Previous changes

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.

January 2024 — minor update. Information on the use of fluoroquinolones and reporting adverse reactions was added in line with the Drug Safety Update published by the MHRA.

October 2023 — minor update. Advice to reduce the dose of ceftriaxone in adults with severe renal impairment in combination with hepatic impairment, if the estimated glomerular filtration rate (eGFR) is less than 10 mL/minute/1.73 m2, has been amended to if creatinine clearance is less than 10 ml/min. This is in accordance with the advice outlined in the BNF.

August 2022 — reviewed. A literature search was conducted in July 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. No major changes to clinical recommendations have been made.

April 2022 — minor update. Drug interactions of azithromycin with hydroxychloroquine and chloroquine have been included in line with the revised manufacturer's summary of product characteristics (SPC). 

February 2022 — minor update. A hyperlink to a patient information leaflet was updated.

November 2020 — minor update. Cautions for prescribing quinolones have been updated in line with the revised manufacturer's SPC. 

March 2019 — minor update. Prescribing information for quinolones has been updated in line with the Medicines and Healthcare products Regulatory Agency (MHRA) guidance Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects [MHRA, 2019].

January 2019 — minor update. The Prescribing information section has been updated in line with the updated British Association for Sexual Health and HIV (BASHH) guideline UK national guideline for the management of gonorrhoea in adults [BASHH, 2019]. 

January 2019 — minor update. Aortic aneurysm and dissection are now listed as adverse effects of ciprofloxacin. 

June 2018 — minor update. The section on Prescribing information has been updated to include information on the drug interaction between azithromycin and colchicine.  

September 2017 — minor update. SPC update on quinolones to align prescribing advice in other CKS topics. 

May to June 2017 — reviewed. A literature search was conducted in May 2017 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. 

December 2016 — minor update. Uveitis, severe liver injury, and exfoliative dermatitis have been added as possible adverse effects of ofloxacin, in line with the manufacturer's updated SPC.

• Drug reaction with eosinophilia and systemic symptoms (DRESS) has been added as a possible adverse effect of azithromycin.
• Information that the World Health Organization (WHO) guideline Treatment of Neisseria gonorrhoeae recommends a lower dose of ceftriaxone has been added to this topic.

September 2014 — minor update. Public Health England (PHE) has released updated guidance on the detection of gonorrhoea in England.

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

January 2013 — minor update. A typographical error has been corrected in the Prescribing information section on Cephalosporins.

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

November 2011 — minor update. Th topic has been updated to reflect recommendations in the revised UK National Guideline for the Management of Gonorrhoea in Adults 2011 published by BASHH. 

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

September 2010 — minor update. Health Protection Agency (HPA) figures for new diagnoses of gonorrhoea in 2008/9 have been added, and the lower age limit for quinolone prescriptions has been raised from 16 years to 18 years. Issued in September 2010.

October 2009 — minor update. The recommendation on the use of amoxicillin during pregnancy and breastfeeding has been clarified. 

October 2009 — minor update. Recommendations from the National Institute for Health and Clinical Excellence (NICE) on when to suspect have been added to the section. 

July to September 2009 — 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

• WHO (2023) WHO releases new guidance to improve testing and diagnosis of sexually transmitted infections. World Health Organisation. [Free full-text]
• UKHSA & NHS (2025) Introduction of new routine mpox and 4CMenB for gonorrhoea vaccination programmes letter. UK Health Security Agency and NHS England. [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 August 2022.

Economic appraisals

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

Systematic reviews and meta-analyses

• Abara, W. E., Kirkcaldy, R. D., Bernstein, K. T., et al. (2024). Effectiveness of MenB-4C vaccine against gonorrhea: a systematic review and meta-analysis. The Journal of Infectious Diseases, jiae383. [Abstract]

Primary evidence

• Luetkemeyer AF, Donnell D, Dombrowski JC, et al. (2023) Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. New England Journal of Medicine. 388(14), 1296-1306. https://www.nejm.org/ [Abstract].

New policies

No new policies or guidelines since 1 August 2022.

New safety alerts

No new safety alerts since 1 August 2022.

Changes in product availability

No changes in product availability since 1 August 2022.

Basis for recommendation

These recommendations are based on the Public Health England (PHE) Guidance for the detection of gonorrhoea in England [PHE, 2021], the British Association for Sexual Health and HIV (BASHH) 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae [Fifer, 2020], the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults [Unemo, 2020], the World Health Organization (WHO) guideline Treatment of Neisseria gonorrhoeae [WHO, 2016], a joint guideline with the Royal College of General Practitioners Sexually transmitted infections in primary care [RCGP, 2013], and expert opinion in a review article [BMJ, 2022].

