Previous changes

August 2024 — minor update. Adverse effects of co-amoxiclav updated in line with manufacturer's SPC.

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. Information on the use of fluoroquinolones was added to the ciprofloxacin prescribing section in line with a review published by the MHRA. Fixed eruption added as an adverse effect for doxycycline as per the manufacturer's SPC.

January 2024 — minor update. Update to drug interactions section for erythromycin to include information on interactions with Lomitapide and Corticosteroids, as per the manufacturer's Summary of Product Characteristics (SPC). Recommendations relating to COVID-19 infection have been removed from this topic. Information on the use of fluoroquinolones and reporting adverse reactions was added in line with the Drug Safety Update published by the MHRA.

November 2023 — minor update. Interactions section for flucloxacillin updated in line with updated manufacturer's summary of product characteristics.

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).

May 2023 — minor update. Added potential adverse effects of co-amoxiclav to include Kounis syndrome (an allergic reaction which can result in myocardial infarction), aseptic meningitis, linear IgA disease (renal deposition of IgA), and drug-induced enterocolitis syndrome (all of unknown frequency). These adverse effects were noted in an update to the manufacturer’s summary of product characteristics.

April 2022 — minor update. Drug interactions with azithromycin to include hydroxychloroquine and chloroquine added in line with the manufacturer's summary of product characteristics. 

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. Cautions for prescribing ciprofloxacin updated in line with revised manufacturer's SPC. 

July to August 2020 — reviewed. A literature search was conducted in July 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. 

April 2020 — minor update. The topic has been updated to take into account the latest BTS guideline on macrolide use.

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

December 2018 — minor update. Topic has been updated in line with newly published guidelines; NICE guideline Bronchiectasis (non-cystic fibrosis), acute exacerbation: antimicrobial prescribing December 2018 and Updated BTS Adult Bronchiectasis Guideline 2018: a multidisciplinary approach to comprehensive care December 2018. Changes have been made to diagnosis, management and antibiotic choice sections.

December 2016 — minor update. The dose of clarithromycin for people with severe renal impairment has been clarified, in line with the manufacturer's Summary of Product Characteristics.

January to February 2016 — reviewed. A literature search was conducted in January 2016 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomised controlled trials (RCTs) published since the last revision of the topic. No major changes to clinical recommendations have been made.

July 2015 — minor update. The prescribing information section for clarithromycin and erythromycin has been re-written for clarity.

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

April 2011 — minor update. Change to recommendation regarding need for additional contraception during or after a course of antibiotics - additional contraception is no longer required when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less. Issued in June 2011.

April to August 2010 — This is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 March 2025.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2025.

Economic appraisals

No new economic appraisals relevant to England since 1 March 2025.

Systematic reviews and meta-analyses

No new systematic reviews and meta-analyses since 1 March 2025.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 March 2025.

New policies

No new national policies or guidelines since 1 March 2025.

New safety alerts

No new safety alerts since 1 March 2025.

Changes in product availability

• New Product Brinsupri (brensocatib) 25 mg film-coated tablets. This competitive and reversible inhibitor of dipeptidyl peptidase 1 (DPP1) is licensed for the treatment of non-cystic fibrosis bronchiectasis in patients 12 years of age and older with two or more exacerbations in the prior 12 months. See more here.

Basis for recommendation

These recommendations are based on the British Thoracic Society (BTS) Guideline for non-CF bronchiectasis [Pasteur, 2010], the BTS Guideline for bronchiectasis in adults [Hill, 2019], the BMJ Best Practice guideline Bronchiectasis [BMJ Best Practice, 2025], and expert opinion in narrative reviews Paediatric and adult bronchiectasis: diagnosis, disease burden and prognosis [Quint, 2019], Recurrent lower respiratory tract infections in children [de Benedictis, 2018], and Bronchiectasis in children: diagnosis and treatment [Chang, 2018].

Basis for recommendation

Basis for recommendation

These recommendations are based on the British Thoracic Society (BTS) Guideline on non-CF bronchiectasis [Pasteur, 2010].

How should I manage a person with suspected bronchiectasis?

