Previous changes

May 2024 — minor update. Information added stating that concomitant treatment with clarithromycin and ivabradine is now contraindicated and caution is now advised when co-administering clarithromycin with edoxaban, as per the manufacturer's updated SPC.

March 2024 — minor update. Fixed eruption added as an adverse effect of doxycycline as per the manufacturer's SPC. 

December 2023 — minor update. Recommendations relating to COVID-19 infection have been removed from this topic.

July 2023 — minor update. The summary of manufacturer’s product characteristics for clarithromycin was updated to include a warning regarding concomitant treatment with domperidone (due to the risk of QT prolongation and cardiac arrhythmias).

June 2021— minor update. Pulse oximetry thresholds for severity in COVID-19 revised from 92% to 91% in line with an update to the NICE COVID-19 rapid guideline. 

May 2021 — minor update. Information that community-acquired pneumonia is an HIV indicator condition has been added to this topic in line with the British HIV Association/British Association for Sexual Health and HIV/British Infection Association Adult HIV testing guidelines 2020.

January 2021 — minor update. Contraindications and drug interactions for erythromycin have been updated in line with an MHRA drug safety update. 

November 2020 — minor update. A new recommendation to consider VTE prophylaxis has been added to the management of community-acquired pneumonia. 

May 2020 — minor update. Links to the COVID-19 management scenario have been added in the Assessment section and the Management of community-acquired pneumonia section to highlight that assessment of suspected chest infection and management of community-acquired pneumonia will differ during the COVID-19 pandemic. 

April 2020 — minor update. New management scenario created to provide information regarding COVID-19. 

July to September 2019 — reviewed. A literature search was conducted in May 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. 

Recommendations on the management, follow up, and referral of acute bronchitis and community-acquired pneumonia have been added and amended in line with the 2019 National Institute for Health and Care Excellence guidelines on Cough (acute): antimicrobial prescribing and Pneumonia (community-acquired): antimicrobial prescribing. Prescribing information has been adjusted to reflect these recommendations, including the addition of a section on erythromycin. 

September to November 2015 — reviewed. A literature search was conducted in September 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. No major changes to clinical recommendations have been made.

July 2015 — minor update. Information on the concurrent use of clarithromycin with statins has been clarified.

April 2015 — minor update. The prescribing information on analgesia has been replaced with a link to the CKS topic on Analgesia - mild-to-moderate pain. 

December 2014 — minor update. Additional information regarding the contraindication of clarithromycin and lovastatin or simvastatin. 

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. 

May to July 2012 — reviewed. A literature search was conducted in April 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. No major changes to clinical recommendations have been made.

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

October 2010 — 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. 

September 2010 — minor update. The Supporting evidence on a delayed antibiotic prescribing strategy compared with a no antibiotic prescribing strategy has been updated. 

November 2009 — updated to include the BTS guidelines for the management of community acquired pneumonia in adults: update 2009.

April 2009 — minor update. Dose of erythromycin in the Prescriptions section in the scenario Acute bronchitis has been corrected. Issued in May 2009. 

February 2009 — minor update. Minor change in wording regarding when to prescribe doxycycline, erythromycin, and clarithromycin, in line with updated advice from the Health Protection Agency. 

May to August 2007 — 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. This CKS topic replaces the CKS guidance on Chest infections, together with the CKS topic on Cough - acute with chest signs in children. Advice on the management of acute exacerbations in chronic obstructive pulmonary disease has been removed and can now be found in the CKS topic on Chronic obstructive pulmonary disease. Prescriptions for oxytetracycline and for flucloxacillin have been removed. 

October 2006 — minor update. Analgesia prescriptions updated because new doses of ibuprofen for children are recommend by the British National Formulary.  

November 2005 — minor update. Volumatic® spacer device discontinued and prescriptions removed; advice for using alternative spacer devices included. 

July 2005 — updated to incorporate the Referral guidelines for suspected cancer published by the National Institute for Health and Clinical Excellence. 

March 2004 — reviewed. Validated in May 2004 and issued in July 2004.

March 2001 — reviewed. Validated in July 2001 and issued in October 2001.

June 1998 — written.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 December 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 December 2024.

Economic Appraisals

No new economic appraisals relevant to England since 1 December 2024.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 December 2024.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 December 2024.

New policies

No new national policies or guidelines since 1 December 2024.

