Previous changes

May 2026 — minor update. Typo corrected.

January 2026 — minor update. Minor change to the order of referral criteria in the management section. 

October 2025 — minor update. Removed interaction between calcium channel blockers and theophylline and aminophylline to align with the BNF drug monograph. 

September 2025 — minor update. The sections on monitoring abnormal results for people taking a renin-angiotensin system antagonist have been updated in line with the recommendations in the NICE guideline Chronic heart failure in adults: diagnosis and management.

May 2025 — minor update. QOF indicators updated in line with the NHS England Quality and Outcomes Framework guidance for 2025/26.

March 2025 — minor update. Interaction with DOACs added to the prescribing information for diltiazem. 

December 2023 — minor update. Adverse effect of lupus-like syndrome added and also non-cardiogenic pulmonary oedema in overdose for people prescribed diltiazem in line with an update to the manufacturer's SPC. 

March 2023 — minor update. Adverse effects and contraindications and cautions for diltiazem have been updated in line with the updated manufacturer's Summary of Product Characteristics (SPC) for Slozem capsules.

February 2023 — minor update. The recommendation on managing people with eGFR less than 60 mL/min/1.73 m² and/or the urinary ACR of 3 mg/mmol or more in the annual review section was clarified. Minor typographical error corrected in the diagnosis, basis of recommendation section. 

July 2022 — reviewed. A literature search was conducted in July 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic is now fully in line with the National Institute for Health and Care Excellence (NICE) guideline Hypertension in adults: diagnosis and management, and includes recommendations for adults with type 2 diabetes. As updates had already occurred to align with the NICE guideline, no major new changes to the recommendations have been made. Minor restructuring changes have been made.

March 2022 – minor update. To align with the update in NICE [NG136] Hypertension in adults: diagnosis and management. Acute respiratory toxicity has been added as a very rare adverse effect of thiazide type diuretics in line with the updated manufacturer's Summary of Product Characteristics.  

April 2021 – minor update. Title of topic has been changed from 'Hypertension - not diabetic' to 'Hypertension'.

September 2020 – minor update. Adverse effects updated for thiazide-type diuretics in line with revised manufacturers' SPCs.

July 2020 – minor update. Typographical error corrected in the section on Prescribing information.

May 2020 – minor update. Prescribing information has been added in response to the National Institute for Health and Care Excellence (NICE) COVID-19 rapid evidence summary: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in people with or at risk of COVID-19 to reflect the advice during the COVID-19 pandemic.

October 2019 — minor update. This topic has been updated to align with the National Institute for Health and Care Excellence (NICE) guideline Hypertension in adults: diagnosis and management [NICE, 2019], which updates and replaces the NICE guideline Hypertension: The clinical management of primary hypertension in adults [National Clinical Guideline Centre, 2011]. The topic has also been restructured for clarity. 

• NICE reviewed the evidence and made new recommendations on the following:
• Diagnosing hypertension.
• Starting antihypertensive drug treatment.
• Monitoring treatment and blood pressure targets.
• Choosing antihypertensive drug treatment (treatment steps 1 to 4).
• Who to refer for same-day specialist review.
• NICE also made some changes without an evidence review, including:
• Replacing plasma glucose testing with HbA1c to reflect current practice.
• Adding a footnote to highlight concerns about the risks of salt substitutes in some groups of people.

January 2018 — minor update. Revised SPC for Istin® (amlodipine) 5 and 10mg tablets. Drug interactions updated as per the revised SPC.

May to June 2017 — reviewed. A literature search was conducted in May 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

October 2015 — minor updates.

• The information on beta blockers in the Prescribing information section has been re-worded to reflect advice from the manufacturers' Summary of Product Characteristics, in relation to the cautions and contraindications of beta blockers if the person has a form of obstructive airways disease.
• Based on an update to the Summary of Product Characteristics (SPC) for Tritace^® (ramipril), other common adverse effects of angiotensin- converting enzyme (ACE) inhibitors and a drug interaction with vildagliptin have been added to the section on Prescribing information.
• The recommendation on when to offer a statin to people with hypertension has been deleted and links have been provided to the CKS topics on Lipid modification - CVD prevention and CVD risk assessment and management.
• The advice regarding the concurrent use of renin-angiotensin system (RAS) blocking drugs has been further clarified, based on an update to the Summary of Product Characteristics (SPC) for Tritace^® (ramipril).

May 2015 — minor updates:

• The Medicines and Healthcare products Regulatory Agency (MHRA) warning regarding the concurrent use of RAS drugs has been clarified.
• Information about the increased risk of hyperkalaemia with concurrent use of spironolactone and nonsteroidal anti-inflammatory drugs has been updated in line with the SPC for spironolactone.

February 2015 — minor update. Following external feedback, the text recommending that people who have a blood pressure reading of 220/120 mmHg has been removed. This is not a NICE recommendation and has therefore been removed.

July 2014 — minor update. Advice from the MHRA to not prescribe medicines from different classes of renin-angiotensin system blocking agents in combination (for example an angiotensin-converting enzyme [ACE] inhibitor plus an angiotensin-II receptor antagonist) has been incorporated into the topic.

December 2013 — minor update. Prescribing information has been updated in line with the SPC for perindopril.

July 2013 — minor update. Links to the DVLA website have been updated.

July 2013 — minor update. The management of abnormal results in people who is on an angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist was updated according to the updated National Institute for Health and Care Excellence guideline: Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care.

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

November 2011 to January 2012 — revised. A literature search was conducted in October 2011 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. The topic also reflects new and updated recommendations in the clinical guideline Hypertension. Clinical management of primary hypertension in adults from the National Institute for Health and Care Excellence. Text changes include updates on blood pressure measurement, the use of ambulatory and home blood pressure monitoring, modified blood pressure targets, and antihypertensive drug treatments. Issued in April 2012.

July 2011 — minor update. Included cough as a very rare, but possible adverse effect of candesartan. This information is based on the updated Summary of Product Characteristics for Amias®. Issued in September 2011.

June 2011 — minor update. The 2011/2012 QOF indicators and the 2010/2011 QIPP options for local implementation have been added to this topic. 

March 2011 — technical update. The management section of this topic has been simplified to improve clarity and navigation. There have been no changes to the clinical content or meaning of the recommendations.

October 2010 — minor update. Information on fitness to drive from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive, has been added. 

January 2010 — minor update. Advice regarding how to deal with abnormal urea and electrolyte results for people taking diuretics has been clarified. 

December 2009 — minor update. Text added regarding potential drug interactions between antidepressants and alpha-blockers, beta-blockers, and calcium-channel blockers, in line with NICE guidance Depression in adults with a chronic physical health problem. The recommendations on when to consider antiplatelet treatment for primary prevention of cardiovascular disease have also been updated.

October 2009 — minor update. A reminder from the Medicines and Healthcare products Regulatory Agency (MHRA) that aspirin is not licensed for use in primary prevention of vascular events has been added. 

February to July 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There have been no major changes to the recommendations.

June 2009 — minor update to include drug safety advice from the Medicines and Healthcare products Regulatory Agency on the use of angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists in women who are breastfeeding.

April 2009 — minor update. The Quality and Outcomes Framework (QOF) indicators for hypertension have been updated in the Goals and outcome measures section. Losartan has been reclassified as a black triangle drug by the Medicines and Healthcare products Regulatory Agency (MHRA). However, this is due to harmonisation of the Summary of Product Characteristics across the European Union, not because of any newly identified safety issues.

May 2008 — minor update to text regarding availability of the new perindopril arginine salt. 

January 2008 — updated. The Medicines and Healthcare products Regulatory Agency (MHRA) has recently advised that ACE inhibitors and angiotensin II receptor antagonists should not be used at any stage of pregnancy.

July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007.

November 2005 — minor update. Reference made to the CKS topic on Antiplatelet treatment which outlines gastrointestinal issues that need to be considered in the prescribing of low-dose aspirin for the prevention of cardiovascular events. 

November 2004 — reviewed to incorporate evidence-graded recommendations from the National Institute for Health and Care Excellence (NICE) 2004 guideline on Essential hypertension: managing adult patients in primary care (written by the North of England Hypertension Guideline Development Group) and the British Hypertension Society (BHS) 2004 Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004 — BHS IV. Evidence from systematic reviews and meta-analyses published since the NICE and BHS guidelines were written have also been included where relevant. Validated in March 2005 and issued in July 2005.

November 2002 — reviewed and updated to incorporate evidence-graded recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) guideline on Hypertension in Older People (2001), and evidence from more recent clinical trials. Issued in April 2003.

October 2000 — updated to incorporate National Service Framework for Coronary Heart Disease (NSF for CHD) recommendations. Issued in December 2000.

September 1999 — written, based on the BHS 1999 guidelines on the management of hypertension. Validated in November 1999 and issued in December 1999.

New evidence

Evidence-based guidelines

• McCarthy, C. P., Bruno, R. M., McEvoy, J. W., et al. (2024). 2024 ESC Guidelines for the management of elevated blood pressure and hypertension: what is new in pharmacotherapy? European Heart Journal, 45, 3912-4018. [Free Full-text]
• Jones, D.W., Ferdinand, K.C., Taler, S.J., et al. (2025) AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. https://www.ahajournals.org [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2022.

Economic Appraisals

No new economic appraisals relevant to England since 1 July 2022.

Systematic reviews and meta-analyses

• Steckelmacher, J., Graham, C., Maniero, C., & Gupta, A. (2024). Managing hypertension in older people: current concepts. Drug and Therapeutics Bulletin, 62(10), 149-155. [Abstract]

Primary evidence

• Wen, X., Otoo, M. N., Tang, J., et al. (2024) Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy. JAMA Neurology. [Abstract]

New policies

No new national policies or guidelines since 1 July 2022.

New safety alerts

No new safety alerts since 1 July 2022.

Changes in product availability

• New product jeraygo (aprocitentan) is licensed for treatment of resistant hypertension in adult patients in combination with at least three antihypertensive drugs. See more here.
• New product Xytencorg (propranolol) 10 mg Orodispersible tablets. This new orodispersible formulation of propranolol, also available in a 40mg strength, is licensed for treatment of hypertension, angina, MI, cardiomyopathy, dysrhythmias, thyrotoxicosis, essential tremor, anxiety, and prophylaxis of upper GI bleeding and migraine. See more here.

