RISEDRONATE SODIUM RESIDRON 35 mg Tablet Bisphosphonate Each film coated tablet contains: Risedronate Sedlumhemipentahydrate 40.17 mg Equivalentto Risedronate Sodium 35m Excipiente: Stareh Progolatinisea_Pn.cur, microcrystalline cellulose: Ph.Gur, Grospovidene Ph.Eur. Magnesium stearate Ph eur, Opadry White IH (Titanium dioxide Pn.cur, Lactose Denshyaeais, Phew Meera 4000 Ph Eur, Hypromelions DESCRIPTION: Ricearonate sodium tablet is a pyridiny! bisphosphonate that Inhibits osteoclast mediated bone resorption "and modulates: bone. metabolism. The empirical formula for rlsedronate, Sodium hemicpentahydrate fa CyHyNOyPaNa 2.5 MeO, The chemical ashe of fisedronate sodkamn =. [1-hydroxy-2-(- Byridiny!) oinyldene] bielphosphonic acid] monosodium salt The ‘chemical structure of nsedronate “sodium. hami- antahydrate is the following: Molecular Weight: Annydrous Homicpentahycra Risedronate sodium is a pyridiny! bisphosphonate that binds to Done hydroxyapatite and inhibits osteoclast mediated bone resorption. THe bone tumovar Is reduced while the osteoblast ‘Sctvity and bone minerallzation is preserved, 208.10 390.13 PHARMACOKINETICS: Absorption: Absorption after an oral dose Is relatively rapid Goma Tt nour) and is independant of dos Studied (single dose study, 215 to 30 me mul 2'5\to 5\mg dally and up to 60 mg dosed weekly). Mean oral bieavallabiity of the tablet Is 0.63% and le decreased when Reedronate sodium i= administered with food, Bloavallapinty Distribution: The mean steady state volume of distribution is 6.3 kin humans. Plasma protain binding is about 24%. Metabolism: There is no evidence of systemic metabolism of Elimination: Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous, dose fe recovered in'the urine after 28 days. Mean. ret friminy with the aitforence probably attributed to clearance due {S adsorption to bone. The renal clearance ls not concentration Gependent, and there iz linear relationship between renal Clearance and creatinine clearance. Unabsorbed risedronate: Sodium is oliminated unchanged in feces. After oral Seministration the concentratior-time profile shows, three Slimination phases with a terminal halfife of 480 hours. INDICATIONS: Postmenopausal Osteoporosis. Risedromate fe indicated for tne, treatment and prevention of Sromen with osisoporosia, i raduces the incidence of vertebr fractures" and. a composite endpeint of nonvertebral Ostooporosie-related fractures. Osteoporosis in Men Risearonate is indicated for treatment!o increase bone mass in menwith osteoporosis, DOSAGE AND ADMINISTRATION: ‘Phe recommended dose in aduts is one 35 mg tablet orally Gnee a week The tablet should be taken on the same day each Wook. The absorption of risedronate sodium is affected by food, thus io ensure adequate absorption patients. should take: Risedronate: 2 Before breakfast: Atleast 20 minutes before the fist food, thor medicinal product or drink (other than plain water) of 11 a patient forgets to take the 35mg risedronate tablet in the moming inform him/her not to take itater in the day. Take only 4 Heedronate 35mg tablet the next morning & continue the Ustial Schedule of 35mg (1 tablet on a chosen day of the week). Two tablets should not be taken on the same day. ‘The tablet must be swallowed whole and not sucked or & chewed. To ald delivery of, the tablet to, the, stomach siting) onion wintra gins of pain tar (= 120 tay ations ‘Supplemental calcium and vitamin should be considered if thediotary intake is inadequate, Elderly: No dosage adjustment is necessary since bioavailability Gistrbution and elimination were similar in elderly (260 years of ‘age) compared to younger subjects. This has also been shown inthe vary elderly, 75 years old and above postmenopausal population, Ne dosage adjustment is required for those patients with mild to moderate ronal impairment. The use of risedronate sodium 1s Eontraindicated "In patients with severe renal Impairment Groatinine clearance lower than 30 milmin), Children: Safety°and efficacy of risedronate 35 mg