• If bronchiectasis is suspected:
  • Take a thorough history and examine the person. 
  • Arrange the following investigations:
    • Sputum culture — to identify colonizing pathogens.
    • Chest X-ray — to exclude other pathology; to help confirm the diagnosis where the disease is severe; and to obtain a baseline against which any subsequent clinical deterioration can be compared.
    • Spirometry — to assess the severity of airflow obstruction and identify any co-existent diagnoses (such as chronic obstructive pulmonary disease).
    • Oxygen saturation levels.
    • Full blood count including differential white cell count. 
    • Other investigations — guided by clinical findings to confirm or rule out underlying causes for bronchiectasis.
  • Assess for the presence of anxiety or depression, particularly in people who have severe breathlessness. For more information, see the CKS topics on Generalized anxiety disorder and Depression. 
  • Document the person's smoking history — if they currently smoke, offer support to stop. For more information, see the CKS topic on Smoking cessation.
  • Measure the person's weight and calculate and document the person's body mass index (weight in kg/height in m²).
• Refer all people with suspected bronchiectasis to a respiratory consultant for investigations to confirm the diagnosis and determine the underlying cause, and for appropriate treatment.

How should I follow up a person who has been diagnosed with bronchiectasis?

• People at high risk of future exacerbations and all children should be reviewed in secondary care.
• People at lower risk can be reviewed in primary care.
  
  • A baseline severity score may have been calculated in secondary care using a tool such as the Bronchiectasis Severity Index. 
• Review people with bronchiectasis at least annually, including: 
  • An assessment of symptoms and how they affect their daily life — offer pulmonary rehabilitation to people with breathlessness that affects their daily life.
  • Measurement of BMI — if the person's BMI is less than 20, seek specialist nutritional advice.
  • The exacerbation frequency — refer people with three or more infective exacerbations a year, and people with fewer exacerbations that are causing significant morbidity to a respiratory specialist. Long-term prophylactic antibiotic treatment may be considered.
  • Taking a sputum sample for bacterial culture — specialist follow up is required for people with chronic colonization with Pseudomonas aeruginosa, opportunistic Mycobacteria, or meticillin-resistant Staphylococcus aureus (MRSA). 
  • The Medical Research Council dyspnoea scale. 
  • Spirometry.
  • Oxygen saturation levels.
  • Compliance with sputum clearance exercises.
• Do not repeat chest X-rays unless clinically indicated. 
• Offer people who smoke advice and support to help them stop — for further information, see the CKS topic on Smoking cessation. 
• Offer immunization against Streptococcus pneumoniae COVID-19, and seasonal influenza. For more information, see the CKS topics on Immunizations - pneumococcal and Immunizations - seasonal influenza.
• Ensure all people with bronchiectasis:
  • Understand the condition, know how to recognize exacerbations and what to do if they experience them — a patient information leaflet on bronchiectasis is available from the British Lung Foundation.
  • Have been taught an airway clearance technique by a physiotherapist. 
    • Refer the person to a physiotherapist if they have not been taught an airway clearance technique.

How should I manage a person with an infective exacerbation of bronchiectasis?

• Arrange hospital admission for people who:
  • Have any significant comorbidities and/or psychosocial factors that indicate that they cannot be managed safely in the community.
  • Demonstrably need intravenous antibiotics, for example, have symptoms or signs suggesting a more serious illness or condition (such as cardiorespiratory failure or sepsis), including:
    • Cyanosis.
    • Confusion.
    • Marked breathlessness, rapid respiration, or laboured breathing.
    • Peripheral oedema.
    • A temperature of 38°C or higher.
• Seek specialist advice for people with an acute exacerbation of bronchiectasis if they:
  • Have symptoms that are not improving with repeated courses of oral antibiotics.
  • Have bacteria in their sputum that are resistant to the available oral antibiotics.
  • Are unable to tolerate oral therapy.
• For people not requiring hospital admission:
  • Reassess if symptoms worsen rapidly or significantly at any time, and take into account: 
    • Other possible diagnoses, such as pneumonia.
    • Any symptoms or signs suggesting a more serious illness or condition, such as cardiorespiratory failure or sepsis.
    • Previous antibiotic use, which may have led to resistant bacteria. 
  • Send sputum for culture and sensitivity testing before starting antibiotics, but do not delay treatment waiting for results. 
  • Prescribe an antibiotic for 7–14 days.
    • If the person is taking long-term antibiotics, advise them to stop, and instead prescribe an antibiotic from a different class. 
  • Ensure that a suitable airway clearance technique (which has been taught by a respiratory physiotherapist) is used during the exacerbation.
    • Arrange an urgent appointment with a physiotherapist if the person has not already been taught this or if they cannot manage this alone.
  • Review the response to empirical treatment when sputum culture and sensitivity results are available.
    • If there is no clinical improvement, modify antibiotic treatment guided by the culture and sensitivity results.
  • Do not routinely offer inhaled corticosteroids to people with bronchiectasis without other indications (for example, asthma or COPD).
  • Offer a trial of long-acting bronchodilator therapy in people with symptoms of significant breathlessness.
• Consider prescribing a course of antibiotics for people to keep at home to facilitate prompt treatment of future exacerbations (if appropriate and depending on clinical judgement). 
• If the person was previously taking long-term antibiotics, after the exacerbation has been treated, prescribe a prophylactic dose of a new antibiotic based on the results of sputum culture and sensitivity testing, and contact their respiratory physician to notify them of the change in antibiotics.

