Oral Antihypertensives Summary PDF

ORAL ANTIHYPERTENSIVES: Summary/Guidelines Comparison Chart B Jensen BSP, L Regier BSP BA © www.RxFiles.ca...

ORAL ANTIHYPERTENSIVES: Summary/Guidelines Comparison Chart B Jensen BSP, L Regier BSP BA © www.RxFiles.ca July 2023 Indications / Contraindications CI Initial Dose Usual Dose $ Generic / TRADE / Strength Comments / Drug Interactions 11 DI Adverse Events AE 8,10 2020 HTN CND Guidelines by Class (MAX dose) /30days Indapamide Less effect on lipid/glucose Still THIAZIDE type Indapamide: headache, dizziness Diuretic: First among equals initial or add-on.12 1.25mg daily 1.25-2.5mg daily LOZIDE, g 1.25, 2.5mg tab Possibly more effective than other thiazides in pts with CrCl 1st line: Diastolic HTN, ISH, LVH, diabetes (5mg daily) $9-12 HydroCHLOROthiazide (HCTZ) Low doses well tolerated; but rash, without below complications see 2nd line, past HYDRODIURIL, g 12.5-25mg effective & ↓AEs Evidence for morbidity/mortality   Ineffective if CrCl5.5 or  SCr rise >30% over baseline may warrant discontinuation. 1 Well tolerated in general but fatigue, 1st line: diastolic HTN, ISH, DM, CAD, LVH, 75mg daily AVAPRO, g 75, 150, 300mg; Less effective in African Americans unless with a THIAZIDE, 8 but headache, rash ,BP diuretics/volume depletion, pediatrics 150-300mg daily $17 AVALIDE , g 150/12.5; 300/12.5 & 25mg still used for compelling indications esp if ACEi intolerance eg. MI, HF, renal dx. /HCTZ (300mg daily) K + K supplements/K sparing diuretics/ renal fx & Losartan, g tab COZAAR 25,50,100mg acute renal failure with bilateral renal Alternative to ACEi: HFrEF, MI, non-DM CKD DI:  lithium; Losartan: fluconazole & rifampin losartan &uric acid 12.5-25mg daily HYZAAR/HCTZ 50/12.5mg tab artery stenosis, angioedema less than ACEi, 50-100mg daily $21 level; (100mg daily) ARB HYZAAR/HCTZ DS 100//12.5/25mg tab CI: artery stenosis (solitary kidney or Telmisartan:digoxin level; Irbesartan: fluconazole ’s irbesartan effect dysgeusia,pancreatitis & blood dyscrasias. bilateral), hx angioedema, pregnancy  fetal Valsartan DIOVAN,g 40, 80, 160, 320mg tab Delay diabetic nephropathy IDNT/IRMA II: irbesartan; RENAAL: losartan. Less cough,headache,dizziness than ACEi. mortality 2nd/3rd trimester 80mg daily DIOVAN- HCT, g HF Val-HeFT: valsartan; CHARM: candesartan. (320mg daily) 80-320mg daily $17 80/12.5 & 160&320mg//12.5/25 tab ?concern of cancer Meta-Sipahi’10, NNH=143/4yr HTN Candesartan LIFE: losartan. ATACAND 4,8,16,32 daily=$17 CALMmg tab; ATACAND PLUS/HCTZ 16/12.5 daily=$17; 32//12.5/25 mg tab; Eprosartan TEVETEN 400, 600mg, PLUS/HCTZ 600/12.5mg tab daily=$48; Olmesartan OLMETEC 20,40 daily $20 mg tab; OLMETEC PLUS/HCTZ 20/12.5mg & 40/12.5 & 40/25 daily $20 mg tab; Telmisartan MICARDIS 40,80 mg tab, PLUS/HCTZ 80/12.5, 80/25mg tabdaily=$17 AmLODIPine (1mg/mL soln) store in fridge Long acting: long t½ DI: ?cyclosporine,fluconazole,grapefruit juiceeffect LA-CCBs amlodipine, nifedipine XL, 1st line: LA-CCB: diastolic HTN, ISH, 2.5-5mg daily 5-10mg daily $14-16 NORVASC, g 2.5, 5, 10mg tab May be beneficial in diastolic dysfunction stable angina, LVH, pediatrics (10mg daily) CCB (DHPs) felodipine, diltiazem CD/ER/XC, verap SR Felodipine RENEDIL, g Less negative inotropic effects than nifedipine Don't crush/chew 1st line: DHP-CCB: uncomplicated DM, 2.5-5mg daily 5-10mg daily HOT DHPsamlodipine, felodipine, 2nd line for BP control in HFrEF PLENDIL, g 2.5, 5, 10mg ext. release tab Safe HF DI:CBZ,?cyclosporin,fluconazole, grapefruit juiceeffect (20mg daily) $22-28 nicardipine, nifedipine & nimodipine  Felodipine HTN, ALT systolic Dysfx NIFEdipine ADALAT, g Negative inotropicpotential Reflex HR DI:cimetidine,digoxin,grapefruit juice 