Sample content. Australian Medicines Handbook Pty Ltd

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1 .3.3 ACE inhibitors.3.3 ACE inhibitors See lso p 237, Acute coronry syndromes p 320, p 252 Also known s ngiotensin converting enzyme inhibitors. Cptopril p 22 Enlpril p 22 Fosinopril p 22 Lisinopril p 23 Perindopril p 23 Quinpril p 24 Rmipril p 24 Trndolpril p 25 Mode of ction ACE inhibitors block conversion of ngiotensin I to ngiotensin II nd lso inhibit the brekdown of brdykinin. They reduce the effects of ngiotensin II-induced vsoconstriction, sodium retention nd ldosterone relese. They lso reduce the effect of ngiotensin II on sympthetic nervous ctivity nd growth fctors. Dibetic nephropthy Prevention of progressive renl filure in ptients with persistent proteinuri (> g dily) Precutions Volume or sodium depletion my ctivte the renin ngiotensin system; this my result in excessive hypotension when n ngiotensinblocking drug is strted; correct (eg by reducing diuretic dosge) before tretment nd/or monitor crefully. Primry hyperldosteronism n ACE inhibitor my be ineffective; seek specilist dvice. Blck Africn or Cribben descent ntihypertensive effect of ACE inhibitor monotherpy my be reduced (generlly clcium chnnel blocker or thizide diuretic is more effective). Tretment with drugs tht cn increse potssium concentrtion, eg trimethoprim, ciclosporin increses risk of hyperklemi; void combintion or monitor potssium concentrtion. Crdiovsculr Limited dt suggest tht ACE inhibitors re beneficil in selected ptients with ortic stenosis (theoreticlly they my cuse coronry hypoperfusion, systemic hypotension nd reduced renl function); cution is needed to void hypotension. Ptients with peripherl vsculr disese or therosclerosis my be more likely to hve renl rtery stenosis, incresing the risk of renl filure. Angioedem Tretment with scubitril with vlsrtn is contrindicted with n ACE inhibitor due to the incresed risk of ngioedem (llow 3 hours between stopping n ACE inhibitor nd strting scubitril with vlsrtn). ACE inhibitors increse the risk of further episodes of ngioedem in people with hereditry, idiopthic or ACE inhibitor-induced ngioedem; use lterntive clss or seek specilist dvice. Tretment with n mtor inhibitor (eg everolimus), dipeptidyl peptidse-4 inhibitor (eg sitgliptin), or lteplse my lso increse the risk of ngioedem. Renl Renl impirment increses risk of hyperklemi nd my ffect the excretion of some ACE inhibitors; use lower initil doses nd monitor potssium concentrtion. Renl impirment my worsen, especilly in people with hypovolemi, or if used with NSAIDs (including selective COX-2 inhibitors). Serum cretinine my increse fter strting tretment or incresing the dose (usully stbilises within the first 2 months): if increse is <30% or glomerulr filtrtion rte (GFR) reduction is <25%, there is no need to djust dose if increse is >30% (or GFR reduction is >25%), investigte other cuses nd if necessry, reduce dose or stop ACE inhibitor nd consider specilist referrl. ACE inhibitors increse risk of renl filure in bilterl renl rtery stenosis. Hemodilysis with high flux polycrylonitrile membrnes (AN 9) my result in nphylctoid rections; similr rections my occur in ptients on low density lipoprotein pheresis with dextrn sulfte. Surgery Excessive hypotension my occur during nesthesi nd fter surgery. Elderly My be more predisposed to first-dose hypotension, hyperklemi nd renovsculr disese thn younger ptients. Strt tretment with lower doses; monitor renl function closely. Women Avoid in women plnning to conceive or who re using indequte contrception. Pregnncy Avoid use; chnge women to n lterntive ntihypertensive s soon s possible during the first trimester. Use in the second nd third trimesters my cuse fetl renl dysfunction nd oligohydrmnios, nd subsequently fetl deth. Contrindicted by mnufcturers. Brestfeeding No dverse effects in infnts reported with cptopril or enlpril; insufficient informtion to confirm sfety of other ACE inhibitors. Adverse effects Common (>%) hypotension, hedche, dizziness, cough (below), hyperklemi, ftigue, nuse, renl impirment Infrequent (0. %) ngioedem (below), rsh (especilly cptopril), dirrhoe, elevted heptic minotrnsferses nd bilirubin Smple content Austrlin Medicines Hndbook Pty Ltd