Basis for recommendation

These recommendations are based entirely on the National Institute for Health and Care Excellence (NICE) guideline Hypertension in adults: diagnosis and management [NICE, 2022]. For information on why NICE made these recommendations and how they might affect practice, see the section on Rationale and impact in the NICE guideline Hypertension in adults: diagnosis and management [NICE, 2022].

Although not specified in the NICE guideline, other guidelines, such as the European Society of Cardiology and the European Society of Hypertension, make it clear that diagnosis and classification of hypertension relies on systolic AND/OR diastolic blood pressure ranges. The category is defined by the higher reading. For example, stage 1 hypertension is defined as a clinic systolic blood pressure of 140–159 mmHg and/or a diastolic blood pressure of 90–99 mmHg (as well as the appropriate ambulatory or home blood pressure measurements). If either systolic or diastolic measurement fits into a stage 1 definition, it should be classed as stage 1 hypertension and managed accordingly [Williams, 2018].

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Hypertension in adults: diagnosis and management [NICE, 2022]. 

How should I manage a person with hypertension?

These recommendations may not apply to women who are considering pregnancy, pregnant, or breastfeeding. For specific information on managing hypertension in women who are considering pregnancy, pregnant, or breastfeeding, see the CKS topic on Hypertension in pregnancy. The recommendations apply otherwise to all adults, but there may be further specific guidance for those with type 1 diabetes or chronic kidney disease (CKD). For management of hypertension in these groups, see also the CKS topics on Diabetes - type 1 and Chronic kidney disease.

• Refer for same-day specialist assessment if the person has: 
  • A clinic blood pressure of 180/120 mmHg and higher with:
    • Signs of retinal haemorrhage and/or papilloedema (accelerated hypertension), or
    • Life-threatening symptoms, such as new onset confusion, chest pain, signs of heart failure, or acute kidney injury. 
  • Suspected phaeochromocytoma, for example labile or postural hypotension, headache, palpitations, pallor, abdominal pain, or diaphoresis.
• For adults aged under 40 years with hypertension, consider seeking specialist evaluation of secondary causes of hypertension and a more detailed assessment of the long-term balance of treatment benefit and risks.
• If referral is not indicated: 
  • Carry out investigations for target organ damage, followed by a formal assessment of the person's cardiovascular risk, if not already done. For more information, see the section on Investigations.
  • Offer lifestyle advice, and continue to offer it periodically.
    • Diet and exercise — explain that a healthy diet and regular exercise can reduce blood pressure. If the person is overweight or obese, offer weight loss advice. For more information, see the CKS topic on Obesity. 
    • Caffeine — discourage excessive consumption of coffee and other caffeine-rich products.
    • Dietary sodium — encourage people to keep their dietary sodium intake low, by reducing or substituting sodium salt, as this can reduce blood pressure. Be aware that salt substitutes containing potassium chloride should not be used by older people, people with diabetes, pregnant women, people with kidney disease, and people taking some antihypertensive drugs (such as angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers). Encourage salt reduction in these groups of people.
    • Smoking — offer advice and help to smokers to stop smoking. For more information, see the CKS topic on Smoking cessation.
    • Alcohol — if the person drinks excessively, encourage a reduced intake because this can reduce blood pressure and has broader health benefits. For more information, see the CKS topic on Alcohol - problem drinking.
  • Offer patient information leaflets on hypertension, for example the National Institute for Health and Care Excellence (NICE) have produced a patient decision aid on treatment options for hypertension to help people and their healthcare professionals discuss the different types of treatment and make a decision that is right for each person. Other information leaflets include those on Blood pressure from the British Heart Foundation (BHF) and Hypertension and diet from the British Dietetic Association (BDA).
  • Inform people about local initiatives supporting healthy lifestyle changes.
  • For stage 2 hypertension (clinic blood pressure of 160/100 mmHg or higher but less than 180/120 mmHg and subsequent ambulatory daytime average or home blood pressure average of 150/95 mmHg or higher):
    • Offer antihypertensive drug treatment in addition to lifestyle advice to adults with persistent stage 2 hypertension, regardless of age.
    • Use clinical judgement for people with frailty or multimorbidity. For more information, see the CKS topic on Multimorbidity.
  • For stage 1 hypertension (clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg and subsequent ambulatory daytime average or home blood pressure average ranging from 135/85 mmHg to 149/94 mmHg):
    • Discuss starting antihypertensive drug treatment, in addition to lifestyle advice, with people aged under 80 years with persistent stage 1 hypertension who have one or more of the following: target organ damage, established cardiovascular disease (CVD), renal disease, diabetes, an estimated 10-year risk of CVD of 10% or more. 
    • Consider antihypertensive drug treatment in addition to lifestyle advice for people aged under 60 years with stage 1 hypertension and an estimated 10-year CVD risk below 10%. Bear in mind that 10-year cardiovascular risk may underestimate the lifetime probability of developing CVD.
    • Consider antihypertensive drug treatment in addition to lifestyle advice for people aged over 80 years with a clinic blood pressure of over 150/90 mmHg.
    • Use clinical judgement for people with frailty or multimorbidity. For more information, see the CKS topic on Multimorbidity.
  • Discuss with the person their individual CVD risk and their preferences for treatment, including no treatment, and explain the risks and benefits before starting antihypertensive drug treatment. Continue to offer lifestyle advice, and support them to make lifestyle changes whether or not they choose to start antihypertensive drug treatment.
  • Monitor response to lifestyle changes or drug treatment. 

NICE has produced a 2-page visual summary on the recommendations for diagnosing and treating hypertension.

How should I prescribe antihypertensive drug treatment?

These recommendations may not apply to people with type 1 diabetes or chronic kidney disease (CKD) or to women who are considering pregnancy, pregnant, or breastfeeding. For information on managing hypertension in people with diabetes or CKD, see the CKS topics on Diabetes - type 1 and Chronic kidney disease. For information on managing hypertension in women who are considering pregnancy, pregnant, or breastfeeding, see the CKS topic on Hypertension in pregnancy. For people with hypertension and cardiovascular disease follow the recommendations relevant to their specific condition. See the CKS topics on Angina, Heart failure - chronic, MI - secondary prevention, and Stroke and TIA for more information. 

• General principles
  • A single antihypertensive drug is often inadequate in the management of hypertension, and additional antihypertensive drugs are usually added in a stepwise manner until control is achieved. Titrate to the optimum or highest tolerated dose at each step before adding further treatment.
  • Offer people with isolated systolic hypertension (systolic blood pressure 160 mmHg or more) the same treatment as people with both raised systolic and diastolic blood pressure. 
  • When choosing antihypertensive medication for people of black African or African-Caribbean family origin, consider an angiotensin II receptor blocker (ARB) in preference to an angiotensin-converting enzyme (ACE) inhibitor.
  • ACE inhibitors and ARBs should not be used in women who are pregnant, planning pregnancy, or breastfeeding (unless essential, in which case benefits and risks should be discussed with the woman).
  • Use generic drugs where appropriate to minimize cost.
• Step 1 treatment 
  • Offer an ACE inhibitor or an ARB, also known as an angiotensin-II receptor antagonist (AIIRA) first line for people who:
    • Are aged under 55 years and who are not of black African or African-Caribbean family origin.
    • Have type 2 diabetes (irrespective of age or family origin. As above, use an ARB in preference to an ACE for people of black African or African-Caribbean family origin.)
    • If an ACE inhibitor is not tolerated, for example, because of cough, offer an ARB. 
    • Do not combine an ACE inhibitor with an ARB to treat hypertension. 
  • Offer a calcium-channel blocker (CCB) first line for people who:
    • Are aged 55 years or over and do not have type 2 diabetes.
    • Are of black African or African-Caribbean family origin and do not have type 2 diabetes (of any age).
    • If a CCB is not tolerated, for example, because of oedema, offer a thiazide-like diuretic, such as indapamide.
  • If there is evidence of heart failure, offer a thiazide-like diuretic, such as indapamide. See the CKS topic on Heart failure - chronic for more information.
  • If starting or changing diuretic treatment for hypertension, offer a thiazide-like diuretic, such as indapamide, in preference to a conventional thiazide diuretic, such as bendroflumethiazide or hydrochlorothiazide. For people already having treatment with bendroflumethiazide or hydrochlorothiazide who have stable, well-controlled blood pressure, continue with their current treatment.
  • For detailed information on prescribing an ACE inhibitor, ARB, CCB, or thiazide-like diuretic, see the section on Prescribing information.
• Step 2 treatment 
  • Before considering next step treatment for hypertension:
    • Discuss with the person if they are taking their medicine as prescribed.
    • Support adherence to treatment, in line with the National Institute for Health and Care Excellence (NICE) guideline on Medicines adherence.
  • If hypertension is not controlled with step 1 treatment of an ACE inhibitor or ARB, offer the choice of one of the following drugs in addition to step 1 treatment:
    • A CCB, or
    • A thiazide-like diuretic.
  • If hypertension is not controlled with step 1 treatment of a CCB, offer the choice of one of the following drugs in addition to step 1 treatment:
    • An ACE inhibitor or ARB (consider an ARB in preference to an ACE inhibitor in people of black African or African-Caribbean family origin), or
    • A thiazide-like diuretic.
  • For detailed information on prescribing an ACE inhibitor, ARB, CCB, or thiazide-like diuretic, see the section on Prescribing information.
• Step 3 treatment
  • Before considering next step treatment for hypertension:
    • Review the person's medications to ensure they are being taken at the optimal tolerated doses.
    • Discuss adherence to treatment, in line with the NICE guideline on Medicines adherence.
  • If hypertension is not controlled with step 2 treatment, offer a combination of:
    • An ACE inhibitor or ARB (consider an ARB in preference to an ACE inhibitor in people of black African or African-Caribbean family origin), and
    • A CCB, and
    • A thiazide-like diuretic.
  • For detailed information on prescribing an ACE inhibitor, ARB, CCB, or thiazide-like diuretic, see the section on Prescribing information.
• Step 4 treatment
  • If hypertension is not controlled in people taking the optimal tolerated doses of an ACE inhibitor or an ARB plus a CCB and a thiazide-like diuretic, regard them as having resistant hypertension. 
  • Before considering further treatment for a person with resistant hypertension:
    • Confirm elevated clinic blood pressure measurements using ambulatory or home blood pressure recordings.
    • Assess for postural hypotension.
    • Discuss adherence to treatment, in line with the NICE guideline on Medicines adherence.
  • For people with confirmed resistant hypertension, seek specialist advice or add a fourth antihypertensive drug.
    • For people with a blood potassium level of 4.5 mmol/L or less, consider further diuretic therapy with low-dose spironolactone. Use particular caution in people with a reduced estimated glomerular filtration rate because they have an increased risk of hyperkalaemia. Monitor blood sodium and potassium, and renal function within 1 month of starting further diuretic therapy, and repeat as needed thereafter. 
    • For people with blood potassium level of more than 4.5 mmol/L, consider an alpha-blocker or beta-blocker.
  • If blood pressure remains uncontrolled in people with resistant hypertension taking the optimal tolerated doses of four drugs, seek specialist advice. 
  • For detailed information on prescribing spironolactone, an alpha-blocker, or a beta-blocker, see the section on Prescribing information.
• For people with hypertension and cardiovascular disease follow the recommendations relevant to their specific condition. See the CKS topics on Angina, Heart failure - chronic, MI - secondary prevention, and Stroke and TIA for more information. 

