DOCSLIB.ORG

Public Assessment Report Scientific Discussion Riseteva 75 Mg Film

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Public Assessment Report Scientific Discussion Riseteva 75 Mg Film Public Assessment Report Scientific discussion Riseteva 75 mg film-coated tablets Risedronate sodium DK/H/2020/001/DC This module reflects the scientific discussion for the approval of Riseteva. The procedure was finalised on 18 May 2011. For information on changes after this date please refer to the module ‘Update’. 1/7 I. INTRODUCTION Based on the review of the quality, safety and efficacy data, the Member States have granted a marketing authorisation for Riseteva 75 mg film-coated tablets, from Teva Denmark A/S. The product was authorised in Denmark on 28 June 2011. The product is indicated for treatment of osteoporosis in postmenopausal women at increased risk of fractures. Risedronate sodium belongs to the pharmaco-therapeutic group of bisphosphonates (ATC code: M05 BA07). It is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption by binding to bone hydroxyapatite. This decentralised procedure concerns a generic application claiming essential similarity with the reference product Optinate/Optinate Septimum/Actonel which has been registered in the EEA by Aventis Pharma/Sanofi and Procter & Gamble since 1998. In Denmark Optinate film-coated tablets and Optinate Septimum 35 mg film-coated tablets, Sanofi- Aventis, have been registered since 1999 and 2004, respectively. The marketing authorisation is granted based on article 10.1 of Directive 2001/83/EC. II. QUALITY ASPECTS II.1 Introduction Each film-coated tablet contains 75 mg risedronate sodium (equivalent to 69.6 mg risedronic acid). The tablets are pink, round, biconvex, film-coated tablets engraved “R 75” on one side and plain on the other. The tablets are packed in transparent PVC/PVdC – Aluminium blister packs in a cardboard carton in pack sizes of 2, 4, 6, 8 or 12 tablets. However, not all pack sizes may be marketed. Compliance with Good Manufacturing Practice The RMS has been assured that acceptable standards of GMP (see Directive 2003/94/EC) are in place for this product type at all sites responsible for the manufacturing of the active substance as well as for the manufacturing and assembly of this product prior to granting its national authorisation. II.2 Drug Substance rINN: Risedronate sodium Compendial names: Risedronate sodium (USP) Chemical name(s): [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid]monosodium salt Molecular formula: C7H10NO7P2Na.H2O Molecular mass: 323.10 Structural formula: 2/7 Risedronate soidum is a white to pale yellow (or off-white) solid. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents. Several crystal forms of risedronate sodium are known from the literature. Risedronate sodium is not monographed in Ph.Eur. The applicant sources the substance from a single supplier. The documentation on the active substance risedronate sodium is presented as a European Drug Master File/Active Substance Master File (DMF). The Applicant’s Part of the DMF has been forwarded by the Applicant. The Applicant’s and Restricted Part plus a LoA have been forwarded by the ASM. Details on the synthesis, starting materials, methods of analysis and their validations are all satisfactory. Impurities are adequately controlled. Specifications are satisfactory and test methods have been presented in adequate detail. Validation data are satisfactory. Stability studies have been performed with the drug substance. No significant changes in any parameters were observed. The proposed retest period is justified. The applicant specification for risedronate sodium reflects parameters and limits applied by the ASM and the same analytical methods are employed. II.3 Medicinal Product The drug product is film-coated tablets containing 75 mg risedronate sodium. The product is to be marketed in transparent PVC/PVdC/Al blisters. The product composition is adequately described. The development of the product has been satisfactorily performed and explained. No incompatibilities between the active substance and the excipients are observed. Excipients are those commonly used for manufacture of a film-coated tablet. The packaging material is standard and shown suitable by the presented stability studies. Product manufacture is by standard processing and employs a wet granulation process followed by tabletting and film-coating. Validation data are provided for small production scale batches. The results obtained show that the process is adequately controlled, reproducible and robust. The product specifications cover appropriate parameters for this dosage form. Validations of the analytical methods have been presented. Batch analysis has been performed on two batches of the lower range of the proposed production scale batch size. The batch analysis results show that the finished products meet the proposed specifications. The conditions used in the stability studies are according to the ICH stability guideline. The control tests and specifications for drug product are