Hypertension in Adults. Medicines Optimisation. Guide for Primary Care Prescribers

Transcription

1 . Hypertension in Adults Medicines Optimisation Guide for Primary Care Prescribers Please note This document is intended for use by NHS healthcare professionals and cannot be used for commercial or marketing purposes. We make every effort to ensure the information in documents is accurate and correct at the date of publication but this should not replace clinical judgement or be regarded as a substitute for seeking professional advice. Please always check the most up-to-date prescribing information in the BNF or medicines compendium ( This document does not cover the diagnosis of hypertension and prescribing information within this guide is for non-pregnant adults (aged 18 and above). Lead Author Alison Warren, Consultant Pharmacist Cardiology, Central Sussex and East Surrey Commissioning Alliance (South Place) and Brighton and Sussex University Hospitals NHS Trust Issue Date November 2018 Version 1 Editor n/a Expiry date November 2020 Supersedes Reviewer Brighton Area Prescribing Committee (approved October 2018 To be reviewed before expiring date if warranted Page 1

2 Contents Introduction... 3 NICE CG127 RECOMMENDATIONS Hypertension Classification... 4 Postural / Orthostatic Hypotension... 5 Medication review... 5 Home Blood pressure Monitoring... 6 NICE CG127 RECOMMENDATIONS: Blood Pressure Targets... 7 Lifestyle Advice... 8 Dietary Advice: British and Irish Hypertension Society Diet Sheet... 9 DASH DIET NICE CG127 RECOMMENDATIONS: Pharmacological Treatment Pathway Cardiovascular Risk Assessment and Lipid Lowering Therapy Medication Information Angiotensin Converting Enzyme Inhibitors (ACEI) Angiotensin Receptor Blockers (ARB) Calcium channel blockers Thiazide/thiazide like diuretics Spironolactone Alpha-blockers Beta blockers Page 2

3 Introduction High blood pressure (hypertension) is one of the most important preventable causes of premature morbidity and mortality in the United Kingdom (UK) and at least 25% of adults (and more than half of those over the age of 60 years) have high blood pressure. Hypertension is a major risk factor for ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. Untreated hypertension is usually associated with a progressive rise in blood pressure. The vascular and renal damage that this may cause can culminate in a treatment-resistant state. The risk associated with increasing blood pressure is continuous, with each 2-mmHg rise in systolic blood pressure associated with a 7% relative increase risk of mortality from ischaemic heart disease and a 10% relative increase risk of mortality from stroke. In any individual person systolic and/or diastolic blood pressures may be elevated. Diastolic pressure is more commonly elevated in people younger than 50. With ageing, systolic hypertension becomes a more significant problem as a result of progressive stiffening and loss of compliance of larger arteries. The following NICE guidance should be considered when initiating and monitoring lifestyle and pharmacological treatment for hypertension and cardiovascular risk: Hypertension in adults: diagnosis and management. Last updated August Review in progress publication due August Type 2 Diabetes in adults - which includes a section on hypertension. Last updated May Chronic kidney disease in adults: assessment and management. Last updated January Cardiovascular disease: risk assessment and reduction including lipid modification. Last updated September Prescribing for patients who wish to become pregnant or who are pregnant is not covered in this guide. For further information refer to NICE Hypertension in Pregnancy: diagnosis and management Update in progress due for publication March More recently both the American College of Cardiology ( and the European Society of Cardiology ( Guidelines/Arterial-Hypertension-Management-of) have published hypertension guidelines. There are some differences in comparison to the current NICE guidance and clinicians may wish to refer to these in addition when deciding on management of their patients. Page 3