 NICE has produced:

• A patient decision aid on treatment options for hypertension to help people and their healthcare professionals discuss the different types of treatment and make a decision that is right for each person.
• A 2-page visual summary on the recommendations for diagnosing and treating hypertension.

How should I monitor response to lifestyle changes or drug treatment in people with hypertension, and what are the treatment targets?

These recommendations may not apply to people with type 1 diabetes or chronic kidney disease (CKD) or to women who are considering pregnancy, pregnant, or breastfeeding. For information on managing hypertension in people with type 1 diabetes or CKD, see the CKS topics on Diabetes - type 1 and Chronic kidney disease. For information on managing hypertension in women who are considering pregnancy, pregnant, or breastfeeding, see the CKS topic on Hypertension in pregnancy.

• Use clinic blood pressure measurements to monitor the response to lifestyle changes or drug treatment in people with hypertension.
• Aim to reduce blood pressure and maintain it at the following levels:
  • Adults aged under 80 years — clinic blood pressure below 140/90 mmHg.
  • Adults aged 80 years and over — clinic blood pressure below 150/90 mmHg.
  • People with frailty or multimorbidity — use clinical judgement. For more information, see the CKS topic on Multimorbidity.
• For people with type 2 diabetes or symptoms of postural hypotension and people aged 80 years and over, measure standing as well as seated blood pressure.
  • In people with a significant postural drop or symptoms of postural hypotension, treat to a blood pressure target based on standing blood pressure. 
  • If the systolic blood pressure falls by 20 mmHg or more when the person is standing, review their treatment. Consider referral to specialist care if symptoms of postural hypotension persist.
• For people with hypertension identified as having a 'white-coat' effector masked hypertension, consider ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM), in addition to clinic blood pressure measurements.
  • For people who use HBPM, ensure that they are trained on how to use the home blood pressure monitors. Provide information on what they should do if they are not achieving their target blood pressure. 
  • When using ABPM or HBPM to monitor the response to treatment in adults with hypertension, use the average blood pressure level taken during the person's usual waking hours. For more information, see the section on Diagnosis.
  • For those monitoring with ABPM or HBPM, aim to reduce and maintain blood pressure at the following levels:
    • Adults aged under 80 years — ABPM/HBPM below 135/85 mmHg.
    • Adults aged 80 years and over — ABPM/HBPM below 145/85 mmHg.
    • People with frailty or multimorbidity — use clinical judgement. For more information, see the CKS topic on Multimorbidity.
  • Be aware that the corresponding measurements for ABPM and HBPM are 5 mmHg lower than for clinic measurements. For more information on diagnostic thresholds, see the section on Diagnosis.
• For people with hypertension who choose to self-monitor their blood pressure, advise them to use HBPM.
  • Ensure that they are trained on how to use the home blood pressure monitors. Provide information on what they should do if they are not achieving their target blood pressure. 
  • When using HBPM to monitor the response to treatment in adults with hypertension, use the average blood pressure level taken during the person's usual waking hours. For more information, see the section on Diagnosis.
  • Aim to reduce and maintain blood pressure at the following levels:
    • Adults aged under 80 years — HBPM below 135/85 mmHg.
    • Adults aged 80 years and over — HBPM below 145/85 mmHg.
    • People with frailty or multimorbidity — use clinical judgement. For more information, see the CKS topic on Multimorbidity.
  • Be aware that the corresponding measurements for HBPM are 5 mmHg lower than for clinic measurements. For more information on diagnostic thresholds, see the section on Diagnosis.
• Use the same blood pressure targets for people with and without cardiovascular disease.
• Provide an annual review of care to discuss the person's lifestyle, symptoms, and treatment(s), monitor the person's blood pressure and provide support.

How should I review the person annually?

These recommendations do not apply to people with type 1 diabetes or chronic kidney disease (CKD) or to women who are considering pregnancy, pregnant, or breastfeeding. For information on managing hypertension in people with diabetes or CKD, see the CKS topics on Diabetes - type 1, and Chronic kidney disease. For information on managing hypertension in women who are considering pregnancy, pregnant, or breastfeeding, see the CKS topic on Hypertension in pregnancy.

At the annual review:

• Encourage adherence to treatment. 
  • If necessary, use interventions to overcome medication non-adherence, such as suggesting the recording of medicine-taking, encouraging monitoring of the condition, simplifying the dosing regimen, and/or using a multi-compartment medicines system.
• Offer lifestyle advice. Consider factors such as smoking, weight, diet, and physical activity, and offer advice and support where appropriate.
• Check blood pressure.
  • If the person's blood pressure is above the target range, confirm that it is persistently raised:
    • By rechecking blood pressure on 2–3 occasions over the next few weeks or months (depending on clinical judgement), or
    • If a 'white-coat' effect is suspected, considering ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM).  
  • If blood pressure is persistently raised above the target range, ensure that secondary causes for hypertension have been excluded, and consider additional antihypertensive drug treatment.
  • If the person's blood pressure is within the target range but adverse effects of the current antihypertensive drug treatment(s) are unacceptable, consider an alternative antihypertensive drug treatment.
  • If the person's blood pressure is within the target range and the treatment is well tolerated, review the person in a further 12 months.
    • Consider a trial of stopping or reducing antihypertensive drug treatment for people whose blood pressure has been well controlled for years and who have favourable factors, such as use of only one antihypertensive drug, younger age, lower blood pressure, hypertension identified as having a 'white-coat' effect, and the successful implementation of lifestyle measures (such as weight loss, reduced alcohol consumption, regular exercise, and restriction of salt consumption).
    • Withdraw antihypertensive drugs gradually, following the manufacturer's guidance, and follow up the person carefully (for example at 4-weekly intervals for 6 months, then 2 or 3 times a year) to detect any recurrence of hypertension.
• Check renal function by measuring serum creatinine, electrolytes, and estimated glomerular filtration rate (eGFR), and urine to check for albumin:creatinine ratio (ACR).
  
  • If the eGFR is less than 60 mL/min/1.73 m² and/or the urinary ACR is 3 mg/mmol or more, indicating possible chronic kidney disease, see the CKS topic on Chronic kidney disease for information on confirming and managing CKD.
• For people who are not on an antiplatelet drug or a statin, reassess their cardiovascular disease risk using the QRISK® assessment tool.
  
  • For information on the management of people with a 10-year cardiovascular risk of 10% or more (including prescribing statins), see the CKS topics on CVD risk assessment and management, Lipid modification - CVD prevention, and Antiplatelet treatment. 

Which angiotensin-converting enzyme inhibitor is recommended?

• The choice of angiotensin-converting enzyme inhibitor usually depends on the person's comorbidities, local recommendations, and cost.
• Where possible, prescribe a drug that is taken only once a day and prescribe non-proprietary drugs where these are appropriate and minimize cost.

 [BNF, 2022; NICE, 2022]

Contraindications and cautions

• Use of angiotensin-converting enzyme (ACE) inhibitors is contraindicated in:
  • People with history of angio-oedema associated with previous exposure to an ACE inhibitor.
  • People with hereditary or recurrent angio-oedema.
  • People with diabetes mellitus, or with an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73 m², who are also taking aliskiren.
  • Pregnant women and those planning a pregnancy — due to risks to the fetus. Treatment with an ACE inhibitor should ideally be stopped as soon as pregnancy is detected and, if appropriate, alternative treatment should be started.
    • For more information, see the CKS topics on Pre-conception - advice and management and Hypertension in pregnancy.
  • Breastfeeding women — ACE inhibitors are not recommended as there is limited information on their safety.
• ACE inhibitors should be used with caution in people:
  • Of black African or Caribbean origin, or with primary aldosteronism — may respond less well to ACE inhibitors.
  • With renal impairment — hyperkalaemia and other adverse effects are more common, and the dose may need to be reduced. 
  • Taking diuretics.
  • Who have diabetes (increased risk of hyperkalaemia, may lower blood glucose).
  • With hypertrophic cardiomyopathy or aortic or mitral valve stenosis.
  • With peripheral vascular disease or generalized atherosclerosis — due to risk of clinically silent renovascular disease.
  • With severe or unstable heart failure (initiate under specialist supervision).
  • With severe or symptomatic aortic stenosis — due to risk of hypotension.
  • With collagen vascular disease — possible increased risk of agranulocytosis — blood counts recommended.
• Note: people taking high doses of diuretics, on a low sodium diet, on dialysis, who are dehydrated, or who have cerebrovascular disease, ischaemic heart disease or heart failure, may be more likely to experience first-dose hypotension.