adequately drawn up. A shelf-life of 24 months when packaged in transparent PVC/PVdC – aluminium blisters is considered acceptable. III. NON-CLINICAL ASPECTS This product is a generic formulation of Optinate/Optinate Septimum/Actonel, which is available on the European market. No new preclinical data have been submitted, and therefore the application has not undergone preclinical assessment. This is acceptable for this type of application Environmental risk assessment 3/7 The product is intended as a substitute for other identical products on the market. The approval of this product will not result in an increase in the total quantity of risedronate sodium released into the environment. It does not contain any component, which results in an additional hazard to the environment during storage, distribution, use and disposal. IV. CLINICAL ASPECTS IV.1 Introduction Risedronate sodium is a well-known active substance with established efficacy and tolerability. Absorption of risedronate after an oral dose is rapid (tmax approx. 1 hour), and occurs throughout the upper gastrointestinal tract. Linear kinetics in the dose range of 35-75 mg is demonstrated in relation with a biowaiver. The mean oral bioavailability of the tablet formulation is 0.63% and is bioequivalent to a solution. Risedronate is excreted unchanged primarily via the kidney. Since it is not metabolised, risedronate does not induce or inhibit hepatic cytochrome P450 enzymes. The absorption of risedronate is significantly inhibited by food. The extent of absorption when administered 30 minutes before breakfast is reduced by 55% compared to dosing in the fasting state (i.e. no food or drink for 10 hours prior to or 4 hours after dosing). Dosing 1 hour prior to breakfast reduces extent of absorption by 30% compared to dosing in the fasting state. Dosing either 30 minutes prior to breakfast or 2 hours after a meal results in a similar extent of absorption. Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous dose is recovered in the urine over 28 days. Once risedronate is absorbed, the serum concentration-time profile is multiphasic with an initial half-life of about 1.5 hours and a terminal exponential half-life of 480 hours. Although the elimination rate of bisphosphonates from human bone is unknown, the 480-hour half-life is hypothesized to represent the dissociation of risedronate from the surface of the bone. For this generic application, the MAH has submitted two bioequivalence studies under fasting conditions in which the pharmacokinetic profile of the test product Risedronatnatrium “Teva” 35 mg film-coated tablets is compared with the pharmacokinetic profile of the reference product Actonel 35 mg film-coated tablets, Aventis Pharma, from the German market. It is suggested to claim bioequivalence of Riseteva 75 mg film-coated tablets with Actonel 75 mg film-coated tablets based on the two bioequivalence studies performed on the 35 mg tablets. The second study was a confirmatory study, since in the first study the 90% CI for Cmax was just outside the general acceptance limits of 80-125% (79.09-103.50%). The number and type of bioequivalence studies are considered sufficient for the present application for an immediate release formulation. Main study The main study was performed as a single centre, randomized, single dose, 2-period, 2-sequence, crossover study conducted under fasting conditions with a wash out period of 7 days between administrations. 1x35 mg film-coated tablet was administered in each period with 240 ml water after an overnight fast of at least 10 hours. Blood samples were collected pre-dosing and at various time- points up to 24 hours post administration of a single-dose 35 mg tablet with 240 ml of water for the analyses of risedronic acid. 80 healthy non-smoking male subjects (19-53 years; 62 Caucasians, 10 Black and 3 Asian (of the 75 included in data analysis)) participated in the study. 75 subjects completed the study and were used for the pharmacokinetic and statistical analysis. 4/7 The primary pharmacokinetic variables evaluated were AUC0-t, AUC0-∞, and Cmax and bioequivalence was determined based on limits of 80-125% for AUC0-t and AUC0-∞, and 75-133% for Cmax. The 90% confidence interval for both AUC parameters was within the acceptance range of 80-125%, whereas the 90% confidence interval for Cmax was just outside the lower limit of the acceptance range (79.09- 103.5%). Results Pharmacokinetic parameters (non-transformed values; arithmetic mean ± SD, tmax median, range): N=75 Treatment AUC0-t AUC0-∞ Cmax tmax t½ ng.h/ml ng.h/ml ng/ml h h Test 47.705 51.527 14.305 1.26 7.58 (S.D.) (36.063) (39.190) (11.452) (0.25-4.00) (5.47) Reference 49.104 53.000 14.923 1.19 8.66 (S.D.) (32.484) (35.182) (9.830) (0.25-4.00) (6.78) *Ratio (90% 94.15% 94.22% 90.48% - - CI) (83.20- (83.12- (79.09- 106.53%) 106.82%) 103.50%) Intra-subject 48 48 53 - - CV (%) A widening of the limits is not considered acceptable, however taking into account the additional confirmative study (see below), bioequivalence between the test and reference product can be concluded.
