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. Fixed eruption added as an adverse effect of doxycycline as per the manufacturer's SPC. 

January 2024 — reviewed. A literature search was conducted in September 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. No major changes to clinical recommendations have been made. However, the classification of chronic sinusitis has been updated in line with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020).

July 2023 — minor update. The section on clarithromycin drug interactions has been updated to include a possible drug interaction with domperidone (risk of QT prolongation and cardiac arrhythmias). This drug interaction was included in the updated manufacturer's Summary of Product Characteristics (SPC) for clarithromycin.

May 2023 — minor update. The section on co-amoxiclav adverse effects has been updated 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 included in the updated manufacturer’s SPC.

March 2021 — minor update. A link to a patient information leaflet has been removed from the topic.

May to June 2018 — reviewed. A literature search was conducted in May 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. Sections on prevalence, complications, and antibiotic choices for acute sinusitis have been added, and a prescribing information section is now available. There have been minor changes to the sections on diagnosis of acute and chronic sinusitis. The sections on acute and chronic sinusitis management have undergone minor restructuring and have been updated with more detailed information on referrals and links to sources of patient information.

October 2017 — reviewed. The topic has been updated due to the publication of the National Institute for Health and Care Excellence (NICE) guideline Sinusitis (acute): antimicrobial prescribing. The recommendations on prescribing antibiotics, intranasal corticosteroids, and self-management have been revised. 

October 2013 — reviewed. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. The diagnostic criteria for acute and chronic sinusitis in children have been updated in line with recommendations in the European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Recommendations have been added on when to suspect acute bacterial sinusitis, and recommendations on when to prescribe antibiotics have changed accordingly. Recommendations have been added on when to consider prescribing intranasal corticosteroids for the symptomatic treatment of acute sinusitis.

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.

September 2012 — minor update. Ephedrine 0.5% nasal drops are no longer licensed for use in children aged younger than 12 years. Prescriptions have been updated.

July 2011 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has introduced more exact paracetamol dosing for children. Prescriptions have been updated to reflect the revised dosing. 

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

September 2010 — minor update. The likely causative pathogens have been added to the section on causes, and the rationale for using high-dose amoxicillin (if an antibiotic is indicated) has been added to the topic.

August 2009 — minor update. Xylometazoline 0.05% nasal drops (Otrivine Child Nasal Drops^®) are no longer licensed for use in children aged 2–5 years. They can be prescribed for children aged 6 years and over. 

October 2008 to March 2009 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. Recommendations for prescribing antibiotics for acute sinusitis are now based on the NICE guideline Respiratory tract infections — antibiotic prescribing.

January 2008 — updated. Macrolide options have changed to erythromycin or clarithromycin in line with advice from the Health Protection Agency (HPA). 

October 2006 — minor update. The British National Formulary (BNF) has recommended new ibuprofen doses for children. Prescriptions have been updated to reflect the revised dosing.

July to September 2005 — reviewed. Validated in December 2005 and issued in February 2006.

March 2004 — updated with additional information for nurse prescribers. 

March 2002 — rewritten and renamed Sinusitis. Validated in June 2002 and issued in July 2002.

August 1998 — written, replacing guidance on Acute sinusitis and Chronic sinusitis. Validated in November 1998 and issued in December 1998.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2023.

Systematic reviews and meta-analyses

• Conway, S.J., Mueller, G.D., and Shaikh, N. (2024) Antibiotics for Acute Sinusitis in Children: A Meta-Analysis. Pediatrics. https://publications.aap.org/pediatrics [Free Full-text]

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 September 2023.

New policies

No new national policies or guidelines since 1 September 2023.

New safety alerts

No new safety alerts since 1 September 2023.

Changes in product availability

• New product, omlyclo (omalizumab) 150mg solution for injection pre-filled pen, is licensed for the treatment of chronic rhinosinusitis. See more here.

Basis for recommendation

These recommendations are largely based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPO S2020) [Fokkens, 2020], the National Institute for Health and Care Excellence (NICE) guideline Sinusitis (acute): Antimicrobial Prescribing [NICE, 2017], the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR-RS) [Orlandi, 2021], a US Clinical practice guideline (update): adult sinusitis [Rosenfeld, 2015], a Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years [Wald, 2013], and expert opinion in review articles [Bird, 2013; BMJ Best Practice, 2022a].

History and examination  

• A thorough clinical history and examination should be used to establish the diagnosis of acute sinusitis and exclude differential diagnoses, such as allergy or primary headache syndromes [Fokkens, 2020; Orlandi, 2021]. 
  • Expert opinion in ICAR-RS is that the person should be asked about typical allergy symptoms (such as itchy and watery eyes and nose) to distinguish acute sinusitis from an allergy flare and about other syndromes that can cause facial pressure and pain (such as facial pain syndrome) [Orlandi, 2021].
• Anterior rhinoscopy should be performed in primary care to assess for nasal inflammation, mucosal oedema, and purulent nasal discharge [Fokkens, 2020; Orlandi, 2021]. It may also reveal previously unsuspected findings, such as polyps or anatomical abnormalities [Fokkens, 2020].
• Objective evidence of acute sinusitis on nasal endoscopy, antral puncture, or radiographic imaging (X-ray, ultrasonography, or CT) is not required to diagnose uncomplicated cases of acute sinusitis [Fokkens, 2020; Orlandi, 2021].  
  
  • Imaging is unnecessary for people who fulfil the clinical diagnostic criteria as both have similar diagnostic accuracy [Rosenfeld, 2015]. It also increases healthcare costs and may unnecessarily expose people to radiation and intravenous contrast [BMJ Best Practice, 2022a].
  • Imaging may be warranted in recurrent or persistent episodes, suspected anatomical abnormalities, rapidly progressing or suspected acute invasive fungal sinusitis, or to exclude a complication or differential diagnosis [Fokkens, 2020; BMJ Best Practice, 2022a].

Diagnosis

• There are many symptoms and signs potentially associated with acute sinusitis, including sneezing, malaise, fever, cough, nasal discharge, nasal obstruction, cough, sore throat, and headache. However, many are non-specific and can also be seen in isolated nasal infection or inflammation and allergy flares [Orlandi, 2021].
• The information on the diagnostic symptoms of acute sinusitis is based on EPOS 2020 [Fokkens, 2020]. ICAR-RS lists the same diagnostic symptoms but defines acute sinusitis as sinonasal inflammation lasting less than 4 weeks in adults and less than 12 weeks in children [Orlandi, 2021].
• The diagnostic symptoms of acute sinusitis are not evidence-based but have been agreed on over many years by various task forces and consensus groups [Orlandi, 2021]. 
• Features suggestive of acute sinusitis are based on expert opinion in EPOS 2020 [Fokkens, 2020] and ICAR-RS [Orlandi, 2021].

When to suspect acute bacterial sinusitis

• It is difficult to distinguish between viral and bacterial acute sinusitis [NICE, 2017].
• CKS has extrapolated the diagnostic criteria for bacterial sinusitis from the NICE guideline [NICE, 2017], EPOS2020 [Fokkens, 2020], and ICAR-RS [Orlandi, 2021].  
  