What antibiotic treatment is suitable for an acute exacerbation?

• Previous microbiology cultures, where available, should guide antibiotic choice. For more information, see Table 1.
• When previous microbiology cultures are not available: 
  • Prescribe according to local protocols where available, or
  • For adults, prescribe amoxicillin 500 mg three times a day for 7–14 days. 
    • Alternatives for adults with a true allergy to penicillin are clarithromycin 500 mg twice a day for 7–14 days, or doxycycline 200 mg on the first day and then 100 mg once a day for a total of 7–14 days.
    • Alternative choice oral antibiotics (if the person is at higher risk of treatment failure) are co-amoxiclav 500/125 mg three times a day for 7–14 days or levofloxacin 500 mg once or twice daily for 7–14 days.
• See Table 2 for recommendations for empirical treatment of acute exacerbations in children in whom susceptibility data is unavailable.

How should I help prevent acute exacerbations of bronchiectasis?

• Do not routinely offer antibiotic prophylaxis to prevent acute exacerbations of bronchiectasis. 
  • Seek specialist advice about options for preventing exacerbations in people with repeated acute exacerbations, which may include a trial of antibiotic prophylaxis. 
• People with bronchiectasis who have three or more exacerbations per year may be offered antibiotic prophylaxis (oral or inhaled) by a respiratory specialist to reduce further exacerbations.
  • Only start a trial of antibiotic prophylaxis in people with repeated acute exacerbations on the advice of a specialist. 
• Treatment options for adults include: 
  • Azithromycin 500 mg three times a week, or
  • Azithromycin 250 mg daily, or
  • Erythromycin ethyl succinate 400 mg twice a day.
• Use a starting dose of azithromycin 250 mg three times a week to minimize the risk of adverse effects, then titrate according to clinical response. 
• Offer a minimum of 6 months treatment, but up to 1 year may be required. 
• In people with concurrent Pseudomonas aeruginosa infection, first-line therapy is usually inhaled colistin. 
• To ensure shared decision-making, discuss the following with the person: 
  • The potential benefits of antibiotics for reducing exacerbations.
  • The risks of antimicrobial resistance with long-term antibiotics, which may mean fewer effective antibiotics for future exacerbations.
  • The possible adverse effects of long-term antibiotics, such as diarrhoea, hearing loss, or tinnitus with macrolides.
  • The possible interactions of macrolide antibiotics with other medicines.
  • The need to regularly review prophylaxis.
• Before commencing prophylactic oral macrolides:
  • Optimize therapies in accordance with the British Thoracic Society bronchiectasis guidelines before considering long-term macrolide therapy (for example, airway clearance techniques and attendance at pulmonary rehabilitation courses).
  • Perform ECG to assess QTc interval. 
  • Perform baseline liver function tests. 
  • Counsel people with bronchiectasis about potential adverse effects, including gastrointestinal upset, hearing and balance disturbance, cardiac effects, and microbiological resistance.
  • Arrange microbiological assessment of sputum before starting therapy, including investigation for non-tuberculous mycobacteria (NTM). Avoid macrolide monotherapy if NTM infection is identified. When evaluating for NTM infection, macrolides use should be avoided for 2 weeks before microbiological testing.
  • Determine the baseline exacerbation rate. 
• After starting oral macrolides:
  • Check liver function tests after 1 month and every 6 months thereafter.
  • Perform an ECG 1 month after starting treatment to check for new QTc prolongation. If present, stop macrolide treatment. 
• If the desired clinical outcome is achieved, the possibility of breaks in therapy can be considered to reduce the treatment burden.

How should I follow up a person after an infective exacerbation of bronchiectasis?

• Provide a self-management plan that provides personalized information and advice on: 
  • Lifestyle, including diet, exercise, and smoking cessation (if necessary).
  • Respiratory physiotherapy details.
  • Recognizing early signs and symptoms of an infective exacerbation, when to seek help and with what urgency.
  • When to take any rescue medication that has been prescribed by a specialist (if applicable).
  • Contact details for the respiratory team.
• Consider the need for prophylactic antibiotic therapy and any other treatments (after taking specialist advice).
• Provide advice about sources of information and support for people with bronchiectasis, such as the British Lung Foundation, which has a patient information leaflet.

What contraindications and cautions are associated with azithromycin?

