Previous changes

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

October 2024 — minor update. Additional information added regarding referral to cardiology for patients who are contraindicated for both DOACs and warfarin for consideration of other risk reducing procedures including left atrial appendage closure. 

September 2024 — minor update. Minor typographical error corrected in the QOF indicators section. 

June 2024 — reviewed. A literature search was conducted in April 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with current evidence in the literature. The topic structure has been amended to improve clarity and navigation. Information about the further assessment of device-detected atrial fibrillation (AF), including use of patient-initiated mobile or wearable devices has been added, in line with the European Society of Cardiology (ESC) joint guideline (2021). The management section has been split into two scenarios covering new-onset or acute AF, and the routine review of paroxysmal, persistent, or permanent AF.

December 2023 — minor update. Changes to the order of wording for warfarin and direct oral anticoagulants (DOACs) in the anticoagulants section. 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 manufacturers' summary of product characteristics (SPC).

March 2023 — minor update. Adverse effects and contraindications and cautions for diltiazem have been updated in line with the updated manufacturers' SPC for Slozem capsules.

August 2022 — minor update. Added a link to the NHS England Decision support tool. 

January 2022 — minor update. A minor typographical error has been corrected.

October 2021 — minor update. A minor typographical error has been corrected.

May 2021 — minor update. The topic has been updated in line with the updated National Institute for Health and Care Excellence (NICE) guideline Atrial fibrillation: diagnosis and management. This includes the recommendation to use the ORBIT bleeding risk assessment tool when considering starting anticoagulation in people with atrial fibrillation, and a direct oral anticoagulant should be used first-line in people considered to be at risk of stroke.

October 2020 — minor update. A typographical error has been corrected.

August 2020 — minor update. Broken URL links updated.

June 2020 — minor update. Adverse effects of diltiazem added in line with updated manufacturers' SPC.

March 2020 — minor update. Prescribing information for digoxin drug interactions updated.

April to May 2019 — reviewed. A literature search was conducted in April 2019 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.

February 2018 — minor update. Updated QS93 Atrial fibrillation added to new evidence section.

December 2016 — minor update.

• Information to avoid concomitant use of amiodarone and a combination of Sovaldi^® [sofosbuvir] and Olysio® [simeprivir]) unless other antiarrhythmics cannot be given, has been added to this topic. 
• Information that concomitant use of fluconazole with amiodarone is contraindicated has been added to this topic.
• The contraindications, cautions and interactions of verapamil and diltiazem have been updated in line with the manufacturers' Summary of Product Characteristics.
• Information on a possible drug interaction with bupropion and digoxin has been added to this topic, in line with the manufacturer's Summary of Product Characteristics.

October 2016 — minor update. Information added that cases of severe bradycardia and heart block have been observed in people taking concomitant amiodarone and some drugs used to treat hepatitis C.

October 2015 — minor update. 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.

July 2015 — minor update. The section on Treating the arrhythmia has been amended to clarify the National Institute for Health and Care Excellence (NICE) recommendations on how to manage a person with atrial fibrillation who presents acutely with non-life threatening haemodynamic instability.

June 2015 — minor update. Information that concomitant use of amiodarone and some drugs used to treat hepatitis C may increase the risk of severe bradycardia or heart block has been included.

May 2015 — minor update. Information on the potential drug interaction of diltiazem with grapefruit juice has been added to the topic following an update to the manufacturers' Summary of Product Characteristics (SPC) for diltiazem.

March 2015 — minor update. In the section on assessing stroke risk in people with atrial fibrillation, the definition of vascular disease has been clarified to include prior myocardial infarction, peripheral arterial disease, or aortic plaque, in line with definitions in several online CHA₂DS₂VASc score tools.

February 2015 — minor update. Removal of '8 units a week or more' as harmful alcohol consumption with regards to HAS-BLED score for major bleeding risk. This is in line with the NICE recommendation to use clinical judgement to define harmful alcohol consumption.

April 2014 to July 2014 — reviewed. A literature search was conducted in March 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. The following changes have been made in line with the National Institute for Health and Care Excellence (NICE) guideline Atrial fibrillation: the management of atrial fibrillation:

• Following assessment, rate-control treatment is now the first-line treatment for most people with atrial fibrillation (AF). Referral for rhythm-control treatment (cardioversion), in addition to rate-control treatment, may be appropriate if:
  • The person has AF with a reversible cause (for example a chest infection); heart failure thought to be primarily caused, or worsened, by AF; or new-onset AF. If the onset is known to be within 48 hours, referral should be to an acute medical unit (rather than to a cardiologist) for immediate cardioversion without the need for anticoagulation treatment. The urgency of the referral will depend on how soon the person presents within 48 hours.
  • Rate-control or anticoagulation treatment is contraindicated.
  • Rate-control treatment fails to control the symptoms of AF (prompt referral within 4 weeks is required).
  • The person is found to have valve disease or left ventricular systolic dysfunction on echocardiography.
  • Wolff–Parkinson–White syndrome or a prolonged QT interval is suspected on the electrocardiogram.
• The HAS-BLED scoring tool is now recommended for assessing the risk of bleeding in people who are starting or have started anticoagulation, and to highlight, correct, and monitor certain modifiable risk factors (for example uncontrolled hypertension and harmful alcohol consumption).
• Anticoagulation treatment with warfarin or a novel oral anticoagulant (apixaban, dabigatran, or rivaroxaban) is recommended for stroke prevention in people with AF and a CHA₂DS₂VASc score of 2 or more. It should also be considered for men with AF and a CHA₂DS₂VASc score of 1.
• Aspirin is no longer recommended as monotherapy solely for stroke prevention in people with AF.
• The lowest age of people with AF for which these recommendations apply to has been changed from 16 years to 18 years.

March 2014 — minor update. Text about assessing stroke risk in people with AF has been updated to include the CHA₂DS₂VASc tool which takes a risk factor-based approach to guide decisions about antithrombotic treatment, in line with updated European Society of Cardiology (ESC) guidelines.

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

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

April 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. 

June 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic. 

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

October 2010 — minor update. Information on fitness to drive from the Driver and Vehicle Licensing Agency (DVLA) guidance for medical practitioners At a glance guide to the current medical standards of fitness to drive has been added. Advice about flying for people with atrial fibrillation, based on the British Heart Foundation Factfile, Fitness to fly for passengers with cardiovascular disease, which is derived from the British Cardiovascular Society Working Group's expert guidance has also been included. 

May to August 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.

April 2009 — minor update. The Quality and Outcomes Framework (QOF) indicators for atrial fibrillation have been updated in the Goals and outcome measures section. 

September 2008 — minor correction to the Changes section. 