 [BNF, 2022; NICE, 2022]

Adverse effects

Adverse effects of angiotensin-converting enzyme (ACE) inhibitors include:

• Renal impairment — check renal function and electrolytes before starting and 1–2 weeks after starting an ACE inhibitor, after each increase in dose, and regularly throughout treatment.
• Hyperkalaemia — monitor serum electrolytes 1–2 weeks after starting an ACE inhibitor, after each increase in dose, and regularly throughout treatment.
• Cough 
  • Cough is reported to occur in 4–35% of people taking an ACE inhibitor and may occur at any time after starting treatment — if the cough is troublesome (for example it prevents the person from sleeping) and other causes have been ruled out, consider switching to an angiotensin-II receptor blocker.
• Angio-oedema
  • ACE inhibitors can cause a non-allergic drug reaction which can precipitate angio-oedema — stop ACE inhibitor treatment immediately, and consider starting an alternative drug treatment. If possible avoid angiotensin-II receptor blockers as these can also trigger episodes of angio-oedema. For more information see the CKS topic on Angio-oedema and anaphylaxis.
• Dizziness and headaches 
  • Dizziness and headaches occur most commonly in people who are hypovolaemic or hyponatraemic — if hypotension is symptomatic, consider reducing the dose of the ACE inhibitor or stopping it.
• Hepato-biliary disorders — stop treatment if marked elevation of hepatic enzymes or jaundice occur. This is a very rare adverse effect. 
• Other common adverse effects include abdominal discomfort, alopecia, arrhythmias, asthenia, chest pain or angina, constipation, diarrhoea, drowsiness, dry mouth, dyspepsia, dyspnoea, nausea and vomiting, rash (in particular maculo-papular rash), myalgia, muscle spasms, paraesthesia, rhinitis, sleep disorder, syncope, taste disturbance, and vertigo.

For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[Yilmaz, 2019; BNF, 2022; NICE, 2022]

Drug interactions

Drug interactions with angiotensin-converting enzyme (ACE) inhibitors include:

• Angiotensin-II receptor blockers and aliskerin — concomitant use of two drugs affecting the renin-angiotensin system increases the risk of hyperkalaemia, hypotension, and renal impairment.
  • People with diabetic neuropathy are particularly susceptible to developing hyperkalaemia and should not receive combination treatment.
  • For people for whom combination therapy is considered essential, specialist supervision with close monitoring of blood pressure, renal function, and electrolytes, is recommended. Monitoring should be carried out when treatment commences, then monthly, and also after any change in dose or intercurrent illness.
• Diuretics — ACE inhibitors can cause a very rapid fall in blood pressure in a person who is volume-depleted.
  • Treatment should be initiated at very low doses.
  • If the dose of diuretic is greater than 80 mg furosemide or equivalent, the ACE inhibitor should be initiated under close supervision and in some cases the diuretic dose may need to be reduced, or the diuretic discontinued at least 24 hours beforehand.
  • If high-dose diuretic therapy cannot be stopped, close observation is recommended for at least 2 hours following the first dose of ACE inhibitor, or until the blood pressure has stabilized.
• Allopurinol — possible increased risk of leucopenia and hypersensitivity reactions, especially in people with renal impairment.
• Bee/wasp venom extracts — risk of severe anaphylaxis.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — increased risk of renal impairment, and hypotensive effect antagonised with concomitant use.
• Antacids — possible decreased absorption of ACE inhibitors with use of an antacid.
• Amiloride, eplerenone, heparins, ciclosporin, potassium canrenoate, potassium salts, triamterene, trimethoprim — increased risk of hyperkalaemia. Monitoring of electrolytes and renal function may be advised.
• Digoxin — concomitant use with captopril can increase plasma concentrations of digoxin. Regular monitoring of plasma digoxin concentration is advised.
• Everolimus, sirolimus and temsirolimus (mTOR inhibitors) — increased risk of angio-oedema.
• Alpha-blockers, antipsychotics, anxiolytics, beta-blockers, calcium channel blockers, clonidine, co-beneldopa, co-careldopa, diazoxide, hydralazine, hypnotics, levodopa, monoamine oxidase inhibitors, methyldopa, minoxidil, moxisylyte, moxonidine, nitrates, SGLT2 inhibitors, sodium nitroprusside, tizanidine — enhanced hypotensive effect.
• Insulin and oral antidiabetic agents — enhanced hypoglycaemic effect.
• Ciclosporin — hyperkalaemia may occur during concomitant use of ACE inhibitors with ciclosporin. Monitoring of serum potassium is recommended. 
• Heparin — hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin. Monitoring of serum potassium is recommended.
• Lithium — concomitant use can increase plasma levels of lithium. Regular monitoring of serum lithium concentrations is advised.
• NSAIDs and COX-2 inhibitors — can attenuate the antihypertensive effect and increase the risk of deteriorating renal function and hyperkalaemia.
• Sacubitril — manufacturers of most ACE inhibitors advise avoiding concomitant use with sacubitril/valsartan therapy and suggest the ACE inhibitor should not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan.
• Spironolactone — increased risk of severe hyperkalemia — use lowest possible dose of both drugs and monitor renal function closely.

For a full list of potential interactions and any drug-specific information, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022; EMC, 2022a]

Dose and titration

• Start with a low dose of angiotensin-converting enzyme (ACE) inhibitor and gradually titrate upwards (usually every 2–4 weeks depending on the drug) until the target blood pressure has been achieved, or until the person has reached the maximum advised or tolerated dose of ACE inhibitor.
• Traditionally the person is often advised to take the first dose in the evening to avoid feeling dizzy from a first-dose hypotensive effect, then if the drug is well-tolerated, subsequent doses can be taken in the morning. This recommendation for the first dose does not feature in the British National Formulary (BNF) or the information from the manufacturers.
• Check renal function and serum electrolytes 1–2 weeks after each upward titration. Measure blood pressure 4 weeks after each dose change. For more information, see Monitoring.
• For people who are taking diuretics:
  • If the person is taking low-dose diuretics (for example, bendroflumethiazide 2.5 mg daily), give a low starting dose of an ACE inhibitor.
  • Refer people who are taking high-dose diuretics (equivalent to 80 mg furosemide or more) to secondary care to initiate ACE inhibitor treatment.
• Details of low starting doses, usual starting doses, and maintenance and maximum doses of ACE inhibitors are given in Table 2.

Table 2. Low starting, usual starting, maintenance, and maximum doses of ACE inhibitors for hypertension.

When should an angiotensin-converting enzyme inhibitor be initiated in secondary care?

• Angiotensin-converting enzyme (ACE) inhibitors should be initiated under specialist supervision and with careful clinical monitoring in those with severe heart failure or in those:
  • Receiving multiple or high-dose diuretic therapy (for example more than 80 mg of furosemide daily or its equivalent).
  • Receiving concomitant angiotensin-II receptor blocker or aliskiren.
  • With hypovolaemia.
  • With hyponatraemia (plasma sodium level less than 130 mmol/L).
  • With hypotension (systolic blood pressure below 90 mmHg).
  • With unstable heart failure.
  • With haemodynamically significant left ventricular inflow or outflow impediment (such as stenosis of the aortic or mitral valve).
  • Receiving high-dose vasodilator therapy.
  • With known renovascular disease.

[BNF, 2022]

Monitoring

• Measure renal function (serum creatinine and estimated glomerular filtration rate) and serum electrolytes before starting treatment.
• Check renal function and serum electrolytes 1–2 weeks after starting treatment and 1–2 weeks after each dose increase. Thereafter, check renal function and serum electrolytes annually unless clinical judgement or abnormal blood testing parameters indicate a need for more frequent monitoring. 
• Check blood pressure 4 weeks after each dose titration.
• For people who are at higher risk of hyperkalaemia or deteriorating renal function (for example those with peripheral vascular disease, diabetes mellitus, or pre-existing renal impairment or older people), consider checking renal function and serum electrolytes sooner (within 1 week).

[Smellie, 2007; BNF, 2022]

How should I manage abnormal test results in people on an angiotensin-converting enzyme inhibitor?

Some increase in creatinine and potassium levels is expected after starting or increasing the dose of a renin-angiotensin system antagonist.

• Managing serum creatinine levels 
  • If the person's serum creatinine level increases by more than 50%, follow local guidelines.
• Managing creatinine and estimated glomerular filtration rate (eGFR) in people with chronic kidney disease 
  • After introducing or increasing the dose, if either the eGFR decrease from a pretreatment baseline is less than 25%, or the serum creatinine level increase from baseline is less than 30% — do not modify the dose.
  • Repeat the test in 1 to 2 weeks, and do not modify the renin-angiotensin system antagonist dose if the change in eGFR is less than 25% or the change in serum creatinine is less than 30%.
  • If an adult's eGFR change is 25% or more, or the change in serum creatinine is 30% or more: 
    • Investigate other causes of a deterioration in kidney function, such as volume depletion or concurrent medication (for example, NSAIDs).
    • If no other cause for the deterioration in kidney function is found, stop the renin–angiotensin system antagonist or reduce the dose to a previously tolerated lower dose, and add an alternative antihypertensive medication if needed.
• Managing serum potassium level
  • If the person's potassium concentration increases to more than 5.5 mmol per litre, follow local guidelines. 
  • In people with CKD, stop the renin–angiotensin system antagonist if the serum potassium concentration increases to 6.0 mmol/litre or more and other medicines known to promote hyperkalaemia have been discontinued.

[NICE, 2021; NICE, 2025] 

Which angiotensin-II receptor blocker is recommended?

• The choice of angiotensin-II receptor blocker (also known as angiotensin-II receptor antagonist) usually depends on the person's comorbidities, local recommendations, and cost.
• Where possible, prescribe a drug that is taken only once a day and prescribe non-proprietary drugs where these are appropriate and minimize cost.

[BNF, 2022; NICE, 2022]

Contraindications and cautions

• Use of angiotensin-II receptor blockers (ARBs) is contraindicated in:
  • People with diabetes mellitus, or with an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73 m², who are also taking aliskiren.
  • Pregnant women and those planning a pregnancy — due to risks to the fetus. Treatment with an ARB should ideally be stopped as soon as pregnancy is detected and, if appropriate, alternative treatment should be started.
    • For more information, see the CKS topics on Pre-conception - advice and management and Hypertension in pregnancy.
  • Breastfeeding women — ARBs are not recommended as there is limited information on their safety.
• ARBs should be used with caution in people:
  • Of black African or Caribbean origin or with primary aldosteronism — may respond less well to ARBs.
  • With hepatic impairment.
  • With renal impairment — hyperkalaemia and other adverse effects are more common, and the dose may need to be reduced. 
  • With renal artery stenosis.
  • With a history of angio-oedema.
  • With hypertrophic cardiomyopathy.
  • With aortic or mitral valve stenosis.
  • Who are elderly (lower initial doses may be appropriate).

