Paget’s Disease (1 of 11)

1 Patient presents w/ signs & symptoms of Paget’s bone disease

2

DIAGNOSIS No ALTERNATIVE Is Paget’s bone disease DIAGNOSIS confi rmed?

Yes

3 MONITOR EVALUATION No DISEASE Should patient be PROGRESSION treated?

Yes

A Non-pharmacological therapy • Physical therapy B Pharmacological therapy Antiresorptive erapy • 1st-line agents: • 2nd-line agent: Pain management • Paracetamol • MIMSNonsteroidal anti-infl ammatory drugs (NSAIDs) • Selective COX-2 inhibitors C Surgery

E D FOLLOWUP EVERY MONITORING 36 MONTHS DISEASE © COMPLICATIONS

Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS.

B1 © MIMS 2019 PAGET’S BONE DISEASE • • • &Symptoms Signs • • • • • • formation &resorption ofbone tomonitor thedegree markers biochemical Measure • TestsLab • • • &MRI Scan CT • • • • • Scan Bone Radionuclide • • • X-ray Studies Imaging Pelvis &tibiaare oneofthe commonly most aff ected - enlargementBone (eg deformity oflongbones) skullenlargement, orbone bowing orjoint painisthe common most Bone symptom occur &symptoms signs oftimebefore foralongperiod Asymptomatic - - Pathophysiology: - - May aff (polyostotic) bones (monostotic) onebone orseveral ect - may play infection &/orviral arole inthe factors etiology Genetic - w/age, w/men more commonly increases aff Prevalence than women ected - &architecturally unstabledisordered ofthe skeleton causing enlargement parts &thickening inlocalized &turnover that oftheresorption bone is asignifi by ischaracterized deformans, osteitis as known Paget’s also disease, bone inbone cant increase Urinary excretion of & phosphorus may be normal orincreased normal may be excretion &phosphorus ofcalcium Urinary inextensive Paget’s that immobilization elevated may calcium causes be Serum disease N-telopeptide) Icollagen orurinary markers (eg type C-telopeptide breakdown serum Measure resorption: Bone ifpatient osteosarcoma further develops rises alkalinephosphatase Serum - specifi orbone alkalinephosphatase serum Measure turnover: Bone isnormal ifthe previous c alkalinephosphatase w/Paget’s disease suspected bone the 1st-line as isrecommended forpatients test (ALP) screening biochemical totalalkalinephosphatase Serum tool initialdiagnostic as Notroutinely used - stenosis) of Paget’s for assessment complicationsRecommended spinal (eg invagination, disease osteosarcoma, basilar Anatomy iswell demonstrated incomplex (eg structures spine) orMRI CT incross-sectional thickness cortical seen may be coarsening &increased w/trabecular Enlarged bones sign” face, clover“Mouse orheart ofaff pattern onscan vertebra ected uptake oftechnetium-99m ofincreased Areas bones asymptomatic possible identify May also extent involvement ofbone Determines lesions pagetic bone inidentifying test sensitive Most (ie“banana” fractures or“chalk” limbs, bowed fractures) sclerotic bone, transverse thickened lesions, near inthe skull,fl circumscripta Findings include lesions osteolytic inlongbones, lesions ame-shaped compared lesions x-ray w/79%foranabdominal 93%ofbone alone Detect - w/Paget’s inpatients disease tool suspected bone screening an initial diagnostic are as recommended tibias skull & both X-rays of the bones, abdomen, facial Confi ofPaget’s therms diagnosis disease bone © bone w/woven interspersed bone cell isanabnormal bone activity, phase, &chaotic out” lamellar reduced “burn markedly whichLate has abnormal bone ofastructurally indeposition formation which results bone ahighrate producing of activity osteoblastic anincreased by followed enlarged by , resorption Aff bone increased as that ofskeletal lesions starts anevolution shows biopsy) (via specimen bone ected complication serious &most malignancy isdevelopment ofbone on the heart, compression orinterference overgrowth stress supply, duetobone w/blood duetoincreased failure heart Complications include &/orfi fractures fragility, duetobone nerve ssures from symptoms neurologic humeri &clavicles spine,skull&femur, &sacrum, may frequency, bone include pelvic involved bones decreasing By tibia, 1 Paget’s BoneDisease(2of11) CLINICAL MANIFESTATION 2 MIMS DIAGNOSIS B2 © MIMS 2019 PAGET’S BONE DISEASE • • • • • • • • • • • • • Bisphosphonates Antiresorptive erapy • • Physical erapy Patient shouldreceive w/hypercalcemia immobilization from pharmacotherapy resulting &extensive Paget’s disease disease Heart bone - markers turnover orbone scan bone by determined as activity Metabolic - ofpagetic Sites lesions - - ofactivePaget’s (eg &symptoms deformity) Signs painat pagetic site&bone disease bone - onthePatient following: depending treated shouldbe Improvement inpatient’s quality oflife - healing Radiographic - replacement bone Abnormal lamellar w/normal bone - markers ofother turnover bone &normalization level ALP inserum Decrease - Painreduction - factors: the by following totherapy isguided Response Patient shouldreceive pharmacotherapy onpagetic site surgery toelective prior (1500mg/day)Patients ofCa &Vit shouldreceive adequate doses D(800units/day) toavoid hypocalcemia value (ULN) May is>2-4xthe limitofnormal initiate upper treatment level ALP ifthe serum - patients &presence lesion ofcomorbidities oftheImportant tonotethe pagetic bone location intreating asymptomatic complications remission &prevent obtain full oftreatment ofthe pagetic pain,reduce disease, activity Goals are toease - patients inmost upto1-2years last remissions &can are Biochemical sustained - acidisthe potent inthe most approved States United forPaget’sZoledronic disease bone once administered May the be patient isstable - lesion topagetic bone inpatients presenting used w/fracture may secondary Bisphosphonates be pagetic bone foractivePaget’s patientsRecommended complications at offuture of risk tosurgery disease &prior bone Relatively sideeff safew/variable profiect - amongdiffles erent bisphosphonates eff Prolonged effectiveness; - ofwithdrawal remain years after ects - lesions bone heal loss, stabilize hearing complications, pain,improve neurological bone Decrease resorption bone &decrease activity Inhibit Eg ,,Tiludronate, acid,, Zoledronic Helps tomaintain fl endurance &jointexibility range &avoid ofmotion,increase deconditioning Improves muscle strength tohelp control ofpain certain types (eg skull base involvement(eg skullbase that may todeafness) lead