Load more

Recommended publications
  • The Legally Binding Text Is the Original French Version TRANSPARENCY
    The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 21 July 2010 ACTONEL 5 mg, film-coated tablet B/14 (CIP code: 354 362-3) ACTONEL 30 mg, film-coated tablet B/28 (CIP code: 354 366-9) ACTONEL 35 mg, film-coated tablet B/4 (CIP code: 361 577-1) B/12 (CIP code: 366 668-5) ACTONEL 75 mg, film-coated tablet B/2 (CIP code: 384 568-9) B/6 (CIP code: 384 570-3) Applicant: PROCTER & GAMBLE PHARMACEUTICALS risedronate sodium ATC code: M05BA07 List I Date of Marketing Authorisation : ACTONEL 5 mg – 3 May 2000 ACTONEL 30 mg – 3 May 2000 ACTONEL 35 mg – 3 March 2003 ACTONEL 75 mg – 25 March 2008 Reason for request : Re-evaluation of the actual benefit in accordance with article R. 163-21 of the Social Security Code. Medical, Economic and Public Health Assessment Division 1 1 CHARACTERISTICS OF THE MEDICINAL PRODUCT 1.1. Active ingredient risedronate sodium 1.2. Indications “ACTONEL 5 mg, film-coated tablet - Treatment of postmenopausal osteoporosis to reduce the risk of vertebral fractures. - Treatment of confirmed postmenopausal osteoporosis to reduce the risk of hip fractures. - Prevention of postmenopausal osteoporosis in women at increased risk of osteoporosis. - Maintenance or augmentation of bone mass in postmenopausal women, requiring prolonged (more than 3 months’) systemic corticosteroid therapy with doses ≥ 7.5 mg/day prednisone equivalent. ACTONEL 30 mg, film-coated tablet Treatment of Paget’s disease of bone. ACTONEL 35 mg, film-coated tablet - Treatment of postmenopausal osteoporosis to reduce the risk of vertebral fractures.
    [Show full text]
  • Protocol Supplementary
    Optimal Pharmacological Management and Prevention of Glucocorticoid-Induced Osteoporosis (GIOP) Protocol for a Systematic Review and Network Meta-Analysis Supplementary Materials: Sample Search Strategy Supplementary 1: MEDLINE Search Strategy Database: OVID Medline Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present Line 1 exp Osteoporosis/ 2 osteoporos?s.ti,ab,kf. 3 Bone Diseases, Metabolic/ 4 osteop?eni*.ti,ab,kf. 5 Bone Diseases/ 6 exp Bone Resorption/ 7 malabsorption.ti,ab,kf. 8 Bone Density/ 9 BMD.ti,ab,kf. 10 exp Fractures, Bone/ 11 fracture*.ti,ab,kf. 12 (bone* adj2 (loss* or disease* or resorption* or densit* or content* or fragil* or mass* or demineral* or decalcif* or calcif* or strength*)).ti,ab,kf. 13 osteomalacia.ti,ab,kf. 14 or/1-13 15 exp Glucocorticoids/ 16 exp Steroids/ 17 (glucocorticoid* or steroid* or prednisone or prednisolone or hydrocortisone or cortisone or triamcinolone or dexamethasone or betamethasone or methylprednisolone).ti,ab,kf. 18 or/15-17 19 14 and 18 20 ((glucocorticoid-induced or glucosteroid-induced or corticosteroid-induced or glucocorticosteroid-induced) adj1 osteoporos?s).ti,ab,kf. 21 19 or 20 22 exp Diphosphonates/ 23 (bisphosphon* or diphosphon*).ti,ab,kf. 24 exp organophosphates/ or organophosphonates/ 25 (organophosphate* or organophosphonate*).ti,ab,kf. 26 (alendronate or alendronic acid or Fosamax or Binosto or Denfos or Fosagen or Lendrate).ti,ab,kf. 27 (Densidron or Adrovance or Alenotop or Alned or Dronat or Durost or Fixopan or Forosa or Fosval or Huesobone or Ostemax or Oseolen or Arendal or Beenos or Berlex or Fosalen or Fosmin or Fostolin or Fosavance).ti,ab,kf.