[BNF, 2022]

Adverse effects

Adverse effects of angiotensin II receptor blockers (ARBs) include:

• Renal impairment — monitor renal function 1–2 weeks after starting an ARB, after each increase in dose, and regularly throughout treatment.
• Hyperkalaemia — monitor serum electrolytes 1–2 weeks after starting an ARB, after each increase in dose, and regularly throughout treatment.
• Angio-oedema — ARBs can cause a non-allergic drug reaction which can precipitate angio-oedema. Stop ARB treatment immediately, and consider starting an alternative drug treatment. For more information see the CKS topic on Angio-oedema and anaphylaxis.
• Dizziness — dizziness due to hypotension occurs most commonly in people with intravascular volume depletion, such as those taking high dose diuretics.
• Other side effects which may occur include abdominal pain, asthenia, back pain, cough, diarrhoea, headache, nausea, postural hypotension, vertigo, and vomiting.

For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022]

Drug interactions

Drug interactions with angiotensin-II receptor blockers (ARBs) include:

• Angiotensin-converting enzyme (ACE) inhibitors and aliskerin — concomitant use of two drugs affecting the renin-angiotensin system increases the risk of hyperkalaemia, hypotension, and renal impairment.
  • People with diabetic neuropathy are particularly susceptible to developing hyperkalaemia and should not receive combination treatment.
  • For people for whom combination therapy is considered essential, specialist supervision with close monitoring of blood pressure, renal function, and electrolytes is recommended — monitoring should be carried out when treatment commences, then monthly, and also after any change in dose or intercurrent illness.
• Diuretics — prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension.
• Lithium — reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration. Monitoring of serum lithium levels is therefore recommended.
• Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors — attenuation of antihypertensive effect may occur and there may be an increased risk of worsening of renal function, including possible acute kidney injury, and an increase in serum potassium, especially in people with poor pre-existing renal function and elderly people. Consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter, and people should be counselled regarding the importance of adequate hydration.
• Amiloride, ciclosporin, eplerenone, heparins, potassium canrenoate, potassium salts, spironolactone, tacrolimus, triamterene, trimethoprim — increased risk of hyperkalaemia. Monitoring of electrolytes and renal function may be advised.
• Alpha-blockers, alprostadil, antipsychotics, anxiolytics, beta-blockers, baclofen, calcium channel blockers, clonidine, co-beneldopa, co-careldopa, diazoxide, hydralazine, hypnotics, levodopa, methyldopa, minoxidil, monoamine oxidase inhibitors, moxisylyte, moxonidine, nitrates, SGLT2 inhibitors, sodium nitroprusside, tizanidine, tricyclic antidepressants — enhanced hypotensive effect.

For a full list of interactions and any drug-specific information, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022; EMC, 2022a]

Dose and titration

• Start with a low dose of angiotensin-II receptor blocker (ARB) and titrate upwards every 4 weeks until the target blood pressure has been achieved, or the person has reached the maximum prescribable or tolerated dose of ARB.
• Traditionally the person is often advised to take the first dose in the evening to avoid feeling dizzy from a first-dose hypotensive effect, then if the drug is well-tolerated, subsequent doses can be taken in the morning. This recommendation for the first dose does not feature in the British National Formulary (BNF) or the information from the manufacturers.
• Check renal function and serum electrolytes before starting and 1–2 weeks after each upward titration. Monitor blood pressure 4 weeks after each dose titration.
  • For more information, see Monitoring.
• For people who are taking diuretics:
  • If the person is taking a low-dose diuretic (for example bendroflumethiazide 2.5 mg daily), give a low starting dose of an ARB.
  • Refer people who are taking high-dose diuretics (equivalent to 80 mg furosemide or more) to secondary care to initiate ARB treatment.
• Details of the usual starting, maintenance, and maximum doses of ARBs are given in Table 3.

Table 3. Usual starting, maintenance, and maximum doses of ARBs for hypertension.

Monitoring

• Measure renal function (serum creatinine and estimated glomerular filtration rate) and serum electrolytes before starting treatment.
• Check renal function and serum electrolytes 1–2 weeks after starting treatment and 1–2 weeks after each dose increase. Thereafter, check renal function and serum electrolytes annually unless clinical judgement or abnormal blood testing parameters indicate a need for more frequent monitoring. 
• Check blood pressure 4 weeks after each dose titration.
• For people who are at higher risk of hyperkalaemia or deteriorating renal function (for example those with peripheral vascular disease, diabetes mellitus, or pre-existing renal impairment or people taking diuretics or older people), consider checking renal function and serum electrolytes sooner (within 1 week).

[Smellie, 2007; BNF, 2022]

How should I manage abnormal test results in people on an angiotensin-II receptor blocker?

Some increase in creatinine and potassium levels is expected after starting or increasing the dose of a renin-angiotensin system antagonist.

• Managing serum creatinine levels 
  • If the person's serum creatinine level increases by more than 50%, follow local guidelines.
• Managing creatinine and estimated glomerular filtration rate (eGFR) in people with chronic kidney disease 
  • After introducing or increasing the dose, if either the eGFR decrease from a pretreatment baseline is less than 25%, or the serum creatinine level increase from baseline is less than 30% — do not modify the dose.
  • Repeat the test in 1 to 2 weeks, and do not modify the renin-angiotensin system antagonist dose if the change in eGFR is less than 25% or the change in serum creatinine is less than 30%.
  • If an adult's eGFR change is 25% or more, or the change in serum creatinine is 30% or more: 
    • Investigate other causes of a deterioration in kidney function, such as volume depletion or concurrent medication (for example, NSAIDs).
    • If no other cause for the deterioration in kidney function is found, stop the renin–angiotensin system antagonist or reduce the dose to a previously tolerated lower dose, and add an alternative antihypertensive medication if needed.
• Managing serum potassium level
  • If the person's potassium concentration increases to more than 5.5 mmol per litre, follow local guidelines. 
  • In people with CKD, stop the renin–angiotensin system antagonist if the serum potassium concentration increases to 6.0 mmol/litre or more and other medicines known to promote hyperkalaemia have been discontinued.

[NICE, 2021; NICE, 2025] 

Which thiazide-like diuretic should I use?

• The choice of thiazide-like diuretic usually depends on the person's comorbidities, local recommendations, and cost.
• Where possible, prescribe a drug that is taken only once a day and prescribe non-proprietary drugs where these are appropriate and minimize cost.
• Indapamide is the thiazide-like diuretic suggested in the National Institute for Health and Care Excellence (NICE) hypertension guideline. Other thiazide-like diuretics licensed for treatment of hypertension include chlortalidone, xipamide, and metolazone.
• If a person is already taking a conventional thiazide diuretic such as bendroflumethiazide, and their blood pressure is well controlled, continue this treatment.
  • If a thiazide-like diuretic is to be started or changed, indapamide or chlortalidone may be preferred over bendroflumethiazide.

 [BNF, 2022; NICE, 2022]

Contraindications and cautions

• Thiazide-like diuretics should be avoided in:
  • People with:
    • Refractory hypokalaemia.
    • Hyponatraemia.
    • Hypercalcaemia. 
    • Addison's disease. 
    • Symptomatic hyperuricaemia.
    • Severe liver disease.
    • Severe renal impairment — creatinine clearance of less than 30 mL/minute — due to lack of efficacy.
  • Pregnant women — due to risk of neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbance, hypoglycaemia, and reduced placental perfusion.
• Thiazide-like diuretics should be prescribed with caution in the elderly and people with:
  • Diabetes, gout, and systemic lupus erythematosus — due to risk of exacerbation of these conditions.
  • Severe cardiovascular disease, or who are being treated with cardiac glycosides — due to the danger posed by hypokalaemia in these people.
  • Mild to moderate hepatic impairment.

[BNF, 2022]

Adverse effects

• Adverse effects of thiazide-type diuretics include:
  • Postural hypotension.
  • Hyperglycaemia.
  • Hypokalaemia.
  • Other electrolyte imbalances — hyponatraemia, hypomagnesaemia, and hypercalcaemia have also been noted.
    • Electrolytes should be monitored, particularly with high doses and long-term use, and in people with renal impairment.
  • Hypochloraemic alkalosis.
  • Mild gastrointestinal disturbances.
  • Altered plasma-lipid concentrations.
  • Cardiac arrhythmias.
  • Dizziness and headache.
  • Choroidal effusion, acute transient myopia, and acute secondary angle-closure glaucoma.
  • Erectile dysfunction.
  • Blood and lymphatic system disorders (agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, thromobocytopenia) occur very rarely.
• Note: elderly people may be particularly susceptible to the adverse effects of thiazide-like diuretics.

For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[EMC, 2021a; EMC, 2021b; BNF, 2022]

Drug interactions

Drug interactions with thiazide-type diuretics include:

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) — ACE inhibitors and ARBs can cause a very rapid fall in blood pressure in a person who is volume-depleted.
  • If the dose of diuretic is greater than 80 mg furosemide or equivalent, the ACE inhibitor or ARB should be initiated under close supervision and in some cases, the diuretic dose may need to be reduced, or the diuretic discontinued at least 24 hours beforehand.
  • If high dose diuretic therapy cannot be stopped, close observation is recommended for at least 2 hours following the first dose of ACE inhibitor/ARB, or until the blood pressure has stabilized.
• Alpha-blockers — enhanced hypotensive effect and increased risk of first-dose hypotension.
• Amisulpride, atomoxetine, pimozide — increased risk of ventricular arrhythmias.
• Aminophylline, reboxetine — increased risk of hypokalaemia. Monitoring of electrolytes and renal function may be advised.
• Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors — increased risk of nephrotoxicity and antagonism of diuretic effect with concomitant use.
• Corticosteroids, amphotericin, carbenoxolone — may potentiate the hypokalaemic effect.
• Insulin and oral anti-diabetic agents — may require dose adjustment.
• Amiodarone, disopyramide, flecainide — hypokalaemia caused by thiazide diuretics increases the risk of cardiac toxicity of these drugs.
• Rifampicin, lymecycline — concurrent use not advised by manufacturers.
• Aminoglycosides — increased risk of ototoxicity.
• Allopurinol — concurrent use may increase the incidence of hypersensitivity reactions to allopurinol.
• Calcium salts — may increase the risk of hypercalcaemia when given concurrently.
• Tricyclic antidepressants — increased risk of postural hypotension.
• Lithium — risk of increased levels and toxicity. Monitor levels regularly if used concurrently.
• Aldesleukin, alprostadil, anxiolytics, baclofen, beta-blockers, calcium channel blockers, clonidine, co-beneldopa, co-careldopa, hydralazine, hypnotics, levodopa, monoamine oxidase inhibitors, methyldopa, minoxidil, moxonidine, nitrates, phenothiazines, sodium nitroprusside, tizanidine — enhanced hypotensive effect.