Basis for recommendation

Assessment

• These recommendations are based on the British Association for Sexual Health and HIV (BASHH) 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae [Fifer, 2020], the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults [Unemo, 2020], the World Health Organization (WHO) guideline Treatment of Neisseria gonorrhoeae [WHO, 2016], a joint guideline with the Royal College of General Practitioners Sexually transmitted infections in primary care [RCGP, 2013], and expert opinion in review articles [BMJ, 2022; Yonke, 2022].

Possible sexual abuse in children and young people

• These recommendations are based on the BASHH national guideline on the management of sexually transmitted infections and related conditions in children and young people [BASHH, 2021] and the National Institute for Health and Care Excellence (NICE) guideline Child maltreatment: when to suspect maltreatment in under 18s [NICE, 2017].
  • Sexual contact is the most likely mode of transmission in pubertal and pre-pubertal children with gonorrhoea, and sexually transmitted infections (STIs) have been suggested as markers of child sexual exploitation. A large study of 466 children in England aged 13–15 years old found that in matched univariate analysis, an STI diagnosis of gonorrhoea was significantly associated with ’highly-likely/confirmed’ child sexual exploitation and safeguarding concerns. Evidence of an association between STI diagnosis and ’highly-likely/confirmed’ child sexual exploitation persisted after adjustment for partner numbers and prior clinic attendance [BASHH, 2021].
  • The recommendations on when to consider the possibility of sexual abuse are based on the NICE guideline [NICE, 2017].

Basis for recommendation

These recommendations are largely based on the Public Health England (PHE) Guidance for the detection of gonorrhoea in England [PHE, 2021], the British Association for Sexual Health and HIV (BASHH) 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae [Fifer, 2020], and the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults [Unemo, 2020].

Nucleic acid amplification tests (NAATs)

• NAATs amplify and detect nucleic acid sequences that are specific for the organism being detected. 
  • They are extremely sensitive and can detect very small amounts of DNA or ribosomal RNA (rRNA). However, detection does not mean the organism is viable. 
  • NAATs are approved for most anatomical sites and show high sensitivity (more than 96%) in both symptomatic and asymptomatic infection, which is higher than for culture (85–95%). Therefore, although NAATs are not licensed for use at extra-genital sites, their use is recommended.
  • NAATs do not provide information on antimicrobial susceptibility. Culture is essential for monitoring antimicrobial susceptibility and to detect emerging resistance to therapy.
• NAATs show equivalent sensitivity in urine and urethral swab specimens from cisgender men, but a first-pass urine is the preferred sample.
• Vulvovaginal swabs (self-collected or clinician-collected) perform better than endocervical swabs and significantly better than urine for cisgender women. Vulvovaginal swabs are therefore recommended as the optimal approach to obtaining a specimen.

Culture

• Microbial culture is the process by which viable organisms are isolated from an infected patient and grown in the laboratory for identification and antimicrobial susceptibility testing.
• Culture for Neisseria gonorrhoeae is less sensitive than NAATs; however, it is still required to detect clinical isolates with resistance to first-line treatment, to inform individual management (especially where treatment failure is suspected), and for national public health surveillance.
• The sensitivity of a culture depends on several factors, including time from sample collection to plating. Services should seek to minimize this time whether by direct plating in the clinic or use of transport media with prompt transfer for plating in the laboratory.

Pharyngeal testing

Previous guidelines recommended pharyngeal sampling in anyone with genital gonorrhoea who was at risk of ceftriaxone-resistant infection, based on travel history. In practice this is difficult to implement, and resistance is not confined to those with a travel history. Therefore, anyone with genital gonorrhoea (regardless of travel, gender or reported sexual behaviour) should have pharyngeal sampling prior to treatment [BASHH, 2025].

Basis for recommendation

The information on the differential diagnoses of gonorrhoea is based on the British Association for Sexual Health and HIV (BASHH) 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae [Fifer, 2020], the World Health Organization (WHO) guideline Treatment of Neisseria gonorrhoeae [WHO, 2016], a joint guideline with the Royal College of General Practitioners Sexually transmitted infections in primary care [RCGP, 2013], and expert opinion in a review article [BMJ, 2022].

When should I admit or refer a person with gonorrhoea?