4 NICE CG127 (2011) RECOMMENDATIONS Hypertension Classification Stage Definition Threshold for pharmacological treatment Stage 1 hypertension Clinic blood pressure 140/90mmHg and subsequent ABPM* daytime average or HBPM average blood pressure 135/85 mmhg Offer treatment to people aged < 80 years who have at least one of: Established CV disease Target organ damage (left ventricular hypertrophy, CKD, hypertensive retinopathy) Diabetes 10 year CV risk 20% (using Q-risk) Stage 2 hypertension Clinic blood pressure 160/100 mmhg and subsequent ABPM daytime average or HBPM average blood pressure 150/95 mmhg Offer treatment to all patients Severe hypertension Clinic systolic blood pressure 180 mmhg or clinic diastolic blood pressure 110 mmhg Consider starting antihypertensive treatment immediately without waiting for results of ABPM or HBPM *ABPM: Ambulatory blood pressure monitoring HBPM: home blood pressure monitoring White Coat Hypertension A discrepancy of more than 20/10 mmhg between clinic and average daytime ABPM or average HBPM blood pressure measurements at the time of diagnosis. Consider ABPM or HBPM as an adjunct to clinic blood pressure measurements to monitor the response to antihypertensive treatment with lifestyle modification or drugs. Hypertension in patients under 40 years of age For people aged less than 40 years with stage 1 hypertension and no evidence of target organ damage, CVD, renal disease or diabetes, consider seeking specialist evaluation of secondary causes of hypertension and a more detailed assessment of potential target organ damage as the 10 year CV risk can underestimate the lifetime risk of CV events in these people. Isolated systolic hypertension (ISH) Offer people with isolated systolic hypertension (SBP 160mmHg) the same treatment as people with both raised SBP and diastolic BP (DBP 100mmHg) Page 4

5 Postural / Orthostatic Hypotension A sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 minutes of standing. May be asymptomatic but typical symptoms include: Light-headedness/dizziness within a few seconds of standing. Dim, blurred or tunnel vision. Dull pain in the back of the neck and shoulders (coat hanger distribution). Unsteadiness, fainting, or weakness. If these types of symptoms occur when the patient changes to a more vertical position (even if sitting blood pressure is not low) measure sitting and standing blood pressure. The patient should stand for at least 1 minute before a recording made. Measure heart rate expect heart rate to increase as BP drops : exaggerated increase in heart rate (>15 beats/minute) may suggest dehydration/volume depletion. If the systolic blood pressure reading falls by more than 15 mmhg on standing review medication. Medicines that may cause postural hypotension include Antihypertensive medication particularly alpha blockers Diuretics Anticholinergics such as oxybutynin, tricyclic antidepressants, antipsychotics Nitrates, nicorandil, ranolazine Medicines for Parkinson s disease Medication review Avoid NSAIDs and cough/cold remedies or decongestants that may increase blood pressure Advise patient to always check with the pharmacist before purchasing any OTC medicines. Soluble analgesia and indigestion remedies have a high salt content and should also be avoided where possible. Consider review of other medicines that may increase blood pressure in particular combined oral contraceptives or HRT, NSAIDs and COXIBs, steroids, fludrocortisone, midodrine, mirabegron and immunosuppressants. Ask patient about any herbal remedies and if they are taking any of these check if any of these can affect blood pressure or interact with prescribed medication. Illicit drugs that can affect the heart include amphetamines, anabolic steroids and cocaine. Page 5

6 Home Blood Pressure Monitoring (HBPM) HBPM can be used for diagnosis (as an alternative to ABPM) and for on-going monitoring of treatment. It is important to ensure that the patient fully understands how to monitor their blood pressure and records this in line with a standard procedure. Useful information can be found at: Why Use Home Blood Pressure Monitoring How to Measure Blood Pressure Guide for Patients When HBPM is used this should be recorded for at least four (and ideally seven) days. Example of Information for a Home Blood Pressure Monitoring Form Dear. NHS number.. We would like you to measure your blood pressure at home. Often home readings are more accurate than in a clinical setting as some people suffer from white-coat syndrome - a falsely high blood pressure when they attend the surgery. Your blood pressure target is Please follow the instructions below: Ensure that you are sat comfortably for 5 minutes, relaxed and not moving or talking. Ensure your arm is supported at heart level (rest your arm on a table), your back is supported and your feet are flat on the floor. Remember that exercise, talking, drinking coffee or smoking a cigarette before taking a blood pressure measurement will elevate you blood pressure. The blood pressure machine will record your systolic blood pressure (top figure) and your diastolic blood pressure (bottom figure). Take readings twice a day in the morning and again in the evening. Use the same arm each time. Take 2 readings at least 1 minute apart and write down the lowest reading. After 7 days of readings we would like you to work out your average blood pressure: Discard all the readings from day 1 Add together all the remaining AM and PM systolic (top) readings (there should be 12 in total) and divide by 12. This is your average systolic blood pressure. Add together all the remaining AM and PM diastolic (bottom) readings and divide by 12. This is your average diastolic blood pressure Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 AM PM Systolic Diastolic Systolic Diastolic Average blood pressure: Systolic. Diastolic.. Please return this form to. Page 6