For a full list of interactions, and drug-specific information, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[EMC, 2021b; EMC, 2021a; BNF, 2022]

Dose and titration

• Chlortalidone:
  • Starting dose is 25 mg daily, to be taken in the morning.
  • Increase up to 50 mg daily if necessary.
• Indapamide:
  • Dose is 2.5 mg daily, to be taken in the morning (immediate release preparations), or 1.5 mg daily (modified release preparations).
• Metolazone
  • Starting dose is 5 mg daily, to be taken in the morning.
  • Maintenance dose is 5 mg daily on alternate days.
• Xipamide
  • Dose is 20 mg daily, to be taken in the morning.

[BNF, 2022]

Monitoring

• Plasma sodium levels should be measured before starting treatment, then at regular intervals subsequently, depending on clinical judgement. 
  • Monitoring should be more frequent in elderly people and those with cirrhosis.
  • A fall in plasma sodium may be asymptomatic initially and regular monitoring is therefore essential.
• Plasma potassium levels should be monitored prior to initiation of treatment and regularly during treatment, including during the first week. 
  • More frequent monitoring of plasma potassium is required in people who are elderly, malnourished, polymedicated, with cirrhosis, oedema and ascites, coronary artery disease, a long QT interval, and/or cardiac failure. Hypokalaemia (< 3.4 mmol/L) must be prevented in these groups as it increases the cardiac toxicity of digitalis preparations and the risk of arrhythmias.
• Check renal function before starting treatment then monitor at regular intervals subsequently depending on clinical judgement.
  • Thiazide-like diuretics are ineffective if creatinine clearance is less than 30 mL/minute, and are contraindicated in people with severe renal impairment.
• Check liver function before starting treatment and monitor if there is any known or suspected impairment of liver function.
  • They are contraindicated in people with severe impairment of liver function and should be used with caution in people with impaired hepatic function or progressive liver disease, since minor changes in fluid and electrolyte balance may precipitate hepatic coma.

[EMC, 2021b; EMC, 2021a; BNF, 2022]

Which calcium-channel blockers are recommended?

• The decision to use either a rate-limiting or a dihydropyridine calcium-channel blocker depends on the person's comorbidities and other drugs the person is taking.
• Calcium-channel blockers, with the exception of amlodipine, should be avoided in heart failure. 
• Where possible, prescribe a drug that is taken only once a day and prescribe non-proprietary drugs where these are appropriate and minimize cost.
• Dihydropyridine calcium-channel blockers
  • This group includes amlodipine, felodipine, lacidipine, lercanidipine, nicardipine, and nifedipine.
  • The choice of dihydropyridine calcium-channel blocker depends on local recommendations. For people with hypertension alone, amlodipine may be preferred on the basis of cost.
• Rate-limiting calcium-channel blockers
  • This includes verapamil and diltiazem.
  • These may be preferred to dihydropyridine calcium-channel blockers in people with angina when a beta-blocker is contraindicated or not tolerated. For more information, see the CKS topic on Angina.
  • Modified release preparations of diltiazem may be used for hypertension, although their duration of action is equivalent to that of tablets needing more frequent administration. The different versions may not have the same clinical effect. Prescribers should specify the brand for the modified release preparations.
  • Once-daily formulations of verapamil are recommended. Non-proprietary verapamil needs to be taken twice daily. Modified-release verapamil preparations can be given once daily, although higher doses are divided. 

 [BNF, 2022]

Contraindications and cautions

Contraindications and cautions associated with use of calcium-channel blockers include:

• Heart failure
  • All calcium-channel blockers can precipitate heart failure in predisposed people.
  • Calcium-channel blockers should not be used in people with heart failure with reduced ejection fraction or history of significantly impaired left ventricular function, even when controlled.
  • Verapamil and diltiazem should not be used in people with left ventricular failure.
  • Although dihydropyridines rarely aggravate heart failure (any negative inotropic effect is offset by a reduction in left ventricular work), they should not be initiated in people with uncontrolled heart failure. Amlodipine may be used cautiously in stable heart failure.
• Cardiac outflow obstruction (for example significant aortic stenosis or obstructive hypertrophic cardiomyopathy) — vasodilatation may result in reduced cardiac output.
• Cardiogenic shock.
• Diabetes mellitus — diltiazem may increase blood glucose, monitor carefully. 
• Atrioventricular block — verapamil and diltiazem are contraindicated in second or third degree atrioventricular (AV) block, and must be used with caution in first degree AV block.
• Unstable angina or recent myocardial infarction — avoid within 1 month of myocardial infarction. With the exception of amlodipine, they can increase mortality after myocardial infarction in patients with left ventricular dysfunction and pulmonary congestion.
• Hepatic impairment
  • In general caution should be used in prescribing to people with hepatic impairment, due to the risk of increased exposure. Dose adjustments and variation in medicinal form used may be required. Refer to the British National Formulary (BNF) for drug-specific advice.
• Renal impairment — although diltiazem and verapamil are extensively metabolized in the liver, manufacturers recommend caution, dose reduction, or monitoring in people with renal impairment.
• Pregnancy and breastfeeding — mostly manufacturers advise avoiding calcium-channel blockers in pregnant or breastfeeding women, although some may be used at specific stages in pregnancy if benefit outweighs risk. Refer to drug-specific information in the BNF, and see the CKS topics Preconception - advice and management and Hypertension in pregnancy for more information.

Calcium-channel blockers are a large and diverse class. For full information on class and drug-specific contraindications and cautions, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[EMC, 2020a; EMC, 2021c; BNF, 2022; ABPI, 2023]

Adverse effects

Side effects which may occur with any of the calcium-channel blockers include:

• Abdominal pain, nausea, and vomiting.
• Angio-oedema.
• Bronchospasm, including asthma aggravation (diltiazem). 
• Dizziness.
• Depression.
• Drowsiness.
• Erectile dysfunction.
• Flushing.
• Gingival hyperplasia.
• Headache.
• Myalgia.
• Palpitations and tachycardia.
• Peripheral oedema.
• Paraesthesia.
• Skin reactions.
• Syncope.

For people prescribed diltiazem be aware that a lupus-like syndrome may develop and also that there is a risk of non-cardiogenic pulmonary oedema in overdose. 

There is some evidence that sudden withdrawal may be associated with an exacerbation of myocardial ischaemia.

For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022; EMC, 2023]

Drug interactions

Drug interactions with calcium-channel blockers include:

• Alpha-blockers, angiotensin-converting enzyme-inhibitors, angiotensin-II receptor blockers, antipsychotics, anxiolytics and hypnotics, baclofen, clonidine, co-beneldopa, co-careldopa, diazoxide, diuretics, hydralazine, levodopa, methyldopa, minoxidil, monoamine oxidase inhibitors, moxisylyte, moxonidine, nitrates, sodium nitroprusside, tizanidine, and tricyclic antidepressants — enhanced antihypertensive effect.
• Amiodarone — increased risk of bradycardia, atrioventricular (AV) block, and myocardial depression when given with diltiazem or verapamil.
• Atazanavir — plasma concentration of calcium-channel blockers increased with concurrent use leading to risk of hypotension. Caution and clinical monitoring are required, and dose adjustments may be needed.
• Avanafil, bosutinib, ciclosporin — concurrent use with diltiazem or verapamil may lead to increased plasma concentrations of these drugs. Dose alterations may be required.
• Carbamazepine — concurrent use with diltiazem or verapamil may lead to enhanced effects of carbamazepine. Dose alterations may be required.
• Colchicine — diltiazem and verapamil possibly increase risk of colchicine toxicity — suspend or reduce dose of colchicine (avoid concomitant use in hepatic or renal impairment).
• Beta-blockers — hypotensive effect enhanced with all calcium-channel blockers. Extreme caution is needed for verapamil or diltiazem due to the risk of significant adverse cardiac events.
• Carbamazepine — is predicted to reduce exposure to calcium-channel blockers. Diltiazem and verapamil may increase carbamazepine levels. Monitor concentration and clinical respone and adjust dose if necessary.
• Clarithromycin, erythromycin — metabolism of calcium-channel blockers possibly inhibited leading to increased risk of side-effects.
• Dabigatran — verapamil possibly increases plasma concentration.
• Digoxin — concurrent use with diltiazem or verapamil may lead to increased plasma concentrations of digoxin. Monitor for signs of toxicity and consider monitoring plasma digoxin levels.
• Direct oral anti-coagulants — diltiazem (an inhibitor of CYP3A4 and P-gp) may increase the plasma concentrations of DOACs (i.e. apixaban, rivaroxaban, dabigatran) metabolised through these pathways with resulting increases in pharmacodynamic effects such as bleeding risk.
• Disopyramide — concurrent use with verapamil may lead to increased risk of myocardial depression and asystole.
• Dronedarone, flecainide — increased risk of bradycardia and myocardial depression when diltiazem or verapamil given with these drugs.
• mTOR inhibitors (sirolimus, temsirolimus, everolimus) — concurrent use of amlodipine, verapamil, and diltiazem may increase levels of mTOR inhibitors.
• Fingolimod — possible increased risk of bradycardia when diltiazem or verapamil is given with fingolimod.
• Fosphenytoin — predicted to reduce exposure to calcium-channel blockers and dose adjustments may be required. Verapamil and diltiazem may increase plasma concentration of fosphenytoin.
• Ibrutinib, ivabradine, lomitapide, lurasidone, olaparib, tacrolimus, and trazodone — diltiazem and verapamil possibly increase the plasma concentrations of these drugs. Reduce dose of ibrutinib, avoid concomitant use with ivabradine, lomitapide, and olaparib.
• Mefloquine — possible increased risk of bradycardia during concurrent use with calcium-channel blockers.
• Nonsteroidal anti-inflammatory drugs — hypotensive effect of calcium-channel blockers antagonised.
• Phenobarbital, primidone — effects of calcium-channel blockers probably reduced with concurrent use. 
• Phenytoin — diltiazem and verapamil may increase plasma concentration of phenytoin; phenytoin may decrease the exposure to calcium-channel blockers and therefore their effect.
• Rifampicin — plasma concentration of calcium-channel blockers may be decreased with concurrent use.
• Ritonavir — plasma concentration of calcium-channel blockers possibly increased with concurrent use.
• Statins — some calcium-channel blockers interact with some statins, and dose adjustments may be needed. Check the British National Formulary or manufacturers' information for specific advice for the individual calcium-channel blocker and statin.
• St John's Wort — plasma concentrations of calcium-channel blockers may be reduced by St John's wort.