• Prescribe azithromycin with caution in people:
  • Who may be predisposed to prolongation of the QT interval. For example, people with:
    • Congenital or documented acquired QT prolongation.
    • Currently receiving treatment with other active substances known to prolong the QT interval, such as antiarrhythmics of classes IA and III.
    • With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia.
    • With clinically relevant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency, including torsades de pointes.
  • With severe hepatic impairment.
  • With severe renal impairment.
  • With myasthenia gravis — macrolides may aggravate symptoms.

[BNF, 2025; EMC, 2025a]

What are the adverse effects of azithromycin?

• Gastrointestinal — diarrhoea (very common), vomiting, abdominal pain, and nausea (common).
  • Rarely: pancreatitis and pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Nervous system — headache (common), dizziness, somnolence, dysgeusia, and paraesthesia (uncommon).
  • Rarely: convulsions, hyperactivity, syncope, and myasthenia gravis.
• Psychiatric — nervousness and insomnia (uncommon).
  • Rarely or very rarely: agitation, aggression, anxiety, delirium, and hallucination.
• Skin and subcutaneous tissue — rash, pruritus, urticaria, and dermatitis (uncommon).
  • Rarely, or very rarely: drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme.
• Other adverse effects reported rarely, or very rarely, include: 
  • Anaphylaxis.
  • Arrhythmias.
  • Arthralgia.
  • Hearing impairment.
  • Hepatitis and cholestatic jaundice.
  • Oedema.
  • Pancreatitis. 
  • QT interval prolongation.

[BNF, 2025; EMC, 2025a]

What drug interactions are important with azithromycin?

• Antacids — plasma concentrations of azithromycin may be reduced. Simultaneous administration should be avoided — azithromycin should be taken at least 2 hours before, or 1 hour after antacids.
• Chloroquine and hydroxychloroquine — the manufacturer advises that clinicians carefully consider the balance of benefits and risks of co-administration due to increased risk of cardiovascular events and mortality
• Ciclosporin — azithromycin may increase cyclosporin levels. 
• Cisapride — macrolides increase levels of cisapride, increasing the risk of arrhythmias (Torsades de Pointes). Concurrent use is contraindicated.
• Colchicine — azithromycin slightly increases the levels of colchicine. Stop or reduce the dose of colchicine. Avoid concomitant use in renal or hepatic impairment.
• Digoxin — cases of increased digoxin levels have been reported. Monitor for signs of digoxin adverse effects (such as bradycardia). Monitor and reduce the digoxin dose if required.
• Edoxaban — levels may be increased by azithromycin. Dose adjustment of edoxaban may be required.
• Rifabutin — azithromycin increases the risk of neutropenia when given with rifabutin. Monitor closely.
• Statins — there is a possible increased risk of myopathy.
  • Advise the person to report any muscle pain, tenderness, or weakness.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial is stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.
• Warfarin — concurrent use may increase the international normalized ratio (INR). Consider increasing INR monitoring as this interaction appears to develop over the first 7 days.
• Drugs that prolong the QT interval (such as amiodarone, sotalol, and hydroxyzine) — all macrolides can prolong the QT interval, and concomitant use of drugs that prolong the QT interval is not recommended. If concurrent use is unavoidable, consider ECG (electrocardiogram) monitoring.
  • Concurrent use with domperidone, hydroxyzine, or mizolastine is contraindicated.
• Drugs that cause hypokalaemia (such as diuretics, corticosteroids, and short-acting beta-2 agonists) — hypokalaemia is a risk factor for QT prolongation.

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

What contraindications and cautions are associated with amoxicillin?

• Do not prescribe amoxicillin to people with:
  • A true penicillin hypersensitivity — allergic reactions to penicillins occur in 1–10% of exposed individuals. Anaphylactic reactions occur in fewer than 0.05% of treated people.
    • Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
  • Hypersensitivity to cephalosporins.
• Prescribe amoxicillin with caution in people with:
  • Hepatic impairment.
  • Renal impairment — reduce the dose of amoxicillin in severe renal impairment.
  • Cytomegalovirus infection — increased risk of erythematous rashes.
  • 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?

• Gastrointestinal — nausea, diarrhoea, and vomiting (common). 
  • Very rarely: antibiotic-associated colitis.
• Skin — skin rash (common), urticaria, and pruritus (uncommon).
  • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, and acute generalized exanthematous pustulosis.
• 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?