7 NICE CG127 RECOMMENDATIONS: Blood Pressure Targets Page 7

8 Lifestyle advice should be offered to all patients Encourage reducing dietary sodium (avoid salt substitutes containing high levels of potassium). Discourage excessive consumption of coffee and other caffeine rich products Offer advice and help to smokers to stop smoking via GP Surgery or community pharmacy services Encourage regular exercise (30 minutes 5 times/week) Weight reduction Alcohol moderation to within safe limits (up to 14 units per week). Where excessive alcohol intake is suspected to be contributing to high BP, reduction /abstinence should be advised. If patient agrees refer to local services The following may be used as a guide to the potential effect on reducing blood pressure that can be achieved with lifestyle changes. Reproduced with permission from the British Medical Journal (BMJ i5719) Page 8

9 Dietary Advice: British and Irish Hypertension Society Diet Sheet Page 9

10 DASH DIET The DASH diet stands for Dietary Approaches to Stop Hypertension. This diet is: Low in saturated fat, cholesterol and total fat, red meat, sweets and sugary beverages. Encourages fruit, vegetables, fat free or low fat dairy products, whole grain foods, fish, poultry and nuts. Rich in nutrients: potassium, magnesium, calcium, protein and fibre See for further information. Page 10

11 NICE CG127 Pharmacological Treatment Pathway Refers to non- pregnant adults. Consider co-morbidities as there may be compelling indications for use of alternative antihypertensive regimes. Alternatives within the class (in line with CCG formulary) may be used. Aged under 55 years Aged 55 years and above or African /Caribbean family origin of any age Step 1 ACE Inhibitor (ACEI) # Ramipril starting at 2.5mg and increased to a maximum of 10mg/day Calcium Channel Blocker Amlodipine 5mg increased to 10mg if required Step 2 ACE Inhibitor # + Calcium Channel Blocker Step 3 ACE Inhibitor # + Calcium Channel Blocker+ Thiazide- like Diuretic (indapamide 2.5mg) Step 4 Resistant hypertension Consider further diuretic therapy with spironolactone 25mg once a day (if K + 4.5) or increased dose of indapamide (if K + >4.5 and on 1.5mg dose)/switch to loop diuretic (e.g. furosemide) If further diuretic is not tolerated, C/I or ineffective consider addition of alpha-blocker (e.g. doxazosin) or beta-blocker (e.g. bisoprolol) CONSIDER SEEKING SPECIALIST ADVICE # if ACEI is prescribed and not tolerated (e.g. intractable cough) OR African /Caribbean family origin consider offering angiotensin receptor blocker (ARB) instead if you think the patient would benefit from a medication review please consider referring to your medicines optimisation pharmacist within the medicines management team. If blood pressure remains uncontrolled with either optimal or maximum tolerated doses of 4 drugs recheck adherence and consider seeking specialist advice If blood pressure > 180/110 exclude accelerated hypertension Examples of compelling indications for alternative choices (list not exhaustive) Left ventricular systolic dysfunction (LVSD) ACEI/ARB + beta-blocker +/- mineralocorticoid receptor antagonist (spironolactone or eplerenone) Secondary prevention post MI ACEI /ARB + beta-blocker (+/- eplerenone if LVSD) Stable angina Beta blocker and/or calcium channel blocker Atrial fibrillation (rate control) Beta blocker or rate controlling calcium channel blocker CKD with proteinuria (ACR> 30mg/mmol) ARB Page 11