    [Show full text]
  • (GE) Review of TA160, 161 and 204; Technologies for The
    NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE GUIDANCE EXECUTIVE (GE) Review of TA160, 161 and 204; Technologies for the primary and secondary prevention of osteoporotic fractures1 TA160 and TA161 give guidance on alendronate, risedronate, etidronate, strontium ranelate, raloxifene and teriparatide, and were re-issued after the Judicial Review in January 2011. TA204 gives guidance on denosumab and was issued in October 2010. TA160 and TA161 were to be considered for review after the short clinical guideline on risk assessment has been published. TA204 was to be considered for review at the same time that TA160 and TA161 are considered for review. In August 2012 the clinical guideline on assessing the risk of fragility fractures in people with osteoporosis was published (CG146). In July 2012 Guidance Executive agreed to reschedule the review proposal for the above technology appraisals so that we can explore how treatment intervention thresholds from the technology appraisals can be aligned to the assessment of absolute fracture risk recommended in CG146, and to carry out a feasibility study through NICE’s Decision Support Unit. 1 Review of TA160; Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women, TA161; Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women, and TA204; Denosumab for the prevention of osteoporotic
    [Show full text]
  • Denosumab, Raloxifene, Romosozumab and Teriparatide to Prevent Osteoporotic Fragility Fractures: a Systematic Review and Economic Evaluation
    Journals Library Health Technology Assessment Volume 24 • Issue 29 • June 2020 ISSN 1366-5278 Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation Sarah Davis, Emma Simpson, Jean Hamilton, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong, Edward Goka, Neil Gittoes and Peter Selby DOI 10.3310/hta24290 Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation Sarah Davis ,1* Emma Simpson ,1 Jean Hamilton ,1 Marrissa Martyn-St James ,1 Andrew Rawdin ,1 Ruth Wong ,1 Edward Goka ,1 Neil Gittoes 2 and Peter Selby 3 1Health Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK 2University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK 3School of Medical Sciences, University of Manchester, Manchester, UK *Corresponding author Declared competing interests of authors: Neil Gittoes reports personal fees for being a member of the advisory board to Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and personal fees for contributing to educational meeting sponsored by Eli Lilly and Company (Indianapolis, IN, USA), outside the submitted work. He is also a trustee of the National Osteoporosis Society, a member of the advisory board of the National Osteoporosis Guideline Group and Deputy Chairperson of the Specialised Endocrinology Clinical Reference Group, NHS England. Published June 2020 DOI: 10.3310/hta24290 This report should be referenced as follows: Davis S, Simpson E, Hamilton J, James MM-S, Rawdin A, Wong R, et al. Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation.
    [Show full text]
  • WO 2015/123734 Al 27 August 2015 (27.08.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/123734 Al 27 August 2015 (27.08.2015) P O P C T (51) International Patent Classification: (74) Agent: FB RICE; Level 23, 44 Market Street, Sydney, C08B 3/02 (2006.01) C07H 13/06 (2006.01) New South Wales 2000 (AU). C07H 13/04 (2006.0 1) A61K 9/14 (2006.0 1) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/AU2015/050069 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 23 February 2015 (23.02.2015) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 2014900566 2 1 February 2014 (21.02.2014) AU TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicants: THE UNIVERSITY OF SYDNEY (84) Designated States (unless otherwise indicated, for every [AU/AU]; Sydney, Sydney, New South Wales 2006 (AU).
    [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]
  • Pharmaco-Economic Study for the Prescribing of Prevention and Treatment of Osteoporosis
    Technical Report 2: An analysis of the utilisation and expenditure of medicines dispensed for the prophylaxis and treatment of osteoporosis Technical report to NCAOP/HSE/DOHC By National Centre for Pharmacoeconomics An analysis of the utilisation and expenditure of medicines dispensed for the prophylaxis and treatment of osteoporosis February 2007 National Centre for Pharmacoeconomics Executive Summary 1. The number of prescriptions for the treatment and prophylaxis of osteoporosis has increased from 143,261 to 415,656 on the GMS scheme and from 52,452 to 136,547 on the DP scheme over the time period 2002 to 2005. 2. In 2005 over 60,000 patients received medications for the prophylaxis and treatment of osteoporosis on the GMS scheme with an associated expenditure of €16,093,676. 3. Approximately 80% of all patients who were dispensed drugs for the management of osteoporosis were prescribed either Alendronate (Fosamax once weekly) or Risedronate (Actonel once weekly) respectively. 4. On the DP scheme, over 27,000 patients received medications for the prophylaxis and treatment of osteoporosis in 2005 with an associated expenditure of € 6,028,925. 5. The majority of patients treated with drugs affecting bone structure were over 70 years e.g. 12,224 between 70 and 74yrs and 25,518 over 75yrs. 6. In relation to changes in treatment it was identified from the study that approximately 8% of all patients who are initiated on one treatment for osteoporosis are later switched to another therapy. 7. There was a statistically significant difference between the use of any osteoporosis medication and duration of prednisolone (dose response, chi- square test, p<0.0001).