• Allopurinol — increased risk of rash when allopurinol is given with amoxicillin. 
• Methotrexate — amoxicillin may reduce methotrexate clearance, causing an increased risk of toxicity.
  • For people on high-dose methotrexate, routine monitoring will identify any decreases in elimination. For people on low-dose methotrexate, consult local or national guidelines/protocols for recommendations on monitoring and management. 
• Oral anticoagulants (warfarin, phenindione) — 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.
• Tetracyclines — the antibacterial effects of amoxicillin may be antagonized. Avoid concurrent use.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial be stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.

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

What contraindications and cautions are associated with ciprofloxacin?

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA that looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.

• Do not prescribe ciprofloxacin to:
  • Pregnant women — quinolones have been shown to cause arthropathy in animal studies.
  • Breastfeeding women.
  • People with a history of tendon disorders related to quinolone use.
  • People taking tizanidine concomitantly.
  • People who have previously had serious adverse reactions with a quinolone antibiotic (for example, nalidixic acid) or a fluoroquinolone antibiotic.
• Prescribe ciprofloxacin with caution in people with:
  • An age greater than 60 years, renal impairment, or solid-organ transplants, as these people are at a higher risk of tendon injury.
  • Epilepsy or conditions that predispose to seizures, and in people taking other medication that may predispose to seizures, as quinolones can lower the seizure threshold.
    • Quinolones may induce convulsions in patients with or without a history of convulsions, and taking nonsteroidal anti-inflammatory drugs at the same time may also induce them.
  • Diabetes — may affect blood glucose. Blood glucose should be monitored closely.
  • Glucose-6-phosphate dehydrogenase deficiency — haemolytic reactions have been reported.
  • A history of tendonitis — quinolones can very rarely cause tendon damage, and the risk of tendon rupture is increased by co-administration of a corticosteroid.
    • A single dose for the treatment of gonorrhoea is unlikely to be significant.
  • Impaired liver function — liver damage can occur. 
  • Conditions that predispose to QT interval prolongation:
    • Congenital long QT syndrome.
    • Concomitant use of drugs that are known to prolong the QT interval (for example Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
    • Uncorrected electrolyte imbalance (for example hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, or bradycardia).
    • Electrolyte disturbances.
  • History of a psychotic disorder — there have been reports of suicidal thoughts or self-endangering behaviour after use quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
  • Positive family history of aneurysm disease or congenital heart valve disease.
  • Pre-existing aortic aneurysm and/or dissection or heart valve disease, or in presence of other risk factors or conditions predisposing for:
    • Both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis) or additionally
    • Aortic aneurysm and dissection (such as vascular disorders including Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome) or additionally
    • Heart valve regurgitation/incompetence (such as infective endocarditis).

[MHRA, 2023; EMC, 2024b; BNF, 2025]

What are the adverse effects of ciprofloxacin?

• Gastrointestinal — diarrhoea, nausea (common), vomiting, dyspepsia, flatulence, and gastrointestinal and abdominal pains (uncommon).
  • Rarely: pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated).
• Musculoskeletal — pain and arthralgia (uncommon).
  • Rarely: myalgia and arthritis.
  • Very rarely: muscle weakness, tendonitis, and tendon damage — this may occur within 48 hours of starting treatment, or months after stopping. The risk of tendon rupture is increased by co-administration of corticosteroids and in people aged over 60 years.
• Nervous system — headache, dizziness, sleep disorders, and taste disorders (uncommon).
  • Rarely: tremor, vertigo, and lowering of the seizure threshold — this may trigger seizures. 
• Psychiatric — hyperactivity and agitation (uncommon).
  • Rarely: confusion, anxiety, depression, and hallucinations.
• Skin — rash, pruritus, and urticaria.
  • Rarely: Stevens–Johnson syndrome, erythema multiforme, toxic epidermal necrolysis anaphylaxis, drug rash with eosinophilia, systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).
• Other adverse effects include:
  • Anaphylaxis.
  • Hepatic impairment and hepatitis.
  • Renal impairment.
  • Tachycardia.
  • Tinnitus.
  • Visual disturbances.
• Fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses.
  • People should be advised to stop treatment at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice. Remain alert to the risk of suicidal thoughts and behaviours with use of fluoroquinolone antibiotics. 

Report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website: https://yellowcard.mhra.gov.uk/.

[MHRA, 2023; EMC, 2024b; BNF, 2025]

What drug interactions are important for ciprofloxacin?