12 Cardiovascular Risk Assessment and Lipid Lowering Therapy Lipid Modification should be in line with NICE Clinical Guideline The following information relates to the prescribing of lipid lowering agents. Always take into account any contra-indications to therapy and concomitant treatment as there are some important drug interactions with statins that may affect choice of agent and/or dosage. Refer to Brighton and Hove Area Prescribing committee guidelines for full details: Section 2.12 (cardiovascular) lipid management guidelines. Offer a statin where indicated in line with this guidance. Advice on monitoring, side effects, how to manage intolerances and drug interactions is included in this guidance. Primary Prevention Identify and where possible modify risk factors before prescribing lipid lowering therapy For adults up to the age of 84 years NICE recommend assessing cardiovascular disease (CVD) risk using QRISK tool. Offer people information about their absolute risk of CVD and the benefits and risks of intervention over 10 years. Remember particularly in younger patients Q-RISK may underestimate CV risk. An alternative useful tool is the Joint British Society 3 tool that uses lifetime risk, heart age and has some useful features to demonstrate effects of modification of lifestyle risk factors. Secondary prevention Do not use a risk assessment tool for patients with: known or suspected familial hypercholesteraemia, type I diabetes, egfr<60ml/minute and/or albuminuria, or pre-existing cardiovascular disease. These patients are high risk and should be offered lipid lowering therapy Elderly patients For patients 85 years or older consider that statins may be of benefit in reducing the risk of non fatal myocardial infarction but be aware of factors that may make treatment inappropriate and consider each patient on case by case basis. Page 12

13 Medication Information The following section is designed to offer a quick prescribing guide for the common classes of medication used for the management of hypertension and practical information on the prescribing, monitoring and patient information. It is intended to support general practitioners and non-medical prescribers (nurses and pharmacists) who may be managing this cohort of patients. If significant co-morbidities exist some parameters for cautions may be different (for example use of ACEI/ARB in patients with left ventricular systolic dysfunction or significant kidney disease). If unsure seek advice It is not intended to replace the manufacturers product information which should be consulted for the latest full prescribing information at Local formulary choices for medication can be found at: Page 13

14 Angiotensin Converting Enzyme Inhibitors (ACEI) Formulary choices: RAMIPRIL or PERINDOPRIL Contra-indications History of allergy to ACE inhibitors. History of angioedema (hereditary, idiopathic or previous angioedema with ACEI or ARB). Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney. Pregnancy and lactation. Patients prescribed aliskiren or lithium or sacubitril/valsartan or ARB. Baseline potassium > 5.0 mmol/l. Cautions Baseline creatinine > 150 micromol/l (particularly if of unknown cause). Hemodynamically significant aortic or mitral valve stenosis. Unilateral renal artery stenosis with a second functional kidney. Fluid or salt depletion may develop (particularly in patients prescribed diuretics). Correct dehydration first. Liver cirrhosis and/or ascites. Risk of hyperkalaemia with concomitant spironolactone, eplerenone, triamterene, amiloride, trimethoprim, potassium supplements, salt substitutes (such as Lo- salt ), ciclosporin, NSAIDs, digoxin toxicity, non-selective beta-blockers. Dosing for hypertension Ramipril: Initial dose = 2.5mg once a day The dose can be doubled at intervals of two to four weeks to progressively achieve target blood pressure. The maximum dose of ramipril is 10 mg per day - usually once daily. In patients already treated with diuretics, with left ventricular systolic dysfunction, renal impairment or the elderly a starting dose of 1.25mg once a day may be preferred. Perindopril: Initial dose = 4mg once a day. Subsequent dose increase to 8mg once a day (maximum dose). In patients already treated with diuretics, with left ventricular systolic dysfunction, renal impairment or the elderly a starting dose of 2mg once a day may be preferred. Baseline blood test Check sodium, potassium, creatinine and egfr prior to starting treatment Do not initiate if creatinine > 150 micromol/l (check reason first) Do not initiate if potassium > 5.0 mmol/l On-going monitoring of renal function Check sodium, potassium, creatinine and egfr 1-2 weeks after initiation and following any subsequent dosage change. If the serum creatinine rises by more than 15% but less than 30% from baseline continue treatment but re-check in a further 1-2 weeks. Clinical review may be required. Page 14