activePaget’s likely complications butw/biochemically tocause Asymptomatic inthe disease future bone on several drug treatment drug forotheron several conditions effi ofits because Preferred drug whoare already &those inpatients w/more extensive disease especially cacy © &collagen-derived N-telopeptides pyridinoline effBiochemical concentrations excretion ALP ofhydroxyproline, 50%ofserum by &urinary Decrease ects: Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A NON-PHARMACOLOGICAL THERAPY B PHARMACOLOGICAL THERAPY Paget’s BoneDisease(3of11) P RINCIPLES OF THERAPY 3 MIMS EVALUATION B3 © MIMS 2019 PAGET’S BONE DISEASE • • COX-2 Inhibitors • • Anti-inflNonsteroidal (NSAIDs) Drugs ammatory • (Acetaminophen) Paracetamol • • • Pain Management • • • • Calcitonin • • • • • (Cont’d)Bisphosphonates • • • tolerance anti-inflHave analgesic, (GI) improved gastrointestinal w/reported properties &antipyretic ammatory inhibitionofCOX-2Selective pathway inhibitingCOX-1 without pathway anti-inflHave analgesic, properties &antipyretic ammatory (COX)-1 &COX-2 inhibitionofcyclooxygenase non-selective Act pathway as properties w/antipyretic Analgesic therapy pagetic paininadditiontoresorptive Relieve deformity,Manage painduetobone complications orneurological arthritis therapy generally pagetic pain Resorptive relieves - - lesions bone heals loss, hearing stabilizes complications, pain,improves neurological bone Decrease Alternative forpatients tolerate who cannot orwhen bisphosphonates bisphophonates are contraindicated resorption bone &decrease activity Inhibit osteoclast Ccells by ofthe thyroid secreted gland 32 aminoacidhormone subtrochanteric &diaphyseal femur ofatypical risk fractures w/possible Associated intravenously given be &can orintramuscularly trial butisavailablea randomized countries onlyinsome Neridronate is a -containing bisphosphonate w/ comparable effi in shown acid as to Zoledronic cacy inyounger preferred Also patients disease w/limited - Alendronic more eff acidisalso than Etidronicective acid - bisphosphonates w/other treated thanAlendronic Pamidronic acidismoreinpatients effective previously inyounger Preferred patients disease w/limited - acidismore effRisedronic than Etidronicective acid patients resistance acid&some may drug develop Zoledronic Pamidronic acidisanalternative intravenous agent compared longer potent w/ &takes butisless toinfuse Relief ofcompression duetopagetic vertebrae onthe roots spinalcord ornerve - - where pharmacotherapy isineff incases pain,especially mechanical realignment todecrease Knee ective - Pagetic fracture repair - for: Recommended onthe timingofsuch yet recommended treatment trials Noclinical - ofactivePaget’s asymptom disease hypervascularity, bone dueto surgery during bleeding toprevent serious w/ bisphosphonates Surgical patients pretreated should be Eg joint replacement, osteotomy, fracture repair (nausea, fl(nausea, ushing) Short-lived eff recurrences occur withdrawal; rapidly highincidence after eff ofadverse ectiveness; ects treatment longas continuesremain as at levels these effBiochemical hydroxyproline 3-6 within &urinary months ALP & inserum Up to30-50%decrease ect: ©ineff ective (OA) where treatment therapy antiresorptive orosteoarthritis is replacement incases Hip/knee especially B Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Paget’s BoneDisease(4of11) C MIMS SURGERY B4 © MIMS 2019 PAGET’S BONE DISEASE • • • • • ofdisease severity upon depend will offollow-up &extent Frequency • • • • failure heart Congestive • • • Neoplasms • • extremity oflower Bowing • • • Paralysis • • • Osteoarthritis • • loss Hearing oftheBone &Management ofPaget’sComplications Disease Long-term evolution increases the risk for osteosarcoma onpagetic bone theforosteosarcoma risk increases evolution Long-term patient inasymptomatic ALP nadirofserum >25%above - Symptom relapse orpersistence - If treatment isapparent failure consider re-treatment 6months the initialtherapy after forthe following: - oftreatment are inroutine notgenerally monitoring (egscan) useful response bone tests imaging Serial forpatients w/untreated Paget’s monostotic [NTx] measured may assay) be disease collagen β [P1NP], A more specifi 1 oftype propeptide marker other (ieamino-terminal formation/resorption thanc bone ALP - tobisphosphonate therapy 3-6months response the biochemical todetermine every ALP Monitor serum Bisphosphonate treatmentBisphosphonate inpatients w/Paget’s isrecommended failure w/congestive heart disease An eff treatmentective improves the symptoms skeletal involvement resistance are present forpatients vascular suff output peripheral highcardiac &low Both extensive from ering High output may failure cardiac occur, but isnotcommon pagetic bone For surgery, planned pretreatment adjacent from w/ to a reducepotent bisphosphonate bleeding is suggested surgeon anorthopedic by Osteosarcoma oragiant cell tumor patients evaluated shouldbe proliferationA rare complication duetoosteoblast pagetic that bone from arise ofthe extremity lower bowing severe tocorrect onpatients anosteotomy issuggested requiring surgery toelective A potent bisphosphonate prior joint w/impaired pain ambulation &/orsevere Associated optimal although the damage, mayrequired structural outcome surgery be of severe may always not be in cases But therapy patients most recover medical w/paralysis well after ofischemia, tocorrection Due consultation treatment alongw/neurosurgical Immediate bisphosphonate issuggested w/apotent IV - occurs when thereParaplegia isaPaget’s ofthe spine disease joint replacement bisphosphonate therapy undergoing before isrecommended total elective osteoarthritis, In patients w/severe deterioration cartilage  joint by anadjunctive joint therapy paincaused as formild-to-moderate issuggested ofanalgesics euse A relatively common complication, the such hiporknee inweightbearing joints as particularly defiIt apotent bisphosphonate ofhearing toprevent touse worsening issuggested cit A potential complication ofPaget’s when isinvolved the temporal bone disease monostotic disease monostotic months 6-12 treatment after oftreatment inmonitoring helpful may response be inpatients scan w/ Bone activity marker ofbone a as 1-2x/year plateaus measured 3-6 after be ALP Once itcan months ofserum the value ofassessment,