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these reduce the absorption of ciprofloxacin if taken concurrently.
  • Ciprofloxacin should be taken at least 2 hours before these preparations.
• Ciclosporin — increased concentrations and nephrotoxicity might occur in a small number of patients.
• Corticosteroids — Avoid co-administration of a corticosteroid with a fluoroquinolone since this could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.
• Ergot alkaloids (such as ergotamine and dihydroergotamine) — concurrent use with ciprofloxacin may result in acute ergot toxicity. Concurrent use is contraindicated.
• Methotrexate — plasma levels of methotrexate may be increased. The manufacturer recommends that concomitant use be avoided.
  • If concurrent use is necessary, monitor methotrexate levels.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — possible increased risk of seizures when quinolones are given with NSAIDs. Avoid concurrent use in people with epilepsy or people predisposed to seizures, or monitor them very closely.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of ciprofloxacin.
  • 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.
• Phenytoin — concurrent administration of ciprofloxacin can cause an increase or decrease in serum phenytoin levels. Monitor phenytoin levels.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate, so they should not be given together.
• Theophylline, aminophylline — ciprofloxacin increases the plasma concentration of theophylline and may do the same to aminophylline, leading to a possible increased risk of convulsions. Monitor closely.
• Tizanidine — ciprofloxacin markedly increases the plasma concentration of tizanidine (increased risk of toxicity). Avoid concomitant use.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial be stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.
• Warfarin — rarely, ciprofloxacin may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalized ratio (INR) within 3–5 days of starting ciprofloxacin, frequently during, and shortly after administration.
• Zolmitriptan — quinolones increase the plasma concentration of zolmitriptan by inhibiting its metabolism. Manufacturer recommends a maximum dose of 5 mg in 24 hours in people taking a quinolone.
• Drugs that prolong the QT interval (such as Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) — very rare cases of QT interval prolongation have been reported in people taking quinolones and they should therefore be prescribed with caution alongside drugs known to prolong the QT interval.

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

What contraindications and cautions are associated 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, 2024c; BNF, 2025]

What are the adverse effects of clarithromycin?

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

[EMC, 2024c; BNF, 2025]

What drug interactions are important with clarithromycin?

• Calcium channel blockers (CCBs) — there is an increased risk of hypotension if CCBs (such as verapamil, amlodipine, and diltiazem) are taken concurrently with clarithromycin, as they are metabolised by CYP3A4. This may also lead to increased levels of clarithromycin.
• Carbamazepine — clarithromycin significantly increases carbamazepine levels.
  • Reduce the dose of carbamazepine by 30–50% during treatment with clarithromycin and monitor within 3–5 days. 
  • Advise the person to report symptoms of carbamazepine toxicity (such as dizziness, diplopia, ataxia, or confusion).
• Ciclosporin — erythromycin can affect the clearance of ciclosporin. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
• Cisapride — levels may be increased. Avoid concurrent use. 
• Colchicine — clarithromycin moderately increases the levels of colchicine. The manufacturer advises that concurrent use is contraindicated.
• CYP3A enzyme inducers (rifampicin, carbamazepine, 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 significantly increases digoxin levels. Monitor for signs of adverse effects, measure digoxin levels, and reduce the digoxin dose if required.
• Edoxaban — manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
• Ergot alkaloids — concomitant administration is contraindicated, due to the risk of acute 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 concomitant 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.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial is stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.
• 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, sotalol, domperidone) — all macrolides can prolong the QT interval, and concomitant use of drugs that prolong the QT interval is contraindicated.
• Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta-2 agonists). Monitor potassium levels closely.

[CoSRH, 2022; MHRA, 2022; EMC, 2024c; SPS, 2024; BNF, 2025] 

What contraindications and cautions are associated with co-amoxiclav?

• Do not prescribe co-amoxiclav to people with:
  • A true penicillin allergy — allergic reactions to penicillins occur in 1–10% of exposed individuals; anaphylactic reactions occur in fewer than 0.05% of treated patients.
    • Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
  • A history of co-amoxiclav- or penicillin-associated jaundice or hepatic dysfunction.
• Prescribe co-amoxiclav with caution to people with:
  • A hypersensitivity to cephalosporins — there is some evidence of partial cross-allergenicity. 
  • Hepatic impairment – monitor closely.
  • Chronic kidney disease (CKD) — reduce the dose if the estimated glomerular filtration rate (eGFR) is 30 mL/minute/1.73 m² or less.
  • Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection, glandular fever — increased risk of erythematous rashes.

[BNF, 2025; EMC, 2025b]

What are the adverse effects of co-amoxiclav?