15 If serum creatinine increases by more than 30% from baseline and/or egfr decreases by more than 20% clinical review is required. Consider stopping ACEI or reducing to a previously tolerated dosage. Repeat blood test for renal function in 5-7 days: if renal function not improved stop ACEI and consider whether renal or heart failure advice (if applicable) needed. Review other BP lowering medication and diuretics as these may need to be stopped/reduced especially if SBP < 120 mmhg or patient dehydrated. Refer to the Renal Association Think Kidneys document for further guidance Potassium - hyperkalaemia NB hyperkalaemia may be artefactual in samples sent from primary care This can be caused by fist clenching during phlebotomy, use of small gauge needles causing low grade haemolysis, prolonged tourniquet use and delays in sample processing particularly in cold weather Management depends on clinical context Severe hyperkalaemia (potassium 6.5 mmol/l) Refer to hospital via A&E for immediate assessment and treatment Potassium to mmol/l If patient acutely unwell or has acute kidney injury (AKI) STOP ACEI and refer to hospital for immediate assessment and treatment. If patient is clinically stable and the test was done as a routine check and there is no AKI undertake medication review. Consider repeating test following day AND Stop ACEI - and repeat potassium within 1 week (if concomitant heart failure with left ventricular systolic dysfunction, CKD or proteinuria: re-introduce at lower dose once potassium below 5.5 mmol/l and monitor closely) Remove other contributors to hyperkalaemia (see cautions to ACEI) Review patient clinically and reduce/stop diuretics if evidence of over diuresis Potassium 5.5 mmol/l -5.9 mmol/l If patient acutely unwell or has acute kidney injury STOP ACEI and consider referral to hospital for immediate assessment and treatment If patient is clinically stable and the test was done as a routine check and there is no AKI undertake medication review. Consider repeating test within 3 days AND Consider withholding ACEI or dose reduction Where appropriate remove other contributors to hyperkalaemia (see cautions to ACEI) Page 15

16 Potassium 5.0 mmol/l but < 5.5 mmol/l Continue current dose of ACEI and re-check in potassium 2 weeks Where appropriate remove other contributors to hyperkalaemia (see cautions to ACEI) Dietary advice on potassium can be found at: Sodium - hyponatremia Hyponatremia may occur. If sodium level < 130 mmol/l consider whether treatment can be continued and if bloods need to be repeated Check for any other medication that may case hyponatremia (in particular thiazide/thiazide like diuretics or SSRI antidepressants). Advice to patients when prescribing an ACE inhibitor for hypertension ACEI will be introduced at a low dose and increased in stages to achieve blood pressure control. For many patients more than one type of medicine may be required to lower the blood pressure. Blood tests for kidney function and levels of the salts in the body are required initially and after each dosage change and are essential to ensure safe prescribing of this medicine. The most common side effect is a cough this can occur at any time but more commonly occurs early in the course of treatment. The cough tends to be a dry, irritating (nonproductive) cough. It is often worse at night In rare cases patients can be allergic to this medication resulting in angio-oedema. Advise patient to seek urgent medical attention if lip swelling / tongue swelling / difficulty in breathing. It is more common for this to happen early in treatment but it can occur at any time too. For diabetic patients on treatment there is a small increase in the incidence of hypoglycemia (low blood sugar). Blood glucose monitoring may be recommended. Page 16