© collagen of type-1 [β propeptide C-terminal Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not E Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing MONITORING DISEASE COMPLICATIONS D Paget’s BoneDisease(5of11) MIMS FOLLOW-UP & MONITORING B5 CTx], N-terminal propeptide of type 1 collagenCTx], of type propeptide N-terminal © MIMS 2019 PAGET’S BONE DISEASE acid) (Acetylsalicylic Aspirin &Derivatives Acid Salicylic (Acetaminophen) Paracetamol Anilide Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © doses divided in 3.6-5.4 g/day PO dose: Maintenance doses individed PO 2.4-3.6g/day dose: Initial 4g/day dose: Max 4-6hrly 500-1000 mgPO Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage ANALGESICS (NON-OPIOIDS) ANALGESICS Paget’s BoneDisease(6of11) Dosage Guidelines • • • • Instructions Special • • Reactions Adverse • • Instructions Special • Reactions Adverse

MIMS surgery scheduled to days prior several stopped shouldbe Aspirin deficiency, DM impairment, dehydration, uncontrolled G6PD hypertension, ulcer, renal orhepatic orallergic asthma disorders, w/gastric w/caution inpatientsUsed prone todyspepsia, 3rd trimester) (especially hepatic impairment, pregnancy renal or severe toother ofallergy NSAIDs, history disorders, Avoid inpatients use w/hemophilia orother hemorrhagic GIeff todecrease w/food given May be ects large doses of use may confusion) headache, repeated occur after N/V, sweating, deafness, tinnitus, (dizziness, Salicylism Other effdyspnea); (hepatotoxicity) ect (bronchospasm, reactions Hypersensitivity angioedema); eff hypoprothrombinemia);use, Dermatologic (urticaria, ects Hematologic eff ( defiect long-term anemia after ciency GI eff (N/V,ects ulceration, hematemesis); dyspepsia, impairment G6PDdefialcoholic liver disease, ciency, renal severe w/caution inpatientsUsed w/chronic malnutrition, Avoid hepatic oractiveliver inpatients disease use w/severe reactions) hypersensitivity Other effphosphatase); (nephropathy,ects Hepatic effneutropenia); alkaline bilirubin, (increase ects acid,glucose); Hematologic eff uric increase (anemia, ects effDermatologic eff Metabolic (rash); ect (may ects B6 Remarks © MIMS 2019 PAGET’S BONE DISEASE Oxycodone 4-6hrly 30mgPO Dihydrocodeine (Alendronate) Alendronic acid Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All Max dose: 400mg/day dose: Max 5 mgSC4hrly or necessary as increased dose, starting infusion 2 mg/hrIV 1-2 min4hrly or over bolus 1-10 mgIV 4-6hrly or 5 mgPO opioid therapy: Patients onchronic 160mg/day dose: Max 7.5 mgSC24hrly 12 hrly or 5-10mgPO dose: Initial patients: Opioid-naive Individualize dose Max dose: 60mg/dose dose: Max pain forsevere mg/day 240 May increaseupto © 24hrly x6mth40 mgPO Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage Paget’s BoneDisease(7of11) Dosage Guidelines ANALGESIC (OPIOID) BISPHOSPHONATES • • • Instructions Special • • Reactions Adverse