New safety alerts

No new safety alerts since 1 December 2024.

Changes in product availability

No changes in product availability since 1 December 2024.

Basis for recommendation

The information on assessing people with suspected acute bronchitis and community-acquired pneumonia is largely based on expert opinion in the National Institute of Health and Care Excellence (NICE) guidelines Suspected acute respiratory infection in over 16s: assessment at first presentation and initial management [NICE, 2023b], Pneumonia: diagnosis and management [NICE, 2025] as well as the British Thoracic Society Guideline for the management of CAP in adults [BTS, 2015a], the North American CHEST guideline Adult outpatients with acute cough due to suspected pneumonia or influenza [Hill, 2019], the BMJ Best Practice guidelines Acute Bronchitis [BMJ Best Practice, 2022], Community-acquired pneumonia in adults (non COVID-19) [BMJ Best Practice, 2023], and expert opinion in review articles [Prina, 2015; Harris, 2016; Kaysin, 2016; Kinkade, 2016; Smith, 2017]. 

Diagnostic features

• NICE recommends considering whether a person presenting with features of an acute respiratory infection may have sepsis [NICE, 2023b].
• The questions to ask when assessing a person with a suspected chest infection are extrapolated from recognised clinical features, and also based on what CKS considers to be good clinical practice.
  • NICE defines lower respiratory tract infection as 'an acute illness usually with cough as the main symptom and with at least one other lower respiratory tract symptom (such as fever, sputum production, breathlessness, wheeze or chest discomfort or pain) and no alternative explanation (such as sinusitis or asthma)' . 
• CKS advises using clinical judgement when diagnosing community-acquired pneumonia because experts state that its symptoms and clinical signs overlap with other infective and non-infective respiratory tract conditions, making a precise diagnosis challenging [NICE, 2023a]. 
  
  • NICE reinforces the importance of making an accurate diagnosis to ensure appropriate antibiotic prescribing. Pneumonia is usually caused by bacteria and needs antibiotic treatment. In contrast, most other acute respiratory conditions are not bacterial and usually do not require antibiotic treatment.
• Specific examination features reflect advice in North American guidelines on adults with acute cough due to suspected pneumonia or influenza [Hill, 2019] and incorporate features of the CRB-65 score, which is recommended as a disease-severity assessment tool for adults with community-acquired pneumonia by NICE [NICE, 2024; NICE, 2025].
• The differening presentations sometimes seen in older people with pneumonia is based on expert opinion in a NICE guideline [NICE, 2025] and review articles [Prina, 2015; Kaysin, 2016].
• A systematic review and meta-analysis of signs and symptoms that rule out community-acquired pneumonia in outpatient adults concluded that adults with an acute respiratory infection with normal vital signs and normal pulmonary examination are very unlikely to have community-acquired pneumonia (0.4% likelihood) [Marchello, 2019]. 

Assessing disease severity in young people with community-acquired pneumonia

• The indicative features of severe illness in young people with community-acquired pneumonia was based on the expert opinion of the NICE guideline committee for Pneumonia: diagnosis and management [NICE, 2025], due to an absence of validated severity assessment tools for this age group.

The CRB-65 score

• While NICE recommends use of the CRB-65 score to assess the severity of community-acquired pneumonia, it was noted that occasionally, the mortality score may not accurately predict mortality risk, and clinical judgement is needed [NICE, 2024; NICE, 2025].

Investigations

• The recommendations on which investigations to consider in people with suspected acute bronchitis and community-acquired pneumonia are based on expert opinion in the Annotated BTS Guideline for the management of CAP in adults (2009) Summary of recommendations [BTS, 2015a], and the NICE guideline Pneumonia: diagnosis and management [NICE, 2025].
  • Oxygen levels — Pulse oximeters are a simple method of assessing oxygenation [BTS, 2015a]. Unusually low oxygen levels indicate a severe illness, even if the person has a low mortality risk score [NICE, 2025]. 
  • C-reactive protein (CRP) — The results of the CRP test can be used to guide antibiotic prescribing if a person does not have a clinical diagnosis of pneumonia [NICE, 2025].  
  • Chest X-ray — Chest X-rays are not necessary in all people with suspected community-acquired pneumonia who are managed in primary care, as it is accepted that in the community a diagnosis may be made only on clinical grounds. However, the results of a chest X-ray may help with the differential diagnosis and management of the acute illness [BTS, 2015a]. 