17 Angiotensin Receptor Blockers (ARB) Formulary choice: LOSARTAN. Alternatives: IRBESARTAN or CANDESARTAN (preferred choice if LVSD). Contra-indications History of allergy to ARB. Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney. Pregnancy and lactation. Patients prescribed aliskiren or lithium or sacubitril valsartan or ACEI Baseline potassium > 5.0 mmol/l. Cautions History of angioedema (hereditary, idiopathic or previous angioedema with ACEI). Baseline creatinine > 150 micromol/l (particularly if of unknown cause). Hemodynamically significant aortic or mitral valve stenosis. Unilateral renal artery stenosis with a second functional kidney. Fluid or salt depletion may develop (including patients with diuretics) -correct dehydration first. Liver cirrhosis and / or ascites. Risk of hyperkalaemia with concomitant spironolactone, eplerenone, triamterene, amiloride, trimethoprim, potassium supplements, salt substitutes (such as Lo- salt ), ciclosporin, NSAIDs, digoxin toxicity, non-selective beta-blockers. Dosing for hypertension Losartan: Initial dose = 50mg once a day. Dose may be increased to 100mg once a day (maximum dose) In patients already treated with diuretics, with left ventricular systolic dysfunction, renal impairment, hepatic impairment or the elderly a starting dose of 25mg may be preferred. Baseline blood test Check sodium, potassium, creatinine and egfr prior to starting treatment Do not initiate if creatinine > 150 micromol/l (check reason first) Do not initiate if potassium > 5.0 mmol/l On-going monitoring of renal function see section for ACEI -On-going monitoring of renal function Potassium hyperkalaemia see section for ACEI -Potassium - hyperkalaemia Sodium hyponatraemia see section for ACEI -Sodium - hyponatremia Advice to patients when prescribing an ARB for hypertension See section for ACEI on page- Advice to patients when prescribing an ACE inhibitor for hypertension (Except risk of angio-oedema low and no cough) Page 17

18 Calcium Channel Blockers Formulary choice: AMLODIPINE. Alternative: FELODIPINE Contra-indications Hypersensitivity to dihydropyridines derivatives or any of the excipients. Haemodynamically unstable heart failure. Severe aortic stenosis. Pregnancy and lactation. Concomitant tacrolimus or ciclosporin (unless levels monitored specialist advice needed). Cautions Left ventricular systolic dysfunction. Hepatic impairment. Limit the dose of simvastatin to 20mg once a day for patients on amlodipine (consider switching to atorvastatin). Concomitant strong cytochrome P450 inhibitors such as protease inhibitors, azole antifungals (e.g. itraconazole), and macrolide antibiotics may significantly enhance the blood pressure lowering effects. Concomitant strong cytochrome P3450 inducers such as rifampicin, St John s wort, and carbamazepine may alter blood pressure lowering effects. Dosing Amlodipine initial dose is 5mg once a day. Dose may be further increased to 10mg once a day (maximum dose). Felodipine initial dose is 5mg once a day. Dose may be further increased to 10mg once a day (maximum dose). Monitoring Other than blood pressure no specific monitoring is required. Advice to patients prescribed calcium channel blocker for hypertension Will be introduced at a low dose and may be increased to achieve blood pressure control. For many patients more than one type of medicine may be required to lower the blood pressure. Common side effects at start of treatment are headaches and facial flushing. The most common side-effect is ankle swelling. Administration with grapefruit or grapefruit juice is not recommended (bioavailability may be increased in some patients resulting in increased blood pressure lowering effects). Page 18

