안전한약품사용가이드 2019 노인주의의약품및대체약물 Ⅰ (Potentially Inappropriate Medication) Anticholinergics 1 세대 antihistamines - Brompheniramine - Carbinoxamine - Chlorpheniramine - Clemastine - Cyproheptadine - Dexbrompheniramine - Dexchlorpheniramine - Dimenhydrinate - Diphenhydramine( 경구 ) - Doxylamine - Hydroxyzine - Meclizine - Promethazine - Pyrilamine - Triprolidine 강한항콜린작용 : 노인에서 clearance 감소하고, 수면유도목적으로사용시내성이발생할수있음 혼돈, 구갈, 변비등항콜린성부작용증가 심한알러지반응의급성기치료를위한 diphenhydramine 사용은적절할수있음 Intranasal normal saline 2 세대 antihistamine ( 예, cetirizine, fexofenadine, loratadine 등 ) Intranasal steroid ( 예, beclomethasone, fluticasone) Antiparkinsonian agents - Benztropine( 경구 ) - Trihexyphenidyl 항정신병약에의한추체외로증상의예방또는치료목적으로추천하지않음 파킨슨병치료에도더효과적인대체약사용가능 파킨슨병 : carbidopa/ levodopa Antispasmodics - Atropine ( 안약제외 ) - Belladonna alkaloids - Clidinium-Chlordiazepoxide - Dicyclomine - Hyoscyamine - Propantheline - Scopolamine 강한항콜린작용 효능명확하지않음 Antithrombotics Dipyridamole, oral short-acting (aspirin 과의복합서방형제제는제외 ) 기립성저혈압유발가능 효과적인대체약있음 Cardiac stress test 에는 IV 제제사용가능 Ticlopidine* 안전하고효과적인대체약있음 Noncardioembolic stroke 의 2 차예방을위한항혈전제 clopidogrel 등 Anti-infective Nitrofurantoin 장기간사용시폐독성, 간독성, 말초신경병증유발가능 안전하고효과적인대체약있음 CrCl<30mL/min 또는장기간사용 Cardiovascular Peripheral alpha-1 blockers for treatment of hypertension - Doxazosin - Prazosin - Terazosin 특히노인에서기립성저혈압과관련위험성이높으므로고혈압의일반적치료제로추천하지않음 Superior risk/benefit profile 있는대체약있음 항고혈압제로
Cardiovascular Central alpha agonists Clonidine for first-line treatment of hypertension Guanabenz Guanfacine Methyldopa Reserpine (>0.1 mg/day) 중추신경부작용위험높음 서맥, 기립성저혈압유발가능하므로고혈압의일반적치료제로추천하지않음 Clonidine: 고혈압 1 차치료제로 그외 : Thiazide-type diuretic, ACEI, ARB, longacting dihydropyridine CCB( 예, amlodipine) 심부전, 당뇨, 만성신부전 : ACEI or ARB 선호 Disopyramide 노인에서는강력한 negative inotrope 효과로심부전유발가능 항콜린성부작용강함 다른항부정맥제추천 Atrial fibrillation rate control 목적 : nondihydropyridine CCB ( 예, diltiazem), beta blocker rhythm control 목적 : flecainide, propafenone, dofetilide Dronedarone 영구적심방세동또는중증 / 최근의비보상성심부전환자에서부정적인결과보고 해당환자에서 Cardiovascular Digoxin 심방세동 : rate 조절을위해더안전하고효과적인대체약제가존재하므로 1 차치료제로는 심부전 : 사망률증가와관련되어있음용량증가는추가적인이점없이독성위험을높임 신배설감소에따른독성증가, CKD stage 4-5(CrCl<30mL/min) 는추가감량필요 심방세동, 심부전의 1 차치료제로 1 일 0.125mg 초과용량은사용하지말것 좁은치료농도범위 (therapeutic range) 를갖고있으므로사용할경우주기적인혈중농도확인및 TDM 시행추천 Nifedipine, immediate release 저혈압위험 심근허혈유발가능 Long-acting dihydropyridine CCB ( 예, amlodipine) Amiodarone Sinus rhythm 