  • NICE states that a bacterial cause may be more likely if several of the following are present: symptoms for more than 10 days, discoloured or purulent nasal discharge, severe localized unilateral pain (particularly pain over teeth and jaw), fever, and marked deterioration after an initial milder phase [NICE, 2017].
  • EPOS 2020 defines acute bacterial sinusitis as the presence of at least three of the following symptoms/signs: discoloured mucus, severe local pain, fever more than 38°C, raised C-reactive protein (CRP)/erythrocyte sedimentation rate (ESR), and double sickening [Fokkens, 2020].
  • Expert opinion in ICAR-RS is that although CRP and ESR are elevated during acute sinusitis, they are not routinely used for diagnosis because of their limited specificity [Orlandi, 2021]. Therefore, CKS has not included raised CRP and ESR in the diagnostic criteria for bacterial sinusitis.
• Differentiating between bacterial and viral acute sinusitis can be challenging, even with radiographic studies [BMJ Best Practice, 2022a].
  • Normal radiographs or CT or MRI results can ensure that a person with respiratory symptoms does not have acute bacterial sinusitis, but an abnormal image cannot confirm the diagnosis [Wald, 2013]. 
  • In children, it is likely that imaging will be abnormal, even in those with an uncomplicated upper respiratory tract infection; therefore, its usefulness is doubtful [Wald, 2013]. 

Basis for recommendation

These recommendations are based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020) [Fokkens, 2020], the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR-RS) [Orlandi, 2021], a US Clinical practice guideline (update): adult sinusitis [Rosenfeld, 2015], and expert opinion in a review article [BMJ Best Practice, 2022b].

History and examination 

• EPOS 2020 and ICAR-RS recommend a thorough clinical history and examination to help establish a diagnosis of acute sinusitis [Fokkens, 2020; Orlandi, 2021]. CKS has extrapolated this recommendation to chronic sinusitis. For more information, see the section on Acute sinusitis.
• Anterior rhinoscopy should be performed in primary care to assess for nasal inflammation, mucosal oedema, and purulent nasal discharge [Fokkens, 2020; Orlandi, 2021]. It may also reveal previously unsuspected findings, such as polyps or anatomical abnormalities [Fokkens, 2020].

Diagnosis

• The information on the diagnostic symptoms of chronic sinusitis is based on EPOS 2020 [Fokkens, 2020].
• Upper airway diseases present with a variable pattern of common symptoms, such as nasal obstruction and discharge, making the diagnosis of chronic sinusitis difficult to differentiate from allergic and non-allergic rhinitis based on symptoms alone (symptoms alone have high sensitivity but low specificity). Also, not all people presenting with symptoms meeting the criteria for chronic sinusitis have evidence of the disease on endoscopy or CT. Therefore, diagnosis of chronic sinusitis requires at least two diagnostic symptoms plus objective evidence of inflammation demonstrated on rhinoscopy, nasal endoscopy, or radiography [Fokkens, 2020; Orlandi, 2021].
• Features suggestive of chronic sinusitis are based on expert opinion in EPOS 2020 [Fokkens, 2020] and ICAR-RS [Orlandi, 2021].

Basis for recommendation

The information on differential diagnoses of sinusitis is based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020) [Fokkens, 2020], the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR-RS) [Orlandi, 2021], a US clinical practice guideline on adult sinusitis [Rosenfeld, 2015], and expert opinion in review articles [Bird, 2013; BMJ Best Practice, 2022a; BMJ Best Practice, 2022b].

When should I admit or refer a person with acute sinusitis?

• If the person presents at any time and is systemically very unwell, has symptoms and signs of a more serious condition, or is at high risk of complications:
  • Admit to hospital if they have any of the following:
    • A severe systemic infection. 
    • Signs of sepsis. 
    • Intraorbital or periorbital complications, including periorbital oedema or cellulitis, a displaced eyeball, double vision, ophthalmoplegia, or newly reduced visual acuity. 
    • Intracranial complications, including swelling over the frontal bone, symptoms or signs of meningitis, severe frontal headache, or focal neurological signs.
    • Reduced consciousness.
  • If hospital admission is not indicated:
    • Offer an immediate antibiotic prescription or further appropriate investigation and management. See the section on Management for more information.
• If symptoms suggest neoplasm (persistent unilateral symptoms, such as nasal obstruction, nasal discharge or nosebleeds, crusting, or facial swelling):
  • Arrange an urgent suspected cancer pathway referral.
• Refer to an appropriate specialist, for example, an ear, nose, and throat specialist or immunologist (with urgency depending on clinical judgement) if:
  
  • The person is immunocompromised.
  • There is a suspected allergic or immunological cause.
  • There is an anatomic defect causing obstruction.
  • There is a comorbidity complicating management, such as nasal polyps or asthma.
  • Sinusitis is associated with an unusual or resistant bacteria.
  • There is no improvement after 10 days of antibiotic treatment.
  • Symptoms are recurrent or significantly affect quality of life.
  • There is doubt about the diagnosis.

How should I manage a person with acute sinusitis?

If the person has had symptoms for 10 days or less (and immediate referral is not indicated):

• Do not offer an antibiotic prescription.
• Advise the person:
  • On the usual cause and course of acute sinusitis.
    • Acute sinusitis is usually caused by a virus, resolves within 12 weeks, and most people get better without antibiotics.
    • Bacterial sinusitis is usually self-limiting and does not routinely need antibiotics.
    • The NHS website has patient information on Sinusitis (sinus infection).
  • On self-management strategies. Explain that:
    • Paracetamol or ibuprofen can be taken for pain or fever.
    • A trial of nasal saline or nasal decongestants can be considered for congestion, although evidence is lacking to support their use for this indication.
    • The NHS information on Sinusitis (sinus infection) contains instructions on cleaning the nose with a saltwater solution.
  • To seek medical advice if symptoms worsen rapidly or significantly, symptoms do not improve after 3 weeks, or they become systemically very unwell. 
• If symptoms worsen rapidly or significantly:
  • Reassess the person, considering:
    • Alternative diagnoses, such as a dental infection.
    • Any signs or symptoms suggesting a more serious illness or condition.