have not been Sotabliched in children and adolescents: CONTRAINDICATIONS = Hypersensitivity to risedronate sodium or to any of the excipients, = Hypocaicemia = Pregnancy and lactation. + Severe renal impairment (oresttinine clearance <30mi/min) WARNINGS & PRECAUTIONS: Foods. drinks (other than plain water) and medicinal products: Containing polyvalent cations (such ae Calcium, magnesttir, ren ana. aluminium). interfere with the absorption” of Bisphosphonates and should not be taken at the same time ao Rigadronate. In order to achiove the intondad efficacy, stick Suhorence to dosing recommendations is necessary. Erficacy of bisphosphonates in the treatment of osteoporosis is related to the presence of low bone mineral density and/or prevalent iracture. High age or clinical risk factors for fracture alone are not Sufficient reasons to inflate treatment of osteoporosis with & Bisphosphonate. ‘The evidence to support efficacy of Bisphosphonates including risedronate in the very elderly (>80 years) istimited. Bisphosphonates have been associated with oesophagitis Gastritis, oesophageal ulcerations and. gastroduedenal Sicerations: Thus caution should be used + In patients whe have @ history of oesophagea! disorders which delay oesophageal transit oremplying e.g. stricture = Inpatients wno are unable to stay in the upright position for atleast 30 minutes aftertaking the tablet. If risedronate is given to patients with active or recent esophageal or upper gastrointestinal problems, Prescribers should emphasize to patients the importance of paying attention to the dosing instructions and be alert to any Signs and symptoms of possible esophageal reaction. The, Pationta should be instructed to aeek tnaly medical attention it they "develop “sympioms. of esophageal inntation such as dysphagia. pain on swallowing. retrosternal pain or hewiworsened heartburn. Fypocalcemia should be weated fore starting Risedronats therapy. Other disturbances of bone ‘and mineral metabolism (1.0. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Rigedronate therapy. Osteonecrosis of the jaw generally associated with tooth fextraction and/or local Infection {Including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including. primarily intravenously administered bisphophonates. Many of these patients were also recoving chemotherapy and corticosteroids. Osteonecrosis of the jaw has’ alae been reported tn pationte with osteoporosis receMving A dental examination with appropriate preventive dentistry Chotia be considered prior to treatment with bisphosphonates: In patients. ‘with concomitant risk factors. (e.g. cancer chemotherapy, radiotherapy, corticosteroids, poor oral hygiene) While on treatment, these patients should avoid invasive dental procedures if possible. For patiants who develop osteonecrosis. Sr the Jaw while on bisphosphonate therapy, dental surgery. may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether Siscontinuaiion of blephosphonate treatment reduces the Fisk ofosteonecrosis of the jaw. Clinical judament of the treating physician should guide the: management pian of each patient based on individual benelit Inskagsoxsment ‘This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficioncyoF glucose-galactose malabsorption should not take this DRUG INTERACTIONS: No formal interaction studies have been performed, however Ro clinteally relevant interactions with other medicinal products Were found during ‘clinical trials. In the rieedronate sodium Bhase il ostsoportels studies with daly dosing. acelylsancyic cid or NSAID use was reported by 33% and 45% of patients respectively. In the Phase. ill once a week study In postmenopausal women, acetyl tras reported by 57% and 40% of Feguiaracety! Wook) the inéidenes of upper gastrointestinal advarae ovents Fisedronate sodium treated -pationts was similar to that In Control patients. if considered appropriate risedronate sodium may be used concomitantly with estrogen supplementation (Tor ‘women only). Sations (org. calcium, magnesium, iron