19 Thiazide/thiazide like diuretics Formulary choice: INDAPAMIDE (Bendroflumethazide may be continued if already prescribed) Contra-indications Hypersensitivity to indapamide, to other sulfonamides or to any of the excipients. Severe renal failure (creatinine clearance <30 ml/minute). Severe impairment of liver function. Hypokalemia or hyponatraemia. Pregnancy and lactation. Avoid in patient with history of gout. Concomitant lithium. Cautions May cause electrolyte imbalance (see below) Use in combination with medicines that cause QT prolongation (increased risk of ventricular arrhythmias in setting of electrolyte disturbances). Risk of acute renal failure in dehydrated patients (decreased glomerular filtration). Check if any other diuretics prescribed if this is the case review ongoing need for preexisting therapy and whether the thiazide is appropriate. Dosing in hypertension Indapamide 2.5mg once a day (first line) or indapamide s/r 1.5mg once a day. Or Bendroflumethazide 2.5mg once a day if already prescribed may be continued. Baseline blood test Check sodium, potassium, creatinine and egfr prior to treatment. Re-check within 2 weeks. Sodium - hyponatraemia Hyponatremia may occur and typically occurs soon after the onset of treatment If sodium level < 130 mmol/l consider whether treatment can be continued and if bloods need to be repeated. Check for any other medication that may case hyponatremia Potassium - hypokalaemia Hypokalaemia may occur. If potassium level <3.4 mmol/l consider whether treatment can be continued and if bloods need to be repeated. Dietary advice and/or short term potassium supplementation may need to be considered. Advice to patient prescribed thiazide diuretic for hypertension Will be used in combination with other medicines for blood pressure control Medication is a diuretic (water tablet). Take in the morning to avoid nocturia Blood tests for kidney function and levels of the salts in the body are required to ensure safe prescribing of this medicine. Page 19

20 Spironolactone Contra-indications History of allergy spironolactone or eplerenone. Pregnancy and lactation. Patients prescribed aliskiren, lithium, eplerenone. Patients prescribed triamterene or amiloride that cannot be discontinued. Baseline potassium > 5.0 mmol/l. Cautions Baseline creatinine > 150 micromol/l (check reason first and if prescribed start with low dose). Fluid or salt depletion may occur -correct dehydration first. Liver cirrhosis and / or ascites. Dosing for hypertension Spironolactone: Initial dose = 25mg every morning. Dose may be increased to 50mg. Lower doses of 12.5mg once a day or 25mg on alternate can be used if concern over tolerability. Baseline blood tests Check sodium, potassium, creatinine and egfr prior to starting treatment Do not initiate if creatinine > 150 micromol/l (check reason first and if prescribed start with lower dose) Do not initiate if potassium > 5.0 mmol/l On-going monitoring There are no specific guidelines of frequency of monitoring spironolactone when prescribed for hypertension. The following are in line with guidance for management of left ventricular systolic dysfunction. Check sodium, potassium, creatinine and egfr 1 week after initiation then at weeks 4, 8 and 12. Continue to monitor three monthly up to 1 year and 6 monthly thereafter. Potassium hyperkalaemia see section for ACEI - Potassium - hyperkalaemia Note where states stop / reduce ACEI that this also applies to spironolactone. Review whether patient also prescribed ACEI/ARB as this may also need to be stopped /withheld. Sodium- hyponatraemia Hyponatraemia may occur. If sodium level < 130 mmol/l consider whether treatment can be continued and if bloods need to be repeated. Check for any other medication that may case hyponatremia. Advice to patient prescribed spironolactone for hypertension Blood tests for kidney function and levels of the salts in the body are required and are essential to ensure safety of this medication. May cause gynecomastia (males). Advise patient to report breast tenderness. Page 20

