Previous changes

May 2024 — reviewed. A literature search was conducted in April 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring with a section added on Assessment and Clinical features.  No major changes to the recommendations have been made. 

March 2024 — minor update. Information on the use of fluoroquinolones was added to the ofloxacin prescribing section in line with a review published by the MHRA. Adverse effects of doxycycline updated in line with the manufacturer's SPC. 

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.

July 2023 — minor update. The manufacturer's SPC for metronidazole has been updated to note that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

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

August to September 2019 — reviewed. A literature search was conducted in August 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

January 2019 — minor update. Treatment options updated to be brought in line with updated BASHH guideline, Management of non-gonococcal urethritis. 

October 2018 — minor update. Adverse effects updated within prescribing information - metronidazole. 

June 2018 — minor update. Prescribing information updated with information regarding azithromycin interacting with colchicine.  

December 2016 — minor update. Drug reaction with eosinophilia and systemic symptoms (DRESS) has been added as a possible adverse effect of azithromycin.

July 2015 — minor update. Minor typographical errors have been corrected.

February to March 2015 — reviewed. A literature search was conducted in February 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. There are no major changes to the recommendations in this topic. A prescribing information section has been added.

September 2010 — minor update. The Basis for recommendation section for the choice of antibiotic treatment in suspected gonococcal urethritis has been updated. 

July to September 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.

September 2008 — minor correction to the Changes section. 

January to March 2006 — reviewed. Validated in June 2006 and issued in July 2006.

November 2005 — minor technical update. 

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

January 2000 — written. Validated in March 2000.

New evidence

Evidence-based guidelines

• BASHH (2026) British Association of Sexual Health and HIV National guideline on the management of non-gonococcal urethritis (NGU), 2026. British Association of Sexual Health and HIV https://www.bashh.org [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2024.

Economic appraisals

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

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 May 2024.

Primary evidence

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

New policies

No new national policies or guidelines since 1 May 2024.

New safety alerts

No new safety alerts since 1 May 2024.

Changes in product availability

No changes in product availability since 1 May 2024.

Basis for recommendation

This information is based on the British Association for Sexual Health and HIV (BASHH) 2015 UK national guideline on the management of non-gonococcal urethritis [Horner, 2015], the European Association of Urology (EAU) guideline Urological infections [EAU, 2024], the 2016 European guideline on the management of non-gonococcal urethritis [Horner, 2016], the Royal College of General Practitioners (RCGP) and BASHH guideline Sexually transmitted infections in primary care [RCGP, 2013], and the BMJ Best Practice guide Urethritis [BMJ Best Practice, 2023]. 

Basis for recommendation

These recommendations are based on the British Association for Sexual Health and HIV (BASHH) 2015 UK national guideline on the management of non-gonococcal urethritis [Horner, 2015], the 2019 UK National guideline for consultations requiring sexual history taking: Clinical Effectiveness Group British Association for Sexual Health and HIV [Brook, 2020], the BASHH Summary guidance on testing for sexually transmitted infections, 2023 [BASHH, 2023] the European Association of Urology (EAU) guideline Urological infections [EAU, 2024], the Royal College of General Practitioners (RCGP) and BASHH guideline Sexually transmitted infections in primary care [RCGP, 2013], the BMJ Best Practice guide Urethritis [BMJ Best Practice, 2023], and the National Institute for Health and Care Excellence (NICE) quality standard Sexual health [NICE, 2022].

Basis for recommendation

This information is based on the BMJ Best Practice guide Urethritis [BMJ Best Practice, 2023], the British Association for Sexual Health and HIV (BASHH) 2015 UK national guideline on the management of non-gonococcal urethritis [Horner, 2015], expert opinion in a chapter on Urethritis in a medical textbook [Horner, 2020], and a narrative review Urethritis: rapid evidence review [Sell, 2021].

How should I manage a man with suspected urethritis?

• Refer all men with suspected urethritis to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service for confirmation of the diagnosis (and treatment).
  • A sexually transmitted infection (STI) is generally considered to be the underlying cause of urethritis in most cases.
• If the man is unable or unwilling to attend a GUM clinic (or other local specialist sexual health service) manage in primary care. 