Microbiological investigations not routinely recommended

• NICE and the BTS accept that routine microbiologic testing is not necessary in primary care for people with low-severity community-acquired pneumonia [BTS, 2015a; NICE, 2025] and this recommendation is also in line with expert opinion in a review article [Kaysin, 2016]. 
• The recommendation on taking blood and sputum samples and considering pneumococcal and legionella urinary antigen tests for a person with moderate-severity community-acquired pneumonia is based on the NICE guideline Pneumonia: diagnosis and management [NICE, 2025].

How should I manage a person with acute bronchitis?

• Refer or seek specialist advice on further investigation and management, if a person with acute cough has any symptoms or signs suggesting a more serious condition (for example sepsis, a pulmonary embolism, or lung cancer).
  • For more information, see the CKS topics on Sepsis, Pulmonary embolism, and Lung and pleural cancers - recognition and referral.
• Advise the person on self-care strategies such as adequate fluid intake and the use of paracetamol or ibuprofen for symptomatic relief.
  • For more information, see the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues.
• Advise that some people may wish to try the following self-care treatments:
  • Honey.
  • Pelargonium (a herbal medicine).
  • Over-the-counter cough medicines containing guaifenesin (an expectorant). 
  • Over-the-counter cough medicines containing cough suppressants (except codeine) if the person does not have a persistent cough or excessive secretions. 
• If the person smokes, advise them to stop. For more information, see the CKS topic on Smoking cessation. 
• Advise the person to seek medical help if symptoms worsen rapidly or significantly, do not improve after 3–4 weeks, or they become systemically very unwell.
• Do not routinely offer an antibiotic to treat an acute cough associated with acute bronchitis in people who are not systemically very unwell or at higher risk of complications. Inform the person that:
  • Acute bronchitis is usually a self-limiting illness and the cough usually lasts about 3–4 weeks.
  • Antibiotics do not make a large difference to the duration of symptoms, only shortening cough duration by about half a day on average.
  • Adverse effects, including diarrhoea and nausea are possible with antibiotic treatment.
  • Unnecessary antibiotic prescriptions may result in antibiotic resistance.
• Offer an immediate antibiotic prescription if the person is systemically very unwell.
• Consider an immediate antibiotic prescription or a backup antibiotic prescription for a person at higher risk of complications, for example:
  • A pre-existing comorbid condition such as heart, lung, kidney, liver, or neuromuscular disease; immunosuppression; or cystic fibrosis.
  • Older than 65 years of age with two or more of the following, or older than 80 years with one or more of the following:
    • Hospital admission in the previous year.
    • Type 1 or type 2 diabetes mellitus.
    • History of congestive heart failure.
    • Current use of oral corticosteroids.
• If a back-up antibiotic prescription is appropriate:
  • Reassure the person that antibiotics are not currently needed.
  • Advise the person to use the delayed prescription if symptoms get rapidly or significantly worse.
    • Advise the person to seek medical advice if symptoms get rapidly or significantly worse despite taking the antibiotic, or they become systemically very unwell.
• If a C-reactive protein (CRP) test has been carried out, use the results to guide antibiotic prescribing as follows: 
  • CRP less than 20 mg/L — do not routinely offer antibiotics.
  • CRP 20–100 mg/L — consider a delayed antibiotic prescription.
  • CRP greater than 100 mg/L — offer antibiotic therapy. 
• If antibiotics are indicated, for adults 18 years of age and older:
  • First-line choice is oral doxycycline: 200 mg on the first day, then 100 mg once a day for 4 days (5-day course in total). Note doxycycline is not the first-choice antibiotic for pregnant women.
  • Alternative first choices are oral:
    • Amoxicillin (preferred in pregnant women) 500 mg three times a day for 5 days.
    • Clarithromycin 250 mg to 500 mg twice a day for 5 days.
    • Erythromycin (preferred in pregnant women) 250 mg to 500 mg four times a day or 500 mg to 1000 mg twice a day for 5 days.
• If antibiotics are indicated, for young people aged 12–17 years:
  • First-line choice is oral amoxicillin (preferred in young women who are pregnant): 500 mg three times a day for 5 days.
  • Alternative first choices are oral:
    • Clarithromycin 250 mg to 500 mg twice a day for 5 days.
    • Erythromycin (preferred in young women who are pregnant) 250 mg to 500 mg four times a day or 500 mg to 1000 mg twice a day for 5 days.
    • Doxycycline 200 mg on first day, then 100 mg once a day for 4 days (5-day course in total). Note doxycycline should not be given to young women who are pregnant.
• Do not offer an oral or inhaled bronchodilator (for example salbutamol) or an oral or inhaled corticosteroid to a person with an acute cough associated with acute bronchitis unless they have an underlying airway disease such as asthma. 
• Do not offer a mucolytic (for example acetylcysteine or carbocisteine) to treat an acute cough associated with acute bronchitis. 
• Offer written advice, such as NHS information on Chest infection, available at www.nhs.uk.