June 2007 — updated to include a link to the recent Patient Safety Alert from the National Patient Safety Agency (NPSA) on actions that can make anticoagulant therapy safer. Advice from the British Committee for Standards in Haematology on the management of patients on oral anticoagulants requiring dental surgery also included.

July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007. This guidance has been reviewed, restructured and updated following a full literature review and includes an implementation of the 2006 guidance on atrial fibrillation from the National Institute for Health and Care Excellence (NICE).

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

December 2002 — reviewed. Validated in March 2003 and issued in April 2003.

November 2000 — reviewed. Validated in March 2001 and issued in June 2001.

June 1998 — written and validated.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 April 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 April 2024.

Economic appraisals

No new economic appraisals since 1 April 2019.

Systematic reviews and meta-analyses

• Gawałko, M., Middeldorp, M. E., Saljic, A., et al. D. (2024). Diet and risk of atrial fibrillation: a systematic review. European Heart Journal, 45(40), 4259-4274. [Abstract]
• Ko, D., Chung, M.K., Evans, P.T., Benjamin, E.J., Helm, R.H. (2024) Atrial Fibrillation: A review. JAMA. [Abstract]

Primary evidence

• Simon, T. G., Singer, D. E., Zhang, Y., et al. (2024) Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation: A Nationwide Cohort Study. Annals of Internal Medicine. [Abstract]
• Acton, E. K., Hennessy, S., Gelfand, M. A., et al. (2024). Direct-Acting Oral Anticoagulants and Antiseizure Medications for Atrial Fibrillation and Epilepsy and Risk of Thromboembolic Events. JAMA neurology. [Abstract]
• Zimerman, A., Braunwald, E., Steffel, J., et al. (2024). Dose Reduction of Edoxaban in Patients 80 Years and Older With Atrial Fibrillation: Post Hoc Analysis of the ENGAGE AF-TIMI 48 Randomized Clinical Trial. JAMA cardiology. [Abstract]
• McIntyre, W.F., Benz, A.P., et al. (2024) Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial. Circulation. https://www.ahajournals.org/journal/circ [Abstract]
• Berwanger, O., Wojdyla, D. M., Fanaroff, A. C.,et al. (2024). Antithrombotic strategies in atrial fibrillation after ACS and/or PCI: a 4-way comparison from AUGUSTUS. Journal of the American College of Cardiology, 84(10), 875-885. [Abstract]
• Karakasis, P., Pamporis, K., Siontis, K. C., et al. (2024) N. Major clinical outcomes in symptomatic vs. Asymptomatic atrial fibrillation: A meta-analysis. European Heart Journal. [Abstract]
• Best, J. G., Arram, L., Ahmed, N., et al. (2022). Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): protocol for a randomized controlled trial. International Journal of Stroke, 17(5), 583-589. [Abstract]

New policies

No new national policies or guidelines since 1 April 2024.

New safety alerts

No new safety alerts since 1 April 2024.

Changes in product availability

• New product Flecainide Acetate 25mg/5mL Oral solution is indicated for paroxysmal atrial fibrillation in patients with disabling symptoms when treatment need has been established and in the absence of left ventricular dysfunction. See more here.

Basis for recommendation

The recommendations on diagnosis are largely based on the National Institute for Health and Care Excellence (NICE) guideline Atrial fibrillation: diagnosis and management [NICE, 2021], the European Society of Cardiology (ESC) joint guidelines 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) [ESC, 2021], and expert opinion in review articles on atrial fibrillation Diagnosis and treatment of atrial fibrillation [Gutierrez, 2016] and Atrial fibrillation: epidemiology, screening and digital health [Linz, 2024].

Possible symptoms of AF

• The information that atrial fibrillation (AF) may be suspected if a person has an irregular pulse on examination, has possible symptoms, or may be detected incidentally, is based on the NICE guideline, which notes that AF may be asymptomatic. It also states that AF can be intermittent, and detection and diagnosis may be challenging [NICE, 2021]. Expert opinion in a review article notes that detection of an irregular pulse does not reliably indicate a diagnosis of AF [Gutierrez, 2016].
• The information on possible symptoms of AF is based on the NICE guideline, the ESC joint guidelines, and expert opinion in review articles [Gutierrez, 2016].
• Expert opinion in a review article highlights that early detection and appropriate treatment of AF could reduce the frequency of associated complications [Linz, 2024].

Possible complications of AF

• This recommendation is based on the NICE guideline and the ESC joint guidelines.
  • The ESC joint guidelines highlight that previously unknown AF is detected in about 10% of all people presenting with ischaemic stroke. Asymptomatic clinical AF has been independently associated with an increased risk of stroke and mortality compared with symptomatic AF, so a high clinical suspicion for AF is needed in population groups at risk.

Possible risk factors for AF

• This recommendation is extrapolated from the ESC joint guidelines, which state that opportunistic screening for AF is recommended in people with hypertension and may be considered in people with sleep apnoea syndrome.

Possible device notifications of AF

• This recommendation is extrapolated from the ESC joint guidelines, which note that mobile health technologies such as wearable activity monitors, smartphones, smartwatches and wristbands, and health apps are rapidly developing for AF detection and other purposes. They highlight that caution is needed in their clinical use, as many are not clinically validated, with the need for a single-lead ECG tracing of more than 30 seconds or a 12-lead ECG showing AF to confirm a definitive diagnosis of AF.

Basis for recommendation

The recommendations on assessment are largely based on the National Institute for Health and Care Excellence (NICE) guideline Atrial fibrillation: diagnosis and management [NICE, 2021], the European Society of Cardiology (ESC) joint guidelines 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) [ESC, 2021], and expert opinion in review articles on atrial fibrillation 10 steps before you refer for atrial fibrillation [Heath, 2008], Diagnosis and treatment of atrial fibrillation [Gutierrez, 2016] and Atrial fibrillation [Michaud, 2021].

Clinical features on history-taking

• These recommendations are based on the ESC joint guidelines [ESC, 2021] and expert opinion in review articles [Gutierrez, 2016; Michaud, 2021].