    [Show full text]
  • Risedronate Sandoz (Risedronate Sodium) Film-Coated Tablets 1
    NEW ZEALAND DATA SHEET RISEDRONATE SANDOZ (RISEDRONATE SODIUM) FILM-COATED TABLETS 1. PRODUCT NAME Risedronate sodium 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each Risedronate Sandoz 35 mg film-coated tablet contains 35 mg risedronate sodium equivalent to 32.5 mg risedronic acid. Risedronate sodium is a fine, white to off white, odourless, crystalline powder. It is soluble in water and in aqueous solutions and essentially insoluble in common organic solvents. For the full list of excipients, see Section 6.1. 3. PHARMACEUTICAL FORM Risedronate Sandoz 35 mg - orange, oval, biconvex film-coated tablets marked 35 on one side and containing 35 mg risedronate sodium. 4. CLINICAL PARTICULARS 4.1. THERAPEUTIC INDICATIONS Treatment of Osteoporosis. Prevention of Glucocorticoid-induced Osteoporosis. Treatment of Postmenopausal Osteoporosis. 4.2. DOSE AND METHOD OF ADMINISTRATION Dosage The recommended dose is 35 mg once a week, taken on the same day each week. Method of administration Risedronate Sandoz must only be taken with plain water. Plain water is the only drink that should be taken with Risedronate Sandoz tablets. Please note that some mineral waters or water from regional areas may have a higher concentration of calcium and therefore should not be used. Risedronate Sandoz must be taken 30 minutes before the first food or drink other than water. To facilitate delivery to the stomach, Risedronate Sandoz should be taken in an upright position and the patient should avoid lying down for 30 minutes. Patients should not chew or suck on the tablet because of the potential for oropharyngeal irritation. Dosage adjustment in: renal impairment No dose adjustment is necessary in patients with mild to moderate renal insufficiency (creatinine clearance 30 to 60 mL/minute).
    [Show full text]
  • Bone Density Regulators
    Therapeutic Class Overview Bone Density Regulators INTRODUCTION Osteoporosis is the most common bone disease and is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to bone fragility and consequent susceptibility to fracture (Cosman et al 2014). The National Osteoporosis Foundation (NOF) estimates that 10.2 million Americans have osteoporosis and more than 2 million osteoporosis-related fractures occur annually, with more than 70% of these occurring in women. Age is an important risk factor for bone loss; by age 60, half of white women have osteopenia or osteoporosis (Camacho et al 2016). According to the World Health Organization, osteoporosis is defined by a bone mineral density (BMD) at the hip or spine that is less than or equal to 2.5 standard deviations below the expected average for a healthy young person. Utilizing a reference population of young healthy individuals is common when measuring BMD and is known as a T-score (World Health Organization 1994). Fractures are the most clinically significant physical manifestation of postmenopausal osteoporosis, and low bone mass is the primary indicator of fracture risk (Camacho et al 2016). Osteoporotic fractures commonly occur in the wrist, spine, or hip, and can result in complications such as chronic pain, disability, depression, or even death (Cosman et al 2014). To decrease the risk of fractures, the general population should be advised to consume 1200 mg of calcium and 800 to 1000 mg of vitamin D per day from dietary sources or supplements. All individuals should also participate in regular weight-bearing and muscle-strengthening exercise to reduce the risk of falls and fractures.