If a person has had symptoms for around 10 days or more with no improvement or symptoms increase after 5 days (and immediate referral is not indicated):

• Advise the person on:
  • The usual cause and course of acute sinusitis.
    • Acute sinusitis is usually caused by a virus, resolves within 12 weeks, and most people get better without antibiotics.
    • Bacterial sinusitis is usually self-limiting and does not routinely need antibiotics.
    • The NHS website has patient information on Sinusitis (sinus infection).
  • On self-management strategies. Explain that:
    • Paracetamol or ibuprofen can be taken for pain or fever.
    • A trial of nasal saline or nasal decongestants can be considered for congestion, although evidence is lacking to support their use for this indication. The NHS information on Sinusitis (sinus infection) contains instructions on cleaning the nose with a saltwater solution.
    • There is no evidence for using oral decongestants, antihistamines, mucolytics, steam inhalation, or warm face packs. 
• For adults and children aged 12 years and over, consider prescribing a high-dose nasal corticosteroid for 14 days (for example, mometasone 200 micrograms twice daily [off-label use]).
  • Be aware that nasal corticosteroids:
    • May improve symptoms but are not likely to affect how long they last.
    • Could cause systemic effects, particularly in people already taking another corticosteroid.
    • May be difficult for people to use correctly.
• Consider no antibiotic prescription or a back-up antibiotic prescription.
  • Take into account:
    • Evidence that antibiotics make little difference to how long symptoms last or the proportion of people with improved symptoms. 
    • Evidence that withholding antibiotics is unlikely to lead to complications. 
    • Possible adverse effects of antibiotics, mainly diarrhoea and nausea. 
    • Factors that might make a bacterial cause more likely: symptoms for more than 10 days, discoloured or purulent nasal discharge, severe localized pain (often unilateral, particularly pain over teeth and jaw), fever greater than 38°C, and marked deterioration after an initial milder phase (double sickening).
  • A back-up antibiotic may be preferred when a bacterial cause is more likely.  
  • If a back-up antibiotic prescription is given, advise the person to:
    
    • Take the antibiotic if symptoms do not improve within 7 days or worsen rapidly or significantly at any time.
    • Seek medical help if symptoms worsen rapidly or significantly despite taking the antibiotic or if the antibiotic has been stopped because it was not tolerated. 
• If symptoms worsen rapidly or significantly despite treatment:
  • Reassess the person, considering:
    • Alternative diagnoses, such as a dental infection.
    • Any signs or symptoms suggesting a more serious illness or condition.
    • Previous antibiotic use, which may lead to resistant organisms.
• Refer to an appropriate specialist, for example, an ear, nose, and throat specialist or immunologist (with urgency depending on clinical judgement) if:
  
  • The person is immunocompromised.
  • There is a suspected allergic or immunological cause.
  • There is an anatomic defect causing obstruction.
  • There is a comorbidity complicating management, such as nasal polyps or asthma.
  • Sinusitis is associated with an unusual or resistant bacteria.
  • There is no improvement after 10 days of antibiotic treatment.
  • Symptoms are recurrent or significantly affect quality of life.
  • There is doubt about the diagnosis.

Which antibiotics should I prescribe?

If an antibiotic is indicated for acute sinusitis:

• In adults aged 18 years and over:
  
  • If there are no life-threatening symptoms, prescribe phenoxymethylpenicillin 500 mg four times daily for 5 days.
  • If the person is systemically very unwell, has symptoms or signs of a more serious illness or condition, or is at high risk of complications (and immediate referral is not indicated), prescribe co-amoxiclav 500/125 mg three times daily for 5 days.
  • If the person is allergic or intolerant to penicillin, prescribe:
    • Doxycycline 200 mg on the first day, then 100 mg once daily for 4 days (5-day course in total) or
    • Clarithromycin 500 mg twice daily for 5 days.
  • If the person is pregnant and allergic or intolerant to penicillin, prescribe:
    • Erythromycin 250–500 mg four times daily for 5 days or
    • Erythromycin 500–1000 mg twice daily for 5 days.
• In children and young people aged under 18 years: 
  • If there are no life-threatening symptoms, prescribe phenoxymethylpenicillin:
    • Age 1–11 months — 62.5 mg four times daily for 5 days.
    • Age 1–5 years — 125 mg four times daily for 5 days. 
    • Age 6 –11 years — 250 mg four times daily for 5 days.
    • Age 12–17 years — 500 mg four times daily for 5 days.
  • If the child or young person is systemically very unwell, has symptoms or signs of a more serious illness or condition, or is at a high risk of complications (and immediate referral is not indicated), prescribe co-amoxiclav:
    • Age 1–11 months — 0.25 mL/kg of 125/31 suspension three times daily for 5 days.
    • Age 1–5 years — 5 mL of 125/31 suspension three times daily for 5 days or 0.25 mL/ kg of 125/31 suspension three times daily for 5 days.
    • Age 6 –11 years — 5 mL of 250/62 suspension three times daily for 5 days or 0.15 mL/kg of 250/62 suspension three times daily for 5 days.
    • Age 12–17 years — 250/125 mg three times daily for 5 days or 500/125 mg three times daily for 5 days.
  • If the child or young person is allergic or intolerant to penicillin, prescribe clarithromycin:
    • Body weight under 8 kg — 7.5 mg/kg twice daily for 5 days.
    • Body weight 8–11 kg — 62.5 mg twice daily for 5 days.
    • Body weight 12–19 kg — 125 mg twice daily for 5 days.
    • Body weight 20–29 kg — 187.5 mg twice daily for 5 days.
    • Body weight 30–40 kg — 250 mg twice daily for 5 days.
    • Ages 12–17 years — 250 mg twice daily for 5 days or 500 mg twice daily for 5 days.
  • If the child or young person is allergic or intolerant to penicillin and is aged 12–17 years, an alternative is doxycycline 200 mg on the first day, then 100 mg once daily for 4 days (5-day course in total). 

If symptoms are worsening after the first-line antibiotic has been taken for at least 2–3 days:

• In adults aged 18 years and over:
  • Prescribe co-amoxiclav 500/125 mg three times daily for 5 days.
  • If the person has a penicillin allergy or intolerance or the symptoms are still worsening after co-amoxiclav has been taken for at least 2–3 days, seek advice from a local microbiologist.
• In children and young people aged under 18 years:
  • Prescribe co-amoxiclav:
    • Age 1–11 months — 0.25 mL/kg of 125/31 suspension three times daily for 5 days.
    • Age 1–5 years — 5 mL of 125/31 suspension three times daily for 5 days or 0.25 mL/ kg of 125/31 suspension three times daily for 5 days.
    • Age 6 –11 years — 5 mL of 250/62 suspension three times daily for 5 days or 0.15 mL/kg of 250/62 suspension three times daily for 5 days.
    • Age 12–17 years — 250/125 mg three times daily for 5 days or 500/125 mg three times daily for 5 days.
  • If the child or young person has a penicillin allergy or intolerance or the symptoms are still worsening after the second-line antibiotic has been taken for at least 2–3 days, seek advice from a local microbiologist.

For information on prescribing these antibiotics, including contraindications and cautions, adverse effects, and drug interactions, see the section on Prescribing information.

When should I admit or refer a person with chronic sinusitis?