Grapefruit may increase the exposure to calcium-channel blockers, so grapefruit and grapefruit juice are best avoided when taking these drugs.

Calcium-channel blockers are a large and diverse group. The full list of potential interactions for each drug is beyond the scope of this topic. For complete, and drug-specific information on interactions, refer to the British National Formulary (BNF) or the manufacturers' information in the electronic medicines compendium (emc).

[BNF, 2022] 

Dose and titration

• Start with a low dose of calcium-channel blocker and titrate upwards (if necessary) at intervals of 4 weeks until the target blood pressure has been achieved.
• Measure blood pressure 4 weeks after each dose change.
• Dose for rate-limiting calcium-channel blockers
  • Once-daily modified release diltiazem:
    • Recommended doses and dosing intervals differ depending on the preparation prescribed. Some modified release preparations are not appropriate for initial dose titration. For more information, see the British National Formulary. 
  • Modified release verapamil
    • The standard starting dose is 240 mg once a day. For people new to verapamil therapy, consider halving the initial dose to 120 mg.
    • The maximum dose is 240 mg twice a day (doses spaced by an interval of 12 hours).
• Doses for dihydropyridine calcium-channel blockers are shown in Table 4.

Table 4. Usual starting, maintenance, and maximum doses of dihydropyridine calcium-channel blockers for hypertension.

Contraindications and cautions

• Spironolactone should only be used to treat hypertension in those who are starting step 4 treatment for resistant hypertension and who have a blood potassium level of 4.5mmol/L or less. Monitor renal function and sodium and potassium within a month of commencing treatment and repeat as needed.
• Do not prescribe spironolactone to people with:
  • Addison's disease.
  • Acute renal insufficiency, significant renal compromise, anuria.
  • Hyperkalaemia.
• Prescribe spironolactone with caution to:
  • People with acute porphyrias.
  • Elderly people.
  • Pregnant women (unless potential benefit outweighs risk — feminization of male fetus in animal studies.
• Note: consider stopping spironolactone treatment if the person becomes dehydrated due to vomiting and/or diarrhoea, as there is an increased risk of hyperkalaemia and renal failure.

[Tollitt, 2017; Think Kidneys, 2018; BNF, 2022; NICE, 2022]

Adverse effects

• Adverse effects of spironolactone include:
  • Acute kidney injury.
  • Agranulocytosis, leucopenia, thrombocytopenia.
  • Alopecia.
  • Benign breast tumours, breast pain, gynaecomastia.
  • Changes in libido. 
  • Confusion. 
  • Dizziness.
  • Electrolyte disturbances, hyperkalaemia (discontinue if this occurs), hyponatraemia.
  • Gastrointestinal disturbances, nausea.
  • Hepatotoxicity. 
  • Hyperchloraemic acidosis.
  • Hypertrichosis. 
  • Hyperuricaemia.
  • Leg cramps. 
  • Malaise. 
  • Menstrual disturbances.
  • Pruritis.
  • Rash, Stevens-Johnson syndrome.
  • Urticaria.

[BNF, 2022; EMC, 2022b]

Drug interactions

• Drug interactions with spironolactone include:
  • Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor blockers — increased risk of severe hyperkalaemia with concurrent use.
    • Prescribe the lowest possible doses of both drugs and monitor renal function closely.
    • Avoid concurrent use in people with marked renal impairment. 
    • Should hyperkalaemia develop, spironolactone should be discontinued, and if necessary, active measures should be taken to reduce the serum potassium to normal.
  • Antihypertensive drugs — hypotensive effect potentiated. 
  • Ciclosporin, heparins, other potassium-sparing diuretics, potassium supplements, tacrolimus, trimethoprim/sulfamethoxazole (co-trimoxazole) — concomitant use may result in severe hyperkalaemia. 
    • Should hyperkalaemia develop, spironolactone should be discontinued, and if necessary, active measures should be taken to reduce the serum potassium to normal.
  • Aspirin and nonsteroidal anti-inflammatory drugs — attenuate the diuretic effect of spironolactone. There may be an increased risk of renal toxicity and hyperkalaemia, particularly with indomethacin.
  • Digoxin — spironolactone may increase serum concentrations of digoxin and interfere with serum digoxin assays. If digoxin dose needs to be adjusted, monitor the person carefully for signs of an enhanced or reduced digoxin effect.
  • Lithium — concurrent use can reduce excretion of lithium. If using together, monitor plasma lithium concentrations within the first 5–7 days of adding or stopping spironolactone and periodically thereafter.

For the full list of drug interactions, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022; EMC, 2022b]

Dose and titration

• If the person is already taking three antihypertensive drugs and blood pressure is not controlled (resistant hypertension), consider adding spironolactone if blood potassium level is 4.5 mmol/L or lower.
• Prescribe low-dose spironolactone 25 mg once a day, to be taken with food.
• Upward dose titration is not recommended for the treatment of hypertension alone.

[BNF, 2022; EMC, 2022b; NICE, 2022]

Monitoring

• When using spironolactone as adjunctive therapy for resistant hypertension:
  • Measure renal function (serum creatinine and estimated glomerular filtration rate [eGFR]) and serum electrolytes (noting potassium levels) before starting spironolactone.
    • Only prescribe spironolactone for people whose blood potassium level is 4.5 mmol/L or lower.
    • Use particular caution in people with a reduced eGFR because they have an increased risk of hyperkalaemia.
  • Repeat these tests within 1 month of starting treatment.
  • Then, repeat monitoring as required thereafter according to clinical judgement: 
    • For people who are at higher risk of hyperkalaemia or deteriorating renal function (for example elderly people, people on an angiotensin-converting enzyme inhibitor, angiotensin-II receptor blocker, or another drug that increases the risk of hyperkalaemia, and those with pre-existing renal or hepatic impairment), consider checking renal function and serum electrolytes more frequently.
    •  For those with severe heart failure, check monthly for a further 2 months, then every 3 months for 1 year, then every 6 months thereafter.
  • If hyperkalaemia develops (potassium greater than 5 mmol/L), stop spironolactone and treat the raised potassium level if appropriate, using clinical judgement.

[BNF, 2022; EMC, 2022b; NICE, 2022]

Which beta-blocker is recommended?

• The choice of beta-blocker usually depends on the person's comorbidities, local recommendations, and cost.
• Where possible, prescribe a drug that is taken only once a day and prescribe non-proprietary drugs where these are appropriate and minimize cost.
  • For people with hypertension and heart failure, bisoprolol, carvedilol, or nebivolol may be preferred.
    • For more information, see the CKS topic on Heart failure - chronic.
  • For people with hypertension and angina, atenolol, bisoprolol, or metoprolol may be preferred.
    • For more information, see the CKS topic on Angina.
  • For people who have hypertension and have had a previous myocardial infarction (without heart failure), metoprolol (standard release), propranolol (standard release), timolol, or atenolol may be preferred.
    • For more information, see the CKS topic on MI - secondary prevention.

[NICE, 2022]

Contraindications and cautions

• Do not prescribe beta-blockers to people with:
  • A history of obstructive airways disease (such as asthma and chronic obstructive pulmonary disease) or bronchospasm. However, if there is no alternative, a relatively cardioselective beta-blocker (such as atenolol, bisoprolol, metoprolol, and nebivolol) can be used under specialist supervision.
    • Treatment should be initiated at the lowest possible dose and the person should be monitored for new symptoms (such as dyspnea or exercise intolerance). Concomitant bronchodilator therapy is recommended.
  • Cardiogenic shock or phaeochromocytoma (without a concomitant alpha-blocker).
  • Metabolic acidosis.
  • Phaeochromocytoma (unless co-prescribed with the alpha-blocker phenoxybenzamine hydrochloride to avoid the risk of hypertensive crisis).
  • Prinzmetal's angina.
  • Second- or third-degree heart block (in the absence of a permanent pacemaker).
  • Sick sinus syndrome.
  • Marked bradycardia.
  • Severe hypotension.
  • Severe peripheral arterial disease (pain at rest and sometimes intermittent claudication) — the blood pressure-lowering properties of beta-blockers can exacerbate symptoms.
  • Uncontrolled heart failure.
    • Seek specialist advice before starting a beta-blocker in people with a current or recent exacerbation of heart failure.
• Beta-blockers should be used with caution in people with:
  • Diabetes.
  • First-degree atrioventricular (AV) block.
  • Myasthaenia gravis.
  • Portal hypertension — due to risk of deteriorating liver function.
  • Psoriasis.
  • Note: be aware that use of a beta-blocker can mask symptoms of hypoglycaemia and thyrotoxicosis.
  • Note: seek specialist advice in women who are pregnant or breastfeeding.

[BNF, 2022]            

Adverse effects

Adverse effects of beta-blockers include:

• Bradycardia — acebutolol, celiprolol, and pindolol have less intrinsic sympathomimetic activity and tend to cause less bradycardia.
• Bronchospasm.
• Cold extremities, paraesthesiae, and numbness — these are more common in people with peripheral vascular disease.
  • If troublesome, beta-blockers might need to be stopped.
  • Acebutolol, celiprolol, and pindolol may cause less coldness of the extremities.
• Conduction disorders.
• Confusion.
• Depression.
• Dizziness.
• Dry eye.
• Dyspnoea.
• Erectile dysfunction.
• Exacerbation of psoriasis.
• Exacerbation of Raynaud's phenomenon.
• Fatigue.
• Gastrointestinal disturbances — abdominal discomfort, diarrhoea, nausea, vomiting.
• Hallucination.
• Headache.
• Heart failure.
• Hyperglycaemia/hypoglycaemia— in people with or without diabetes.
• Hypotension.
• Peripheral vascular disease.
• Rash.
• Sleep disturbance or nightmares. Atenolol, celiprolol, and nadolol are water-soluble beta-blockers and are less likely to enter the brain and therefore less likely to cause this side effect.
• Vertigo.
• Visual disturbances.