How should I follow up a person with acute bronchitis?

• Routine follow-up is not necessary for a person with suspected acute bronchitis. 
• Reassess a person with an acute cough if their symptoms get rapidly or significantly worse. 
  • Consider other diagnoses and rule out serious causes for symptoms (such as pneumonia or sepsis). For more information, see the section on Causes in the CKS topic on Cough. 
  • Consider previous antibiotic use and the potential for resistant bacteria.
• If the person has already received a course of antibiotics, seek specialist advice on further management.

When should I refer or seek specialist advice?

• Refer adults with community-acquired pneumonia to hospital (use clinical judgement to determine urgency) if: 
  • Symptoms and signs suggest a more serious illness or condition (for example cardiorespiratory failure or sepsis), or
  • Symptoms are not improving as expected with antibiotics.
• Consider referring adults with community-acquired pneumonia to hospital, or seek specialist advice if:
  • There is bacterial resistance to oral antibiotics, or
  • The person is unable to take oral medication.
• Consider referring young people with community-acquired pneumonia to hospital, or seek specialist paediatric advice on further investigation and management.
• Use the CRB-65 score to help decide whether an adult with suspected community-acquired pneumonia requires hospital admission (for more information, see the section on How should I assess a person with a suspected chest infection?). 
  • Score of 3 or more, arrange urgent admission to hospital. 
  • Score of 1 or 2, hospital assessment should be considered (particularly for people with a score of 2).  
  • Score of 0, treatment at home should be considered, depending on clinical judgement and the person's social circumstances. 
• Use clinical judgement in addition to the CRB-65 score to decide if an adult should be admitted. Other factors that should also be considered include: 
  • The person's wishes. 
  • Social support available. 
  • Pre-existing comorbid conditions and general frailty.
  • Pregnancy. 
  • Pulse oximetry.

How should I manage a person with community-acquired pneumonia?

• Advise the person on self-care strategies such as rest, adequate fluid intake, and the use of simple analgesia such as paracetamol for symptomatic relief (for more information, see the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues). Over-the-counter cough medicines are not recommended.
• Offer antibiotic treatment for people with community-acquired pneumonia. 
• When deciding which antibiotic to prescribe, take into account the severity of the illness, risk of complications, local antimicrobial resistance, recent antibiotic use, and recent microbiological results. For details of contraindications, cautions, adverse effects, and drug interactions of the recommended antibiotics, see the section on Prescribing information.
  • If low severity (based on clinical judgement and guided by a CRB-65 score of 0), for adults:
    • First choice oral antibiotic is amoxicillin 500 mg three times a day for 5 days (higher doses can be used — see the BNF).
    • Alternatively, if there is a penicillin allergy, or amoxicillin is unsuitable (for example atypical pathogens are suspected) options are oral doxycycline 200 mg on the first day then 100 mg once a day for 4 days (total course of 5 days), or oral clarithromycin 500 mg twice a day for 5 days, or oral erythromycin (in pregnancy) 500 mg four times a day for 5 days.
  • If moderate severity (based on clinical judgement and guided by a CRB-65 score of 1 or 2 and microbiological results when available), and it is appropriate for the person to be managed in the community, for adults:
    • Prescribe oral amoxicillin 500 mg three times a day for 5 days (higher doses can be used — see the BNF) and (if atypical pathogens are suspected) oral clarithromycin 500 mg twice a day for 5 days, or oral erythromycin (in pregnancy) 500 mg four times a day for 5 days. 
    • Alternatively, in penicillin allergy, oral doxycycline 200 mg on the first day then 100 mg once a day for 4 days (total course of 5 days), or oral clarithromycin 500 mg twice a day for 5 days.
  • For young people aged 12–17 years, if symptoms or signs are non-severe (based on clinical judgement):
    • First choice oral antibiotic is amoxicillin 500 mg three times a day for 5 days (higher doses can be used — see the BNF for children).
    • Alternative choices if there is a penicillin allergy or amoxicillin is unsuitable (for example atypical pathogens are suspected) are oral clarithromycin 250 mg to 500 mg twice a day for 5 days, or  oral erythromycin (in pregnancy) 250 mg to 500 mg four times a day for 5 days, or oral doxycycline 200 mg on the first day, then 100 mg once a day for 4 days (total course of 5 days).
• Discuss possible adverse effects of the antibiotic and advise the person to seek medical advice if any of the following occur:
  • Symptoms worsen rapidly or significantly.
  • Symptoms do not start to improve with 3 days, or they are not improving as expected.
  • They become systemically very unwell.
• Explain to the person that after starting antibiotic treatment, symptoms should improve, although the speed of improvement will depend on the severity of illness. It is usually expected that by: 
  • 1 week — fever should have resolved.
  • 4 weeks — chest pain and sputum production should have substantially reduced.
  • 6 weeks — cough and breathlessness should have substantially reduced. 
  • 3 months — most symptoms should have resolved but fatigue might still be present.
  • 6 months — symptoms should have fully resolved.
• Offer the person written information on pneumonia, for example:
  • NHS information on Pneumonia.
  • The Asthma + Lung Foundation information on Pneumonia.
• If the person smokes, advise them to stop. For more information, see the CKS topic on Smoking cessation.
• Note: community-acquired pneumonia is an HIV indicator condition. For more information, see the CKS topic on HIV infection and AIDS.  