All people with gonorrhoea should be referred to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service for management. If the person is unwilling or unable to attend a GUM clinic or other local specialist sexual health service, management can be undertaken in primary care if the appropriate expertise is available and in line with local procedures and protocols.

• Arrange hospital admission for:
  
  • People with suspected disseminated gonorrhoea (systemic symptoms may be present, such as fever, malaise, joint pain and swelling, and rash).
  • Women with severe or complicated pelvic inflammatory disease. For more information, see the CKS topics on Pelvic inflammatory disease.
• Refer the following people to the appropriate speciality:   
  • Women with suspected ascending infection. For more information, see the CKS topics on Pelvic inflammatory disease.
  • People with complications. 
  • People with conjunctival gonorrhoea.
  • People who do not respond (or are allergic) to recommended antibiotics.

How should I manage a person with gonorrhoea infection?

All people with gonorrhoea should be referred to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service for management. If the person is unwilling or unable to attend a GUM clinic or other local specialist sexual health service, management can be undertaken in primary care if the appropriate expertise is available and in line with local procedures and protocols.

If the person is unwilling, or unable, to attend a GUM clinic or other local specialist sexual health service despite receiving appropriate information and advice: 

• Prescribe antibiotic treatment. Ideally, a culture should be taken before prescribing antibiotics, to test for susceptibility and identify resistant strains.
  • For people with uncomplicated anogenital or pharyngeal infection:
    • Ceftriaxone 1 g intramuscularly (IM) as a single dose. 
  • The following alternative treatments are recommended for people with an allergy, needle phobia, or other contraindications: 
    • Gentamicin 240 mg IM as a single dose plus azithromycin 2 g orally.
    • Cefixime 400mg given orally, followed by another 400mg dose 6-12 hours later; plus azithromycin 2 g orally (which may be divided as two 1g doses 6-12 hours apart) should also be given. Only advisable if an IM injection is contraindicated and antimicrobial susceptibility results are available.
    • Azithromycin 2 g as a single oral dose.
    • Ciprofloxacin 500 mg orally as a single dose. Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA, which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.
    • When using alternative regimens without antibiotic susceptibility data, it is recommended to regularly review local and national trends in gonococcal antimicrobial resistance. 
  • For people with penicillin allergy, ceftriaxone and cefixime are suitable treatment options unless there is a history of severe hypersensitivity (for example, anaphylactic reaction) to any beta-lactam antibacterial agent (penicillins, cephalosporins, monobactams, or carbapenems).
  • For pregnant or breastfeeding women, prescribe ceftriaxone 1 g IM injection as a single dose.
    • Azithromycin 2 g as a single oral dose can be used if adequate alternatives are not available and the isolate is known to be susceptible. Otherwise, seek specialist advice.
    • Do not prescribe ciprofloxacin.
• Offer screening for other sexually transmitted infections (STIs) and HIV.
  • This should be done according to the British Association for Sexual Health and HIV (BASHH) STI testing guidelines. 
• Encourage patient-led partner notification.
  • Advise the person on:
    • The importance and benefits of partner notification.
    • The possibility of sexual partners being infected even if asymptomatic.
    • The risk of reinfection.
  • For more information, see the section on partner notification.
• Provide appropriate information and advice.
  • Advise the person to attend a GUM clinic or other local specialist sexual health service if possible.
  • Discuss the possible complications of untreated gonorrhoea.
  • Advise the person to abstain from sex until 7 days after they and their partner(s) have completed treatment.
  • Advise the person on using safer sexual practice in the future.
  • The NHS website (www.nhs.uk) has useful patient information on gonorrhoea.
  • If appropriate, the patient information found in the MHRA Drug Safety Update on fluoroquinolone antibiotics.
• Follow up the person after about 1 week.
  • Test of cure is recommended for all people who have been treated for gonorrhoea.
    • Note: Routine test of cure is not necessary for anogenital infections treated with ceftriaxone 1g if infection is susceptible to ceftriaxone.
  • For more information, see the section on Follow up.

How should I manage the sexual contacts of a person with gonorrhoea?

Partner notification is essential for all people with newly diagnosed gonorrhoea. Ideally, this should be done by a trained health adviser in genito-urinary medicine (GUM). If this is not possible, it may be done by a primary healthcare professional who has undergone appropriate training and has support from healthcare advisers in GUM.

