8B Bone disorders MUSCULOSKELETAL DISORDERS 2VOLTAREN-XR Novartis __Ik NSAID (benzeneacetic acid deriv). Didofenac sodium 100mg; extel tabs Indications: Chronic therapy of osteoarthritis or rheumatoid arth. ‘Adults: Osteoarthritis: 100mg once cally. Rheumatoid arthitis: 100mg once daly, rately 100mg twice daly may be used: Children: Not recommended. Also: Diclofenac Sodium Delayed- 12 Release Tablets (various) Didlofenac sodium 25mg, 50mg, 75mg; exc tabs. Indications: Acute or chronic therapy of ostevarthvitis or rheumatoid arthrits. Ankylosing spondylitis. Adults: Osteoarthritis: 50mg 23 times daly ‘or 75mg twice daily. Rheumatoid arthritis: Sting 54 nes daly 78mg tice day Ankylosing sponayiitis: 25mg 4 tmes daily, with an additional 25mg at bedtime i necessary. Children: Not recommended. Contraindications: Aspirin allay. Late pregnancy. Coronary artery bypass graft surgery. Warnings/Precautions: Advanced renal disease: not recommended. Pept ulcers and Gl bleeding. Check SGPT/SGOT within 4 weeks and then periadicelly. Edema. Cardiac fli Hypertension. Bleeding disordes. Renal impairment. Hepatic porphyria. Monitor blood, hepatic, renal, and ocular function in chronic use. Elderly. Debiltated. Pregnancy (Cat.C). Nursing ‘mothers: not recommended, Interactions: Digoxin, methotrexate, cytlosporing, lithium toxicity. Hyper- and hypoglycemia with insulin and sufonylureas Reduced effect of dluretcs increased serun potassium level with K* sparing diuretics. ‘Avoid aspirin, Monitor oral anticoaguants. ‘Adverse reactions: Papticulcers, Gl bleeding, elevated SGPT or SGOT levels, araphyactoid eactiors, abdominal aiscomtor, constipation, ciarthea, ines, usta, tdaralesteton, headache, dizziness, fui retention, rash (disconsnueif occurs), prutitus, tinnitus. See literature re: risk of cardiovescular events. Generic availability: YES How supplied: XR—100; Tabs—contact supplier >XEWJANZ Prizer R Janus kinase (JAK) inhibitor Tofacitinio ‘5g; tabs. Indications: Moderately-to-severely active theumetoid arthritis (RA) in aduls who have had an inadequate resoons® or intolerance tomethotrexate (MTX; may be used as ‘monotherapy or in combination with MTX corothes narbiolagic dsease-modifyrg ant rheumatic drugs (DARDS). Adults: Smg twice daly. Moderate-te-severe renal impairment or moderate hepatic impairment; concomitant patent CYP3A4 infibitos, or drugs that result in both moderate CYP3AS and potent CYP2C19 inhibition: 5g ance dally. Concomitant potent CYP3A4 inducers: not recommended. Dose adjustments: see ful labeling Children: Not established. 126 Warnings/Precautions: Increase risk of serious oF fatal infections (eg, 18, bacteral, vir, invasive fungal, ar cther opportunistic pathogens). Active, serious orlocalzed infections: do rot initiate therapy. Chronic or history of reurrirg or opportunistic infections. Travel to, or residence in, areas with endemic TB or mycoses. Condtions that predispose to infection Test/treat latent TB infection pror to initiating therapy. Montor casey if ew ifcton, ace TB (even if initial latent test is negative), or reactivation of herpes virus occurs;mtetupt treatmentf seious or opportunistic infection, o sepsis develops. known malignancy. History of G perforations. Monitor hmphooyts at baseling then every 3 months:neutrophis and hemoglobin at baseline, after 4-8 weeks, ten every 3 months thereafter Do not initiate therepy if ymphocyes <500cells/mm?, ANC <1000cels/mm?, or hemoglobin ZORVOLEX troko R NSAID (benzeneacetic add derivative). Diclofenac 18mg, 35mg; hard gelatin cops. Indications: Osteoarthts pein Adults: Use lonesteffecive cose forthe Shortest rat Tke on em stat >18ys: 35mg threetimes dail. Hepatic impaitment: start atlowest dose; discontinue