2 .3.3 ACE inhibitors Rre (<0.%) heptitis (cholesttic or heptocellulr), pncretitis, hypontremi, photosensitivity, psorisis Cough A persistent, nonproductive cough is common; it is not dose-dependent nd is unlikely to respond to tretment. It cn occur within dys to months of strting tretment. The cough my be mild nd tolerble, however, some ptients need to stop tretment (usully improves within 4 weeks of stopping). Angioedem My ffect the fce, lips, tongue, upper irwy, nd less often, the GI trct (cusing bdominl pin, vomiting nd dirrhoe). It cn occur within the first week of tretment, but is possible months or yers lter. Comprtive informtion Advntges for specific ACE inhibitors re climed bsed on phrmcokinetic, metbolic or tissue ACE-binding chrcteristics, however, these do not trnslte into significnt clinicl differences. Most (except cptopril) mintin n ntihypertensive effect for up to 24 hours nd cn be given once dily. Most re vilble s fixed-dose combintions (p 254) with diuretic (hydrochlorothizide or indpmide) or clcium chnnel blocker. in hert filure Begin with low dose (risk of hypotension, prticulrly if the ptient is elderly or tking diuretic), then grdully titrte upwrds t short intervls (eg every 2 4 weeks) to the highest tolerble mintennce dose. A more rpid dose escltion my be possible in closely monitored situtions. Counselling You my feel dizzy when you strt tking this medicine. Get up grdully from sitting or lying to minimise this effect; sit or lie down if you become dizzy or light-heded. Do not tke potssium supplements while you re tking this medicine unless your doctor tells you to. Prctice points when strting n ACE inhibitor: stop potssium supplements nd potssiumspring diuretics in hert filure, consider reducing dose or withholding other diuretics for 24 hours before strting n ACE inhibitor review use of NSAIDs (including selective COX-2 inhibitors) strt with low dose check renl function nd electrolytes before strting n ACE inhibitor nd review fter 2 weeks Tretment with n ACE inhibitor nd srtn See lso Tble Mngement of systolic hert filure p 237 in trils the combintion worsened renl function nd incresed the risk of symptomtic hypotension nd hyperklemi the combintion did not provide dditionl benefit in ptients t high risk of vsculr disese nor improve survivl in ptients with left ventriculr filure/dysfunction fter MI despite conflicting tril results, it my be n option, eg for selected ptients with chronic hert filure or non-responsive BP, seek specilist dvice Cptopril in ptients with left ventriculr dysfunction Dibetic nephropthy (type dibetes) Precutions Collgen vsculr disorders (eg scleroderm, systemic lupus erythemtosus), severe renl impirment my predispose to neutropeni or grnulocytosis. Adverse effects Infrequent (0. %) tste disturbnces Rre (<0.%) pemphigus Adult Orl, initilly 2.5 mg twice dily, incresed t intervls of 2 4 weeks to mg twice dily. See lso in hert filure p 2 Orl, initilly.25 mg 3 times dily, incresed t 2-week intervls to mg twice dily. Mximum 50 mg dily. Strt tretment in stble ptients 3 dys post MI t.25 mg 3 times dily; increse up to 25 mg 3 times dily over severl dys to finl trget dose of 50 mg 3 times dily. Dibetic nephropthy Orl, 25 mg 3 times dily. Renl impirment, elderly or tking diuretic Initilly.25 mg twice dily. Child month 2 yers Orl, mg/kg 2 or 3 times dily, incresing if needed to mximum of mg/kg dily (4 mg/kg dily if < yer). Give the first dose under medicl supervision. Administrtion dvice Orl liquid: mix with drink such s wter, fruit juice, te, coffee or col, nd tke immeditely. tb, 2.5 mg (scored), 90, Zedce, PBS tb, 25 mg (scored), 90, Cpoten, Zedce, PBS tb, 50 mg (scored), 90, Cpoten, Zedce, PBS orl liquid, 5 mg/ml, 95 ml, Cpoten, PBS-R if unble to tke n ACE inhibitor s tblet/cpsule Smple content Austrlin Medicines Hndbook Pty Ltd