For men being managed in primary care:

• Offer empirical treatment for non-gonococcal urethritis with doxycycline 100 mg twice daily for 7 days. Where doxycycline is contraindicated or not tolerated, possible alternatives are:
  • Azithromycin 1g, single dose for 1 day, then 500 mg once daily for 2 days (Note: people taking azithromycin should be advised to abstain from sexual intercourse until 14 days after the start of treatment and until symptoms have resolved). 
  • Ofloxacin 200 mg twice daily or 400 mg once daily for 7 days.
    • 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 in reducing the identified risk of disabling and potentially long-lasting or irreversible side effects. 
• If gonococcal urethritis is suspected (for example, if there is a local outbreak of gonorrhoea), consider treating for gonorrhoea. For more information, see the CKS topic on Gonorrhoea.  
• If trichomoniasis is suspected (for example, if the partner has trichomoniasis), consider treating for trichomoniasis. For more information see the CKS topic on Trichomoniasis. 
• Give advice about:
  • The most likely cause of urethritis which is usually, but not always, due to an STI. 
  • Possible short-term and long-term complications for them and their partners(s).
  • The importance of adhering to treatment, as well as possible side effects. 
  • Abstaining from sex (including oral sex) until they and their partner(s) have completed treatment. 
  • The importance of safer sexual practices in reducing the future risk of acquiring STIs (for example, the consistent and correct use of condoms).
    • Note: patient information leaflets on male urethritis are available from the British Association for Sexual Health and HIV (BASHH) and the Family Planning Association.
  • The use of fluoroquinolones, if appropriate. Information is available in the MHRA Drug Safety Update on fluoroquinolone antibiotics.
• Advise the person that all their recent sexual partners should be notified and advised to attend a GUM clinic. 
• Consider arranging follow-up 1-2 weeks after treatment: 
  • Review the person for persistent symptoms which may indicate treatment failure.
  • Confirm that contact tracing has been carried out. The duration of contact tracing varies:
    • For men who have tested positive for chlamydia, see the CKS topic Chlamydia - uncomplicated genital.
    • For men who have tested positive for gonorrhoea, see the CKS topic Gonorrhoea.
    • For all other men, the recommended duration is all partners within the previous 4 weeks. 
  • Discuss the results of the STI screen and manage appropriately. For more detailed information on management see the CKS topics on Gonorrhoea, Chlamydia - uncomplicated genital, Trichomoniasis, HIV infection and AIDS, Syphilis, Hepatitis A, Hepatitis B, and Hepatitis C.

How should I manage treatment failure?

• If symptoms persist or recur after treatment is completed, strongly advise the person to attend a genito-urinary medicine (GUM) clinic or other local specialist sexual health service. If this is declined or not possible:
  • Check adherence to the drug treatment regime.
  • Exclude the possibility of re-infection. Check that current partner(s) have been treated appropriately and simultaneously. 
  • Reconsider the diagnosis. Ensure that other causes of symptoms or alternative diagnoses have been excluded.
  • If treated with doxycycline regimen first line, then prescribe azithromycin 1 g single dose for one day, then 500 mg once daily for the next 2 days, plus metronidazole 400 mg twice daily for 5 days. 
    • Azithromycin should be started within 2 weeks of finishing doxycycline.
  • Patients should be advised to abstain from sexual intercourse until 14 days after the start of treatment and until symptoms have resolved. 
  • If treated with azithromycin regimen first line, then prescribe moxifloxacin 400 mg once daily for 10 days, plus metronidazole 400 mg twice daily for 5 days. 
    • Or alternatively, prescribe doxycycline 100 mg twice daily for 7 days, plus metronidazole 400 mg twice daily for 5 days. (Note: if Mycoplasma genitalium detection assays have not been carried out and a negative result has not been confirmed, consider trying this regimen rather than using moxifloxacin).
  • If symptoms persist despite a second course of antibiotics, seek specialist advice. 

Contraindications and cautions

• Do not prescribe doxycycline to:
  • Pregnant women.
  • Breastfeeding women.
  • 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).
  • Myasthenia gravis — muscle weakness may be increased.
  • Systemic lupus erythematosus — symptoms may be exacerbated.
  • Alcohol dependence — alcohol may decrease the half-life of doxycycline.