• Gastrointestinal — diarrhoea (very common), nausea and vomiting (common), and drug-induced enterocolitis syndrome (unknown frequency).
  • Very rarely: antibiotic-associated colitis.
• Nervous system — headache, dizziness (uncommon), and aseptic meningitis (unknown frequency).
• Skin — skin rash, urticaria, pruritus (uncommon), and drug reaction with eosinophilia and systemic symptoms (DRESS) (unknown frequency).
  • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, and acute generalized exanthematous pustulosis.
• Other rare, or very rare adverse effects include:
  • Hepatitis and cholestatic jaundice.
  • Hyperactivity amd convulsions.
  • Hypersensitivity reactions (serious and occasionally fatal).  
  • Interstitial nephritis.
  • Linear IgA disease (renal deposition of IgA).  
  • Leucopenia, thrombocytopenia, haemolytic anaemia.
  • Kounis syndrome (an allergic reaction which can cause myocardial infarction). 
• Symmetrical Drug-related Intertriginous and Flexural Exanthema (SDRIFE) are adverse effects of unknown frequency.

 [EMC, 2024d; BNF, 2025; EMC, 2025b]

What drug interactions are important for co-amoxiclav?

• Allopurinol — concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes.
• Methotrexate — co-amoxiclav may reduce methotrexate clearance, causing an increased risk of toxicity.
  • For people on high-dose methotrexate, routine monitoring will identify any decreases in elimination. For people on low-dose methotrexate, consult local or national guidelines/protocols for recommendations on monitoring and management. 
• Mycophenolate — reduction in the level of active metabolite may occur when given with co-amoxiclav. Monitor mycophenolate efficacy.
• Oral anticoagulants (warfarin, phenindione) — prolongation of prothrombin time has been reported in people taking penicillins and warfarin concurrently.
  • Monitor the prothrombin time or international normalized ratio (INR) within 3 days of starting or stopping a penicillin. Adjustment of the anticoagulant dose may be necessary.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of co-amoxiclav.
  • 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 — concomitant administration may result in increased levels of amoxicillin, but not clavulanic acid.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial be stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.

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

What contraindications and cautions are associated 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.

What are the adverse effects of doxycycline?

• Blood disorders — haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia (frequency unknown).
• Gastrointestinal — nausea, vomiting (common), dyspepsia (uncommon), abdominal discomfort, diarrhoea, and tooth discolouration and enamel hypoplasia in children (frequency unknown).
  • Rarely: dysphagia, oesophagitis, oesophageal irritation, and pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Hepatic disorders — hepatotoxicity, hepatitis, jaundice, and hepatic failure (frequency unknown).
• Renal disorders — blood urea increased.
• Skin — photosensitivity and rash (common).
  • Rarely: 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 and myalgia.
  • Bulging fontanelles in infants.
  • Flushing.
  • Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension, a rare but serious adverse effect.
  • Tinnitus.

[EMC, 2024e; BNF, 2025]

What drug interactions are important with doxycycline?

• Antacids (containing aluminium, bismuth, calcium, or magnesium) and other medications containing iron or zinc — these reduce the absorption of tetracyclines if taken concurrently.
  • Avoid taking antacids and other medications containing iron or zinc, 2 hours before or after taking tetracyclines.
• CYP3A enzyme inducers (phenobarbital, carbamazepine, or phenytoin) — these may reduce the serum half-life of doxycycline. Monitor and adjust the dose if necessary.
• Insulin — the blood-glucose-lowering effect may be increased if taken with doxycycline. Monitor blood-glucose levels.
• Lithium — levels may be increased by doxycycline. Consider increasing the frequency of lithium monitoring.
• Methotrexate — levels may be increased by doxycycline.
• 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 — doxycycline levels are markedly reduced, which may lead to treatment failure. Monitor the effects and increase doxycycline dose if necessary.
• Typhoid vaccine — antibacterials might reduce the immune response. The World Health Organization (WHO) recommends that the antibacterial be stopped from 3 days before to 3 days after receiving live oral typhoid vaccine.
• Warfarin — the concurrent use of warfarin with tetracyclines may increase the anticoagulant effect. However, there is little evidence to suggest clinical relevance.
  • Consider monitoring the person's international normalized ratio (INR) regularly and within 3 days of starting the tetracycline. Adjust the warfarin dose accordingly.

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

What contraindications and cautions are associated with erythromycin?

• Do not prescribe erythromycin to people with:
  • Electrolyte disturbances.
  • 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 to people with:
  • Coronary artery disease, severe cardiac insufficiency, conductive disturbances, or clinically relevant bradycardia.
  • Hepatic impairment (or people concomitantly receiving potentially hepatotoxic drugs) — erythromycin is mainly excreted by the liver.
  • Moderate to severe renal impairment:
    • Give a maximum dose for erythromycin of 1.5 g a day in severe renal impairment due to the risk of ototoxicity.
  • Myasthenia gravis — macrolides may aggravate weakness symptoms.