Clinical features on examination

• These recommendations are based on the NICE guideline [NICE, 2021], the ESC joint guidelines [ESC, 2021], and expert opinion in review articles [Heath, 2008; Gutierrez, 2016].
  • The information that absence of an irregular pulse makes a diagnosis of AF unlikely, but its presence does not reliably indicate AF is extrapolated from expert opinion in a review article, which notes that pulse palpation has a high sensitivity, but relatively low specificity for detecting AF, so is useful for ruling out a diagnosis [Gutierrez, 2016]. The information that pulse rate and regularity should always be assessed by auscultation at the apex rather than solely palpation of the radial pulse is based on expert opinion in a review article, which also states that detection of an irregular pulse may be challenging if the pulse rate is very fast or very slow [Heath, 2008].
  • The recommendation to check blood pressure manually is based on expert opinion in a review article, which notes that an automated measurement in people with AF may be inaccurate [Heath, 2008].
  • The recommendation to assess for signs of haemodynamic instability is based on the ESC joint guidelines and expert opinion in a review article [Gutierrez, 2016].
  • The recommendation to auscultate the heart is based on the ESC joint guidelines, which note that AF may sometimes be a marker of undiagnosed conditions, therefore all people with AF should have a comprehensive cardiovascular assessment to assess for underlying pathology. This approach is supported by expert opinion in a review article [Gutierrez, 2016].
  • The recommendation to examine the lungs is based on the ESC joint guidelines and expert opinion in a review article [Gutierrez, 2016].
  • The recommendation to assess for other signs of heart failure is based on expert opinion in review articles [Heath, 2008; Gutierrez, 2016].

Arranging a 12-lead ECG

• The recommendation to arrange a 12-lead electrocardiogram (ECG) to confirm the diagnosis is based on the NICE guideline [NICE, 2021] and the ESC joint guidelines [ESC, 2021].
  • The ESC joint guidelines state that a 12-lead ECG, or single-lead ECG rhythm strip tracing for at least 30 seconds, is recommended in all people with suspected AF to establish the diagnosis, assess ventricular rate during AF, and check for the presence of conduction defects, ischaemia, or signs of structural heart disease.
  • The information about the diagnostic features of AF on ECG is based on the ESC joint guidelines and expert opinion in a review article [Gutierrez, 2016].
  • The information about the ventricular rate of untreated AF is based on expert opinion in a review article [Gutierrez, 2016].

Arranging additional investigations

• These recommendations are based on the NICE guideline [NICE, 2021], the ESC joint guidelines [ESC, 2021], and expert opinion in review articles [Heath, 2008; Gutierrez, 2016].
  • The recommendation to arrange blood tests is based on the ESC joint guidelines which note that infection or anaemia may precipitate or contribute to poor rate control in acute AF, together with expert opinion in review articles [Heath, 2008; Gutierrez, 2016]. It is also pragmatic, based on what CKS considers to be good medical practice.
  • The recommendation to arrange a chest X-ray is based on expert opinion in a review article  [Gutierrez, 2016].
  • The recommendation to arrange a transthoracic echocardiogram is based on the NICE guideline, and is supported by the ESC joint guidelines, which note that information such as left ventricular size and function, left atrial size, valvular heart disease, and right heart size and systolic function are needed to guide treatment. Expert opinion in a review article also notes that echocardiogram can refine stroke risk stratification and help predict the likelihood of successful cardioversion [Heath, 2008].
    • The NICE guideline does not recommend arranging an echocardiogram solely for stroke risk stratification in people with AF if the need to start anticoagulation treatment has already been decided.
    • CKS notes that the NICE recommendation to arrange a transthoracic echocardiogram for selected people with AF differs from that in the ESC joint guidelines, which recommend echocardiogram assessment for all people with AF.

Arranging ambulatory ECG if suspected paroxysmal AF

• These recommendations are based on the NICE guideline [NICE, 2021], the ESC joint guidelines [ESC, 2021], and expert opinion in a review article [Gutierrez, 2016].
  • The NICE guideline recommends to use an ambulatory ECG monitor, event recorder, or other ECG technology for a period appropriate to detect AF if symptomatic episodes are more than 24 hours apart. It notes that longer durations of detection increase the accuracy of paroxysmal AF diagnosis.
  • The ESC joint guidelines note that in selected people with AF, long-term ECG monitoring may be used to assess the adequacy of rate control, or to assess the relation of symptoms to AF episodes if the person has paroxysmal AF. They highlight the relationship of symptoms to AF episodes should be confirmed, as non-specific symptoms may be due to undiagnosed or suboptimally managed comorbid cardiovascular risk factors or other underlying conditions.

Basis for recommendation

The information on the differential diagnosis of atrial fibrillation is based on the BMJ Best Practice publication New-onset atrial fibrillation [BMJ Best Practice, 2023] and expert opinion in a medical textbook ABC of atrial fibrillation: differential diagnosis of atrial fibrillation [Lip, 1995].

When should I admit or refer a person with AF?

Consider whether emergency admission or cardiology referral is needed for a person with atrial fibrillation (AF), depending on the onset and severity of symptoms, likely underlying cause(s), and comorbidities.

• Arrange emergency hospital admission if a person has:
  • New-onset AF within the past 48 hours and is haemodynamically unstable.
  • Severe symptoms of AF due to rapid (more than 150 beats per minute) or very slow (less than 40 beats per minute) ventricular rate.
  • Concomitant acute decompensated heart failure. See the CKS topic on Heart failure - chronic for more information.
  • A serious or life-threatening underlying cause or complication of AF, such as stroke or transient ischaemic attack (TIA). See the CKS topic on Stroke and TIA for more information.
  • An acute, potentially reversible trigger or intercurrent illness such as pneumonia or thyrotoxicosis. See the CKS topics on Chest infections - adult and Hyperthyroidism for more information.
• Arrange hospital admission or seek urgent specialist cardiology advice if a person has:
  • New-onset AF within the past 48 hours and is haemodynamically stable.
  • A suspected or confirmed pre-excitation syndrome such as Wolff-Parkinson-White syndrome or another accessory pathway syndrome.
• Arrange cardiology referral or seek specialist cardiology advice if a person has:
  • AF of unknown duration or onset more than 48 hours ago, if there is any uncertainty about management.
  • Stable AF and heart failure thought to be primarily caused by AF. See the CKS topic on Heart failure - chronic for more information.
  • Suspected paroxysmal AF and there is any uncertainty about management.
  • AF and pre-existing or newly diagnosed structural heart disease, such as valvular heart disease or cardiomyopathy.

What drug treatment should I initiate in primary care?

If a person has atrial fibrillation (AF) and does not need hospital admission or referral, consider prescribing anticoagulation and rate-control drug treatment in primary care, depending on clinical judgement.