30mg XL daily (Relatively: more peripheral  AmlodipineHTN,Stable Angina, Alt systolic Dysfx 30mg XL daily $30 Reg 5, 10mg cap Reg. caps NOT for acute  BP due to assoc. of MI/stroke, except pregnancy XL 20, (30, 60)g mg tab Used in pregnancy vasodilation & less heart effect)  NifedipineXL form: HTN, Stable Angina, Coronary Spasm (120mg XL daily) 60mg XL daily $41 AE: dizzy,headache nifedipine12%, rash,  Diltiazem HTN:SR ,CD & Tiazac; Coronary Artery Spasm: DilTIAZem, g CARDIZEM, Negative inotropic Reg; Stable Angina:All dosage forms titrate Reg. 60mg TID $42 CARDIZEM CD, TIAZAC cap XC tab DI: CBZCBZ level, cimetidine & protease inhibitors diltiazem, flushingdose related,constipation verapamil 7%,  VerapamilHTN: Reg&SR; Stable Angina & Coronary Artery 120mg CD daily $33 CCB (non-DHPs) 240mg CD daily $31 Reg: 30,60 mg tab cyclosporin cyclo level , digoxin dig level ; lovastatin & simvastatin  myopathy peripheral edema esp. with DHPs & females, Spasm: Reg; AF, SV arrhythmia, (420mg CD daily) 240mg XC daily $50 CD/ER: 120,180,240,300,360mgTIAZAC/XC cap HRDHPs,HRdiltiazem,verapamil , gingival Cardiomyopathy- obstructive hypertrophic {XC $ at all doses} Verapamil Most negative inotropic & chronotropic hyperplasia>20%, gynecomastia; dyspnea Useful: AF, SVT, Raynaud’s & black people. ISOPTIN, g Regular/SR tab DI:amiodarone, dofetilide, CBZ, cyclosporine, digoxin, & pulmonary edema in pts. with LVD, as CI: SBP 20 or DBP >10mmHg above target, consider combined category diuretic GRADE A , or ARB GRADE B ARB + thiazide / thiazide-like diuretic therapy as initial tx (caution: elderly, autonomic neuropathy) ACEi HOPE, EUROPA or ARB ONTARGET, GRADE A; - Avoid short-acting nifedipine ( of angina episodes GRADE D) Combination therapy; ACEi + DHP-CCB β-blocker or CCB as initial therapy in those - Avoid combining ACEi + ARB GRADE B, ONTARGET Coronary Artery Disease preferred in selected patients GRADE A, with stable angina but without prior HF, MI or ACCOMPLISH - Caution with lowering SBP to target if DBP ≤60mmHg, especially CABG GRADE B if LVH, re: concerns of exacerbating myocardial ischemia GRADE D CARDIOVASCULAR DISEASE ACEi (ARB if ACEi intolerant) + β-blocker Long-acting CCB if β-blocker - Avoid non-DHP-CCB in HF patients (e.g. diltiazem, verapamil) Recent Myocardial Infarction GRADE A contraindicated or not effective GRADE D Heart Failure reduced EF (220mmHg) ischemic stroke phase) PROGRESS (perindopril + indapamide) - Avoid ACEi + ARB GRADE B, ONTARGET Non-DM CKD with proteinuria - Monitor renal function & K+ ACEi GRADE A (ARB if ACEi intolerant GRADE B) ± (urinary protein >150mg/24hrs or - Diuretics: add (thiazide / thiazide-like diuretic), or loop diuretic if diuretic GRADE D; ACEi or ARB at highest Combination of additional agents GRADE D ACR >30mg/mmol) HTN CANADA 2020, volume overloaded GRADE D CKD approved or maximally tolerated dose KDIGO’20 KDIGO 2021 - Avoid ACEi + ARB GRADE B, ONTARGET Does not affect initial treatment - Caution: ACEi or ARB if bilateral renal artery stenosis or unilateral Renovascular Disease Combination of additional agents recommendations disease with solitary kidney Peripheral Artery Disease Does not affect initial treatment choice Combination of additional agents - Avoid β-blockers with severe PAD Psychiatric Disease ISH 2020 ACEi, ARB, diuretic; β-blocker except metoprolol if antidepressant / antipsychotic tachycardia - Caution: CCB or -blocker + SSRI / SRNIorthostatic hypotension Oral labetalol, oral nifedipine XL, Combine 1st line tx, or clonidine, - Avoid ACEi,GRADE C ARB, GRADE D; atenolol, MRAs, renin inhibitor ACOG Pregnancy 2020 Hypertension Canada oral methyldopa;GRADE C guidelines differ on hydralazine, thiazide