if efcacys nat achieved Children: <18yrs:not established. Contraindications: spin o: other NSAID allergy. Coronary artery bypass graft surge Warnings/Precautions: Not interchangeable to othe forms of oral didofenac. Increased risk of seious cardiovascular events, Ml, and stroke. Increased rick of serus Gl adverse events (eq, inflammation, bleeding, ulceration, perforation). History of ulcer disease or Gi bleeding, Fluid retention, Heart flue Hypertension; monitor BP closely Advanced renal disease! rot recommended. Pe-exsting asthma, Hepatic of renal dysfunction. Coagulation disorders. Moniter CBCs, blood chemistry hepatic and renal function in long- tem thefapy. Measure ALT andor AST within 4-8 weeks ater stating ard peiodcally inlong-term therapy. Discontinue if signs? symptoms o' liver or renal cisease develop, orif abnormal lve function tests persist or worsen, Dehydration. May mask signs of infection or painful conditions. Discontinue if ash or other signs ot hypersensitiviy occur Eldery Debilitated, Labor & delvery. Pregnancy (Cat.C: <30 weeks gestation); (CaLD:230 weeks gestation; avoid). Nursing mothers Interactions: Avsid concomitant aspirin, Increased risk of GI bleed with anticoagulants (rontor), oral corticosteroid, smoking, alcohol, or prolonged NSAID therapy. May antagonize ACE inhibitors, diuretics; monitor closely. Caution with lithium or mathotrexate; monitor for toxicity. Increased nephrotoxicity with cyclosporine; caution, May affect or be alfected by ¥P.2C9 inhibitors or substiates. Caution vith concomitant hepatotoxic drugs (eg, acetaminophen, certain antibiotics, antiepileptic) Adverse reactions: Edema, nausea, headache, dzziness, vomiting, constipation, pruritus, diarrhea, flatulence, pain in eatremity, abdominal pain, sinustis, ‘AlT/creatinine increase, dysgepsia; anemia, cardiovascular events, Gl ulcers, hepatotoncty, hypertension, renal paplary necrosis, rash. Generic availability: NO How supplied: Cps—30, 90 De ed 2ACTONEL Warner Chilcott B Bisphosphonate. Risecronate (as sodium) Smg, 30mg, 35mg, 150mg; tabs. Indications: Prevention and treatment of posimengnausal osteonarosisand alucocorticid-induced osteoporosis (men & ‘Womer). Treatment toincrease bone mass inmen with osteqporess.Teatment af Pager’ disease of bone, Limitations of use: optimal duration of use has not been determined. Fr patients at ow-tsk for fracture consider drug discontinuation after 3-5ys. Adults: Swallow whole; take in the AM with a ill giass (6-802) plan (not mineral water atleast 30min before other food or dink; take in upricht position; do not lie down for atleast 30min aftewwerds Postmenopausal Smig once dally or 35mg once weekly oF one 75mg tab taken on 2 consecutive days pet month or one 150mg tab once monthly. Glucocorticcid-induced: 5g once daly Osteaparosisin ren: 35mg once weekly. Paget’: 30g once dy 2 ons may reveat after a 2-month post-treatment evaluation period. Children: Not applicable. Contraindications: Esophagus abnormalities which delay esophageal emptying (eg, stricture, achalasia). Inability tostand or st upright for at least 30min. Hypocalcemia, ‘Warings/Precautions: Active upper Gleiseas; ciscontinue and reevaluate iMUSCULOSKELETAL DISORDERS Bone disorders 8B signs/symptoms of esephaceal reaction ‘occur, Severe renal impairment (CrCl -<30mL/min): not recommended. Corract preexisting hypocalcemia, other mineral orbone disturbances before staring Risk of osteonecrosis cf the jaw; consider discontnuing therapy during invasive dental procedures (e0, tooth extraction, implants, surgery). History of bisphosphonate exposure: evaluat for atypical fractures if ighgroin pain develops consider withholding therapy unl rik/benefit assessment, Obtain