• Assess the person's stroke risk using the CHA2DS2-VASc stroke risk score.
• Assess the person's bleeding risk using the ORBIT bleeding risk score if considering starting anticoagulation. Manage any modifiable risk factors for bleeding where possible, such as:
  • Uncontrolled hypertension. See the CKS topic on Hypertension for more information.
  • Frailty and falls risk. See the CKS topics on Falls - risk assessment and Multimorbidity for more information.
  • Reduced creatinine clearance. See the CKS topic on Chronic kidney disease for more information.
  • Concomitant antiplatelet, selective serotonin reuptake inhibitor (SSRI), or nonsteroidal anti-inflammatory drug (NSAID) treatment.
  • Excessive alcohol consumption. See the CKS topic on Alcohol - problem drinking for more information.
  • Any reversible causes of anaemia. See the CKS topics on Anaemia - iron deficiency and Anaemia - B12 and folate deficiency for more information.
• Consider starting anticoagulation drug treatment for stroke prevention.
  • Discuss the potential benefits and risks of starting anticoagulation and the drug choices available, taking into account the person's risk profile and preferences.
    • For most people the benefits of stroke prevention with anticoagulation outweigh the bleeding risk.
    • For people with an increased risk of bleeding, the benefits of anticoagulation may not always outweigh the bleeding risk, and more frequent monitoring may be needed. See the section on Reviewing drug treatment for more information.
    • Do not withhold anticoagulation solely based on a person's age or falls risk. See the CKS topic on Falls - risk assessment for more information.
• Offer anticoagulation with a direct-acting oral anticoagulant (DOAC) first-line if a person has AF and a CHA₂DS₂-VASc score of 2 or above, and consider a DOAC for a man with AF and a CHA₂DS₂-VASc score of 1, taking into account the risk of bleeding.
  • Options include apixaban, dabigatran, edoxaban, and rivaroxaban, depending on contraindications, cautions, adverse effects, potential drug interactions, and local prescribing guidelines. See the CKS topic on Anticoagulation - oral for more information.
    • If a DOAC is contraindicated, not tolerated, or not suitable, offer treatment with a vitamin K antagonist such as warfarin, and refer to a local warfarin clinic or specialist pharmacist for initiation and monitoring, depending on local referral pathways. See the CKS topic on Anticoagulation - oral for more information.
    • If warfarin is contraindicated consider referral to a cardiology specialist, who may advise other risk reducing procedures including left atrial appendage closure (LAAC). 
  • Do not offer anticoagulation to a person aged under 65 years with AF and no risk factors other than their sex (a very low risk of stroke equating to a CHA₂DS₂-VASc score of 0 for men or 1 for women).
  • Arrange to review the person to monitor drug treatment. See the section on Reviewing drug treatment for more information.
• Consider starting drug treatment for rate control, depending on clinical judgement.
  • Do not offer rate control as first-line treatment if a person has AF with any of the following:
    • A potentially reversible cause.
    • Heart failure thought to be primarily caused by AF.
    • New-onset AF within the past 48 hours.
    • A rhythm-control strategy is felt to be more suitable clinically — this will usually be a specialist decision. See the section on Admission or referral for more information.
  • If clinically appropriate, offer rate-control drug treatment with either a standard beta-blocker (other than sotalol) or a rate-limiting calcium-channel blocker (diltiazem [off-label indication] or verapamil) first-line, depending on the person's symptoms, heart rate, comorbidities, and preferences. See the sections on Beta-blockers (except sotalol) and Diltiazem and verapamil in Prescribing information for more information.
    • Consider prescribing digoxin monotherapy if a person is sedentary with non‑paroxysmal AF, or if other drug options are contraindicated, not tolerated, or not suitable. See the section on Digoxin in Prescribing information for more information.
  • Arrange to review the person within one week of starting rate-control treatment to assess symptom control, resting heart rate, blood pressure, adherence to treatment, and any adverse effects. See the section on Reviewing drug treatment for more information.

How should I monitor drug treatment in primary care?

If a person with atrial fibrillation (AF) has started anticoagulation and/or rate-control drug treatment in primary care, arrange appropriate drug monitoring.

Anticoagulant drugs

• If a person is taking a direct-acting oral anticoagulant (DOAC), assess adherence to treatment and ask about any adverse effects. See the CKS topic on Anticoagulation - oral for more information on drug monitoring and follow-up.
• If a person is taking a vitamin K antagonist such as warfarin, ensure anticoagulation control is reviewed regularly, usually by a local warfarin clinic or specialist pharmacist.
  • This involves frequent monitoring of the international normalized ratio (INR) until the INR is within the therapeutic range, according to local prescribing protocols. See the CKS topic on Anticoagulation - oral for more detailed information on prescribing and monitoring warfarin.
  • Be aware that a person on long-term warfarin may have sub-optimal anticoagulation control indicated by:
    • Time in therapeutic range (TTR) of less than 65%.
    • Two INR values higher than 5, or one INR value higher than 8, within the past 6 months.
    • Two INR values less than 1.5 within the past 6 months.
  • Modify any factors contributing to sub-optimal anticoagulation control if possible, such as:
    • Impaired cognitive function. See the CKS topic on Dementia for more information.
    • Poor adherence to drug treatment.
    • Acute illness.
    • Use of concurrent medications that may interact with warfarin, such as antiplatelets, selective serotonin reuptake inhibitors (SSRIs), and nonsteroidal anti-inflammatory drugs (NSAIDs).
    • Lifestyle factors such as excess alcohol consumption. See the CKS topic on Alcohol - problem drinking for more information.
  • Liaise with the local warfarin clinic or specialist pharmacist if there is sub-optimal anticoagulation control or any uncertainty about warfarin doses or prescribing.
• If a person is taking warfarin and has sub-optimal anticoagulation control or low TTR which cannot be improved, consider switching to a DOAC. See the CKS topic on Anticoagulation - oral for more information on drug switching.

Rate-control drugs

• Arrange to review the person within one week of starting rate-control treatment or each dose titration, to assess symptom control, resting heart rate, blood pressure, adherence to treatment, and any adverse effects. See the sections on Beta-blockers (except sotalol) and Diltiazem and verapamil in Prescribing information for more information on adverse effects.
  
  • Strict ventricular rate targets are less than 80 beats per minute at rest, and less than 110 beats per minute during moderate exercise. 
    • A more lenient ventricular rate target of less than 110 beats per minute at rest may be appropriate, unless symptoms require stricter rate control. The target heart rate during exercise may need to be adjusted depending on the person's exercise tolerance.
  • If the person cannot tolerate a specific rate-control drug, offer an alternative or seek specialist cardiology advice if there is any uncertainty about drug choice, doses, or target ventricular rate. See the section on Initiating drug treatment for more information.
• If the person's symptoms are not controlled on treatment and are thought to be due to poor ventricular rate control, consider one of the following options:
  • Increase the drug dose up to the maximum if needed to control symptoms.
  • If the person is taking the maximum dose of one drug, consider combination treatment with one of the following regimens. See the sections on Beta-blockers (except sotalol), Diltiazem and verapamil, and Digoxin in Prescribing information for more information.
    • A beta-blocker and digoxin, or
    • Digoxin and diltiazem (off-label indication).
    • Note: seek specialist advice before prescribing diltiazem with a beta-blocker, as there is a serious risk of bradycardia, atrioventricular block, asystole, or sudden death with concurrent use.
• If the person's symptoms are not controlled with combination treatment despite good rate control, or a rate-control strategy is unsuccessful, arrange prompt cardiology referral (to be seen within 4 weeks) for specialist management.