• If the person presents at any time and is systemically very unwell, has symptoms and signs of a more serious condition, or is at high risk of complications:
  • Admit to hospital if they have any of the following:
    • A severe systemic infection. 
    • Signs of sepsis. 
    • Intraorbital or periorbital complications, including periorbital oedema or cellulitis, a displaced eyeball, double vision, ophthalmoplegia, or newly reduced visual acuity. 
    • Intracranial complications, including swelling over the frontal bone, symptoms or signs of meningitis, severe frontal headache, or focal neurological signs.
    • Reduced consciousness.
  • If hospital admission is not indicated:
    • Offer an immediate antibiotic prescription or further appropriate investigation and management. See the section on Management for more information.
• If symptoms suggest neoplasm (persistent unilateral symptoms, such as nasal obstruction, nasal discharge or nosebleeds, crusting, or facial swelling):
  • Arrange an urgent suspected cancer pathway referral.
• Refer to an appropriate specialist, for example, an ear, nose, and throat specialist or immunologist (with urgency depending on clinical judgement) if:
  
  • There is cacosmia (immediate referral).
  • The person is immunocompromised.
  • Symptoms persist despite compliance with 3 months of treatment.
  • Symptoms significantly affect quality of life.
  • There is a suspected allergic or immunological cause.
  • There is an anatomic defect causing obstruction.
  • There is a comorbidity complicating management, such as nasal polyps or asthma.
  • Sinusitis is associated with an unusual or resistant bacteria.
  • There are recurrent episodes of otitis media and pneumonia in a child.
  • There is suspicion of adenoid hypertrophy.
  • There is doubt about the diagnosis.

How should I manage a person with chronic sinusitis?

If immediate referral is not indicated:

• Advise the person on the course of chronic sinusitis.
  • Symptoms of chronic sinusitis persist for 12 weeks or longer, and antibiotics are not routinely needed.
  • The NHS website has patient information on Sinusitis (sinus infection).
• Advise the person to:
  • Avoid allergic triggers.
  • Stop smoking (and avoid passive smoking), where applicable.
  • Practise good dental hygiene to reduce the risk of dental infection (which can be associated with bacterial sinusitis).
  • Avoid underwater diving if there are prominent symptoms.
• If the person has an associated disorder, such as such as allergic rhinitis or asthma:
  • Advise that good control of these is also likely to benefit their sinusitis symptoms.
    • For more information, see the CKS topics on Allergic rhinitis and Asthma.
• Consider the need for symptomatic treatment. 
  • Consider nasal irrigation with saline solution to relieve congestion and nasal discharge. 
    • The NHS information on Sinusitis (sinus infection) contains instructions on cleaning the nose with a saltwater solution.
  • In adults, consider a course (up to 3 months) of intranasal corticosteroid (for example, mometasone or fluticasone), especially if there is suspicion of an allergic cause (such as concurrent allergic rhinitis). 
    • For more information on using intranasal corticosteroids, see the section on Intranasal corticosteroids in the CKS topic on Allergic rhinitis.
    • In situations where the nose is very blocked, consider temporarily adding a nasal decongestant to nasal corticosteroid treatment.
• Consider seeking specialist advice if considering the following:
  
  • Intranasal corticosteroid for a child.
  • Oral corticosteroid.
  • Long-term antibiotics.
• Refer to an appropriate specialist, for example, an ear, nose, and throat specialist or immunologist (with urgency depending on clinical judgement) if:
  
  • There is no improvement in 6–12 weeks. 
  • The person is immunocompromised.
  • Symptoms significantly affect quality of life.
  • There is a suspected allergic or immunological cause.
  • There is an anatomic defect causing obstruction.
  • There is a comorbidity complicating management, such as nasal polyps or asthma.
  • Sinusitis is associated with an unusual or resistant bacteria.
  • There are recurrent episodes of otitis media and pneumonia in a child.
  • There is suspicion of adenoid hypertrophy.
  • There is doubt about the diagnosis.

Contraindications and cautions

• Do not prescribe clarithromycin to people with:
  
  • Electrolyte disturbances (hypokalaemia or hypomagnesaemia) — risk of prolongation of the QT interval.
  • A history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes arrhythmias.
  • Severe hepatic impairment in combination with renal impairment.
• Prescribe clarithromycin with caution to people with:
  • Impaired hepatic function (or concurrently taking potentially hepatotoxic drugs) — clarithromycin is principally excreted by the liver. 
  • Coronary artery disease, severe cardiac insufficiency, conduction disturbances, or clinically relevant bradycardia — risk of QT interval prolongation.
  • Myasthenia gravis — may aggravate symptoms.
  • Renal impairment — dosage reduction may be indicated:
    
    • For immediate-release preparations, use half the recommended dosage if creatinine clearance (CrCl) is less than 30 mL/minute.
    • For modified-release preparations, use half the recommended dosage if  CrCl is 30–60 mL/minute. Avoid if CrCl is less than 30 mL/minute.
• Be aware of severe drug interactions with clarithromycin.

[EMC, 2023a; BNF, 2024]

Adverse effects

• For all macrolides
  • The most common adverse effects are:
    • Gastrointestinal adverse effects, such as diarrhoea, nausea, vomiting, abdominal discomfort, and dyspepsia.
    • Decreased appetite and altered taste.
    • Dizziness, headache, vasodilation, and vision disorders.
    • Hearing impairment.
    • Insomnia.
    • Pancreatitis.
    • Paraesthesia and skin reactions.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in people who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatment, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Other possible adverse effects include:
    • Uncommon — angioedema, anxiety, arrhythmias, candidal infection, chest pain, constipation, drowsiness, eosinophilia, hepatic disorders, leucopenia, neutropenia, palpitations, QT interval prolongation, severe cutaneous adverse reactions (SCARs), tinnitus, and vertigo.
    • Rare or very rare — myasthenia gravis and nephritis tubulointerstitial.
    • Frequency not known — altered smell, hallucination, hypotension, seizure, thrombocytopenia, and tongue discolouration.
• For clarithromycin
  • Hepatic dysfunction has been reported.
    
    • This includes increased liver enzymes, and hepatocellular and/or cholestatic hepatitis (with or without jaundice). 
    • Hepatic dysfunction may be severe and is usually reversible. Cases of fatal hepatic failure have been reported.
    • Advise people taking clarithromycin to stop treatment and seek medical advice if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen.
  • Other possible adverse effects include:
    
    • Uncommon — burping, dry mouth, epistaxis, muscle complaints, oral disorders, thrombocytosis, and tremor.
    • Frequency not known — abnormal dreams, agranulocytosis, depersonalization, depression, mania, myopathy, psychotic disorder, renal failure, tooth discolouration, and urine discolouration.

 [EMC, 2023a; BNF, 2024]

Drug interactions

• Drug interactions of clarithromycin include:
  • Antidiabetic drugs — concurrent use with oral hypoglycaemic drugs (such as sulfonylureas) or insulin can result in significant hypoglycaemia.
    
    • Monitor blood glucose levels closely, and adjust the antidiabetic dose if necessary.
  • Calcium channel blockers — clarithromycin possibly inhibits the metabolism of calcium channel blockers, such as verapamil and amlodipine, increasing the risk of hypotension and other adverse effects.
    • Monitor for hypotension and other adverse effects, and adjust the dose of the calcium channel blocker if necessary.
  • Digoxin — clarithromycin increases the plasma concentration of digoxin.  
    • Monitor for signs of digoxin adverse effects (bradycardia).
    • Measure digoxin concentrations, and adjust the dose if problems develop.
  • Direct oral anticoagulants (DOACs) — clarithromycin increases the exposure to dabigatran, slightly increases the exposure to apixaban, and is predicted to increase the exposure to edoxaban.
    