3 .3.3 ACE inhibitors Enlpril (includes fixed-dose combintion with hydrochlorothizide or lercnidipine) Asymptomtic left ventriculr dysfunction Adult, child >50 kg Orl, initilly 5 mg dily, incresed t intervls of 2 weeks up to 0 40 mg dily in or 2 doses. Child <50 kg Orl, 0. mg/kg (mximum 2.5 mg) dily in or 2 doses, incresing grdully if necessry over 2 weeks to mximum 0. mg/kg (not to exceed 20 mg) dily in or 2 doses. Give the first dose under medicl supervision. Fixed-dose combintion with hydrochlorothizide or lercnidipine For dditionl informtion see Hydrochlorothizide p 258, Lercnidipine p 272 Adult, tblet once dily (of ny strength). See lso in hert filure p 2 Adult, orl, initilly 2.5 mg dily, incresed grdully up to usul mintennce dose of 0 20 mg dily given in or 2 doses. Left ventriculr dysfunction Adult, orl, initilly 2.5 mg dily, incresed grdully up to 0 mg twice dily. Renl impirment, elderly or tking diuretic Adult, initilly 2.5 mg once dily. tb, 5 mg, 30, Enlpril, PBS tb, 5 mg (scored), 30, Acetec, Mlen, PBS tb, 5 mg (scored), 30, Renitec M tb, 0 mg, 30, Enlpril, PBS tb, 0 mg (scored), 30, Acetec, Mlen, Renitec, PBS tb, 20 mg, 30, Renitec, PBS tb, 20 mg (scored), 30, Acetec, Mlen, PBS tb, enlpril 20 mg, hydrochlorothizide mg, 30, Renitec Plus 20/, PBS-R tb, enlpril 20 mg, hydrochlorothizide mg (scored), 30, Enlpril/HCT 20/, PBS-R tb, enlpril 0 mg, lercnidipine 0 mg, 28, Zn-Extr 0/0, PBS-R tb, enlpril 20 mg, lercnidipine 0 mg, 28, Zn-Extr 0/20, PBS-R hypertension (not for strting tretment), see PBS Fosinopril (includes fixed-dose combintion with hydrochlorothizide) Adult, orl, initilly 0 mg once dily, incresed up to 40 mg once dily. Fixed-dose combintion with hydrochlorothizide For dditionl informtion see Hydrochlorothizide p 258 tblet once dily. See lso in hert filure p 2 Adult, orl, initilly 5 0 mg once dily, incresed up to 0 40 mg once dily. Renl impirment, elderly or tking diuretic Initilly 5 0 mg once dily. tb, 0 mg, 30, Fosinopril, PBS tb, 0 mg, 30, Monopril tb, 0 mg (scored), 30, Fosipril, Monce, PBS tb, 20 mg, 30, Fosipril, PBS tb, 20 mg (scored), 30, Monce, PBS tb, fosinopril 20 mg, hydrochlorothizide 2.5 mg, 30, Fosetic 20/2.5, PBS-R hypertension (not for strting tretment), see PBS Lisinopril, cute tretment Adult, orl, initilly 5 0 mg once dily; if necessry, increse t intervls of 2 4 weeks up to 20 mg once dily. Mximum 40 mg dily. Child > yers, orl 0.07 mg/kg (mximum 5 mg) once dily; if necessry, increse up to 40 mg once dily. Give first dose under medicl supervision. See lso in hert filure p 2 Adult, orl, initilly 2.5 mg once dily, incresed t 4-week intervls up to mg once dily ccording to clinicl response. Adult, orl, initilly 5 mg within 24 hours of the onset of symptoms (2.5 mg in ptients with systolic BP <20 mm Hg), followed by 5 mg fter 24 hours; then 0 mg once dily for weeks; continue tretment in ptients developing hert filure. Renl impirment, elderly or tking diuretic Adult, initilly mg once dily. tb, 5 mg (scored), 30, Fibsol, Zestril, Zinopril, PBS tb, 0 mg, 30, Zestril, Zinopril, PBS tb, 0 mg (scored), 30, Fibsol, PBS tb, 20 mg, 30, Zestril, Zinopril, PBS tb, 20 mg (scored), 30, Fibsol, PBS Smple content Austrlin Medicines Hndbook Pty Ltd