How should I follow up a person with community-acquired pneumonia in primary care?

• Reassess people with community-acquired pneumonia if symptoms and signs do not improve as expected or worsen rapidly or significantly.
  • Be aware of non-bacterial causes of community-acquired pneumonia such as flu.
• Assess symptoms and signs and disease severity and review the need for hospital admission or seeking specialist advice. 
  • For more information on the CRB-65 score and other factors influencing the decision to admit a person with community-acquired pneumonia to hospital, see the sections on Assessment and Referral and specialist advice.  
• If a sample has already been sent for microbiological testing, when the results are available review the choice of antibiotic and consider changing the antibiotic(s) according to the results (using a narrower spectrum antibiotic if appropriate).
• Arrange a chest X-ray after 6 weeks for adults:
  • With symptoms and signs that persist despite treatment. 
  • Who are at higher risk of underlying malignancy (particularly smokers and people aged more than 50 years).
• Advise people who smoke to stop. For more information, see the CKS topic on Smoking cessation. 
• Consider whether pneumococcal or influenza immunization is necessary after the person has recovered from the acute illness. For more information, see the CKS topics on Immunizations - pneumococcal and Immunizations - seasonal influenza.

What contraindications and cautions are associated with amoxicillin?

• Do not prescribe amoxicillin in people with a true penicillin hypersensitivity or hypersensitivity to another beta-lactam agent (for example a cephalosporin).
  • Allergic reactions to penicillins occur in 1–10% of exposed individuals. Anaphylactic reactions occur in fewer than 0.05% of treated patients.
• Prescribe amoxicillin with caution to people with:
  • Renal impairment — reduce the dose of amoxicillin in severe renal impairment.
  • Glandular fever (infective mononucleosis) — these people are especially susceptible to amoxicillin-induced skin rashes.

[EMC, 2024a; BNF, 2025]

What are the adverse effects of amoxicillin?

The adverse effects of amoxicillin include:

• Gastrointestinal — nausea, diarrhoea (common); vomiting (uncommon); and antibiotic-associated colitis (Very rare).
• Skin — skin rash (common); urticaria and pruritus (uncommon); mucocutaneous candidiasis (rare or very rare); erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) (very rare).
• Other very rare adverse effects include:
  • Hepatitis and cholestatic jaundice.
  • Hyperkinesia, dizziness, and convulsions.
  • Interstitial nephritis.
  • Leucopenia, thrombocytopenia, and haemolytic anaemia.
  • Severe allergic reactions.

[EMC, 2024a; BNF, 2025]

What drug interactions are important with amoxicillin?