유지에는효과적이지만심방세동에서타항부정맥제에비해독성증가 rhythm 조절이 rate 조절보다선호된다면심부전또는좌심실비대가동반된경우의 1 차치료제로합당 심부전또는좌심실비대가동반된경우가아니라면심방세동의 1 차치료제로 Central nervous system Antidepressants Amitriptyline Amoxapine Clomipramine Desipramine Doxepin >6 mg/day Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine 강한항콜린작용 : 진정, 기립성저혈압유발 저용량 doxepin ( 6mg/day): placebo 와 safety profile 유사 Depression: SSRI (paroxetine 은제외 ), SNRI, bupropion Neuropathic pain - SNRI, gabapentin, pregabalin - capsaicin topical, lidocaine patch
Central nervous system, - 1st (conventional) generation - 2nd (atypical) generation 치매환자에서뇌졸중위험증가, 사망률증가, 인지기능저하의속도증가 치매또는섬망환자행동문제의치료를위해서는비약물학적치료가실패했거나불가능하고스스로또는타인에게잠재적인위험이되는경우에만사용 - 조현병 - 양극성장애 - 항암치료중항구토제로서단기간사용 치매또는섬망환자행동문제치료 : 최단기간동안저용량 nonanticholinergic agent ( 예, risperidone, quetiapine) 조현병 : non-anticholinergic antipsychotics (chlorpromazine, olanzapine, perphenazine 은제외 ) Barbiturates Amobarbital Butabarbital Butalbital Mephobarbital Pentobarbital Phenobarbital Secobarbital 신체적의존성높음 수면효과에대한내성률높음 낮은용량에서도부작용증가할위험높음 Epilepsy: other antiepileptics ( 예, lamotrigine, levetiracetam) Central nervous system Short and intermediate acting: Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Long acting: Clorazepate Chlordiazepoxide (alone or in combination with amitriptyline or clidinium) Clonazepam Diazepam Flurazepam Quazepam 노인에서 benzodiazepines sensitivity 증가, 대사감소 인지장애, 섬망, 낙상, 골절, 차량충돌위험증가 - Seizure disorder - REM(rapid eye movement) sleep disorder - withdrawal - Ethanol withdrawal - Severe generalized anxiety disorder - Periprocedural anesthesia Meprobamate 신체적의존성높음 진정효과강력 Anxiety: buspirone, SSRI, SNRI Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics - Zolpidem benzodiazepines 와부작용유사 : 섬망, 낙상, 골절, 차량충돌위험등 응급실방문과입원률증가 수면대기시간과유지에대한효과미비 Ergoloid mesylates dehydrogenated ergot alkaloids 효과미비함 Acetylcholinesterase inhibitors( 예, donepezil), Memantine, Vitamin E Endocrine Androgen Methyltestosterone Testosterone 심질환위험증가 전립선암남성에서 임상적징후를동반한성선기능저하증에만사용가능 Desiccated thyroid 심장문제에대한우려 안전한대체약있음 Levothyroxine
Estrogens with or without progestins 유방및자궁내막에대한발암성입증 여성노인에서심장보호효과, 인지기능보존에대한근거부족 경구제 & 패취제 질정이나질에적용하는크림은재발성하부요로감염증및기타질증상시저용량으로사용가능 외음부질염치료에적합한 vaginal estrogen 제제선택 Vasomotor 증상 : SSRI, SNRI, gabapentin Endocrine Growth hormone 신체구성에대한영향은적음 부종, 관절통, carpal tunnel syndrome, gynecomastia, 공복혈당이상과연관있음 - 확증된원인으로인한 growth hormone 결핍과함께 evidencebased criteria 에의해진단된경우 Insulin, sliding scale : basal 또는 