21 Alpha-Blockers Formulary choice: DOXAZOSIN (immediate release tablets) Contra-indications History of allergy doxazosin or any other alpha blocker. Patients with a history of orthostatic hypotension. Patients with benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones. Pregnancy and lactation. Patients with the rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Cautions Patients with left ventricular systolic dysfunction. Hepatic impairment. Conditions which may increase risk of postural hypotension such as diabetes, Parkinson s disease, aortic stenosis and hypovolemia. Concomitant administration with phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, and vardenafil) - may lead to symptomatic hypotension. (If new prescription of PDE5 inhibitor initiate with lowest dose). Where possible avoid PDE5 inhibitor within 6 hours of dose of doxazosin. Dosing for hypertension Doxazosin initial dose = 1mg once a day. Dose may be increased in stages to a maximum dose of 16mg daily. Monitoring Monitor sitting and standing blood pressure prior to starting treatment and at each dose change. If postural drop > 20 mmhg do not initiate and/or increase dose. Advice to patient prescribed alpha-blocker for hypertension Will be introduced at a low dose and increased in stages to achieve blood pressure control. Postural hypotension may occur particularly when starting treatment or after dose changes. Advise patient to avoid rapid changes of position including getting out of bed. If symptoms occur (and continue) either discontinue (if new Rx) or reduce dose back to previously tolerated dosage. If patient Rx PDE5 inhibitor (e.g. sildenafil) emphasise risk of postural hypotension. Suggest avoid PDE5 inhibitor for the first few days after starting /any dose change of doxazosin. Cataract surgery - 'Intraoperative Floppy Iris Syndrome' may lead to increased procedural complications during the cataract operation. Current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery. Prolonged erections and priapism have been reported with alpha-1 blockers including doxazosin in post marketing experience. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. Page 21

22 Beta Blockers Formulary choice: BISOPROLOL Contra-indications Acute heart failure / decompensated heart failure / cardiogenic shock. Second or third degree AV block (without a pacemaker). Sick sinus syndrome, sinoatrial block, and symptomatic bradycardia. Severe bronchial asthma or severe chronic obstructive pulmonary disease. Late stages of peripheral arterial occlusive disease and Raynaud's syndrome. Untreated phaeochromocytoma. Metabolic acidosis. Hypersensitivity to bisoprolol or to any of the excipients. Pregnancy and lactation. Concomitant VERAPAMIL (risk of AV block). Cautions Bronchospasm (bronchial asthma, obstructive airways diseases). Diabetes mellitus - symptoms of hypoglycemia (e.g. tachycardia, palpitations or sweating) can be masked. May increase both the sensitivity towards allergens and the severity of anaphylactic reactions and adrenaline treatment does not always give the expected therapeutic effect. First degree AV block. Prinzmetal's angina (coronary spasm). Peripheral arterial occlusive disease (intensification of complaints might happen especially at the start of therapy). May worsen psoriasis. In patients with phaeochromocytoma bisoprolol must not be administered until after alphareceptor blockade. May mask the symptoms of an overactive thyroid. Concomitant centrally acting antihypertensive drugs such as clonidine, methyldopa, moxonodine. Drug interactions Diltiazem or other medicines that slow the heart rate -- e.g. digoxin, donepezil, mefloquine. Calcium antagonists of the dihydropyridine type (e.g. felodipine and amlodipine) may increase in the risk of a further deterioration in patients with heart failure Class-I antiarrhythmic drugs (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone). May be co-prescribed on specialist advice. Class-III antiarrhythmic drugs (e.g. amiodarone): may slow heart rate. May be coprescribed on specialist advice. Page 22

23 Topical beta-blockers (e.g. eye drops for glaucoma treatment) possible additive effects Insulin and oral antidiabetic drugs. Increase in blood sugar lowering effect. May mask symptoms of hypoglycaemia. Monoamine oxidase inhibitors (except MAO-B inhibitors) - enhanced hypotensive effect of the beta-blockers but also risk for hypertensive crisis Ergotamine derivatives: Exacerbation of peripheral circulatory disturbances. Dosing for hypertension Bisoprolol initial dose = 2.5 mg once a day. Lower initial dose (e.g mg once a day) in patients with left ventricular failure. Dose may be increased in stages to a maximum dose of 10mg daily. Monitoring Monitor heart rate to prevent bradycardia. For patients in sinus rhythm resting heart rate should be > 60 bpm. For patients in atrial fibrillation rate control to resting heart rate bpm. Advice to patient Will be introduced at a low dose and may be increased in stages to achieve blood pressure control. It is likely that more than one type of medicine may be required. Especially in patients with ischemic heart disease the cessation of therapy with bisoprolol should not be done abruptly unless clinically indicated, because this may lead to transient worsening of heart condition. If any history of airway disease advise patient to report worsening of symptoms Page 23