diuretics GRADE D - LACTATION: enalapril, nifedipine XL, labetalol, amlodipine, Also see Peri-Pregnancy pg 171 the role of other β-blockers as 1st line metoprolol, diuretics are compatible. Methyldopa: depression risk. OTHERS African / Black ISH 2020 Thiazide-like diuretic + DHP-CCB, DHP-CCB + ARB Combine 1st line, diuretic, or ACEi see caution - Caution: ACEi as risk of angioedema 3x greater in black patients - Avoid ACEi GRADE C and ARBs GRADE D in black patients ACEi or ARB GRADE C , or LA-CCB GRADE D; Refer to specialist if BP not controlled after Pediatrics - Avoid β-blocker if asthma, DM, high-performance athletes GRADE D or β-blocker but less preferred re: AE GRADE D  6 months of standard-dose monotherapy - Caution with ACEi, ARB, MRA in teen  (in case of unplanned pregnancy) BP above target despite concurrent use of 3 antihypertensives at optimal doses, preferably including a diuretic, LA-CCB, & ACEi or ARB; Step 1: rule-out white Resistant Hypertension coat syndrome; Step 2: optimize drug therapy (4Ds: drug, dose, duration, long-acting diuretic); Step 3: assess for non-adherence / lifestyle; Step 4: refer to specialist. 4th agent options: spironolactone, amiloride, bisoprolol, doxazosin, clonidine; 5th agent options: additional agent from class not already used Drugs that  BP: e.g. NSAIDs (3/1mmHg)/COX-2, estrogen >50mcg (6/3mmHg), sympathomimetics, cyclosporine, tacrolimus, erythropoietin, VEGF inhibitors, EtOH, SRNI/TCA, glucocorticoids, mineralocorticoids, licorice, nicotine, yohimbine. Combinations to Avoid: Hydralazine & Diureticstimulate renin & sympathetic activity unless used with -blocker; Verapamil or diltiazem & -blockernegative effects on heart (e.g.  heart rate & cardiac output); -blocker & Clonidineconcern about rebound HTN if clonidine withdrawn abruptly; CCBs & -blockersrisk of excessive hypotension; increased risk of falls, etc. ACEi+ARB: no additional CV benefit & AE. See Hypertension Trial Summary Synergistic Combinations: AB  CD: A: ACEi or ARB CCB or with diuretic B: -BLOCKER CCB or with diuretic (+ACEi if post MI/HF) C: CCB ACEi or ARB or with -Blocker D: DIURETICS ACEi or ARB or with -Blocker. Average BP lowering of a single agent 10/5mmHg, but variation in individual response of ± 4.4mmHg.29 No difference between dosing antihypertensives at bedtime vs in the morning.TIME 9 HYPERTENSION SUMMARY Acknowledgements: Written by Loren Regier and Brent Jensen. Ongoing edits provided by Lynette Kosar (2018-2022) and Alex Crawley (2023). Thanks to our reviewers: Dave Blackburn, Jennifer Yu, Laurie Dunn. Disclosures: No conflicts of interest are reported by Loren Regier or Brent Jensen. Disclaimer: RxFiles Academic Detailing is part of the College of Pharmacy and Nutrition at the University of Saskatchewan. The content of this work represents the research, experience and opinions of the authors and not those of the University of Saskatchewan. Neither the authors nor the University of Saskatchewan nor any other party who has been involved in the preparation or publication of this work warrants or represents that the information contained herein is accurate or complete, and they are not responsible for any errors or omissions or for the result obtained from the use of such information. Any use of the materials will imply acknowledgment of this disclaimer and release any responsibility of the University of Saskatchewan, its employees, servants or agents. Readers are encouraged to confirm the information contained herein with other sources. Other Antihypertensives: Generic/ TRADE / Strength Comments/ Drug Interactions 11 DI Adverse Events 8,10 AE Indications , Contraindication CI Initial Dose (Max) Usual