long-acting insulin 없이현재의혈당에따라 short- 또는 rapid-acting insulin 을단독으로투여하는것 고혈당조절의개선없이저혈당위험증가 (Care setting 에관계없음 ) Megestrol 체중에대한영향적음 노인에서혈전생성및사망의위험성증가 Sulfonylureas, long-duration Chlorpropamide Glimepiride Glyburide(Glibenclamide) Chlorpropamide: 노인에서반감기의증가로인해저혈당이지속되고, 항이뇨호르몬부적절분비증후군 (SIADH) 을야기할수있음 Glimepiride, Glyburide: 노인에서심각한저혈당지속의위험성높음 Short-acting sulfonylureas ( 예, glipizide, gliclazide) Metformin Metoclopramide Tardive dyskinesia 를포함한 extrapyramidal effects 유발 장기간사용과노쇠한노인에서위험성증가 - 12 주를초과하지않는위마비치료목적 Mineral oil, given orally Aspiration 과부작용가능성 안전한대체약있음 Gastrointestinal Proton-pump inhibitors(ppis) Clostridium difficile 감염증가 골밀도감소및골절위험성증가 8 주초과한사용은 - 경구스테로이드및만성 NSAIDs 사용시 - Erosive esophagitis - Barrett's esophagitis - Pathological hypersecretory condition - 유지치료의필요성이입증된경우 ( 예. 약물중단또는 H2-receptor antagonist 사용의실패 )
Meperidine 섬망을포함한신경독성위험성증가 안전한대체약있음 중등증 - 중증통증 : tramadol, morphine, oxycodone immediate release with acetaminophen 마약성진통제를처음사용하는경우장시간작용, 서방형제형피할것 Pain medications Non-COX selective NSAIDs, oral - Aceclofenac, Ketoprofen, Meloxicam 등 고위험군에서위장관출혈또는소화기궤양위험증가하며, 사용기간과관련있음. PPI 또는 misoprostol 병용은위험을감소시키나, 없애지는못함 * 고위험군 : 다음세가지중하나이상에해당되는경우 - 75 세초과 - 경구 / 주사 corticosteroids 병용 - 항응고제, 항혈소판제병용 혈압상승과신손상을일으킬수있음 부작용은용량과관련있음 장기간투여 - 대체약이효과없고 PPI, misoprostol 병용한경우 Celecoxib 등 COX-2 selective NSAIDs Pain: acetaminophen, SNRI, capsaicin topical, lidocaine patch Indomethacin Ketorolac( 경구, 주사 ) 위장관출혈, 소화기궤양, 급성신손상위험증가 다른 NSAIDs 에비해중추신경계부작용이많음 모든 NSAIDs 중에서 indomethacin 이부작용가장많음 경증 - 중등증만성통증 : 만약심부전이없거나 egfr 30mL/min 초과되고 PPI 를처방받는다면 acetaminophen, nonacetylated salicylate( 예, salsalate), propionic acid 유도체 ( 예, ibuprofen, naproxen 등 ) Pain medication Skeletal muscle relaxants - Carisoprodol - Chlorzoxazone - Cyclobenzaprine - Metaxalone - Methocarbamol - Orphenadrine 항콜린성부작용, 진정, 골절위험성높음 고령환자의 tolerated dosage 에서의효과가명확하지않음 경증 - 중등증급성통증 : 7 일초과해서사용하는경우, 만약심부전이없거나 egfr 30mL/ min 초과되고 PPI 를처방받는다면 acetaminophen, nonacetylated salicylate( 예, salsalate), propionic acid 유도체 ( 예, ibuprofen, naproxen 등 ) Genitourinary Desmopressin 저나트륨혈증발생위험높음 안전한대체약있음 야간뇨, 야간다뇨증치료에 * Ticlopidine: 2019 AGS Beers criteria 에서는미국내유통되지않는다는사유로목록삭제됨 <Reference> 1. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, J Am Geriatr Soc. 2019 Jan 29:1-21 2. Alternative Medications for Medications in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly Quality Measures, J Am Geriatr Soc, 63:e8-e18, 2015.