4 .3.3 ACE inhibitors Perindopril (includes fixed-dose combintion with indpmide) Reduction of risk of MI or crdic rrest in people with estblished coronry hert disese without hert filure Fixed-dose combintion with mlodipine if lredy mintined on perindopril nd mlodipine Stble coronry hert disese if lredy mintined on perindopril nd mlodipine Dose equivlence 2.5 mg of perindopril rginine is equivlent to 2 mg of perindopril erbumine. Perindopril rginine, dult, orl, strt t 5 mg once dily. Mximum 0 mg once dily. Perindopril erbumine, dult, orl, strt t 4 mg once dily. Mximum 8 mg once dily. Elderly or t risk of ACE inhibitor-induced hypotension Perindopril rginine, strt t 2.5 mg once dily. Perindopril erbumine, strt t 2 mg once dily. Fixed-dose combintion of perindopril rginine or erbumine with indpmide For dditionl informtion see Indpmide p 259 tblet once dily (of ny strength). See lso in hert filure p 2 Perindopril rginine, dult, orl, strt t 2.5 mg once dily; increse up to 5 mg once dily. Perindopril erbumine, dult, orl, strt t 2 mg once dily; increse up to 4 mg once dily. Reduction of risk of crdiovsculr events Perindopril rginine, dult, orl, strt t 5 mg once dily for 2 weeks; increse up to 0 mg once dily depending on tolernce nd renl function. Perindopril erbumine, dult, orl, strt t 4 mg once dily for 2 weeks; increse up to 8 mg once dily depending on tolernce nd renl function. Elderly Perindopril rginine, strt t 2.5 mg once dily for week, then 5 mg once dily the next week; increse up to 0 mg once dily depending on tolernce nd renl function. Perindopril erbumine, strt t 2 mg once dily for week, then 4 mg once dily the next week; increse up to 8 mg once dily depending on tolernce nd renl function. Renl impirment Initil dose for perindopril rginine is 2.5 mg, perindopril erbumine 2 mg, then give this dose ccording to CrCl: 30 0 ml/minute, once dily ml/minute, on lternte dys. <5 ml/minute, on dy of dilysis. Fixed-dose combintion of perindopril rginine with mlodipine For dditionl informtion see Amlodipine p 270 If chnging from perindopril erbumine, use the dose equivlence bove to estblish the correct strength of perindopril rginine. Adult, tblet once dily (of ny strength). Prctice points helth professionls should be wre of the possibility of errors due to confusion between perindopril rginine nd perindopril erbumine Perindopril rginine tb, 2.5 mg, 30, Coversyl, Prexum, PBS tb, 5 mg (scored), 30, Coversyl, Prexum, PBS tb, 0 mg, 30, Coversyl, Prexum, PBS tb, perindopril rginine 5 mg, mlodipine 5 mg, 30, Coverm 5/5, Reptn 5/5, PBS-R,2 tb, perindopril rginine 5 mg, mlodipine 0 mg, 30, Coverm 5/0, Reptn 5/0, PBS-R,2 tb, perindopril rginine 0 mg, mlodipine 5 mg, 30, Coverm 0/5, Reptn 0/5, PBS-R,2 tb, perindopril rginine 0 mg, mlodipine 0 mg, 30, Coverm 0/0, Reptn 0/0, PBS-R,2 tb, perindopril rginine 2.5 mg, indpmide 0.25 mg (scored), 30, Coversyl Plus LD 2.5/0.25, Prexum Combi LD 2.5/0.25, PBS tb, perindopril rginine 5 mg, indpmide.25 mg, 30, Coversyl Plus 5/.25, Prexum Combi 5/.25, PBS-R Perindopril erbumine tb, 2 mg, 30, Idprex, Indosyl Mono, Perindo, PBS tb, 4 mg (scored), 30, Idprex, Indosyl Mono, Perindo, PBS tb, 8 mg, 30, Idprex, Indosyl Mono, Perindo, PBS tb, 8 mg (scored), 30, Perindopril, PBS tb, perindopril erbumine 4 mg, indpmide.25 mg, 30, Idprex Combi 4/.25, Indosyl Combi 4/.25, Perindo Combi 4/.25, PBS-R hypertension; not for initition of tretment, see PBS 2 stble coronry hert disese when stbilised on both drugs Quinpril, Quinpril p 929 (includes fixed-dose combintion with hydrochlorothizide) Adult, orl, initilly 5 0 mg once dily; increse t 4-week intervls to 0 40 mg dily in or 2 doses. Fixed-dose combintion with hydrochlorothizide For dditionl informtion see Hydrochlorothizide p 258 Adult, tblet once dily (of either strength). See lso in hert filure p 2 Adult, orl, initilly 5 mg dily; increse t weekly intervls to 5 0 mg twice dily. If 0 mg twice dily is tolerted, chnge to 20 mg once dily fter month. Renl impirment, elderly or tking diuretic Initilly mg once dily. Smple content Austrlin Medicines Hndbook Pty Ltd