    • Monitor for signs and symptoms of bleeding or anaemia, especially in older people and people with renal impairment.
  • Drugs that prolong the QT interval — clarithromycin can prolong the QT interval. Concurrent use with other drugs that prolong QT intervals can increase the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
    • Concurrent use with domperidone, ivabradine, or pimozide is contraindicated. Seek advice from a medical microbiologist regarding a suitable alternative antibiotic.
    • Most manufacturers advise avoiding the use of two or more drugs that are associated with QT prolongation.
    • Increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation.
  • Drugs that cause hypokalaemia (such as diuretics) — concurrent use with clarithromycin can predispose to QT prolongation.
    
    • Monitor potassium concentrations closely.
  • Drugs that induce cytochrome P450 (CYP3A4) enzyme — concurrent use may decrease plasma concentrations of clarithromycin, leading to sub-therapeutic levels and reduced efficacy.  
    • Monitor concurrent use of clarithromycin and CYP3A4 enzyme inducers, such as rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort.
    • It may also be necessary to monitor the plasma levels of the CYP3A4 inducer, which could be increased due to the inhibition of CYP3A4 by clarithromycin. For example, concurrent treatment with rifabutin and clarithromycin increases rifabutin levels and decreases clarithromycin levels.
  • Edoxaban — manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
  • Ivabradine — concomitant treatment is contra-indicated, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
  • Statins — clarithromycin is a CYP3A4 enzyme inhibitor. Concurrent use with a statin metabolized by CYP3A4 will increase the plasma concentration of the statin, leading to an increased risk of myopathy (including rhabdomyolysis). 
    • Simvastatin is extensively metabolized by CYP3A4. Concurrent use with clarithromycin is contraindicated. If clarithromycin treatment cannot be avoided, withhold simvastatin for the duration of the clarithromycin course.
    • Atorvastatin is moderately metabolized by CYP3A4. Avoid concurrent use with clarithromycin. If concurrent use cannot be avoided, do not exceed 20 mg of atorvastatin daily. Advise the person to report any muscle pain, tenderness, or weakness.
    • Pravastatin is not associated with cytochrome P450 interactions. However, the Medicines and Healthcare products Regulatory Agency (MHRA) advises caution with clarithromycin. Advise the person to report any muscle pain, tenderness, or weakness.
    • Rosuvastatin is not associated with cytochrome P450 interactions. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness.
    • Fluvastatin is not dependent on CYP3A metabolism. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness. 
  • Other drugs metabolized by CYP3A4 — concurrent use with clarithromycin may increase plasma concentrations of the concurrent drug, leading to increased or prolonged therapeutic and adverse effects of the concurrent drug.
    • Concurrent use with domperidone, pimozide, or terfenadine is contraindicated due to the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
    • Concurrent use with ergot alkaloids, oral midazolam, colchicine, ticagrelor, or ranolazine is contraindicated.
    • Concurrent use of clarithromycin with other drugs metabolized by CYP3A4 should be done with caution, especially if the other drug has a narrow safety margin (such as carbamazepine) or is extensively metabolized by CYP3A4. Dosage adjustments may be considered, and when possible, serum concentrations of the CYP3A4 substrate should be monitored closely.
  • Warfarin — clarithromycin may enhance the anticoagulant effect of warfarin.
    • Monitor the international normalized ratio (INR) closely, and adjust the warfarin dose if necessary.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of clarithromycin.
  • However, advise women that if diarrhoea, vomiting, or breakthrough bleeding occurs, 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 Contraception - progestogen-only methods.
• For further information on clarithromycin drug interactions, see the electronic Medicines Compendium (eMC) or the British National Formulary (BNF).

[MHRA, 2014; BNF, 2024; Preston, 2024; EMC, 2024a]

Contraindications and cautions

• Do not prescribe co-amoxiclav to people with:
  • A true penicillin hypersensitivity — gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute a penicillin allergy.
  • History of urticaria or rash immediately after penicillin administration — risk of immediate penicillin hypersensitivity.
  • History of a severe immediate hypersensitivity reaction (for example, anaphylaxis) to cephalosporins — there is some evidence of partial cross-allergenicity between cephalosporins and penicillins. 
  • History of co-amoxiclav-associated jaundice or hepatic dysfunction. 
  • History of penicillin-associated jaundice or hepatic dysfunction.
• Prescribe co-amoxiclav with caution to people with:
  • History of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration — possibility of an allergic reaction to penicillins.
  • History of allergy to cephalosporins or other medications.
  • History of atopic allergy (including asthma, eczema, or hay fever) — high risk of anaphylactic reactions to penicillins.
  • Hepatic impairment — monitor hepatic function regularly.
  • Acute or chronic lymphocytic leukaemia — increased risk of erythematous rashes.
  • Cytomegalovirus infection — increased risk of erythematous rashes.
  • Glandular fever — erythematous rashes are common.
  • Renal impairment — dosage reduction may be indicated:
    • For adults and children weighing 40 kg or more: if creatinine clearance (CrCl) is 10–30 ml/minute, prescribe 500 mg/125 mg twice daily. If CrCl is less than 10 ml /minute, prescribe 500 mg/125 mg once daily.
    • For children weighing less than 40 kg: if CrCl is 10–30 ml/minute, prescribe 15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily). If CrCl is less than 10 ml /minute, prescribe 15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg).

[EMC, 2023b; BNF, 2024]

Adverse effects

• For all penicillins
  • The most common adverse effects are:
    • Gastrointestinal adverse effects, such as diarrhoea, nausea, and vomiting.
    • Hypersensitivity.
    • Skin reactions.
    • Thrombocytopenia.
  • The most significant adverse effect of penicillins is hypersensitivity, which causes rashes and anaphylaxis and can be fatal.
    
    • Allergic reactions occur in 1–10% of people treated with a penicillin; anaphylactic reactions occur in fewer than 0.05% of people. 
    • People with a history of atopic allergy (for example, asthma, eczema, and hay fever) are at a higher risk of anaphylactic reactions to penicillins.
    • People with a history of anaphylaxis, urticaria, or rash immediately after penicillin administration are at risk of immediate hypersensitivity and should not take co-amoxiclav.
    • People with a history of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration are probably not allergic to penicillin. Co-amoxiclav should not be withheld unnecessarily for serious infections, but the possibility of an allergic reaction should be noted. Other beta-lactam antibiotics (including cephalosporins) can be used.
    • People allergic to one penicillin will be allergic to all because the hypersensitivity is related to the basic penicillin structure.
    • People with a history of immediate hypersensitivity to penicillins may also react to cephalosporins and other beta-lactam antibiotics and so should not receive these antibiotics. There is some evidence of partial cross-allergenicity of penicillins and cephalosporins. 
    • If a penicillin (or another beta-lactam) antibiotic is essential in a person with immediate hypersensitivity to penicillins, specialist advice should be sought on hypersensitivity testing or using a beta-lactam antibiotic with a different structure to the penicillin that caused the hypersensitivity.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in people who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatments, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Other possible adverse effects include:
    • Uncommon — arthralgia and leucopenia.
    • Rare or very rare — agranulocytosis, angioedema, haemolytic anaemia, hepatic disorders, nephritis tubulointerstitial, neutropenia, seizure, and severe cutaneous adverse reactions (SCARs).
• For co-amoxiclav
  • Hepatic events have been reported predominantly in males and older people and may be associated with prolonged treatment. 
    