• The following partners should be notified:  
  • For men with symptomatic urethral infection, all sexual partners within the preceding 2 weeks, or their most recent partner if this was longer than 2 weeks ago.
  • For all other people (that is, women and men with asymptomatic gonorrhoea or gonorrhoea at other sites), all partners within the preceding 3 months.
• Empirical treatment is not needed for all sexual contacts.
  • For those presenting after 14 days of exposure, empirical treatment is recommended only following a positive test for gonorrhoea.
  • For those presenting within 14 days of exposure, empirical treatment should be considered based on a clinical risk assessment and following a discussion with the person. In asymptomatic individuals, it may be appropriate to not give epidemiological treatment, and to repeat testing 2 weeks after exposure.
• The British Association for Sexual Health and HIV (BASHH) statement on partner notification outlines the general principles on partner notification for sexually transmitted infections (STIs).

What follow up is required for a person with gonorrhoea?

• Follow up all people with gonorrhoea about 1 week after treatment to:
  • Confirm that the person has adhered to treatment and symptoms have resolved.
  • Ask about adverse reactions.
  • Confirm that partner notification has been carried out.
  • Ask about recent sexual history (and the possibility of re-infection).
  • Reinforce advice on safe sexual practice.
• A test of cure (TOC) is recommended for all people who have been treated for gonorrhoea.
  • If it is not possible or practical to perform a TOC in all people treated for gonorrhoea, prioritize the following groups:
    • People with persistent symptoms or signs.
    • People with pharyngeal infection.
    • People who have been treated with anything other than the first-line antibiotic regimen when antimicrobial susceptibility was unknown.
    • People who acquired the infection in the Asia-Pacific region when antimicrobial susceptibility was unknown.
  • A positive TOC could be due to treatment failure, reinfection, or residual non-viable organism, and should be interpreted in the clinical context:
    • If signs or symptoms persist, test with culture performed at least 3 days after completion of treatment. Consider additional testing with NAAT (for increased sensitivity) after 1 week if culture is negative.
    • If the person is asymptomatic, test with nucleic acid amplification testing (NAAT) where available (followed by culture if positive), at least 2 weeks after completion of treatment.
  • The time to a negative TOC using NAATs is variable and there are limited data to inform optimum time to TOC. However, most people should be negative 7 days following treatment where an RNA NAAT is used and 14 days following treatment when using a DNA NAAT.
• Cases of possible ceftriaxone treatment failure in England should be reported to Public Health England (PHE) via the online HIV and STI web portal.
  • Only authorised users are permitted to access this secure website.
  • All specialist sexual health clinics should have access.
  • If required, usernames and passwords can be obtained from gumcad@phe.gov.uk.

Contraindications and cautions

• Do not prescribe cephalosporins to people with:
  • Known hypersensitivity to any cephalosporins.
  • A history of immediate hypersensitivity to penicillin and other beta-lactams. 
    
    • Cross-reactivity between penicillins and first- and early second-generation cephalosporins has been reported to occur in up to 10%, and for third-generation cephalosporins in 2–3%, of people with a penicillin allergy. 
    • Note that gastrointestinal adverse effects alone (for example, nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
• Prescribe ceftriaxone with caution to people with:
  • A history of:
    • Hypercalciuria.
    • Kidney stones.
    • Gastrointestinal disorders (for example, colitis).
  • Sensitivity to penicillin and other beta-lactams.
  • Severe hepatic impairment.
  • Severe renal impairment in combination with hepatic impairment — reduce the dose and monitor the efficacy of the treatment.
    • In adults: reduce the dose if creatinine clearance is less than 10 mL/minute (maximum of 2 g daily). 
• Prescribe cefixime with caution in:
  • People with severe renal impairment.
    • In adults: reduce the dose if the creatinine clearance is less than 20 mL/minute (maximum of 200 mg once daily). 

[Fifer, 2020; ABPI, 2022a; ABPI, 2022b; BNF, 2022]

Adverse effects

• Adverse effects of all cephalosporins include:
  • Common or very common — abdominal pain, diarrhoea, dizziness, eosinophilia, headache, leucopenia, nausea, neutropenia, pseudomembranous enterocolitis, skin reactions, thrombocytopenia, vomiting, and vulvovaginal candidiasis.
  • Uncommon — anaphylactic reaction and angio-oedema.
  • Rare or very rare — agranulocytosis, haemolytic anaemia, nephritis tubulointerstitial (reversible), and severe cutaneous adverse reactions (SCARs).
• Adverse effects of ceftriaxone also include:
  • Uncommon — anaemia, coagulation disorder, and fungal infection.
  • Rare or very rare — bronchospasm, glycosuria, haematuria, and oedema.
  • Frequency not known — antibiotic-associated colitis, cholelithiasis, hypersensitivity, nephrolithiasis, oral disorders, pancreatitis, seizure, and vertigo. Precipitates of calcium ceftriaxone can occur in the gall bladder and urine (particularly in those who are very young, dehydrated, or immobilized) — consider discontinuation if the person is symptomatic.
• Adverse effects of cefixime also include:
  
  • Frequency not known — acute kidney injury, arthralgia, drug fever, dyspepsia, dyspnoea, facial oedema, flatulence, genital pruritus, hypereosinophilia, jaundice, serum sickness-like reaction, and thrombocytosis.