There are differences between the beta-blockers which may lead to differences in tolerability. For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022]          

Drug interactions

Drug interactions with beta-blockers include:

• Alpha-blockers, alprostadil, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, anxiolytics, baclofen, co-beneldopa, co-careldopa, diazoxide, diuretics. hydralazine, hypnotics, levodopa, monoamine oxidase inhibitors, methyldopa, minoxidil, moxonidine, nitrates, phenothiazines, sodium nitroprusside, tizanidine — enhanced hypotensive effect.
• Antidepressants
  • Tricyclics, mirtazapine, and trazodone should be prescribed with caution in people taking beta-blockers, as there is an increased risk of postural hypotension.
• Calcium-channel blockers
  • The combination of a beta-blocker and verapamil should not be prescribed because bradycardia, asystole, severe hypotension, and heart failure can occur.
  • Caution should be used if prescribing diltiazem with a beta-blocker — monitor pulse and blood pressure carefully, as bradycardia and atrioventricular block can occur. 
  • The combination of a beta-blocker and other calcium-channel blockers can lead to enhanced antihypertensive effect.
• Class I anti-arrhythmics (such as quinidine, disopyramide, flecainide)
  • The combination of a beta-blocker and a class I anti-arrhythmic is not recommended because bradycardia and myocardial depression can occur.
• Class III anti-arrhythmics (such as amiodarone)
  • The combination of a beta-blocker and amiodarone should be avoided or prescribed with caution as there is an increased risk of bradycardia, atrioventricular (AV) block, and myocardial depression — monitor pulse and blood pressure and check for signs of worsening heart failure.
• Clonidine — increased risk of bradycardia, hypotension, and withdrawal hypertension. 
• Digoxin — concomitant administration of a beta-blocker and digoxin can reduce heart rate and prolong AV conduction time, increasing the risk of AV block and bradycardia. Monitor the pulse carefully; consider monitoring with electrocardiography (ECG).
• Dobutamine — increased risk of severe hypertension and bradycardia when non-cardioselective beta-blockers (nadolol, pindolol, propranolol, timolol) are given with dobutamine.
• Insulin and anti-diabetic agents — risk of exacerbation of blood sugar lowering effects, and symptoms of hypoglycaemia may be masked.
• Fingolimod, mefloquine — increased risk of bradycardia. 
• Moxisylyte — increased risk of severe postural hypotension.
• Nonsteroidal anti-inflammatory drugs — hypotensive effect antagonized with concomitant use.

Beta-blockers are a very large class of drugs, with many licensed for the treatment of hypertension. For full information on interactions specific to each one, refer to the British National Formulary (BNF) or the manufacturers' information in the electronic medicines compendium (emc).

[EMC, 2021d; BNF, 2022; EMC, 2022c]               

Dose and titration

• Acebutolol
  • Initially, prescribe 400 mg daily in up to two divided doses.
  • If necessary, increase doses at an interval of 2 weeks.
  • The maximum dose is 1.2 g daily.
• Atenolol
  • The usual dose is 25–50 mg daily (single dose). Higher doses are rarely necessary.
  • If necessary, increase doses at an interval of 2 weeks.
  • The maximum dose is 100 mg daily (single dose).
• Bisoprolol
  • Initially prescribe 5 mg daily.
  • The usual dose is 10 mg daily (single dose taken in the morning). 
  • The maximum dose is 20 mg daily (single dose taken in the morning).
• Carvedilol
  • Initially, prescribe 12.5 mg once daily for 2 days, then increase to 25 mg once a day (12.5 mg daily may provide adequate control in elderly people).
  • The maximum dose is 50 mg daily, in single or divided doses.
  • Increase doses above 25 mg at an interval of at least 2 weeks.
• Celiprolol
  • Initially prescribe 200 mg daily (single dose taken in the morning). 
  • If necessary, increase the dose at intervals of 2–4 weeks to a maximum of 400 mg daily (single dose taken in the morning).
• Labetolol
  • Initially, prescribe 100 mg twice daily (50 mg twice daily to be used in elderly people).
  • If necessary, increase doses at an interval of 2 weeks. The usual dose is 200 mg twice daily.
  • Doses of up to 800 mg can be given as two divided doses to be taken with food.
  • The maximum dose is 2.4 g daily, in 3–4 divided doses.
• Metoprolol
  • For immediate-release preparations:
    • Initially, prescribe 100 mg daily.
    • If necessary, increase to 200 mg daily in 1 or 2 doses.
    • The maximum dose is 400 mg daily.
  • For modified-release preparations, prescribe 200 mg once daily.
• Nadolol
  • Initially, prescribe 80 mg once daily.
  • If necessary, increase in steps of up to 80 mg each week.
  • The maximum dose is 240 mg daily.
• Nebivolol
  • The usual dose is 5 mg once daily.
  • In elderly people and people with renal impairment, initially prescribe 2.5 mg daily and increase to 5 mg daily if necessary. It may take up to 4 weeks for the optimum effect to be realised.
• Pindolol
  • Initially, prescribe 10–15 mg daily in 2–3 divided doses.
  • If necessary, increase doses at weekly intervals. The usual dose is 15–30 mg daily.
  • The maximum dose is 45 mg daily.
• Propranolol
  • Initially, prescribe 80 mg twice daily.
  • If necessary, increase doses at weekly intervals. The usual dose is 160–320 mg daily.
• Timolol
  • Initially, prescribe 10 mg daily in up to 2 divided doses.
  • If necessary, increase doses gradually. The usual dose is 10–30 mg daily.
  • Doses of over 30 mg daily should be given in divided doses. The maximum daily dose is 60 mg.

Note: avoid abrupt withdrawal of beta-blockers. Withdraw gradually over a period of 7–14 days.

[EMC, 2021d; BNF, 2022; EMC, 2022d]

Which alpha-blocker is recommended?

• Once-daily doxazosin and terazosin are recommended alpha-blocker drug options. Prazosin is also used but may reduce blood pressure rapidly after the first dose and so should be used with caution.
• Prescribe non-proprietary drugs where these are appropriate and minimize cost.

 [BNF, 2022]

Contraindications and cautions

• Alpha-blockers are contraindicated if there is a history of: 
  • Postural hypotension.
  • Micturition syncope (in people with benign prostatic hypertrophy).
• Alpha-blockers are indicated only as add-on treatment in managing resistant hypertension as an option in Step 4.
• Do not use modified-release doxazosin tablets in people with gastrointestinal obstruction, oesophageal obstruction, or any degree of stricture, as the outer membrane of the formulation is not digested.
• Prescribe with caution to people with heart failure. Prazosin is not recommended for congestive heart failure due to mechanical obstruction (for example aortic stenosis).
• There may be a risk of Intraoperative Floppy Iris Syndrome during cataract surgery for people taking alpha-blockers. The surgeon operating should be made aware the person is taking this medication.
• There is a risk of hypotension on the first dose. It is advised that the first dose of terazosin and prazosin are given at bedtime, and doxazosin given initially as a very low dose before titrating up.
• Alpha-blockers should not be used in pregnant or breastfeeding women unless potential benefit outweighs the risk.

[EMC, 2017; EMC, 2020b; EMC, 2021e; EMC, 2021f; BNF, 2022; NICE, 2022]

Adverse effects

Side effects common to all the alpha-blockers include:

• Arrhythmias.
• Chest pain.
• Constipation and diarrhoea.
• Depression.
• Dizziness.
• Drowsiness.
• Dry mouth.
• Dyspnoea.
• Epistaxis.
• First dose hypotension.
• Headache.
• Joint pain.
• Nausea.
• Oedema.
• Palpitations.
• Postural hypotension and syncope.
• Sexual dysfunction.
• Skin reactions.
• Tinnitus.
• Vertigo.
• Vision disorders.
• Weakness.

For full information on class and drug-specific adverse effects, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[BNF, 2022]

Drug interactions

Drug interactions with alpha-blockers include:

• Alprostadil, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, antipsychotics, anxiolytics, baclofen, beta-blockers, calcium channel blockers, clonidine, co-beneldopa, co-careldopa, diazoxide, diuretics. hydralazine, hypnotics, levodopa, monoamine oxidase inhibitor, methyldopa, minoxidil, moxonidine, nitrates, sodium nitroprusside, tizanidine — enhanced hypotensive effect.
• Cytochrome P450 3A4 (CYP 34A) inhibitors — the manufacturer advises that caution should be exercised if doxazosin is administered with CYP 34A inhibitors, such as clarithromycin, itraconazole, ritonavir, and voriconazole.
• Moxisylyte — increased risk of severe postural hypotension.
• Phosphodiesterase-5 inhibitors (for example avanafil, sildenafil, tadalafil, vardenafil) — combined use with alpha-blockers may lead to symptomatic hypotension in some people. 

For further information about drug interactions for alpha-blockers, refer to the British National Formulary (BNF) and the electronic medicines compendium (emc).

[EMC, 2017; EMC, 2020b; EMC, 2021f; BNF, 2022]

Dose and titration

• Doxazosin (non-modified release)
  • Standard initiation dosage is 1 mg per day.
  • The dose may be doubled after 1–2 weeks if tolerated, then further increased to 4 mg if necessary.
  • Usual maintenance dosage is 4 mg per day.
  • Maximum dosage is 16 mg per day.
• Doxazosin (modified release)
  • Standard initiation dosage is 4 mg per day (optimal effect can take up to 4 weeks).
  • Usual maintenance dosage is 4 mg per day.
  • If necessary, increase the dose after 4 weeks.
  • Maximum dosage is 8 mg per day.
• Prazosin 
  • Standard initiation dose is 500 micrograms 2–3 times a day, with the first dose to be taken in the evening.
  • After 3–7 days, this dose can be increased to 1 mg 2 or 3 times a day for a further 3–7 days. 
  • Thereafter, increase the dose gradually if required.
  • Maximum dosage is 20 mg per day in divided doses.
• Terazosin
  • Standard initiation dose is 1 mg daily, with the first dose taken at bedtime.
  • After 1 week, increase if necessary to 2 mg daily.
  • Usual maintenance dosage is 2–10 mg once daily.
  • Maximum dosage is 20 mg daily.

[EMC, 2021e; BNF, 2022]

ACE inhibitors and ARBs

• People who are taking angiotensin-converting enzyme inhibitor and angiotensin receptor blocker medications for any indication should not stop taking these drugs during the COVID-19 pandemic, whether they are unaffected by the virus or have contracted the disease.
• The reason for this is that there is no evidence from the published literature that taking these medications adversely affects outcomes from COVID-19 or the likelihood of acquiring the infection.
• Stopping the medications, however, is associated with adverse outcomes.

[Hippisley-Cox, 2020; NICE, 2020]