    • Signs and symptoms usually occur during or shortly after treatment, but in some cases, they may occur several weeks after discontinuation. These are usually reversible. 
    • Hepatic events may be severe, and in extremely rare circumstances, deaths have been reported. These have almost always occurred in people with a serious underlying disease or concurrently taking potentially hepatotoxic drugs.
  • Other possible adverse effects include: 
    • Common or very common — mucocutaneous candidiasis and increased risk of infection.
    • Uncommon — dizziness, dyspepsia, headache, pruritus, skin rash, and urticaria.
    • Rare or very rare — erythema multiforme, reversible leucopenia (including neutropenia), and thrombocytopenia.
    • Frequency unknown — akathisia, aseptic meningitis, black hairy tongue, cholangitis, crystalluria, drug-induced enterocolitis syndrome, hypersensitivity vasculitis, Kounis syndrome (an allergic reaction which can cause myocardial infarction), and linear IgA disease (renal deposition of IgA).
  • Symmetrical Drug-related Intertriginous and Flexural Exanthema (SDRIFE) are adverse effects of unknown frequency.

Drug interactions

• Drug interactions of co-amoxiclav include:
  • Allopurinol — concurrent use of allopurinol and amoxicillin may increase the incidence of skin rashes.
    • There would seem to be no strong reason for avoiding concurrent use, but prescribers should recognize that the development of a rash is not unusual.
  • Methotrexate — reduced clearance and acute methotrexate toxicity have been attributed to concurrent use with some penicillins. Serious interactions are uncommon, but risk factors are as yet unknown. People taking low-dose methotrexate have been affected.
    • High-dose methotrexate: standard routine monitoring will identify any decreases in elimination, which should be managed according to local guidelines.
    • Low-dose methotrexate: consult local or national guidelines for recommendations on appropriate monitoring and management.
  • Probenecid — concurrent use of probenecid may result in increased and prolonged blood levels of amoxicillin but not clavulanic acid.
    • Concurrent use can be beneficial. However, consider any detrimental effect elevated penicillin concentrations may have on the person.
  • Warfarin — amoxicillin potentially alters the anticoagulant effect of warfarin.   
    • Monitor the international normalized ratio (INR) closely, and adjust the warfarin dose accordingly.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of co-amoxiclav.
  • However, advise women that if diarrhoea, vomiting, or breakthrough bleeding occurs, 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 Contraception - progestogen-only methods.

 [EMC, 2023b; BNF, 2024; Preston, 2024]

Contraindications and cautions

• Do not prescribe erythromycin to people with:
  • A history of QT interval prolongation or ventricular arrhythmia (including torsade de pointes) — risk of QT interval prolongation.
  • Electrolyte disturbances (hypokalaemia or hypomagnesaemia) — risk of QT interval prolongation. 
• Prescribe erythromycin with caution to:
  • People with:
    • Impaired hepatic function (or concurrently receiving potentially hepatotoxic drugs) — erythromycin is excreted principally in the liver.
    • Moderate to severe impairment — consider dosage reduction due to the risk of ototoxicity.
    • With cardiac disease or heart failure, conduction disturbances, or clinically relevant bradycardia (or concurrently receiving drugs associated with QT interval prolongation) — risk of QT interval prolongation.
    • Myasthenia gravis — macrolides may aggravate symptoms.
    • Acute porphyrias.
  • Older people — may be more susceptible to drug-associated effects on the QT interval.

[MHRA, 2020; EMC, 2023c; BNF, 2024]

Adverse effects

• For all macrolides
  • The most common adverse effects are:
    • Gastrointestinal adverse effects, such as diarrhoea, nausea, vomiting, abdominal discomfort, and dyspepsia.
    • Decreased appetite and altered taste.
    • Dizziness, headache, vasodilation, and vision disorders.
    • Hearing impairment.
    • Insomnia.
    • Pancreatitis.
    • Paraesthesia and skin reactions.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in people who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatment, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Other possible adverse effects include:
    • Uncommon — angioedema, anxiety, arrhythmias, candidal infection, chest pain, constipation, drowsiness, eosinophilia, hepatic disorders, leucopenia, neutropenia, palpitations, QT interval prolongation, severe cutaneous adverse reactions (SCARs), tinnitus, and vertigo.
    • Rare or very rare — myasthenia gravis and nephritis tubulointerstitial.
    • Frequency not known — altered smell, hallucination, hypotension, seizure, thrombocytopenia, and tongue discolouration.
• For erythromycin
  • Increased risk of cardiotoxicity (QT interval prolongation) has been reported.
    • Therefore, erythromycin should not be given to people with a history of QT interval prolongation, ventricular arrhythmia (including torsade de pointes), or electrolyte disturbances. See the section on Contraindications and cautions for more information.
  • Infantile hypertrophic pyloric stenosis has been reported.
    • The risk is highest in the first 14 days after birth.
    • Assess the benefit-risk balance of erythromycin treatment in infants.
    • Advise parents and carers to seek medical attention if vomiting or irritability with feeding occurs in infants during treatment with erythromycin.
  • Other possible adverse effects include:
    • Uncommon — hepatic dysfunction, including increased liver enzymes and/or cholestatic hepatitis (with or without jaundice).
    • Rare or very rare — hearing loss (can occur after large doses).
    • Frequency not known — cerebral impairment.

[MHRA, 2020; EMC, 2023c; BNF, 2024]

Drug interactions

• Drug interactions of erythromycin include:
  • Calcium channel blockers — erythromycin possibly inhibits the metabolism of calcium channel blockers, such as verapamil and amlodipine, increasing the risk of hypotension and other adverse effects.
    • Monitor for hypotension and other adverse effects, and adjust the dose of the calcium channel blocker if necessary.
    • Hypotension, bradyarrhythmias, and lactic acidosis have been observed in people receiving concurrent verapamil.
  • Ciclosporin — erythromycin significantly increases ciclosporin concentrations, and cases of toxicity have been reported. Erythromycin-related ototoxicity has also been reported.
    • Monitor the concentration and effects (for example, on renal function) of ciclosporin more frequently if erythromycin is started or stopped.
    • Adjust the ciclosporin dose as necessary.
  • Cimetidine — cimetidine may inhibit the metabolism of erythromycin, leading to an increased plasma concentration.
    • The general clinical importance of this interaction is uncertain.
    • Monitor concurrent use for erythromycin adverse effects.
    • Stop erythromycin if deafness occurs. 
  • Digoxin — erythromycin increases the plasma concentration of digoxin.
    • Monitor for signs of digoxin adverse effects (bradycardia).
    • Measure digoxin concentrations, and adjust the dose if problems develop.
  • Direct oral anticoagulants (DOACs) — erythromycin is predicted to increase the exposure to DOACs, resulting in an increased risk of bleeding.
    • Monitor for signs and symptoms of bleeding or anaemia, especially in older people and people with renal impairment.
  • Drugs that prolong the QT interval — erythromycin can prolong the QT interval. Concurrent use with other drugs that prolong QT intervals can increase the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and torsades de pointes.
    