[BNF, 2022]

Drug interactions

• Drug interactions of ceftriaxone include:
  • Calcium chloride — ceftriaxone increases the risk of cardio-respiratory arrest when given with calcium chloride.
    • Manufacturer advises avoid.
  • Colistimethate (particularly intravenous [IV]) — potentially increases the risk of nephrotoxicity when given with ceftriaxone.
    • Manufacturer makes no recommendation.
  • Phenindione — ceftriaxone potentially increases the risk of bleeding events when given with phenindione.
    • Manufacturer makes no recommendation.
  • Warfarin — cephalosporins may enhance the anticoagulant effect. 
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Drug interactions of cefixime include:
  • Colistimethate (particularly IV) — potentially increases the risk of nephrotoxicity when given with ceftriaxone.
    • Manufacturer makes no recommendation.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after a course of ceftriaxone or cefixime. However, women should be advised on the importance of correct contraceptive practice if they experience vomiting or diarrhoea. 

See the electronic Medicines Compendium (eMC) or the British National Formulary (BNF) for a complete list of the drug interactions of ceftriaxone and cefixime.

[ABPI, 2022a; ABPI, 2022b; BNF, 2022]

Contraindications and cautions

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which 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 — ciprofloxacin has been shown to cause arthropathy in animal studies.
  • Breastfeeding women — ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, it should not be used during breastfeeding.
  • People who have previously had serious adverse reactions with a quinolone antibiotic (for example, nalidixic acid) or a fluoroquinolone antibiotic.
• Prescribe ciprofloxacin with caution to people with:
  • An age greater than 60 years, for those with renal impairment, or solid-organ transplants, as these people are at a higher risk of tendon injury.
  • Risk factors for QT interval prolongation, such as:
    • Uncorrected electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, symptomatic arrhythmias, or bradycardia).
    • Electrolyte disturbances.
    • Congenital long QT syndrome.
    • Concurrent use of drugs that are known to prolong the QT interval (for example, Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
  • Epilepsy, or conditions that predispose to seizures, and in people taking other medication that may predispose to seizures.
    • Quinolones can lower the seizure threshold.
    • Quinolones may induce convulsions in people with or without a history of convulsions, and taking nonsteroidal anti-inflammatory drugs (NSAIDs) at the same time may also induce them.
    • A single dose for the treatment of gonorrhoea is unlikely to be significant.
  • History of a psychotic disorder — there have been reports of suicidal thoughts or self-endangering behaviour after use of quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
  • Diabetes  — may affect blood glucose.
  • G6PD deficiency.
  • 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 (for example, 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).

[ABPI, 2020; BNF, 2022; MHRA, 2023]

Adverse effects

• Adverse effects of quinolones include:
  • Seizures — quinolones may induce convulsions in people with or without a history of convulsions. Taking nonsteroidal anti-inflammatory drugs (NSAIDs) at the same time may also induce them.
  • Musculoskeletal and nervous systems disorders — disabling, long-lasting, or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with quinolones. Tendon damage, including rupture has been reported rarely in people receiving quinolones. Tendon rupture may occur within 48 hours of starting treatment; cases have also been reported several months after stopping a quinolone.
    