and conect sex steroid hormonal status before initiating therapy in glucacortcoid-nduced osteoporosis. Ensure adequate Vit. D and calcium intake. Reevaluate petioicaly. Pregnancy (Cal.C). Nursing mothers:not commended. Interactions: Cacium, aluminum, magnesium, other divalent cations reduce absorption (separate dosing). Caution with other Gl iritants. May interfere with bone- imaging agents, ‘Adverse reactions: Back pain, arthralgia, atdominal pain, dyspepsia constipation, others; atypical femur ractures rarely: dysphagia, esophagitis gastric uce, aw osteonecrosis; hypersensitty. Generic availability: YES How supplied: Tabs §ma, 30mo—30; 35mg—4, 12; 150mg—I, 3 >BINOSTO Mission B Bisphosphonate.Alencronate (as sodum) Toma; effenescent tats for oral son; strawbery flavor; contains 650mg sodium! Tab. Indications: Treatment of postmenopausal osteoporosis To increase bone mass in men with osteoporosis Limitations of use: optimal duration of use has not been determined. Adults: Dissolve one tab in 4oz plain (not mineral) water ony; ater effervescence ‘stops, wait Smins and stir soln for 10secs. Take in the AM atleast 30mins before the first food, dink, or medication of the day Do notlie dewn for atleast 30mins and unt after the first food of the day. 70mg ‘once weekly. Children: Not applicable. Contraindications: Esophagus abnormalities which delay esophageal emptying (eg, sticture, achalasia). inability tostand or stupignorateas soins Increased risk of aspiration. Hypocalcemia. Warnings/Precautions: ive upper Gl disease, discontinue and reevaluate if signs! symptoms of esophageal reaction occu ‘Severe renal impairment (CrCl <35mLimin}: not recommended. Correct preexisting hypocalcemia or ather mineral metabolism disorders (eg, Vit.D deficiency) before starting, Monitor for hypocalcemia during therapy. Ensure adequate Vit. D and calcium intake. Sodium restriction {including heart failure, hypertension, or ther casdiovascular diseases). Risk of osteonecrosis af the jaw; consider discontinuing therapy daring invasive dental procedures eg, tooth excaction, implant, suger). History - Contraindi + Tabs: Esophagus abnormalities which of bisphosphonate exposure: evaluate for aypical fractures i tnghigroin pain develops; consider withholding therapy until rskibeneft assessment, Reevaluate § periodically Pregnancy (Cat.C). Nutsing mothers. Interactions: Calcu supplements, antacids, other mulvalent catons reduce absorption (separate dosing by at least 30min). ncreesed upper Gl events with | asprn-containng products ard alendronate > lOmg/day; caution with NSAIDs. May be + antagonized by levathyraxine. Adverse reactions: Abdominal pain, acid requigtation, constipation, ciarthea, dyspepsia musculoskeletal pan (may be severe), nausea; esophauits, esophageal ulcers or erosions; jaw osteonecross atypical femur fractures, rarely: gastric or duodenal ulcer. Generic eNO How supplied: Tats—4, 12 2BONIVA Roche BR Bisphosptonate.lbendranate (as monosodium monohydrate) 150mg; tabs. Indications: Prevention and teatrient of ostmencpausal osteoporosis, imitations of use: optimal duration of use has not been determined. Far patients at low-risk for fracture: consider drug discontinuation after 3-5ys. Adults: Swallow whole. Take in the AM with plain (not mineral) water (6—Boz), at least 60mins before the frst food, drink, or medication ofthe day: do not le down for at least 6Omins ater. 156mg once monthly (ake gn tre same day each month) Dono ke two 150mg tablets within the same week Children: Not established. ‘Also: BONIVA INJECTION R Ibandranete (as manasodium monohydrate) 3mg/3ml; soln for IV in. ‘Adults: Must be given by healthcare professional. Give as IV bolus inj over 15-30secs. 3mg