MIMS inpatients foruse Contraindicated <18yr Oxycodone: myasthenia gravis inflshock, disorders, bowel orobstructive ammatory hypotension, prostatic hyperplasia, hepatic function, insuffiadrenocortical impairedciency, renal or asthma, Use w/caution inpatients w/hypothyroidism, intracranial pressure injuries &raised head disorders, acutealcoholism, convulsive disease, airways obstructive in patients Contraindicated depression, w/resp coma &deepening failure w/ circulatory &hypotension may depression toresp lead High doses potentially fatal) muscle which may rigidity, edema be miosis, pulmonary libido, decreased restlessness, hypothermia, (sweating, intracranial pressure); Other eff raised confusion, ects GI eff (N/V,ects eff constipation); CNS (drowsiness, ects • • • • • Instructions Special • Reactions Adverse B7 inadequate dietary intake inadequate dietary &VitCa Dsupplementation if isrecommended period evaluation 6mth ofrelapse after evidence post-treatment Re-treatment considered may forpatients be w/ eff toassess ALP Monitor serum oftreatmentectiveness - Do not administer at bedtime or before arising for arising orbefore notadminister at Do bedtime - - donot the tablet, swallow Inanupright position, - ofthe day ormedication toenhancebeverage absorption Administer w/plainwater 1stfood, 30minbefore impairment (Cr renal inpatientsContraindicated w/severe (occasionally w/photosensitivity) ulcers); Rashes Upper GIeff esophageal esophagitis, (GIdiscomfort, ects the day tostomach &toavoidirritation delivery esophageal administration drug tofacilitate 30 minfollowing for liquid ordrugs any oringest food, notliedown Do orsuck chew Cl <35 mL/min),pregnancy, lactation Remarks Remarks © MIMS 2019 PAGET’S BONE DISEASE (Risedronate) (Risedronate) acid Risedronic (Pamidronate) acid Pamidronic (Etidronate) Etidronic acid Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 24 hrly x2mth 30 mgPO occurs orrelapse disease remission of 6mthafter until dose May repeat 90 mg/L dose: Max ≤15-30 mg/2hr) rate of (60 mg:infusion of210mg dose uptototal week other once every IV 60 mgslow initially, then IV 30 mgslow or of180mg dose wkly uptototal once IV 30 mgslow 20 mg/kg/day dose: Max a time mth for>3 given at should notbe & cases for severe reserved should be >10 mg/kg/day Doses x<6mthPO 5 mg/kg/day dose: Initial & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © Dosage Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing BISPHOSPHONATES (CONT’D) Paget’s BoneDisease(8of11) Dosage Guidelines • • • • • • Instructions Special • Reactions Adverse • • • • • Instructions Special • Reactions Adverse • • • • Instructions Special • Reactions Adverse hypocalcemia &VitCa Dsupplementation tohelp isrecommended prevent eff toassess ALP Monitor serum oftreatmentectiveness dose phosphate each before & Ca electrolytes, creatinine,Monitor renal serum function, the during 1st2wkoftreatment closely monitored should be orthrombocytopenia leukopenia Patients w/pre-existing anemia, infusions Ca-containing IV inj orw/other bolus or bisphosphonates as notgive Do ofrenal >90mgduetorisk toxicity shouldnotbe dose Each - impairment, disease cardiac Use w/caution inpatients hepatic w/renal impairment, severe Other eff (GUinfection) ect Renal effgranulocytopenia); creatinine); inserum (increase ect (N/V, pain);Hematologic abdominal eff anorexia, (anemia, ects effMetabolic GIeff hypokalemia); (hypophosphatemia, ects ects effCNS (transient fever,ects insomnia); headache, fatigue, intake, but to be taken a few hr apart from Risedronic acid Risedronic hrapart from takenintake, afew buttobe &VitCa Dsupplementation ifinadequate dietary isrecommended ofrelapse 2mthevidence period post-treatment after evaluation Re-treatment w/the samedosage considered may forpatients be w/ eff toassess ALP Monitor serum oftreatmentectiveness AlendronateAdminister same as renal impairment severe stricture, achalasia), (eg inpatientsContraindicated ofthe w/abnormalities esophagus ofthe jaw) osteonecrosis eff rarely infection, tinnitus, (musculoskeletal pain,cataract, ects eff CV depression); Other edema); peripheral (hypertension, ects eff CNS N/V); diarrhea, glossitis, dizziness, (headache, ects MIMSGI eff ulcers, esophageal esophagitis, discomfort, (abdominal ects period evaluation for patients 3mth ofrelapse after w/evidence post-treatment dosage) considered may be Re-treatment (w/initialorincreased administration Separate w/Etidronic 2hr acidby - intake &VitCa Dsupplementation ifinadequate dietary recommended eff toassess ALP Monitor serum oftreatmentectiveness minerals administration orantacids orafter 2hrbefore taken vitamins, onanemptyShould