    • Concurrent use with domperidone, tolterodine, mizolastine, or amisulpride is contraindicated.
    • Most manufacturers advise avoiding the use of two or more drugs that are associated with QT prolongation.
    • Increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation.
  • Drugs that cause hypokalaemia (such as diuretics) — concurrent use with erythromycin can predispose to QT prolongation.
    
    • Monitor potassium concentrations closely.
  • Drugs that induce cytochrome P450 (CYP3A4) enzyme — concurrent use with drugs such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John's Wort may induce the metabolism of erythromycin, leading to sub-therapeutic levels of erythromycin and a decreased effect. The induction decreases gradually two weeks after discontinued treatment with the CYP3A4 inducers.
    • Avoid erythromycin during (and for two weeks after) treatment with a CYP3A4 inducer. If concurrent use is unavoidable, be alert for decreased erythromycin efficacy.
    • It may also be necessary to monitor the plasma levels of the CYP3A4 inducer, which could be increased due to the inhibition of CYP3A4 by erythromycin. For example, concurrent treatment with rifabutin and erythromycin increases rifabutin levels and decreases erythromycin levels. 
  • Statins — erythromycin is a CYP3A4 enzyme inhibitor. Concurrent use with a statin metabolized by CYP3A4 will increase the plasma concentration of the statin, leading to an increased risk of myopathy (including rhabdomyolysis).
    • Simvastatin is extensively metabolized by CYP3A4. Concurrent use with erythromycin is contraindicated. If erythromycin treatment cannot be avoided, withhold simvastatin for the duration of the erythromycin course.
    • Atorvastatin is moderately metabolized by CYP3A4. Avoid concurrent use with erythromycin. If concurrent use cannot be avoided, withhold atorvastatin for the duration of the erythromycin course or consider a lower maximum dose of atorvastatin.
    • Pravastatin is not associated with cytochrome P450 interactions. However, the Medicines and Healthcare products Regulatory Agency (MHRA) advises caution with erythromycin. Advise the person to report any muscle pain, tenderness, or weakness.
    • Rosuvastatin is not associated with cytochrome P450 interactions. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness.
    • Fluvastatin is not dependent on CYP3A4 metabolism. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness. 
  • Other drugs metabolized by CYP3A4 — concurrent use with erythromycin may increase plasma concentrations of the concurrent drug, leading to increased or prolonged therapeutic and adverse effects of the concurrent drug.
    • Concurrent use with pimozide or terfenadine is contraindicated. Erythromycin significantly alters the metabolism of these drugs, and rare cases of serious, potentially fatal cardiovascular events, including cardiac arrest, torsade de pointes, and other ventricular arrhythmias, have been observed.
    • Concurrent use with ergot alkaloids is contraindicated.
    • For other medications, appropriate monitoring should be undertaken and dosages adjusted as necessary. 
  • Theophylline — erythromycin can reduce theophylline clearance, leading to raised theophylline levels and potential theophylline toxicity. Oral erythromycin exposure may be reduced by theophylline. Theophylline can cause hypokalaemia, increasing the risk of torsade de pointes, which might be additive with the effects of erythromycin.
    • Monitor theophylline levels, and adjust the dose accordingly.
    • Monitor the effects of erythromycin to ensure they are adequate.
    • Monitor potassium concentrations closely.
  • Warfarin — erythromycin increases the anticoagulant effect of warfarin. 
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of erythromycin.
  • However, advise women that if diarrhoea, vomiting, or breakthrough bleeding occurs, 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 Contraception - progestogen-only methods.
• For further information on erythromycin drug interactions, see the electronic Medicines Compendium (eMC) or the British National Formulary (BNF).

[MHRA, 2014; EMC, 2023d; EMC, 2023c; BNF, 2024; Preston, 2024]

Contraindications and cautions

• Do not prescribe doxycycline to:
  • Pregnant women — effects on skeletal development have been documented in the first trimester in animal studies. Administration during the second or third trimester may cause discolouration of the child’s teeth.
  • Breastfeeding women — tetracyclines are excreted into milk (although absorption, and therefore discolouration of teeth in the infant, is probably usually prevented by chelation with calcium in milk).
  • Children younger than 12 years of age — tetracyclines can bind to calcium ions and be deposited in growing bone and teeth, causing staining. Enamel hypoplasia has also been reported.
    
    • In children aged under 8 years, use only in severe or life-threatening conditions (such as Rocky Mountain spotted fever) when there are no adequate alternatives.
    • In children aged 8–11 years, use only in acute or severe infections when there are no adequate alternatives.
• Prescribe doxycycline with caution to people with:
  • Hepatic impairment (or concurrently receiving potentially hepatotoxic drugs) — abnormal hepatic function has been reported rarely.
  • Myasthenia gravis — muscle weakness may be increased.
  • Systemic lupus erythematosus — symptoms may be exacerbated.
  • Alcohol dependence — alcohol may decrease the half-life of doxycycline.

[EMC, 2021; BNF, 2024]

Adverse effects

• For all tetracyclines
  • The most common adverse effects include:
    • Angioedema.
    • Gastrointestinal effects, such as diarrhoea, nausea, and vomiting.
    • Headache.
    • Pericarditis.
    • Henoch-Schöenlein purpura.
    • Hypersensitivity.
    • Skin reactions.
  • Photosensitivity reactions are common.
    • Advise people to avoid exposure to sunlight or sun lamps during treatment with a tetracycline.
    • Discontinue the treatment at the first evidence of skin erythema.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in people who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatment, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported.
    