every 3 months; fdose is | missed, give as Soon as possible, then every 3 months from the date of asin Children: Not established. jons: Hypocalcemia, delay esophageal emptying (eg, sticture, + achalasia. Inability 10 stand or sit upright for atleast 6Omins Warnings/Precautions: Active upper disease; discontinue and reavaluate it signs/symotoms of esophageal reaction cccus Severe renal impaiment (CrCl -<30mL/min): not recommended. Correct preexisting hypocalcemia, other mineral or bone dsturbances before starting Risk of osteonecrosis of the jam; consider discontinuing therapy duing invasive dental procedures (eg, tooth extracion, implants, surgery), History of bisphosphonate exposure: evaluate for atypical fractures if thigh/groin pain develops; consider withholding therapy unt riskfoeneft assessment, Ensure adequate Vit, D and calcium intake. Reexaluate periodically In check renal function before each dose. Pregnancy (Cat.Q). Nusing mothers. Interactions: CAcium, aluminum, magnesium, other divalent cations reduce absorption (separate dosing). Caution with asprin, NSAIDs, oer Gl intants May interfere ‘with bone-maging agents. Concomitant nephrotoxic agents; monitor for ‘enal toxic. Adverse reactions: Back pain, dyspepsia, pain in extremity diarfnea, neadache, myalgia; musculoskeletal pain (may be seve) hag, esuphals esoplageel or gastic ules, jam osteonecrosis, atypical fenut fate. iin ste eatin, 4 syndrome, anaphylaxis Generic availability: Tabs (YES); inj (NO) How supplied: Tabs 'S0mg—3;Prelled syringe (Sml}—1 (w, supplies) EVISTA Lilly R _ Sect estogen eepformodator I (SERIM). Raloxifene HCl 60mg; tabs, Indications: Prevention and treatment of osteoporosis in postmenopausal women, ‘Adults: 601mg once daly Children: Not recommended. Contraindications: Active or history of venous thromboemboic events. Nursing mathers. Pregnancy (CatX). Women who may become pregnant. ‘Warnings/Precautions: Nat for use in premeropeusal wore. Concomitant systemic estiogen therapy: not recommended. Dscontinue 72 hours before, and dung prolonged immobilization; resume when fully ambulatory. Coronary heart dsease or rsk of coronary event (ineeased rk of death due to stroke Hepatic dysfunction. Moderate to severe renal impaiment. Interactions: May antagonize warfatin; imonito: Avoid concomitant cholestyramine, ather anion exchange resin. Caution with other highly protein-bound drugs (eg, diazepam, dazoxide,idocane) Adverse reactions: ot fishes leg cs, patipheral edema flu syndrome, arthralgia, sweating; rare: venous thromboembaic events Generic availability: YES How supplied: I3bs—30, 100, 2000 >FORTEO Lilly R ‘Hormone (human parathyroid hormone, recombinant Terparatide (ecombinant) 250mey/ml; soln tor SC inj contains m-cresol. Indications: Posmenopausal osteoporosis + Inwomen who are at high isk for fracture. Toincrease bone mass in men with primary orhypagonadal esteoporosis who are at high risk for fracture. Treatment of men and ‘women with osteoporosis associated with sustained glucocorticad therapy at high risk ‘oi fracture (see literature). ‘Adults: 20mcg SC once daly into thigh or abdominal wall; may treat for up to 2 years. Children: Not recommended, Warnings/Precautions:ineased baseline risk for osteosarcoma (eg, Paget's disease (©) FDA 505(b)(2) APPROVAL PATHWAY REFERENCE: Reviewon page 139 1278B Bone disorders MUSCULOSKELETAL DISORDERS ‘of bone, unexplained increased alkaline phosphatase, open epiphyses, pror skeletal ratiation therapy), bore metastases, history of skeletal malignancies, metabolic bene ease pecker ok terete, hyperparathyroidism): not recommender Uralthiais.dypercalcuria, Hepatic, renal, or catdiaccisesse.Preanancy (Cat.C). Nusino mothers: not ecommendes. Interactions: Caution with digoxin (teriparatide-induced hypercalcemia Increases tisk of toxiciy) Adverse reactions: Athralaa, pain, nausea; transient orthostatic hypotension, hypercalcemia, hyperuricemia, inj site reactions. Generic availability: NO How supplied: Multidose Pen (2.4m.