be stomach w/nofood, rarely rashes) defect, Otherheadache); eff mineralization painfrom bone (increased ects eff CNS hypocalcemia); hyperphosphatemia, (depression, ects GI eff eff Metabolic diarrhea); cramps, (abdominal ects (mild ects B8 Remarks © MIMS 2019 PAGET’S BONE DISEASE acid Zoledronic (Tiludronate) Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed yearly singledose as infusion 5 mgIV 24 hrly x 3 mth 400 mgPO & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © Dosage Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing BISPHOSPHONATES (CONT’D) Paget’s BoneDisease(9of11) • • • • • • • Instructions Special • • Reactions Adverse • • • • • Instructions Special • Reactions Adverse Dosage Guidelines after administration after Supplement 1500mg/day w/Calcium &Vit D800units/day 14days 3-4mth every oforalcavity tissues hard &soft Assess - Avoid dental whileon treatment invasive procedures - ofthe jaws osteonecrosis initiating treatment in patients at ofosteomyelitis & risk Consider dental w/appropriate exam actionbefore corrective dose each before renal function Assess - phosphate &Mg Ca, electrolytes, Monitor serum eff toassess ALP Monitor serum oftreatmentectiveness Ensure adequate hydration throughout therapy &maintain - other from 15mininalineseparate over medications Infuse Use w/caution inpatients w/mildtomoderate renal impairment renal in patientsContraindicated impairment w/severe dyspnea) neutropenia, anemia, Other eff insomnia); fever,(fatigue, dizziness, headache, (rigors, ects back pain);Renal effdefect, eff (renal CNS deterioration); ect ects effMusculoskeletal mineralization painfrom bone (increased ects GI eff (N/V,ects pain); abdominal constipation, anorexia, effMetabolic (dehydration, hypophosphatemia); ects hypocalcemia, Acute may reaction infusion the occur within 1st3days following Tiludronic acid &VitEnsure Ca Dsupplementation taken 2hrapart from tobe eff toassess ALP Monitor serum oftreatmentectiveness the tablet w/plenty ofplainwater swallow Inanupright position, - other timeofthe day bedtime or30minbefore at any &medication beverage Administer food, 2hrapartfrom Use w/caution inpatients w/mildtomoderate renal impairment renal in patientsContraindicated impairment, pregnancy w/severe ofthe jaw)rarely osteonecrosis eff disturbances, ocular asthenia, (musculoskeletal pain, rashes, ects eff Metabolic N/V); Other hypophosphatemia); (hypocalcemia, ects GIeff dizziness); headache, insomnia, (fatigue, (dysphagia, ects effCV (flects eff CNS hypertension); edema, peripheral ushing, ects MIMS output of2L/day urinary orsuck (200 mL),donotchew B9 Remarks © MIMS 2019 PAGET’S BONE DISEASE Salcatonin) salmon, (Calcitonin Calcitonin Etoricoxib 120 mg PO 24hrly 120mgPO Etoricoxib Celecoxib Inhibitor COX-2 Selective 12hrly 100-200mgPO Tolmetin Sulindac 6-8hrly 200-400mgPO (Indomethacin) Indometacin Etodolac sodium) Diclofenac potassium, (Diclofenac Diclofenac Derivatives Acetic Acid Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed NONSTEROIDAL ANTI-INFLAMMATORY DRUGS(NSAIDs) 120 mg PO 24hrly for8days 120mgPO dose: Max 12hrly 200mgPO dose: Maintenance on1stday 200mgifnecessary by once followed 400mgPO dose: Initial 1800mg/day dose: Max doses divided in 600-1800mg/day PO dose: Maintenance 8hrly 400mgPO dose: Initial 400mg/day dose: Max onresponse based May dose lower doses) rectal 200mg/day (combined dose: oral& Max at orsupprectally bedtime 100 mgPO For stiff ofmorning relief pain: &night ness 150-200mg/day dose: Max intervals 25-50mg/day by at dose wkly May increase dose: Initial 1g/day dose: Max 75 mgIM12-24hrly or 75-150 mg/day rectally suppadministered or doses individed 75-150 mg/day PO 3-18 mth Duration: doses divided orin intranasal 200-400 IU/day spray: Nasal other day 24 hrly or every 50-100 IUIM/SC & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © Dosage Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 25-50 mg PO 8-12hrly 25-50 mgPO Paget’s BoneDisease(10of11) Dosage Dosage Guidelines • • • • Instructions Special • Reactions Adverse Avoid ofosteoporosis risk ethanol increase which can spray ofnasal foruse irritation Monitor fornasal used parenteral be will soln initiating before administered therapy shouldbe Skin if test concentration eff toassess oftreatmentectiveness hydroxyproline &urinary alkalinephosphatase Monitor serum rashes) reaction, (musculoskeletal pain,fl inj abnormal vision, site u-like symptoms, GI eff inj after (N/V,ects pain);Other eff abdominal diarrhea, ects eff CNS hypertension); angina, dizziness); depression, (fatigue, ects effResp eff ulceration) nasal CV (rhinitis, ects (flects ushing, CALCITONIN