Possible drug interactions with amoxicillin include:

• Allopurinol — increased risk of rash when allopurinol is given with amoxicillin. 
• Methotrexate — amoxicillin may reduce methotrexate excretion, causing an increased risk of toxicity. Monitor. 
• Oral anticoagulants (for example warfarin) — international normalized ratio (INR) may be increased. Monitor the INR closely during concomitant use. Dosage adjustments may be necessary.  
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of amoxicillin.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.  
• Probenecid — may cause increased and prolonged blood levels of amoxicillin. The manufacturer recommends avoiding concurrent use.
• Tetracyclines — the antibacterial effects of amoxicillin may be antagonised.

[CoSRH, 2022a; EMC, 2024a; BNF, 2025]

What contraindications and cautions are important with clarithromycin?

• Do not prescribe clarithromycin in people:
  • Taking drugs that prolong the QT interval — macrolides can also prolong the QT interval, which is a risk factor for Torsades de Pointes.
  • With a history of QT prolongation or ventricular cardiac arrhythmia, including Torsades de Pointes.
  • With hypokalaemia — due to the risk of prolongation of the QT interval.
  • With severe hepatic impairment if they also have renal impairment.
• Prescribe clarithromycin with caution in people with:
  • Coronary artery disease, severe cardiac insufficiency, conduction disturbances, or clinically relevant bradycardia.
  • Electrolyte disturbances, such as hypomagnesaemia.
  • Impaired hepatic function – clarithromycin is principally excreted by the liver.
  • Myasthenia gravis — macrolides may aggravate symptoms.
  • Severe renal impairment (eGFR less than 30 mL/min/1.73m²).
    • Use half the normal dose. Avoid Klaricid XL^®  or clarithromycin modified-release preparations.

[FDA, 2018; EMC, 2024b; BNF, 2025]

What are the adverse effects of clarithromycin?

The adverse effects of clarithromycin include:

• Gastrointestinal — diarrhoea, vomiting, dyspepsia, nausea, abdominal pain and (common);  pancreatitis and pseudomembranous colitis (rare). For more information, see the CKS topic on Diarrhoea - antibiotic associated. 
• Nervous system — headache and dysgeusia (common); dizziness, somnolence, and tremor (uncommon); convulsions and paraesthesia (rare).
• Psychiatric — insomnia (common); anxiety and nervousness (uncommon); psychotic disorders, depression, mania, and hallucination (rare or very rare).
• Skin — rash and hyperhidrosis (common); pruritus and urticaria (uncommon); drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome, and toxic epidermal necrolysis (rare or very rare).
• Other adverse effects reported rarely, or very rarely, include: 
  • Anaphylaxis.
  • Arrhythmias.
  • Deafness.
  • Hepatic failure, jaundice.
  • QT interval prolongation.

[EMC, 2024b; BNF, 2025]

What drug interactions are important with clarithromycin?

Possible drug interactions with clarithromycin include:

• Calcium channel blockers (CCBs) — there is an increased risk of hypotension if CCBs, such as verapamil, amlodipine, and diltiazem are taken concomitantly with clarithromycin, as they are metabolised by CYP3A4. This interaction may also lead to increased levels of clarithromycin. Bradyarrhythmias and lactic acidosis have also been reported when verapamil and clarithromycin are taken together. 
• Ciclosporin — clarithromycin increases ciclosporin concentration. The manufacturer advises caution with concurrent use.
• Colchicine — clarithromycin should not be used in people taking colchicine as there have been reports of toxicity with concurrent use. 
• CYP3A enzyme inducers (for example rifampicin, phenytoin, carbamazepine, and phenobarbital) — these may induce the metabolism of clarithromycin, resulting in sub-therapeutic levels.
  • It may be necessary to monitor the levels of these drugs, as CYP3A is inhibited by clarithromycin leading to higher plasma levels of the inducer.
• Digoxin — clarithromycin increases serum digoxin concentrations. Monitor digoxin levels.
• Edoxaban — The manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
• Ergot derivatives — concomitant administration is contraindicated, due to the risk of ergot toxicity.
• Ivabradine — concomitant treatment is contraindicated, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of clarithromycin.
  • However, women should be advised that if diarrhoea, vomiting or breakthrough bleeding occur there is a possibility of contraceptive failure. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.  
• Oral hypoglycaemic drugs (sulfonylureas) and insulin — the concurrent use of clarithromycin and oral hypoglycaemic drugs and/or insulin can result in significant hypoglycaemia. Monitor glucose levels.
• Statins (atorvastatin, simvastatin) — these are extensively metabolised by CYP3A4. Concomitant administration with clarithromycin increases the plasma levels and the risk of myopathy. 
  • Simvastatin — do not prescribe clarithromycin to a person taking simvastatin. If treatment with clarithromycin cannot be avoided, stop treatment with simvastatin temporarily.
  • Atorvastatin — avoid concurrent use with clarithromycin. If concurrent use cannot be avoided, prescribe the lowest dose of atorvastatin. Monitor for symptoms and signs of myopathy.
  • Other statins — if concurrent use cannot be avoided, use with caution, prescribe the lowest dose of statin, and monitor for symptoms and signs of myopathy. 
• Warfarin — clarithromycin increases the anticoagulant effect of warfarin. Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Drugs that prolong the QT interval (such as amiodarone, domperidone, or sotalol) — clarithromycin can prolong the QT interval, and concomitant use of drugs that prolong the QT interval should be avoided.
• Drugs that cause hypokalaemia (such as furosemide, prednisolone) — hypokalaemia is a risk factor for QT interval prolongation and Torsade de Pointes arrhythmias, and clarithromycin should not be given to patients with hypokalaemia.
• Hydroxychloroquine or chloroquine — co-administration with a macrolide can increase the risk of cardiovascular events and cardiovascular mortality. Use caution when considering co-prescription in people with risk factors for cardiac events.

[CoSRH, 2022b; MHRA, 2022; EMC, 2024b; SPS, 2024]

What contraindications and cautions are important with doxycycline?

• Doxycycline is not generally recommended in women who are pregnant or breastfeeding. Tetracyclines are deposited in growing bone and teeth which can result in discolouration of teeth and occasionally dental hypoplasia.
  • However, doxycycline can be used during the first trimester if there is no other suitable alternative, as this stage of pregnancy is prior to fetal tooth and bone development and there is no good evidence of other adverse fetal effects [UKTIS, 2024].
• Prescribe doxycycline with caution in people with:
  • Hepatic impairment and those receiving potentially hepatotoxic drugs.
  • Myasthenia gravis — tetracyclines may increase muscle weakness in people with myasthenia gravis.
  • Systemic lupus erythematosus (SLE) — tetracyclines may exacerbate SLE symptoms.
  • Renal impairment — avoid excessive doses.

[EMC, 2021; BNF, 2025]

What are the adverse effects of doxycycline?

Adverse effects of doxycycline include:

• Blood disorders — haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia, and porphyria.
• Gastrointestinal — usually mild symptoms, but may include nausea, vomiting, dyspepsia, abdominal discomfort, diarrhoea, and tooth discolouration and dental hypoplasia in children.
  • Rarely: dysphagia, oesophagitis, and oesophageal irritation, For more information, see the CKS topic on Diarrhoea - antibiotic associated. 
• Hepatic disorders – hepatitis, jaundice, and hepatic failure (rare).
• Renal disorders — blood urea increased.
• Skin — photosensitivity, rash, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS), and fixed eruption.
• Other rare adverse effects include:
  • Anaphylaxis.
  • Arthralgia, myalgia.
  • Flushing.
  • Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension.
  • Tinnitus.
  • Porphyria.

[EMC, 2021; BNF, 2025]

What drug interactions are important with doxycycline?

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron, zinc, or bismuth — these may reduce the absorption of doxycycline if taken concurrently. 
• Barbiturates, carbamazepine, phenytoin, primidone — these may reduce the exposure to doxycycline. Monitor and adjust the dose if necessary.
• Methotrexate — doxycycline increases the risk of methotrexate toxicity.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of doxycycline.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods. 
• Retinoids — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with retinoids (such as isotretinoin).
  • Avoid the concurrent use of tetracyclines and retinoids.
• Rifampicin — rifampicin decreases exposure to doxycycline. Monitor the effects and increase the doxycycline dose if necessary.
• Warfarin — the concurrent use of warfarin with doxycycline may increase the anticoagulant effect.
  • Monitor the person's international normalized ratio (INR) and adjust the warfarin dose accordingly.

[EMC, 2021; CoSRH, 2022b; BNF, 2025]

What contraindications and cautions are important with erythromycin?