5 .3.3 ACE inhibitors tb, 5 mg (scored), 30, Accupril, Acquin, Qpril, PBS tb, 0 mg (scored), 30, Accupril, Acquin, Qpril, PBS tb, 20 mg (scored), 30, Accupril, Acquin, Qpril, PBS tb, quinpril 0 mg, hydrochlorothizide 2.5 mg (scored), 30, Accuretic 0/2.5, PBS-R tb, quinpril 20 mg, hydrochlorothizide 2.5 mg (scored), 30, Accuretic 20/2.5, PBS-R hypertension (not for strting tretment), see PBS Rmipril (includes fixed-dose combintion with felodipine) in ptients with hert filure Prevention of MI, stroke, crdiovsculr deth or need for revsculristion procedures in ptients >55 yers with: coronry rtery disese, stroke or peripherl vsculr disese, or dibetes nd or more risk fctors (hypertension, smoking, microlbuminuri, high totl cholesterol, low HDL cholesterol, previous vsculr disese) Prevention of progressive renl filure in ptients with persistent proteinuri (> g dily) Adult, orl 2.5 mg once dily, increse fter 2 3 weeks to 5 mg if necessry. Mximum 0 mg dily in or 2 doses. Fixed-dose combintion with felodipine For dditionl informtion see Felodipine p 272 Adult, tblet once dily (of either strength). Adult, orl, initilly 2.5 mg twice dily, beginning 2 0 dys fter MI in ptients who re hemodynmiclly stble; increse t intervls of 3 dys up to 0 mg dily in 2 doses. Incresed crdiovsculr risk Adult, orl, initilly 2.5 mg once dily, increse fter week to 5 mg once dily nd fter 3 weeks to 0 mg once dily. Proteinuri Adult, orl, initilly.25 mg once dily, double t intervls of 2 3 weeks, depending on tolernce, up to 5 mg once dily. Renl impirment, elderly or tking diuretic Initilly.25 mg once dily. tb,.25 mg, 30, Tryzn, PBS tb,.25 mg (scored), 30, Rmce, Tritce, Vsclce, PBS tb, 2.5 mg (scored), 30, Rmce, Tritce, Tryzn, Vsclce, PBS tb, 5 mg (scored), 30, Rmce, Tritce, Tryzn, Vsclce, PBS tb, 0 mg (scored), 30, Tritce, Tryzn, Vsclce, PBS cp,.25 mg, 30, Tryzn, Vsclce, PBS cp, 2.5 mg, 30, Tryzn, Vsclce, PBS cp, 5 mg, 30, Tryzn, Vsclce, PBS cp, 0 mg, 30, Rmce, Tritce, Tryzn, Vsclce, PBS tb, rmipril 2.5 mg, felodipine (controlled relese) 2.5 mg, 30, Trisyn 2.5/2.5, PBS-R tb, rmipril 5 mg, felodipine (controlled relese) 5 mg, 30, Trisyn 5/5, PBS-R hypertension (not for strting tretment), see PBS Trndolpril, including fixed-dose combintion with verpmil (p 274) in ptients with left ventriculr dysfunction Precutions Heptic Use lower strting dose in those with heptic impirment. Adult Orl, mg once dily; if necessry, increse fter 2 4 weeks to 2 mg once dily. Mximum 4 mg once dily. Orl, strt tretment in stble ptients 3 dys post MI. Use initil 0.5 mg test dose followed by mg once dily for 3 dys. Increse to 2 mg once dily for 4 weeks then to mximum dose of 4 mg once dily if tolerted. Renl or heptic impirment, elderly or tking diuretic Initilly 0.5 mg once dily. Other products contining trndolpril re listed in Verpmil p 274. cp, 0.5 mg, 28, Dolpril, Gopten, Trnlph, PBS cp, mg, 28, Dolpril, Gopten, Trnlph, PBS cp, 2 mg, 28, Dolpril, Gopten, Trnlph, PBS cp, 4 mg, 28, Dolpril, Gopten, Trnlph, PBS Smple content Austrlin Medicines Hndbook Pty Ltd

of comorbid conditions, interventions Diagnosis and treatment, treatment reduction of risk factors for CVD to slow disease progression,

of comorbid conditions, interventions Diagnosis and treatment, treatment reduction of risk factors for CVD to slow disease progression, Tble 5.1. NKF Clssifiction of Chronic Kidney Disese nd Clinicl Fetures Stge Description GFR (ml/ min/1.73 m 2 ) U.S. Prevlence, b # Affected (%) Clinicl Fetures Action Pln c At incresed risk for CKD >60