Dose; $ /30d CloNIDine CATAPRES, g CENTRAL ALPHA AGONIST (3rd line): use if others CI/ refractory HTN Sedation,dry mouth,HR,depression & On the Beers Criteria for older patients list 0.1mg BID 0.1-0.2mg BID $19-27 0.1, 0.2 mg tab; (0.025mg tab)  Clonidine: Used for acute BP DI: cyclosporine,mirtazapine,TCA's rebound HTN on withdrawal,impotence CI:HF/heart block,diabetes autonomic neuropathy (0.2mg TID) Methyldopa Methyldopa:  DI: levodopaBP,TCAsBP Sedation, dry mouth, impotence, depression, Used in pregnancy; 125mg BID 250mg BID $21 ALDOMET, g 125, 250, 500mg tab hepatotoxic, lupus like sx &  platelets/RBC An option for pheochromocytoma (500mg QID) ALPHA BLOCKERS (3rd line): use if others CI / refractory HTN 0.5mg BID Prazosin MINIPRESS, g 1, 2, 5 mg tab Useful for lower urinary tract symptoms 2mg BID $34 Doxoazosin  removed from ALLHAT due to  HF/stroke Sedation, dizziness, vertigo,headache, (5mg TID) First dose syncope: minimize by gradual dose titration & give @HS (LUTS) e.g. poor stream, hesitancy, dribbling, Terazosin HYTRIN, g 1,2,5,10mg tab palpitations, HR, fluid retention, 1mg HS (10mg BID) 5mg HS $21 incomplete voiding, prostatism 8,19 weakness, nasal congestion & priapism. OTHER An option for pheochromocytoma 1mg HS Doxazosin CARDURA, g 1,2 ,4 mg tab   (16mg daily) 4mg HS $28 HydrALAZINE VASODILATOR HR, aggravate angina,headache,dizzy, Alt: HFrEF hydralazine with isosorbide A-HeFT 10mg QID fluid retention,lupus like>200mg/d & hepatitis CI: LVH. IV 1st line HTN emergency in pregnancy 25mg QID $18 APRESOLINE, g 10, 25, 50mg tab Reflex HR, edema&renin sx activation; often add β-blocker/diuretic  (50mg QID) Labetalol ALPHA & BETA BLOCKADE Postural hypotension & Used in pregnancy; 100mg BID 200mg BID $44 TRANDATE, g 100, 200 mg tab  BP more than other β-blockers hepatotoxicity more than other Beta-Blockers 7 CI: as per β-Blockers above (400mg TID) Aliskiren DIRECT RENIN INHIBITOR RASILEZ 150,300mg tab  DI: cyclosporine, furosemide, grapefruit juice, irbesartan, juices, keto- & diarrhea, HA, K+, rash, allergy & RASILEZ-HCTZ itra -conazole, + ACEi or ARB(CV eventsALTITUDE; prehypertension NS pharyngitis.Rare: cough ~1%, angioedema, CI: pregnancy $55 AQUARIUS). High-fat meals reduce absorption. 150/12.5mg, 150/25mg tab  gout 0.2%. (rats: colonic mucosal hyperplasia). 300/12.5mg, 300/25mg tab  Contraindications to Antihypertensives by Class: DIURETICS CI: symptomatic gout, allergy sulpha: cross reactivity not proven, anuria, hyponatremia. -BLOCKERS CI: asthma, 2nd or 3rd degree heart block, severe bradycardia, uncompensated HF, severe PAD. ACEi / ARB CI: bilateral artery stenosis (or kidney solitary stenosis if only 1 kidney), angioedema hx, (ACEi/ARB + aliskiren) diabetes, pre-contrast concern coronary angio , pregnancy (2nd & 3rd trimester; ? 1st trimester – appears safe). Less effective/safe in black people? CCB CI: systolic BP80 Years of Age: Cohort Study Using Electronic Health Records. Circulation. 2017 Jun 13;135(24):2357-2368. Rawlings AM, Juraschek SP, Heiss G, et al. Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline. Neurology. 2018 Jul 25. 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No evidence of a difference in total mortality and serious adverse events was found between treating to a lower or to a standard blood pressure target in people with hypertension and cardiovascular disease. This suggests no net health benefit from a lower systolic blood pressure target despite the small absolute reduction in total cardiovascular serious adverse events. There was very limited evidence on adverse events, which lead to high uncertainty. At present there is insufficient evidence to justify lower blood pressure targets (