant morbidity in patients with chronic renal fail- tion. Although, these agents are effective, therapy is frequently ure [1, 2]. Decreased renal production of calcitriol (1,25 limited by hypercalcemia, hyperphosphatemia, and/or eleva- vitamin D ), hypocalcemia, and hyperphosphatemia are ϫ 3 tions in the calcium-phosphorus (Ca P) product. In clinical the major contributing factors to the development of studies, paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or secondary hyperparathyroidism [1, 3–5]. Calcitriol is syn- hyperphosphatemia as compared to placebo. A comparative thesized from previtamin D3 by hydroxylation on carbons study was undertaken in order to determine whether paricalci- 25 and 1 in the liver and kidney, respectively [6]. The tol provides a therapeutic advantage to calcitriol.
    [Show full text]
  • Vitamin D Analog (Oral) Step Therapy Program
    STEP THERAPY POLICY POLICY: Vitamin D Analog (Oral) Step Therapy Program APPROVAL DATE: 08/07/2019 DRUGS AFFECTED: • Hectorol® (doxercalciferol capsules – Genzyme; generics) Rayaldee® (calcifediol extended-release capsule – OPKO) Rocaltrol® (calcitriol capsules and oral solution – Validus; generics) Zemplar® (paricalcitol capsules – Abbvie; generics) OVERVIEW Vitamin D analogs are therapeutic options for the reduction of elevated parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) who have secondary hyperparathyroidism (SHPT).1 SHPT is a common complication of CKD, affecting nearly all of the more than 400,000 patients receiving dialysis (CKD Stage 5D classification) in the US.2,3 It may also affect CKD patients not yet on dialysis.2,3 SHPT is associated with increased PTH levels and alterations in calcium and phosphorus levels.2 These alterations can then lead to bone disease, bone pain and fractures, and vascular and soft tissue calcifications which may lead to cardiovascular (CV) morbidity and mortality. Exogenous calcitriol is a synthetic vitamin D analog, which is active in the regulation of the absorption of calcium from the gastrointestinal (GI) tract and its utilization in the body.4,7 Doxercalciferol is a synthetic vitamin D2 analog which undergoes metabolic activation in vivo to form 1α,25-(OH)2D2, a 5 naturally occurring biologically active form of vitamin D2. Paricalcitol is a synthetically manufactured analog of calcitriol.6 Rayaldee is a synthetically manufactured prohormone of calcitriol, calcifediol, which is also known as calcidiol.7 Calcifediol/calcidiol is converted to calcitriol in the kidney; calcitriol then binds to vitamin D receptors (VDRs) in the target tissues.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • Nephrology II BONE METABOLISM and DISEASE in CHRONIC KIDNEY DISEASE
    Nephrology II BONE METABOLISM AND DISEASE IN CHRONIC KIDNEY DISEASE Sarah R. Tomasello, Pharm.D., BCPS Reviewed by Joanna Q. Hudson, Pharm.D., BCPS; and Lisa C. Hutchison, Pharm.D., MPH, BCPS aluminum toxicity. Adynamic bone disease is referred to as Learning Objectives low turnover disease with normal mineralization. This disorder may be caused by excessive suppression of PTH 1. Analyze the alterations in phosphorus, calcium, vitamin through the use of vitamin D agents, calcimimetics, or D, and parathyroid hormone regulation that occur in phosphate binders. In addition to bone effects, alterations in patients with chronic kidney disease (CKD). calcium, phosphorus, vitamin D and PTH cause other 2. Classify the type of bone disease that occurs in patients deleterious consequences in patients with CKD. Of these, with CKD based on the evaluation of biochemical extra-skeletal calcification and increased left ventricular markers. mass have been documented and directly correlated to an 3. Construct a therapeutic plan individualized for the stage increase in cardiovascular morbidity and mortality. The goal of CKD to monitor bone metabolism and the effects of of treatment in patients with CKD and abnormalities of bone treatment. metabolism is to normalize mineral metabolism, prevent 4. Assess the role of various treatment options such as bone disease, and prevent extraskeletal manifestations of the phosphorus restriction, phosphate binders, calcium altered biochemical processes. supplements, vitamin D agents, and calcimimetics In 2003, a non-profit international organization, Kidney based on the pathophysiology of the disease state. Disease: Improving Global Outcomes, was created. Their 5. Devise a therapeutic plan for a specific patient with mission is to improve care and outcomes for patients with alterations of phosphorus, calcium, vitamin D, and CKD worldwide by promoting, coordinating, collaborating, intact parathyroid hormone concentrations.
    [Show full text]
  • Nuclear Receptors in Renal Disease Moshe Levi
    Nuclear receptors in renal disease Moshe Levi To cite this version: Moshe Levi. Nuclear receptors in renal disease. Biochimica et Biophysica Acta - Molecular Basis of Disease, Elsevier, 2011, 10.1016/j.bbadis.2011.04.003. hal-00706531 HAL Id: hal-00706531 https://hal.archives-ouvertes.fr/hal-00706531 Submitted on 11 Jun 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ÔØ ÅÒÙ×Ö ÔØ Nuclear receptors in renal disease Moshe Levi PII: S0925-4439(11)00077-9 DOI: doi: 10.1016/j.bbadis.2011.04.003 Reference: BBADIS 63278 To appear in: BBA - Molecular Basis of Disease Received date: 13 January 2011 Revised date: 21 March 2011 Accepted date: 6 April 2011 Please cite this article as: Moshe Levi, Nuclear receptors in renal disease, BBA - Molecular Basis of Disease (2011), doi: 10.1016/j.bbadis.2011.04.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form.
    [Show full text]