What information and advice should I give?

• Advise on who to contact and when to arrange urgent review if symptoms are uncontrolled.
• Advise about lifestyle modification, including:
  • Weight loss and exercise if overweight or obese. See the CKS topic on Obesity for more information.
  • Smoking cessation if relevant. See the CKS topic on Smoking cessation for more information.
  • Alcohol consumption if relevant. See the CKS topic on Alcohol - problem drinking for more information.
• Advise about support networks and sources of information, such as:
  • The British Heart Foundation patient information on Atrial fibrillation, a booklet I'm in control of my Atrial fibrillation (AF), and information on Holidays and travel.
  • The Stroke Association resources on Atrial fibrillation and Atrial fibrillation and stroke.
  • The NHS information Atrial fibrillation.
  • The NHS England Atrial fibrillation decision support tool for people with AF taking drug treatment(s) who are still symptomatic.
• Advise about driving safety, depending on the underlying cause of atrial fibrillation (AF) and the severity and nature of any symptoms, complications, or comorbidities.
  • See the Driver and Vehicle Licensing Agency (DVLA) publication Assessing fitness to drive: a guide for medical professionals for more information.
  • Advise the person to check with their insurer that they are still covered for driving.

How should I review a person with paroxysmal, persistent, or permanent AF?

Review a person with paroxysmal, persistent, or permanent atrial fibrillation (AF) at least annually once symptoms are controlled, or more frequently depending on clinical judgement and any shared care arrangement.

• Assess for and manage any underlying cause or risk factor(s), depending on clinical judgement.
  • Give lifestyle modification advice. See the section on Information and advice for more information.
  • Assess and manage the person's cardiovascular disease (CVD) risk. See the CKS topic on CVD risk assessment and management for more information.
• Assess for and manage any complication(s) of AF, depending on clinical judgement.
• Advise on sources of information and support. See the section on Information and advice for more information.
• Review the person's drug treatment(s) to ensure appropriate and optimal prescribing.
  • Ask about any symptoms at rest, during exercise, and impact on quality of life.
  • Examine the person to assess the resting heart rate and rhythm, and check manual blood pressure.
  • Assess adherence to treatment and identify and manage any factors affecting this, such as cognitive impairment, polypharmacy and drug interactions, adverse effects, and the person's understanding of the treatment regimen. See the section on Prescribing information for more information.
• If the person is not currently prescribed an anticoagulant, reconsider the need for treatment, depending on the person's current stroke and bleeding risk. See the section on Initiating drug treatment for more information.
  • Ensure stroke risk is reviewed when a person reaches 65 years of age, or if at any age they develop comorbidities such as diabetes mellitus, heart failure, peripheral arterial disease, coronary heart disease, stroke or transient ischaemic attack, or thromboembolism.
• If the person is already taking an anticoagulant drug:
  • Reassess the person's stroke risk using the CHA2DS2-VASc stroke risk score at least annually.
  • Reassess the person's bleeding risk using the ORBIT bleeding risk score at least annually and manage any modifiable risk factors for bleeding, such as:
    • Uncontrolled hypertension. See the CKS topic on Hypertension for more information.
    • Frailty and falls risk. See the CKS topics on Falls - risk assessment and Multimorbidity for more information.
    • Reduced creatinine clearance. See the CKS topics on Acute kidney injury and Chronic kidney disease for more information.
    • Concomitant antiplatelet, selective serotonin reuptake inhibitor (SSRI), or nonsteroidal anti-inflammatory drug (NSAID) treatment.
    • Ensure a direct-acting oral anticoagulant (DOAC) is taken at the correct dose, if using, or optimize time in therapeutic range (TTR) if using a vitamin K antagonist. See the CKS topic on Anticoagulation - oral for more information.
    • Excessive alcohol consumption. See the CKS topic on Alcohol - problem drinking for more information.
    • Any reversible causes of anaemia. See the CKS topics on Anaemia - iron deficiency and Anaemia - B12 and folate deficiency for more information.
  • Do not stop anticoagulation solely because AF is no longer clinically detectable. Base this decision on the person's stroke risk, bleeding risk, and preferences.
  • If the person is taking a DOAC, see the CKS topic on Anticoagulation - oral for more information on drug monitoring and review.
  • If the person is taking a vitamin K antagonist such as warfarin, assess anticoagulation control. See the section on Reviewing drug treatment for more information.
    • If the person is stable and there is good TTR, discuss the option of switching to a DOAC, taking into account the person's preferences.
    • If there is low TTR, consider switching to a DOAC and advise on the importance of good adherence to treatment, or implement strategies to improve the TTR. See the section on Reviewing drug treatment for more information.
• If the person is taking rate-control treatment and is still symptomatic, or the ventricular rate is above the recommended target, see the section on Reviewing drug treatment for more information on possible combination treatment options.
  • If the person's symptoms are not controlled with combination treatment, arrange prompt cardiology referral (to be seen within 4 weeks) for further assessment.
• If the person is taking specialist rhythm-control drug treatment or has had electrical cardioversion and has recurrent or persistent symptoms, arrange prompt cardiology referral (to be seen within 4 weeks) for further assessment.
  • If the person is taking rhythm-control drugs that were started by a cardiologist, such as amiodarone or sotalol, arrange appropriate monitoring in primary care, depending on the shared care arrangement. If there is any uncertainty about drug monitoring or doses, seek specialist advice.
  • Be aware that amiodarone should not be used for long-term rate control.

What information and advice should I give?

• Advise on who to contact and when to arrange urgent review if symptoms are uncontrolled.
• Advise about lifestyle modification, including:
  • Weight loss and exercise if overweight or obese. See the CKS topic on Obesity for more information.
  • Smoking cessation if relevant. See the CKS topic on Smoking cessation for more information.
  • Alcohol consumption if relevant. See the CKS topic on Alcohol - problem drinking for more information.
• Advise about support networks and sources of information, such as:
  • The British Heart Foundation patient information on Atrial fibrillation, a booklet I'm in control of my Atrial fibrillation (AF), and information on Holidays and travel.
  • The Stroke Association resources on Atrial fibrillation and Atrial fibrillation and stroke.
  • The NHS information Atrial fibrillation.
  • The NHS England Atrial fibrillation decision support tool for people with AF taking drug treatment(s) who are still symptomatic.
• Advise about driving safety, depending on the underlying cause of atrial fibrillation (AF) and the severity and nature of any symptoms, complications, or comorbidities.
  • See the Driver and Vehicle Licensing Agency (DVLA) publication Assessing fitness to drive: a guide for medical professionals for more information.
  • Advise the person to check with their insurer that they are still covered for driving.