• Do not prescribe erythromycin to people with:
  • Known hypersensitivity to erythromycin.
  • Porphyria.
  • A history of QT interval prolongation or ventricular cardiac arrhythmia.
  • Conditions that predispose to QT interval prolongation such as electrolyte disturbances and people taking drugs that prolong the QT interval.
• Prescribe erythromycin with caution in people with:
  • Renal impairment.
  • Impaired hepatic function (or people concomitantly receiving potentially hepatotoxic drugs) — erythromycin is principally excreted by the liver. 
  • Myasthenia gravis — erythromycin may aggravate the symptoms of people with myasthenia gravis.

[MHRA, 2020; EMC, 2023; BNF, 2025]

What are the adverse effects of erythromycin?

The adverse effects of erythromycin include:

• Gastrointestinal symptoms are the most common adverse effects of macrolides, for example, nausea, vomiting, abdominal discomfort, and diarrhoea. Other gastrointestinal effects that have been reported include pancreatitis and anorexia.
  • Consider pseudomembranous colitis if a person develops diarrhoea during or after treatment with erythromycin. For more information, see the CKS topic on Diarrhoea - antibiotic associated. 
• Anaphylaxis has been reported to occur with erythromycin. For more information, see the CKS topic on Angio-oedema and anaphylaxis.  
• Other adverse effects include:
  • Hepatobiliary disorders, for example, cholestatic or hepatocellular hepatitis, jaundice, hepatomegaly, and hepatic dysfunction.
  • Cardiac disorders, for example, QT interval prolongation, palpitations, and arrhythmias.
  • Skin disorders, for example, urticaria, rash, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
  • Reversible hearing loss and tinnitus.

[MHRA, 2020; EMC, 2023; BNF, 2025]

What drug interactions are important with erythromycin?

• Carbamazepine — erythromycin markedly increases the concentration of carbamazepine. Monitor carbamazepine levels and adjust the dose.
• Calcium channel blockers (CCBs) — hypotension, bradyarrhythmias, and lactic acidosis have been reported in people taking erythromycin and verapamil. Erythromycin is also predicted to increase exposure to other CCBs. 
• Contraceptives — additional contraceptive precautions are not required during or after a course of erythromycin.
  • However, advise women on the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods. 
• Drugs that prolong the QT interval (such as amiodarone, or sotalol) — erythromycin can prolong the QT interval, and concomitant use of erythromycin and drugs that prolong the QT interval should be avoided.
• Drugs that cause hypokalaemia (such as diuretics and prednisolone). Hypokalaemia is a risk factor for Torsade de Pointes arrhythmias.
• Edoxaban — erythromycin slightly increases exposure to edoxaban and the edoxaban dose may need to be adjusted. 
• Statins — erythromycin is an inhibitor of liver isoenzyme cytochrome P450 CYP3A4, which is particularly involved in the metabolism of simvastatin and atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased with higher plasma concentrations of statins.
  • For simvastatin — do not prescribe erythromycin to a person taking simvastatin. If treatment with erythromycin cannot be avoided, stop treatment with simvastatin during the course of the treatment.
  • For atorvastatin — avoid concurrent use with erythromycin. If concurrent use cannot be avoided, prescribe the lowest dose of atorvastatin, and advise the person to report any muscle pain, tenderness, or weakness, or dark-coloured urine.
  • Other statins — fluvastatin, pravastatin, and rosuvastatin are not metabolised by cytochrome P450 3A4, but until more information is available about other potential mechanisms of interaction, these drugs should be used with caution in combination with erythromycin and the person should be advised to report any muscle pain, tenderness, or weakness, or dark coloured urine (signs of myopathy).
• Theophylline — erythromycin increases serum concentrations of theophylline, and theophylline may also reduce the clearance of erythromycin. Monitor and adjust the theophylline dosage as necessary
• Rivaroxaban — erythromycin may increase levels of rivaroxaban, increasing the risk of bleeding. 
• Warfarin — the anticoagulant effect of warfarin may be increased by erythromycin. Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Hydroxychloroquine or chloroquine — co-administration with a macrolide can increase the risk of cardiovascular events and cardiovascular mortality. Use caution when considering co-prescription in people with risk factors for cardiac events.

[MHRA, 2020; CoSRH, 2022b; MHRA, 2022; EMC, 2023; SPS, 2024; BNF, 2025]