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

What are the adverse effects of erythromycin?

• 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, 2023a; 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, 2022; MHRA, 2022; EMC, 2023a; SPS, 2024; BNF, 2025]

What contraindications and cautions are associated with flucloxacillin?

• Do not prescribe flucloxacillin in people with:
  • A true penicillin allergy — allergic reactions to penicillins occur in 1–10% of exposed individuals; anaphylactic reactions occur in fewer than 0.05% of treated patients.
    • Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
  • History of flucloxacillin-associated jaundice or hepatic dysfunction.
• Prescribe flucloxacillin with caution in people with:
  • Hepatic dysfunction (not flucloxacillin-related), especially if they are 50 years of age or older, or have a serious underlying medical condition.
  • Severe renal impairment — reduce the dose if the person's estimated glomerular filtration rate (eGFR) is less than 10 mL/minute/1.73 m².
  • A history of allergy — these people are more likely to develop a sensitivity reaction.

[EMC, 2023b; BNF, 2025]

What are the adverse effects of flucloxacillin?

• Gastrointestinal — nausea and vomiting (common).
  • Very rarely: antibiotic-associated colitis.
• Nervous system — headache and dizziness (uncommon).
• Skin and subcutaneous tissue — skin rash, urticaria, and purpura (uncommon).
  • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, and generalized exanthematous pustulosis.
• Other rare or very rare adverse effects include:
  • Anaphylaxis.
  • Arthralgia and myalgia (very rare).
  • Hepatitis, cholestatic jaundice — this may occur up to several weeks after treatment with flucloxacillin has been stopped. Risk factors include treatment for more than 2 weeks and increasing age.
  • Interstitial nephritis.
  • Neutropenia, thrombocytopenia, and haemolytic anaemia.

[EMC, 2023b; BNF, 2025]

What drug interactions are important for flucloxacillin?

• Methotrexate — methotrexate clearance may be reduced, causing an increased risk of toxicity; however, serious interactions are uncommon. 
  • Standard routine monitoring will identify any decreases in elimination in people on high-dose regimens. For people on low-dose regimens, consult local or national guidelines/protocols for monitoring and management.
• Coumarin and indanedione anticoagulants (warfarin, phenindione) — consider increased monitoring of international normalized ratio (INR) and adjust the dose accordingly.
• Posaconazole, voriconazole — concentrations of antifungal is greatly decreased. If concurrent use is unavoidable, monitor for decreased efficacy and consider increasing the dose of the azole (although this may not resolve the issue). 
• Probenecid — concomitant administration may result in increased levels of flucloxacillin.
• Live cholera vaccine — the efficacy of the vaccine may be reduced. Avoid flucloxacillin from 14 days before to 10 days after receiving live cholera vaccine.
• Live typhoid vaccine — the immune response to the vaccine may be reduced. Avoid flucloxacillin from 3 days before to 3 days after receiving live typhoid vaccine.

[EMC, 2023b; BNF, 2025; Preston, 2025]

What contraindications and cautions are important with beta-2 agonists?

• Prescribe beta-2 agonists with caution to people with:
  • Arrhythmias.
  • Cardiovascular disease.
  • Hypertension.
  • Hyperthyroidism — beta-2 agonists may stimulate thyroid activity.
  • Diabetes mellitus — additional blood glucose measurements are recommended when treatment with a beta-2 agonist is commenced.
  • Susceptibility to QT-interval prolongation.
  • Hypokalaemia — plasma potassium concentration may be reduced by beta-2 agonists (particularly high doses).
  • Convulsive disorders.

  [BNF, 2025]

What are the adverse effects of beta-2 agonists?

• Adverse effects of short-acting beta-2 agonists are usually dose-related and include:
  • Fine tremor — occurs particularly in the hands and is usually worse in the first few days of treatment.
  • Anxiety.
  • Arrhythmia, palpitations, tachycardia, myocardial ischaemia.
  • Headache, dizziness.
  • Hypokalaemia.
    • Monitor potassium levels in people on high doses of beta-2 agonists (for example people receiving nebulized beta-2 agonists).
  • Paradoxical bronchospasm (rare).

[BNF, 2025]

What drug interactions are important with beta-2 agonists?

• Corticosteroids, diuretics, and theophylline — beta-2 agonists can cause hypokalaemia (particularly at high doses), and this can be increased by other potassium-depleting drugs, such as corticosteroids, loop diuretics, and theophylline.
  • Monitor potassium levels.
• Digoxin — beta-2 agonists possibly reduce digoxin levels.
  • Monitor digoxin levels.

[BNF, 2025; Preston, 2025]