Choice of beta-blocker

• The beta-blockers atenolol, acebutolol, metoprolol, nadolol, oxprenolol, and propranolol are licensed to treat arrhythmias. The choice of beta-blocker will usually depend on the person's comorbidities, local prescribing guidelines, and cost.
  • For AF without comorbidities, atenolol once a day may be used.
  • For people with AF and a previous myocardial infarction (without heart failure), metoprolol (standard release), propranolol (standard release), or atenolol may be preferred. See the CKS topic on MI - secondary prevention for more information.
  • For people with AF and heart failure, bisoprolol (off-label indication), carvedilol (off-label indication), or nebivolol (off-label indication) may be preferred. See the CKS topic on Heart failure - chronic for more information.
  • For people with AF and diabetes mellitus, a cardioselective beta-blocker (such as atenolol, bisoprolol [off-label indication], metoprolol, nebivolol [off-label indication], or acebutolol) may be preferred. Avoid beta-blockers in people who experience frequent hypoglycaemia. See the CKS topics on Diabetes - type 1 and Diabetes - type 2 for more information.

[BNF, 2024]

Contraindications and cautions

• Do not prescribe beta-blockers to people with:
  • Asthma, chronic obstructive pulmonary disease (COPD), or bronchospasm — if there is no alternative, a cardioselective beta-blocker (such as bisoprolol or atenolol) may be used cautiously under specialist supervision.
  • Cardiogenic shock.
  • Phaeochromocytoma (without a concomitant alpha-blocker).
  • Second- or third-degree atrioventricular (AV) block.
  • Sick sinus syndrome.
  • Marked bradycardia.
  • Severe hypotension.
  • Severe peripheral arterial disease.
  • Uncontrolled heart failure.
• Beta-blockers should be used with caution in people with:
  • Diabetes mellitus — symptoms of hypoglycaemia may be masked.
  • First-degree AV block.
  • Myasthaenia gravis.
  • Portal hypertension — risk of deteriorating liver function.
  • Psoriasis.
  • Thyrotoxicosis — symptoms may be masked.

[BNF, 2024]

Adverse effects

Possible adverse effects of beta-blockers include:

• Bradycardia; heart failure; atrioventricular block (uncommon).
• Dyspnoea; bronchospasm (uncommon).
• Cold extremities, paraesthesiae, and numbness; peripheral arterial disease.
• Dizziness; syncope.
• Exacerbation of psoriasis.
• Fatigue; headache; confusion; depression; sleep disorders; visual impairment; hallucination (very rare).
• Abdominal discomfort; diarrhoea; nausea; vomiting.
• Erectile dysfunction.
• Rash (reversible on stopping).

[BNF, 2024]

Drug interactions

Potential drug interactions associated with beta-blockers include:

• Alpha-blockers, alprostadil, angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-II receptor antagonists, anxiolytics, baclofen, co-beneldopa, co-careldopa, diuretics, hydralazine, hypnotics, levodopa, monoamine oxidase inhibitors (MAOIs), methyldopa, minoxidil, moxonidine, nitrates, phenothiazines, sildenafil, tadalafil, tizanidine — enhanced hypotensive effect.
• Aminophylline and theophylline — beta-blockers such as atenolol may increase the risk of bronchospasm. Manufacturer advises avoid. 
• Antidepressants such as tricyclics, mirtazapine, and trazodone — increased risk of hypotension.
• Antidiabetics — beta-blockers may mask warning signs of hypoglycaemia. Concomitant use with dapagliflozin or empagliflozin can increase the risk of hypotension.
• Calcium-channel blockers
  • The combination of beta-blockers and verapamil should be avoided due to the risk of cardiovascular adverse events such as bradycardia, asystole, severe hypotension, and heart failure. Manufacturer advises use with caution or avoid.
  • The combination of diltiazem with a beta-blocker — increased risk of bradycardia, atrioventricular block, and cardiodepression. Manufacturer advises avoid or monitor.
  • The combination of a beta-blocker and nifedipine — increased risk of hypotension.
  • The combination of a beta-blocker and other calcium-channel blockers — can increase the risk of hypotension.
• Class I anti-arrhythmics (such as quinidine, flecainide)
  • Increased risk of cardiovascular adverse events. Manufacturer advises use with caution or avoid.
• Class III anti-arrhythmics (such as amiodarone)
  • Increased risk of bradycardia, atrioventricular (AV) block, and myocardial depression. Manufacturer advises use with caution or avoid.
• Clonidine — increased risk of withdrawal hypertension. Withdraw beta-blockers several days before slowly withdrawing clonidine.
• Corticosteroids, oestrogens — hypotensive effect antagonised with concomitant use.
• Digoxin
  • Concomitant use with digoxin increase the risk of bradycardia.
  • An increase in plasma digoxin levels has been noted with carvedilol — monitor for signs of digoxin toxicity (confusion, anorexia, nausea, disturbance of colour vision) when starting, adjusting, or stopping carvedilol.
• Dobutamine — increased risk of severe hypertension and bradycardia when non-cardioselective beta-blockers (nadolol, oxprenolol, pindolol, propranolol, timolol) are given with dobutamine.
• Donepezil — increased risk of bradycardia.
• Mefloquine — increased risk of bradycardia. Manufacturer makes no recommendation.

[BNF, 2024]

Dose and titration

Diltiazem and verapamil are usually started at a low dose and titrated upwards, the dose adjusted according to response until ideally rate-control is achieved.

• Diltiazem (off-label indication)
  • The usual starting dose (immediate-release preparation) is 60 mg three times a day. Maximum dose is 360 mg per day (extrapolated from doses used for the treatment of angina).
  • In the elderly and people with impaired hepatic or renal function, a starting dose of 60 mg twice daily is recommended (extrapolated from treatment doses for angina).
  • Different modified-release preparations of diltiazem are available for the treatment of angina, and different maintenance doses and dosing regimens are recommended depending on the specific brand used. If prescribing modified-release diltiazem, ensure that the brand is specified each time.
• Verapamil
  • The usual starting dose (immediate-release preparation) is 40 mg three times a day. The recommended maximum dose is 120 mg three times a day.