}—1 2MIACALCIN Novartis K Hormone. Calcitonin-salmon 200 1Ukpray; nasal spray. Indications: Posimenopausal osteoporosis Inwomen >5ys postmenopausal Limitations of use: not shown to increase bone mineral densty in early pstmenopause. Adults: | spray (200 1) in alternating nests daily Children: Not established, Also: MIACALCIN INJECTION RB Caldtonin-saimon 200 IU/mL; SC or IM in Indications: Paget’ cisease of bone. Hypercalcemia, Postmenopausal osteaporosis inwomen >Syts postmenopausal ‘Adults: Paget's: 100 1U SC or IM daily. Hypercalcemia: intially 4 IUikg SC or M every 12hrs, may increase after 1-2 days to 8 IUikg cevary'12hrs,and then after2 moce days to ‘max 8 IU/kg every is, Postmenopausal osteoporosis: 100 1U SC or IM dally Children: Not established. Warnings/Precautions: Correct hypocalcemia an¢ other mineral metabolism dsordess belore initiating; monitar setumn calcium and hypocalcemia symptoms during therapy. Increased rsk of malignancies Re-evakiat petotcaly Fo nasal spay. do periodic nasal exams; discontinue ifsevere keratin ocr Fri consid pe occ exams of urine sediment; serum alkaline bhosohaas andunay hycronprlne InPagat.Pxtmenopaislosteporss supplement diet with calcium 1g/day and Vib 400 lUlday. Pregnancy (Cat.C). Nursing mothers, Interactions: May antagonize lithium (consider lithium dose adjustment) Adverse reactions: Nasal pray: hints, epistaxis, other nasal symptoms, back pain, arthralia, headache. Inj nausea, vomiting, local intammation, flushing, rast. Both: hypersensitivity reactions, anaphylaxis antibody formation. Generic availability: Spray (YES); n|(NO} How supplied: Nasal spray bot (3.7m) — 1 (30 doses) Muki-dose vies (2mL}—1 >PROLIA Amgen R Osteocast inhibitor (RANKL inhibitor). Denosumab 60mgiml; sln for SC in presenativesree Indications: n postmenopausal women with osteoporosis: at high rsk fracture, definedas a histor of osteoporetc facture, 128 cof multiple risk factrs for fracture; or patients who have failed or are intolerant to other therapy; to reduce incidence of vertebral, nonvertebral, and hi fractures, To increase bone mass in men with costeoporesis at high risk for fracture. To increase bone mass in men athigh risk for fracture receiving androgen deprivation thetepy for nonmetastatic prostate cancer; to reduce incidence of vertebral fractures. To increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibtor therapy for breast cance. Adults: Siould be administered bya healthcare proiesienal. 60mg SC once every 6 months; inject into upper afm, upper thigh, of abdomen. Children: Not established. Contraindications: Hypocalcemia Pregnancy (Cat.X), Warnings/Precautions: Correct hypocalcemia before starting; ensure adequate daily calcium (21000mg) and Vit. D (24001) intake, esp. in renal impairment (CrCle30mL/min). Monitor calcium, pphosohorus, magnesium levels in susceptible patients (eg, hypoparathyroidism, thyroid or Parahyrod sugerymalebsoiption,excion ‘of small intestine, severe renal impairment, on days). Monitor fr infectons, aw osteonecrosis, bone oversuppression. Do bhaseine cal exam ond preventive dents if risks forjaw osteonecrosis exist (e, toot extraction dental implants, otal surgery, poor oral hygiene, periodontal disease and/or other pre-existing dental disease, i-fiting dentures, cancer anemia, coagulopathy, infection). Consider discontinuing i severe skin feactons or musculoskeletal pain develop. Maintain qood oral hyaiene. Evaluate