    • Advise the person to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and contact their doctor immediately.
  • Aortic aneurysm and dissection — there is a small increased risk of aortic aneurysm and dissection with quinolone treatment.
    • Advise the person to seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops. 
  • Heart valve regurgitation — there is a small risk of heart valve regurgitation with quinolones.
    • Advise the person to seek immediate medical attention if they experience a rapid onset of shortness of breath (especially when lying down flat in bed), swelling of the ankles, feet, or abdomen, or new-onset heart palpitations.
• Other adverse effects of quinolones include:
  • Common or very common — arthralgia, asthenia, constipation, decreased appetite, diarrhoea, dizziness, dyspnoea, eye discomfort, eye disorders, fever, fungal infection, gastrointestinal discomfort, headache, myalgia, nausea, QT interval prolongation, skin reactions, sleep disorders, altered taste, tinnitus, vision disorders, and vomiting.
  • Uncommon — abnormal sensation, altered smell sensation, anaemia, anxiety, arrhythmias, chest pain, confusion, cough, depression, drowsiness, dry eye, eosinophilia, eye inflammation, flatulence, hallucination, hearing impairment, hepatic disorders, hyperglycaemia, hyperhidrosis, hypersensitivity, hypoglycaemia, hypotension, leucopenia, muscle weakness, neutropenia, pain, palpitations, peripheral neuropathy (sometimes irreversible), pseudomembranous enterocolitis (in adults), renal impairment, seizure, stomatitis, tendon disorders, thrombocytopenia, tremor, and vertigo.
  • Rare or very rare — abnormal gait, agranulocytosis, angioedema, arthritis, coordination abnormal, haemolytic anaemia, idiopathic intracranial hypertension, myasthenia gravis aggravated, pancreatitis, photosensitivity reaction, polyneuropathy, psychotic disorder, severe cutaneous adverse reactions (SCARs), suicidal behaviours, syncope, and vasculitis.  
  • Frequency not known — heart valve incompetence.
• Adverse effects of ciprofloxacin also include:
  
  • Uncommon — akathisia and fungal superinfection.
  • Rare or very rare — antibiotic-associated colitis, asthma, bone marrow disorders, crystalluria, erythema nodosum, haematuria, increased muscle tone, intracranial pressure, leucocytosis, migraine, muscle cramps, nephritis tubulointerstitial, oedema, olfactory nerve disorder, status epilepticus, thrombocytosis, and vasodilation.
  • Frequency not known  — altered mood and self-injurious behaviour.
• 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, 2018; MHRA, 2019; MHRA, 2020; BNF, 2022; MHRA, 2023]

Drug interactions

• Drug interactions of ciprofloxacin include:
  • 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 people.
  • 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.
  • Food —  the manufacturer advises avoiding concurrent administration of dairy products and mineral-fortified drinks with oral ciprofloxacin due to reduced exposure.
  • Methotrexate — plasma levels of methotrexate may be increased.
    • The manufacturer recommends that concomitant use is 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.
    • Avoid concurrent administration. 
  • 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 is 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.
    • Concurrent administration should be done with caution.

See the electronic Medicines Compendium (eMC) or the British National Formulary (BNF) for a complete list of the drug interactions of ciprofloxacin.

[Preston, 2020; ABPI, 2021; BNF, 2022; MHRA, 2023]

Contraindications and cautions

• Prescribe azithromycin with caution in people with:
  • Risk factors for QT interval prolongation, such as:
    • Uncorrected electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, symptomatic arrhythmias, or bradycardia).
    • Congenital long QT syndrome.
    • Concurrent use of drugs that are known to prolong the QT interval (for example Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
  • Hepatic impairment — the manufacturer advises to consider avoiding in severe impairment (no information available).
  • Renal impairment — use with caution if estimated glomerular filtration rate (eGFR) is less than 10 mL/minute/1.73 m².
  • Myasthenia gravis — macrolides may aggravate symptoms.

[ABPI, 2022c; BNF, 2022] 

Adverse effects

• Adverse effects of all macrolides include:
  • Common or very common — decreased appetite, gastrointestinal adverse effects (such as nausea, vomiting, diarrhoea, gastrointestinal discomfort, altered taste), dizziness, headache, hearing impairment, insomnia, pancreatitis, paraesthesia, skin reactions, vasodilation, and vision disorders.
  • Uncommon — angio-oedema, anxiety, arrhythmias, Candida 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 — antibiotic-associated colitis, myasthenia gravis, and nephritis tubulointerstitial.
  • Frequency not known — altered smell, hallucination, hypotension, seizure, thrombocytopenia, and tongue discolouration.
• Adverse effects of azithromycin also include:
  • Common or very common — arthralgia.
  • Uncommon — numbness, oedema, and photosensitivity reaction.
  • Frequency not known — acute kidney injury, aggression, akathisia, haemolytic anaemia, and syncope.

[BNF, 2022]

Drug interactions

• Drug interactions of azithromycin include:
  • 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 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).
    • 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.

See the electronic Medicines Compendium (eMC) or the British National Formulary (BNF) for a complete list of the drug interactions of azithromycin.

[Preston, 2020; ABPI, 2021; BNF, 2022]