[BNF, 2024]

Contraindications and cautions

• Do not prescribe verapamil or diltiazem to people with:
  • Heart failure with reduced ejection fraction; history of significantly impaired left ventricular function.
  • Severe bradycardia.
  • Cardiogenic shock.
  • Second- and third-degree atrioventricular (AV) block — verapamil and diltiazem may induce complete AV block (unless pacemaker fitted).
  • Severe hypotension.
  • Significant aortic stenosis (diltiazem).
  • Sick sinus syndrome; sino-atrial block.
  • Wolff-Parkinson-White syndrome (or other accessory pathway syndromes; verapamil).
  • Acute porphyrias.
  • Pregnancy — manufacturer advises avoid diltiazem in pregnancy; manufacturer advises avoid verapamil in the first trimester unless absolutely necessary, as it may reduce uterine blood flow with fetal hypoxia.
• Prescribe verapamil or diltiazem with caution to people:
  • Who are elderly — risk of syncope and falls.
  • Bradycardia — avoid if severe.
  • First-degree AV block.
  • Prolonged PR interval (diltiazem).
  • Hepatic impairment — risk of increased exposure; manufacturer advises initial dose reduction.
  • Renal impairment — risk of increased exposure; manufacturer advises initial dose reduction. 
  • With neuromuscular disorders (verapamil).

[BNF, 2024]

Adverse effects

Possible adverse effects of verapamil and diltiazem include:

• Abdominal pain, dizziness, drowsiness, flushing, headache, nausea, palpitations, peripheral oedema, skin reactions, tachycardia, vomiting (common).
• Angio-oedema, depression, erectile dysfunction, gingival hyperplasia, myalgia, paraesthesia, syncope (uncommon).
• Diltiazem specifically — cardiac conduction disorders, constipation, gastrointestinal discomfort, malaise (common). Arrhythmias, diarrhoea, insomnia, anxiety, postural hypotension (uncommon). Dry mouth (very rare).
• Verapamil specifically — hypotension (common). Atrioventricular block, extrapyramidal symptoms, gynaecomastia, Stevens-Johnson syndrome, vertigo (frequency not known).

[BNF, 2024; EMC, 2023]

Drug interactions

Potential drug interactions associated with verapamil and diltiazem include:

• Alpha-blockers, angiotensin-converting enzyme (ACE)-inhibitors, angiotensin-II receptor antagonists, antipsychotics, anxiolytics and hypnotics, baclofen, clonidine, co-beneldopa, co-careldopa, diuretics, hydralazine, levodopa, monoamine oxidase inhibitors (MAOIs), methyldopa, minoxidil, moxonidine, nitrates, and tizanidine — increased risk of hypotension.
• Antidepressants (tricyclics and trazodone) — increased risk of hypotension with tricyclics; diltiazem and verapamil are predicted to increase the exposure to trazodone. Manufacturer makes no recommendation.
• Antidiabetic drugs (sodium-glucose co-transporter 2 [SGLT2] inhibitors) — increased risk of hypotension.
• Atazanavir — plasma concentration of diltiazem increased with concurrent use. Reduce dose of diltiazem.
• Carbamazepine — concurrent use with diltiazem or verapamil may lead to increased concentration of carbamazepine, and carbamazepine is predicted to decrease exposure to diltiazem. Manufacturer advises monitor concentration and adjust dose with diltiazem.
• Cimetidine — increases exposure to diltiazem and verapamil. Manufacturer advises monitor and adjust dose with diltiazem.
• Colchicine — diltiazem and verapamil predicted to increase exposure to colchicine. Manufacturer advises adjust colchicine dose.
• Beta-blockers — verapamil increases the risk of cardiovascular adverse effects including bradycardia and hypotension. Manufacturer advises use with caution or avoid. Diltiazem increases the risk of cardiodepression, bradycardia, and hypotension. Manufacturer advises avoid or monitor.
• Clarithromycin, erythromycin — predicted to increase exposure to diltiazem and verapamil. Manufacturer advises caution with clarithromycin and diltiazem use, and monitor use with verapamil.
• Dabigatran — verapamil possibly increases plasma concentration.
• Digoxin — concurrent use with diltiazem or verapamil may lead to increased plasma concentrations of digoxin. Increased risk of bradycardia. Manufacturer advises monitor and adjust dose.
• 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 cardiodepression and asystole.
• Domperidone — diltiazem and verapamil are predicted to increase exposure to domperidone. Manufacturer advises avoid.
• Donepezil — diltiazem and verapamil can increase the risk of bradycardia.
• Dronedarone, flecainide, amiodarone — increased risk of bradycardia and cardiodepression. Manufacturer advises avoid use with amiodarone, and use with caution with verapamil.
• Itraconazole, ketoconazole, miconazole — predicted to increase the exposure to diltiazem and verapamil. Manufacturer advises caution with itraconazole and miconazole.
• Lithium — diltiazem and verapamil are predicted to increase the risk of neurotoxicity when given with lithium. Manufacturer advises caution with diltiazem; no recommendation with verapamil.
• Tacrolimus — diltiazem and verapamil predicted to increase the plasma concentrations of tacrolimus. Manufacturer advises monitor.
• Mefloquine — increased risk of bradycardia when given with diltiazem and verapamil. Manufacturer makes no recommendation.
• Methylprednisolone — diltiazem and verapamil are predicted to increase exposure to methylprednisolone. Manufacturer advises monitor and adjust dose.
• Phenobarbital, primidone — phenobarbital is predicted to decrease the exposure to diltiazem and verapamil. Manufacturer makes no recommendation. 
• Phenytoin — diltiazem and verapamil increase plasma concentration of phenytoin, effect of diltiazem and verapamil also reduced. Manufacturer makes no recommendation.
• Rifampicin — plasma concentration of diltiazem and verapamil decreased with concurrent use. Manufacturer advises monitor.
• Ritonavir — plasma concentration of calcium-channel blockers possibly increased with concurrent use.
• Sildenafil, tadalafil, vardenafil — diltiazem is predicted to increase drug exposure. Manufacturer advises adjust dose.
• Statins — increased risk of exposure to atorvastatin and simvastatin. Manufacturer advises monitor and adjust dose.

[BNF, 2024]

Dose and titration

When prescribing loading and maintenance doses of digoxin, seek specialist advice if there is any clinical uncertainty, or if a person is elderly or has renal impairment (doses will need to be reduced).

• Prescribe a loading dose of 250–750 micrograms a day for 7 days, followed by a maintenance dose. A clinical response is usually seen within one week.
  • The BNF recommends a loading dose for rapid digitalisation of 750 micrograms to 1.5 mg in divided doses, dose to be given over 24 hours. A previous expert reviewer of this CKS topic, however, advised that usually no more than 1000 micrograms (1 mg) is needed in 24 hours. If a more rapid clinical response is needed, consider arranging hospital admission. 
• Prescribe a maintenance dose of 125–250 micrograms a day; adjust according to renal function, initial loading dose, and the ventricular rate at rest.