B10 MIMS • • • Instructions Special • • Reactions Adverse - Coxibs should be used w/caution in used shouldbe Coxibs - hepatic orrenal impairmentdisorders, hemorrhagic allergic disorders, or asthma infections, hypertension, Use w/ caution inpatients w/ - Coxibs should not be used inpatients used shouldnotbe Coxibs - orother NSAIDs toAspirin allergy of history failure, ulceration, heart severe s Avoid inpatients use w/activepeptic t c ff e e GI todecrease w/food given May be GIeff lesser has Coxibs ects photosensitivity, pancreatitis) flhematuria, uid retention, (hepatotoxicity, nephrotoxicity, Other effneutropenia); ects eff thrombocytopenia, (anemia, ects occur rarely); Hematologicsyndrome Stevens-Johnson rashes, bronchospasm, (angioedema, reactions Hypersensitivity insomnia); drowsiness, depression, tinnitus, nervousness, dizziness, effCNS vertigo, (headache, ects ulceration, peptic GIbleeding); diarrhea, GI eff GIdiscomfort, (nausea, ects Remarks disease heart fordeveloping factors risk w/ failure, ofcardiac history edema, patients ventricular failure, w/left disease, cerebrovascular disease disease, arterial peripheral disease, heart ischemic failure, w/ moderate heart Remarks © MIMS 2019 PAGET’S BONE DISEASE 1 Preparations containing information. the forprescribing Ibuprofen latest MIMS &Paracetamol see are available. Please Ibuprofen Fenbufen 24hrly 20mgPO Derivatives Propionic Acid Tenoxicam singledose as 7.5-15mg/day PO Piroxicam 8-12hrly divided 8-16mg/day PO Meloxicam 8hrly 250-500mgPO Lornoxicam Derivatives Oxicam Mefenamic Fenamic Derivatives Acid Nimesulide 100-200 mg PO 12 hrly 100-200mgPO Nimesulide at bedtime asingledose as 1000mgPO 24hrly 8hrly or60-120mgPO 60mgPO Nabumetone Loxoprofen Agents Other Difl unisal &Derivative Acid Salicylic Naproxen 6-8hrly 25-50mgPO Ketoprofen Drug 1 NONSTEROIDAL ANTI-INFLAMMATORY (CONT’D) DRUGS(NSAIDs) Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed evening inthe inthe & 600 mgPO morning 300 mgPO or inthe evening in the &450mgPO morning or doses individed 900 mg/day PO 10mg/day dose: Maintenance 24hrly x1-2wk 20 mgPO dose: Maintenance x2days doses 24hrly orindivided 40 mgPO dose: Initial 15mg/day dose: Max morning dose in severe cases insevere dose morning a as Additional added 500-1000mgmay be 1500mg/day dose: Max 8-12hrly PO initially,500-1000 mgPO then 250-500mg 1000 mg/day thereafter 1275mg/day onthe dose: 1stday,Max then 6-8hrly 250mgPO dose: Maintenance once 500mgPO dose: Initial 12-24 hrly supp as rectally administered 100 mgtobe or 300mg/day dose: Max 2.4g/day dose: Max required as dose May increase doses individed 600-1800 mg/day PO & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please Paget’s BoneDisease(11of11) Dosage Dosage Guidelines 450 mg PO 450 mgPO