    • If these occur, discontinue treatment immediately and initiate appropriate management.
  • Benign intracranial hypertension (pseudotumor cerebri) has been associated with tetracyclines.
    • Headache and visual disturbances may indicate benign intracranial hypertension.
    • If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted.
    • Since intracranial pressure can remain elevated for weeks after drug cessation, monitor the person until they stabilize. 
    • Discontinue treatment if raised intracranial pressure develops.
  • Permanent teeth discolouration (yellow-grey-brown) may occur if a tetracycline is used during tooth development.
    • This adverse effect is more common during long-term use of tetracyclines but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported.
    • For more information, see the section on Contraindications and cautions.
  • Other possible adverse effects include:
    • Uncommon — dizziness and pancreatitis.
    • Rare or very rare — bulging fontanelle (in infants), decreased appetite, discolouration of the thyroid gland, dysphagia, eosinophilia, gastrointestinal disorders, fixed eruption, glossitis, haemolytic anaemia, hepatic disorders, idiopathic intracranial hypertension, increased risk of infection, neutropenia, and thrombocytopenia.
• For doxycycline
  • Other possible adverse effects include:
    • Common or very common — dyspnoea, hypotension, peripheral oedema, and tachycardia.
    • Uncommon — gastrointestinal discomfort.
    • Rare or very rare —  anxiety, arthralgia, flushing, intracranial pressure increased with papilloedema, Jarisch-Herxheimer reaction, myalgia, photoonycholysis, skin hyperpigmentation (long-term use), stomatitis, tinnitus, and vision disorders.

[EMC, 2021; BNF, 2024; EMC, 2024c]

Drug interactions

• Drug interactions of doxycycline include:
  • Antacids — the absorption of doxycycline may be impaired by concurrently administered antacids containing aluminium, calcium, or magnesium, or other drugs containing these cations, as well as oral zinc, iron salts, or bismuth preparations.
    • Separate the doses by at least 2–3 hours to avoid this interaction.
    • Histamine H2-receptor antagonists do not interact and could be a suitable alternative.
  • Carbamazepine and phenytoin — serum levels of doxycycline are reduced and may fall below the accepted therapeutic minimum in people on long-term treatment with carbamazepine or phenytoin. 
    • It has been suggested that the doxycycline dose could be doubled.
  • Ciclosporin — doxycycline is predicted to increase ciclosporin concentrations.
    • Monitor ciclosporin concentrations and effects (for example, on renal function) more frequently when starting or stopping doxycycline.
    • Adjust the ciclosporin dose as needed.
  • Lithium — doxycycline is predicted to increase the risk of lithium toxicity.
    • If concurrent use cannot be avoided, monitor for lithium toxicity (tremors, dysarthria, ataxia, and confusion).
    • Adjust the lithium dose as needed.
  • Penicillins — bacteriostatic drugs (such as doxycycline) may interfere with the bactericidal action of penicillin.
    • Avoid concurrent use. 
  • Retinioids — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with retinoids (such as isotretinoin).
    • Avoid concurrent use.
     Warfarin — doxycycline increases the anticoagulant effect of warfarin.
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose as needed.
  • Rifampicin — doxycycline levels are markedly reduced, which may lead to treatment failure. Monitor the effects and increase doxycycline dose if necessary.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of doxycycline.
  • However, advise women that if diarrhoea, vomiting, or breakthrough bleeding occurs, 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 Contraception - progestogen-only methods.
• For further information on doxycycline drug interactions, see the electronic Medicines Compendium (eMC) or the British National Formulary (BNF).

[EMC, 2021; Preston, 2024; BNF, 2024]

Contraindications and cautions

• Do not prescribe phenoxymethylpenicillin to people with:
  • A true penicillin hypersensitivity — gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute a penicillin allergy.
  • History of urticaria or rash immediately after penicillin administration — risk of immediate penicillin hypersensitivity.
  • History of a severe immediate hypersensitivity reaction (for example, anaphylaxis) to cephalosporins — there is some evidence of partial cross-allergenicity between cephalosporins and penicillins. 
• Prescribe phenoxymethylpenicillin with caution to people with:
  • History of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration — possibility of an allergic reaction to penicillins.
  • History of allergy to cephalosporins or other medications.
  • History of atopic allergy (including asthma, eczema, or hay fever) — high risk of anaphylactic reactions to penicillins.
  • Allergic diathesis or bronchial asthma.
  • Impaired liver function plus renal failure — dosage adjustment may be necessary. In this situation, the liver may be a major excretion route.
  • Renal impairment — the safe dosage may be lower than usually recommended. 

[EMC, 2019; BNF, 2024]

Adverse effects

• For all penicillins
  • The most common adverse effects are:
    • Gastrointestinal adverse effects, such as diarrhoea, nausea, and vomiting.
    • Hypersensitivity.
    • Skin reactions.
    • Thrombocytopenia.
  • The most significant adverse effect of penicillins is hypersensitivity, which causes rashes and anaphylaxis and can be fatal.
    
    • Allergic reactions occur in 1–10% of people treated with a penicillin; anaphylactic reactions occur in fewer than 0.05% of people. 
    • People with a history of atopic allergy (for example, asthma, eczema, and hay fever) are at a higher risk of anaphylactic reactions to penicillins.
    • People with a history of anaphylaxis, urticaria, or rash immediately after penicillin administration are at risk of immediate hypersensitivity and should not take phenoxymethylpenicillin.
    • People with a history of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration are probably not allergic to penicillin. Phenoxymethylpenicillin should not be withheld unnecessarily for serious infections, but the possibility of an allergic reaction should be noted. Other beta-lactam antibiotics (including cephalosporins) can be used.
    • People allergic to one penicillin will be allergic to all because the hypersensitivity is related to the basic penicillin structure.
    • People with a history of immediate hypersensitivity to penicillins may also react to cephalosporins and other beta-lactam antibiotics and so should not receive these antibiotics. There is some evidence of partial cross-allergenicity of penicillins and cephalosporins. 
    • If a penicillin (or another beta-lactam) antibiotic is essential in a person with immediate hypersensitivity to penicillins, specialist advice should be sought on hypersensitivity testing or using a beta-lactam antibiotic with a different structure to the penicillin that caused the hypersensitivity.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in people who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatments, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Other possible adverse effects include:
    • Uncommon — arthralgia and leucopenia.
    • Rare or very rare — agranulocytosis, angioedema, haemolytic anaemia, hepatic disorders, nephritis tubulointerstitial, neutropenia, seizure, and severe cutaneous adverse reactions (SCARs).
• For phenoxymethylpenicillin
  • Adverse effects also include: 
    • Frequency unknown — circulatory collapse, coagulation disorder, eosinophilia, soft faeces, stomatitis, glossitis, fever, increased risk of infection, neurotoxicity, oral disorders, and paraesthesia.

[BNF, 2024]

Drug interactions

• Drug interactions of phenoxymethylpenicillin include:
  • Methotrexate — reduced clearance and acute methotrexate toxicity have been attributed to concurrent use with some penicillins. Serious interactions are uncommon, but risk factors are as yet unknown. People taking low-dose methotrexate have been affected.
    • High-dose methotrexate: standard routine monitoring will identify any decreases in elimination, which should be managed according to local guidelines.
    • Low-dose methotrexate: consult local or national guidelines for recommendations on appropriate monitoring and management.
  • Warfarin — phenoxymethylpenicillin potentially alters the anticoagulant effect of warfarin.   
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of phenoxymethylpenicillin.
  • However, advise women that if diarrhoea, vomiting, or breakthrough bleeding occurs, 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.

[EMC, 2019; Preston, 2024; BNF, 2024]