    [Show full text]
  • Therapeutic Class Overview Bisphosphonates
    Therapeutic Class Overview Bisphosphonates Therapeutic Class • Overview/Summary: Osteoporosis is the most common bone disease in humans and is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to bone fragility and consequent susceptibility to fracture.1 According to the World Health Organization, osteoporosis is defined by a bone mineral density (BMD) at the hip or spine that is less than or equal to 2.5 standard deviations below the expected average for a healthy young person.2 Utilizing a reference population of young healthy individuals is common when measuring BMD and is known as a T-score.1 Fractures are the most clinically significant physical manifestation of postmenopausal osteoporosis and low bone mass is the primary indicator of fracture risk.3 Osteoporotic fractures commonly occur in the wrist, spine, or hip, and can result in complications such as chronic pain, disability, depression, or even death.1 Osteoporosis and related fractures represent a significant public health and economic burden. The management of osteoporosis is intended to prevent initial or subsequent fractures by maximizing skeletal strength and/or minimizing skeletal trauma, as well as increase the patient’s quality of life.3 The bisphosphonates are primarily Food and Drug Administration (FDA)-approved for the prevention and/or treatment of osteoporosis in postmenopausal women, in men, and in patients taking prolonged courses of glucocorticoids. Bisphosphonates inhibit osteoclast activity by binding to bone surfaces that are undergoing active bone resorption resulting in the impairment of the ability for osteoclasts to form the ruffled border, adhere to the bony surface, and produce the protons necessary to continue bone resorption.4-11 In general, the bisphosphonates are available for oral once-daily, once-weekly, or once-monthly administration.
    [Show full text]
  • Bisphosphonates for Treatment of Osteoporosis Expected Benefts, Potential Harms, and Drug Holidays
    Clinical Review Bisphosphonates for treatment of osteoporosis Expected benefts, potential harms, and drug holidays Jacques P. Brown MD Suzanne Morin MD MSc William Leslie MD Alexandra Papaioannou MD Angela M. Cheung MD PhD Kenneth S. Davison PhD David Goltzman MD David Arthur Hanley MD Anthony Hodsman MD Robert Josse MD Algis Jovaisas MD Angela Juby MD Stephanie Kaiser MD Andrew Karaplis MD David Kendler MD Aliya Khan MD Daniel Ngui MD Wojciech Olszynski MD PhD Louis-Georges Ste-Marie MD Jonathan Adachi MD Abstract Objective To outline the effcacy and risks of bisphosphonate therapy for the management of osteoporosis and describe which patients might be eligible for bisphosphonate “drug holiday.” Quality of evidence MEDLINE (PubMed, through December 31, 2012) was used to identify relevant publications for inclusion. Most of the evidence cited is level II evidence (non-randomized, cohort, and other comparisons trials). Main message The antifracture effcacy of approved frst-line bisphosphonates has been proven in randomized controlled clinical trials. However, with more extensive and prolonged clinical use of bisphosphonates, associations have been reported between their administration and the occurrence of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femur fractures might be related to the use of bisphosphonates in osteoporosis, but they are exceedingly rare and they often occur with other comorbidities or concomitant medication use. Drug holidays should only be considered in low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy. Conclusion When bisphosphonates are prescribed to patients at high risk of fracture, their antifracture benefts considerably outweigh their potential for harm.
    [Show full text]
  • DOWNLOAD SPC Risedronate Sodium
    Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Risedronate Sodium Accord 5 mg film coated tablets 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains 5 mg risedronate sodium (equivalent to 4.64 mg risedronic acid). Excipient with known effect: Each film-coated tablet contains lactose. For the full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Film-coated tablet. Oval yellow film-coated tablet with RSN on one side and 5 mg on the other. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures. Treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures. Prevention of osteoporosis in postmenopausal women with increased risk of osteoporosis (see section 5.1) To maintain or increase bone mass in postmenopausal women undergoing long-term (more than 3 months), systemic corticosteroid treatment at doses '27.5 mg/day prednisone or equivalent. 4.2 Posology and method of administration Posology The recommended daily dose in adults is one 5 mg tablet orally. Special populations Elderly No dosage adjustment is necessary since bioavailability, distribution and elimination were similar in elderly (>60 years of age) compared to younger subjects. Rena/Impairment No dosage adjustment is required for those patients with mild to moderate renal impairment. The use of risedronate sodium is contraindicated in patients with severe renal impairment (creatinine clearance lower than 30 ml/min) (see sections 4.3 and 5.2). Paediatric population Risedronate sodium is not recommended for use in children below age 18 due to insufficient data on safety and efficacy (see section 5.1).
    [Show full text]