B11 MIMS • • • Instructions Special • • Reactions Adverse - Coxibs should be used w/caution in used shouldbe Coxibs - hepatic orrenal impairmentdisorders, hemorrhagic allergic disorders, or asthma infections, hypertension, Use w/caution inpatients w/ - Coxibs should not be used in used shouldnotbe Coxibs - orother NSAIDs toAspirin of allergy history failure, ulceration, heart severe Avoid inpatients use w/activepeptic s t c ff e e GI todecrease w/food given May be GIeff lesser has Coxibs ects pancreatitis) retention, photosensitivity, nephrotoxicity, fl hematuria, uid Other eff (hepatotoxicity,ects neutropenia); thrombocytopenia, rarely); Hematologic eff (anemia, ects occur syndrome Stevens-Johnson rashes, bronchospasm, (angioedema, reactions Hypersensitivity insomnia); drowsiness, depression, tinnitus, nervousness, vertigo, dizziness, eff CNS bleeding); (headache, ects ulceration, peptic GI diarrhea, GI eff GIdiscomfort, (nausea, ects disease heart fordeveloping factors risk w/ failure, ofcardiac history edema, patients ventricular failure, w/left disease cerebrovascular disease, arterial peripheral disease, ischemic heart failure, patients w/moderate heart Remarks © MIMS 2019