and ‘aluminiura) wil Intertore with the absorption of Risedronate. Risedronate sodium is not systemically metabolized, does not Induce cytochrome 450 enzymes, and has low protein binding. Pregnaney and lactation: ‘There are no adequate data from the use of risedronate sodium, In pregnant women. Studies. in. animals have” shown reproductive toxielly, The potential riak for humans is unknowe Studies in animal indicate that a small amount of risedronate, Soaium pass into breast milk Risedronate sodium must nat be used during pregnancy or by Breast foading women. Effects on ability to drive and use machines No affects on ability to drive and use machines have been Observed. ADVERSE REACTIONS: Risecronate sodium has been studied in phase Ill clinical trials involving more than 15,000 pationts. ‘The majority of undesirable effects observed in clinical trials were mild 19 moderate in severity and usually did not require Sossation ofthorapy. postmenopausal women with osteoporosis tested for Upto 36 fronthe with risecronate sodium Smg/day (n=5020) oF placobo (n-5048) and considered possibly or probably related to Hsedronate. sodium are listed below Using the. following Convention (incidences versus placebo are shown in brackets) Very common (1/10); commen (> 7/100; <1/10); uncommon (211,000; =1/100); rare (= 1/10,000; =1/1,000); very rare (110,000). Nervous system disorders: Common: neadache (1.8% vs. 1.4%) Eye disorders: Gastrointestinal disorders: Gommon: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs a3%), hausea (4.3% vs. 4.0%), abdominal pain (3.5% vs. 3.3%) Giarrhea (3.0% va. 2.7%) Uncommon: gastritis (0.9% vs. 0.7%), esophagitis (0.9% ve 0.9%), dysphagia (0.4% vs. 0.2%), duodenitis (0.2% Vs. 0.1%), ‘esophageal ulcer (0.2% vs. 0.2%) Rare: glossitis (<0.1% ve. 0.1%), esophageal stricture (<0.1% v5.0.0%) Musculoskeletal and connective tissues disorders: ‘Common: musculoskeletal pain (219¢ve.1-8%) Investigations: Rare: abnormal iver function teste” = No relevant incidences from Phase ill osteoporosis studios: frequency based, on adverse evenUlaboratory/rechallenge findings in earlier clinical tials. In @ one-year, double-blind, multicentre study comparing gedronate sodium mg dally (1=480) and risedronate sodium 58° mg weekly (n=405) in postmenopausal women wi osteoporosis, the overall safely and tolerability profiles wore Similar. The following. additional adverse. ‘experiences Ponsldered possibly or probably crag related by investigators than in risedronate ‘sodium 5 mg_group).. gastrointestinal disorder (1.6% va. 1.0%) and pain (1-2% vs. 0.8%). In. 2.year study in men with osteoporosis, the overall safety fan tolerability wore ‘similar betwoon the iveatment and the: Placebo groups, Adverse experiences were consistent with those previously observed in women Laboratory findings: Early, transient, asymptomatic and rnlld docroases In serum calcium and phosphate levels have been Sbeorvedin some patente overvose: No specific Information is available on the treatment of Overdose ‘with risedronate sodium. Decreases in serum calcium following substantial overdose may be expected, Signs and symptome of hypocalcemia may also oecurin some. ofthese pationts. Millk oF antacids containing magnesium, calcium or aluminium Should be given fo pind neadronate and reduce Sbsorption of Reedronate socium. In cases of substantial overdase, gastic lavage may be considered to remove unabsorbed risedronate Storage Conditions: Store at temperatures not exceeding 30°C, Protect from light Keep out of roach of children. Avaitabitity: TAIWPVCIPE/PVDC Blister Pack x 4's (Box of 4's) Caution: DR-xv45055 EBD we care Manufactured by 5, Dorvonaklon Streat, 153 51 Pall | Attkie, Greece: For MEGA LIFESCIENCES (AUSTRALIA) PTY LTD, Imported & Distributed by METRO DRUG, INC. Manalac Avenue, Bagumbayan, Taguig City, Philippines For suspected adverse drug reaction, fopon to the FDA: www.fda.gov.ph Date of First Authorization: 15 February 2016 Date of Revision of Package Insert: October 2018