[BNF, 2024]

Drug monitoring

If there is any uncertainty about the need for, or frequency of, digoxin drug monitoring or interpretation of results, seek specialist advice.

• Monitor serum electrolytes and renal function at least annually (more frequently in elderly people and people with renal impairment). Toxicity increased by electrolyte disturbances.
• Regular monitoring of plasma digoxin level during maintenance treatment is not needed, unless clinically indicated. If checking plasma digoxin levels, blood should be taken at least 6 hours after a dose.
• Consider checking plasma digoxin levels if there is:
  • Suspected digoxin toxicity (suggested by symptoms such as confusion, nausea, vomiting, anorexia, dizziness, palpitations, or disturbance of colour vision).
  • Concomitant drug use which increases risk of digoxin toxicity. See the section on Drug interactions for more information.
  • Renal impairment (estimated glomerular filtration rate less than 30 mL/min/1.73m²); thyroid disease.
  • Suspected poor adherence to treatment.
• The likelihood of toxicity depends on the serum concentration of digoxin, and the likelihood of toxicity is increased through the range 1.5–3 micrograms/L. 
  • Levels less than 1.5 micrograms/L in the absence of hypokalaemia suggest digoxin toxicity is unlikely.
  • Levels greater than 3 micrograms/L suggest digoxin toxicity is likely.
  • Levels between 1.5–3 micrograms/L suggest digoxin toxicity is possible.
  • Be aware that digoxin toxicity can occur even when the plasma digoxin concentration is within the therapeutic range. Always interpret levels in the context of clinical presentation.

[EMC, 2022; BNF, 2024]

Contraindications and cautions

• Do not prescribe digoxin to people with:
  • Supraventricular arrhythmias associated with accessory pathways (such as Wolff-Parkinson-White syndrome).
  • Intermittent complete heart block; second-degree atrioventricular (AV) block.
  • Myocarditis.
  • Ventricular tachycardia or ventricular fibrillation.
• Prescribe digoxin with caution to people:
  • With constrictive pericarditis.
  • With hypertrophic cardiomyopathy.
  • With recent myocardial infarction.
  • With sick sinus syndrome.
  • With thyroid disease.
  • With severe respiratory disease.
  • With hypokalaemia, hypomagnesaemia, hypercalcaemia, and hypoxia — increased risk of digitalis toxicity.
  • With renal impairment — consider reducing initial and maintenance doses and monitor plasma digoxin concentration. Risk of toxicity increased.
  • Who are elderly — reduce dose; increased susceptibility to digitalis toxicity.

[BNF, 2024]

Adverse effects

Possible adverse effects of digoxin include:

• Arrythmias, cardiac conduction disorder, cerebral impairment, diarrhoea, dizziness, eosinophilia, nausea, skin reactions, vision disorders, vomiting (common).
• Depression (uncommon).
• Reduced appetite, asthenia, confusion, gastrointestinal disorders, gynaecomastia, headache, malaise, psychosis, thrombocytopenia (rare).

[BNF, 2024]

Drug interactions

Possible drug interactions associated with digoxin include:

• Alfacalcidol, calcipotriol, calcitriol, colecalciferol, ergocalciferol — predicted to increase the risk of digoxin toxicity. Manufacturer advises monitor.
• Aminophylline, theophylline — predicted to increase the risk of digoxin toxicity. Manufacturer advises caution.
• Amiodarone — predicted to moderately increase exposure to digoxin; increased risk of bradycardia Manufacturer advises monitor and adjust digoxin dose.
• Antacids — oral antacids decrease the absorption of oral digoxin. Manufacturer advises separate administration by 2 hours.
• Azithromycin, clarithromycin, erythromycin — increases concentration of digoxin. Manufacturer advises monitor digoxin concentration.
• Beta-blockers — concomitant administration of a beta-blocker and digoxin can increase the risk of bradycardia. Monitor pulse carefully.
• Bupropion — may decrease exposure to digoxin levels. Manufacturer advises monitor.
• Calcium-channel blockers (diltiazem, verapamil, and possibly nifedipine) — increase the concentration of digoxin; increased risk of bradycardia. Manufacturer advises monitor and adjust dose.
• Carbimazole — carbimazole affects the concentration of digoxin. Manufacturer advises monitor and adjust dose.
• Clonidine — both digoxin and clonidine can increase the risk of bradycardia.
• Diuretics, ciclosporin, acetazolamide, and amphotericin — increased risk of digoxin toxicity. Manufacturer advises caution.
• Donepezil — increased risk of bradycardia.
• Dronedarone — dronedarone is predicted to moderately increase exposure to digoxin. Manufacturer advises monitor and adjust digoxin dose.
• Flecainide — both digoxin and flecainide can increase the risk of bradycardia.
• Itraconazole, ketoconazole — predicted to markedly increase the concentration of digoxin. Manufacturer advises monitor digoxin level with ketoconazole and adjust dose.
• Levothyroxine — levothyroxine is predicted to affect the concentration of digoxin. Manufacturer advises monitor and adjust dose.
• Mefloquine — mefloquine is predicted to increase the risk of bradycardia when given with digoxin. Manufacturer makes no recommendation.
• Mirabegron — mirabegron slightly increases the exposure to digoxin. Manufacturer advises monitor concentration and adjust dose.
• Neomycin — neomycin decreases the absorption of digoxin. Manufacturer advises monitor digoxin concentration.
• Phenytoin — phenytoin is predicted to decrease the concentration of digoxin. Manufacturer makes no recommendation.
• Quinine — quinine increases the concentration of digoxin. Manufacturer advises monitor and adjust digoxin dose.
• Rifampicin — rifampicin decreases the concentration of digoxin. Manufacturer advises monitor digoxin concentration.
• Salbutamol, salmeterol, terbutaline — predicted to increase the risk of digoxin toxicity when given with digoxin. Manufacturer advises caution.
• Spironolactone — spironolactone increases the concentration of digoxin. Manufacturer advises monitor and adjust dose.
• Steroids — predicted to increase the risk of digoxin toxicity. Manufacturer advises caution.
• St John's wort — decreases the concentration of digoxin. Manufacturer advises avoid.
• Sulfasalazine — sulfasalazine decreases the concentration of digoxin. Manufacturer advises monitor digoxin concentration.
• Trimethoprim — trimethoprim increases the concentration of digoxin. Manufacturer advises monitor digoxin concentration.

[BNF, 2024]