안전한약품사용가이드 2019 노인주의의약품및대체약물 II (Drug Disease or Drug Syndrome Interactions) 질환및증상노인부적절약물근거권고예외대체약물 Cardiovascular Cilostazol 사망률증가가능성 Heart failure Nondihydropyridine CCBs (Heart failure with reduced ejection fraction 만해당 ) - Diltiazem - Verapamil NSAIDs COX-2 inhibitors Thiazolidinediones - Pioglitazone - Rosiglitazone Dronedarone 수분저류촉진가능성 심부전악화가능성 Dronedarone: 사망률증가가능성 ejection fraction 이감소된심부전환자에서 증상이있는심부전환자에서는 증상이없는심부전환자에서는주의해서사용 AChEIs - Donepezil - Rivastigmine - Galantamine 서맥유발 서맥으로인한 syncope 인경우 Syncope Nonselective peripheral alpha-1 blockers - Doxazosin - Prazosin - Terazosin 기립성저혈압유발 기립성저혈압으로인한 syncope 인경우 Tertiary TCAs - Chlorpromazine - Thioridazine - Olanzapine 기립성저혈압또는서맥위험성증가
질환및증상노인부적절약물근거권고예외대체약물 Central nervous system Delirium Dementia or Cognitive impairment History of falls or Fractures Anticholinergics Zolpidem Corticosteroid( 경구, 주사 ) H2-receptor antagonist Meperidine Anticholinergics ( 만성및필요시사용 ) Zolpidem Antiepileptics Zolpidem Antidepressants - TCAs - SSRIs - SNRIs Opioids 섬망유발및악화 특히치매환자에서 antipsychotics 는뇌졸중위험증가, 사망률증가와관련되어있음 중추신경부작용증가 특히치매환자에서 antipsychotics 는뇌졸중위험증가, 사망률증가와관련되어있음 운동실조, 정신운동기능결핍, 실신, 추가낙상위험유발가능성 속효성 benzodiazepine 이지속형보다더안전하지는않음 안전한대체약있다면 반드시사용해야하는경우, 해당카테고리의다른 CNS-active medication 사용을줄이고낙상을예방하기위한다른전략을실행해야함 : 치매또는섬망환자행동문제의치료를위해서는약물학적치료가실패했거나불가능하고스스로또는타인에게잠재적인위험이되는경우에만사용 Antiepileptics: Seizure, mood disorder 의경우가능 : 조현병, 양극성장애등특정질환의경우저용량, 단기간사용가능 Opioids: 중증의급성통증 ( 예, 최근의골절, 관절치환술 ) 조절의경우사용가능 섬망 : 단기간만사용 ( 예, haloperidol, quetiapine) 최단기간동안저용량 nonanticholinergic agent ( 예, risperidone, quetiapine) Anxiety: buspirone, SSRI, SNRI New-onset epilepsy: newer agents preferred ( 예, lamotrigine, levetiracetam) and calcium/ vitamin D ± bisphosphonate 권고 Neuropathic pain - gabapentin, pregabalin - capsaicin topical, lidocaine patch Anxiety: buspirone 조현병, 양극성장애 : nonanticholinergic antipsychotics (chlorpromazine, olanzapine, perphenazine 제외 ) Depression: bupropion Neuropathic pain - gabapentin, pregabalin - capsaicin topical, lidocaine patch
질환및증상노인부적절약물근거권고예외대체약물 Parkinson disease 모든 antipsychotics ( 제외 : clozapine, quetiapine, pimavanserin) 항구토제 - Metoclopramide - Prochlorperazine - Promethazine Dopamine receptor antagonist 로파킨슨증상악화 Clozapine, pimavanserin: 파킨슨병악화와연관성적음 Quetiapine: low-quality clinical trial 만있으나 placebo 또는 clozapine 과유사 Gastrointestinal History of gastric or duodenal ulcers Aspirin (>325mg/day) Non-COX-2 selective NSAIDs 궤양악화및새로운궤양유발가능 다른대체약이효과가없고, 위장보호제 (PPI, misoprostol) 를병용할경우가능 Kidney and urinary tract CKD stages 4-5 (CrCl < 30mL/ min) NSAIDs(non-COX and COX-selective, 경구및주사, nonacetylated salicylates) Acute kidney injury, 신기능감소위험증가 Pain: acetaminophen, SNRI, capsaicin topical, lidocaine patch Lower urinary 강력한 anticholinergic drugs tract symptoms, ( 제외 : 요실금치료약물 ) BPH 요속감소, 요정체유발가능 남성에서 요실금치료목적의약제제외 Urinary incontinence in women Estrogen( 경구 & 패취제 ) Peripheral alpha-1 blockers - Doxazosin - Prazosin - Terazosin 효과부족 요실금악화 여성에서 Estrogen: intravaginal estrogen 은가능 Endocrine Syndrome of inappropriate antidiuretic hormone (SIADH) or Hyponatremia Diuretics SNRIs SSRIs Mirtazapine TCAs Carbamazepine Oxcarbazepine Tramadol SIADH 또는저나트륨혈증유발및악화가능 주의 (Use with caution) 투여시작, 용량변경시 serum Na level close monitoring <Reference> 1. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, J Am Geriatr Soc. 2019 Jan 29:1-21 2. Alternative Medications for Medications in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly Quality Measures, J Am Geriatr Soc, 63:e8-e18, 2015 발행번호 2019-1 호발행일 2019.7.10 편집인병원약학분과협의회노인약료분과발행처 ( 재 ) 병원약학교육연구원