fr atypical fractures thigh! roin pain develops; consider withholding therapy unt beret assesment Immunosuppressed. Latex allergy (pre-filled syringe). Nursing mathets: not recommended (mayimpair mammary gfandslactaton) Interactions: Concomitant ather denosumab-containing products (eg, Xgeva): not recommended. Concomitant immunosuppressants (increased infection risk). Cortcosteroids chemotherapy (increased jaw osteonecrosis isk) Adverse reactions: Pain (bak, lower extremities or musculoskeletal, artvalgia, nnasogharyngits, hypercholesteolenia, sti; in'ections (may be serous; 29, celluitis, UT, otic, abdominal), dermatitis, rash, eczema, osteonecrcsis of jaw, atypical femr fractures suppression of bore tumever, exacerbation of hypecalemia, panceatitis, anaphylactic reactions (discontinue if occur). bility: NO Generic How supplied: Sinale-use viel (1mL}—1; Single-dose prefiled syringe (Iml}—1 >RECLAST Novartis BR Bisphosptonate. Zledronic acid Smg/T00mL bottle; soln for IV infusion. Indications: Teatment: postmenopausal steqporesis; to reduce the incidence of new clinical fractures in patients at high risk of fractures (those with recentlow-trauma hip fracture). Prevention of osteoporosis inpostmencpausal women. To increase bbane mass in men with osteoporosis. Paget's disease of bone (men and women). Treatment and prevention: glucocorticoid induced osteoporasis in men and women expected 1008 on glucocorticoids for at least 12 months (see full labeling). ‘Adults: Give by lV infusion over at least 15 minutes, CrCl 235mL/min: Osteoporosis treatment: Smg once a year, Osteoporosis prevention: mig once every 2 yrs Glucocorticcid-induced: 5ing once a year. For al: supplement with calcium and Vit. D, when needed. Paget's disease: asingle dose cof Smg; supplement with calcium 100mg daly in divided doses and Vit. D800 IU daly esp. duiing 2 wks post-treatment Children: Not recommended. Contraindications:rypocalcemia. CCl <35mLmin and evidence of acute renal impairment. Warnings/Precautions: creased tsk of renal impairment: pre-exsting renal compromise, advancec age, concomitant nephrotoxic digs or diuretics, ot severe dehydration. Chronic renal impairment. Monitor creatinine clearance before each dose and in at-isk patents. Corect Prensng hypocalcemia cher mine orbone disturbances before staring. Do baseline oral exam and preventive dentistry if risks for jaw osteonecrosis exist (eg, cancer, chemotherapy, angiogeness inhibitors, radiotherapy, Corvcosterolds, poor ore hygiene, pret cena seas infection, anemia, coagulopathy). Ensure adequate hydration, Vit.D and calcium intake. Histo of bisphosphonate exposure evaluate for atypical fractures if thighigroin pain develops; consider withholding therapy Until ristbenefit assessment. Asgirin-sensitive asthma Avoid dental surgery (da preventative dental work before therapy). Reevaluate periodically. Eldery. Pregnancy (Cat.D); avoid Use, Nutsing mothers: not recommended, Interactions: Avoid concomitant other ‘forms of zoledronic acd (eo, Zometa) Aditive hypocalcemic effect with ‘aminoglycosides, loop diuretics. Caution with ther nephrotoxic drugs (9, NSAIDS). Adverse reactions: Pyrexia, musculoskeletal pain (may be severe), headache, arthalaia, pain in extremity, nausea, vomiting, diarrhea, flu-like illness, eye inflammation, hypertersor, hypocalcemia; acute etal faiure, atypical femur fractures, rere osteonecross of the jaw. Generic availability: ¥é5 How supplied: fottle—t DOSAGE Recommended adult dosage and, where appropriate, the dosage for children. Doses are given for children <12 years of age unless stated otherwise. Assume the adult dosage for children 212 years. Dosages for children are presented in ascending age order.