[MHRA, 2023a; BNF, 2024]

Adverse effects

• Blood disorders
  • Rare: haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia.
• Gastrointestinal 
  • Common: diarrhoea, nausea, and vomiting.
  • Uncommon: dyspepsia, abdominal discomfort, diarrhoea, and tooth discolouration and enamel hypoplasia in children.
  • Rare: dysphagia, oesophagitis, oesophageal irritation, and pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Hepatic disorders
  • Rare: hepatotoxicity, hepatitis, jaundice, and hepatic failure.
• Skin 
  • Common: photosensitivity and rash.
  • Rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, exfoliative dermatitis, photo-onycholysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and fixed eruption.
• Other rare adverse effects include:
  • Anaphylaxis.
  • Anxiety.
  • Arthralgia and myalgia.
  • Blood urea increased.
  • Bulging fontanelles in infants.
  • Flushing.
  • Intracranial hypertension.
  • Jarisch-Herxheimer reaction.
  • Porphyria and reduced appetite.
  • Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension, a rare but serious adverse effect.
  • Tinnitus.

[MHRA, 2023a; BNF, 2024]

Drug interactions

Possible drug interactions 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. 
  • Doxycycline dose may need to 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, and 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), and adjust the lithium dose as needed.
• Retinoids — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with retinoids (such as isotretinoin). Concurrent use is contraindicated.
• Rifampicin — doxycycline levels are markedly reduced, which may lead to treatment failure. Monitor the effects and increase doxycycline dose if necessary.
• Coumarin anticoagulants (for example, warfarin) — doxycycline may increase the anticoagulant effect of warfarin. Consider increasing monitoring of INR.
• Live cholera vaccine — the efficacy of the vaccine may be reduced. Avoid concurrent use and for 14 days before, and for 10 days after, receiving live cholera vaccines.
• Live typhoid vaccine — immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]

Contraindications and cautions

• Do not prescribe azithromycin to people:
  • With severe hepatic impairment. 
• Prescribe azithromycin with caution to people with:
  • Risk factors for QT interval prolongation, such as:
    • Electrolyte disturbance (particularly hypokalaemia or hypomagnesaemia). 
    • Clinically relevant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency. 
    • Congenital or acquired QT prolongation. 
    • Concurrent use of drugs that are known to prolong the QT interval (for example, Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics). 
  • Mild to moderate hepatic impairment. 
  • Renal impairment — use with caution if estimated glomerular filtration rate (eGFR) is less than 10 mL/min/1.73 m². 
  • Myasthenia gravis — may aggravate symptoms. 

[EMC, 2023; BNF, 2024]

Adverse effects

• Gastrointestinal
  • Common or very common: abdominal pain, nausea, vomiting, diarrhoea, dyspepsia, flatulence.
  • Uncommon: constipation, dysphagia, dry mouth, mouth ulceration, salivary hypersecretion. 
• Infections and infestations
  • Uncommon: candidiasis, oral candidiasis, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory disorder, rhinitis.
• Nervous system
  • Common: dizziness, headache, paraesthesia, dysgeusia.  
• Skin and subcutaneous tissue
  • Common: pruritus, rash.
  • Uncommon: Stevens-Johnson syndrome, photosensitivity reaction, urticaria, dermatitis, dry skin, hyperhidrosis.
• Other adverse effects include:
  • Arthralgia, myalgia.
  • Dyspnoea.
  • Ear disorders.
  • Fatigue. 
  • Hepatitis.
  • Palpitations.
  • Visual disturbances.

[EMC, 2023; BNF, 2024]

Drug interactions

Possible drug interactions include:

• Antacids — plasma concentrations of azithromycin may be reduced. Simultaneous administration should be avoided. Azithromycin should be taken at least 1 hours before, or 2 hours after antacids.
• Apixaban — azithromycin is predicted to increase the exposure to apixaban, increasing its effects. Monitor patients for signs of bleeding.
• Colchicine — azithromycin slightly increases the levels of colchicine. Concurrent use is contraindicated in renal or hepatic impairment.
• Digoxin — digoxin levels may be increased. Monitor for signs of digoxin adverse effects, measure digoxin concentrations, and reduce the dose if required.
• Edoxaban — levels may be increased by azithromycin. Monitor for signs and symptoms of bleeding or anaemia, especially, in elderly people and in those with renal impairment. Dose adjustment of edoxaban may be required.
• Ergot derivatives — there is a theoretical possibility of ergot toxicity if taken concomitantly with azithromycin. Advise people to report symptoms including numb, cold extremities, tingling, muscle pain.
• Rifabutin — azithromycin increases the risk of neutropenia when given with rifabutin. Monitor closely.
• Statins — there is a possible increased risk of myopathy. Monitor concurrent use.
  • Advise the person to report any muscle pain, tenderness, or weakness.
• Warfarin — occasionally and unpredictably, the effects of warfarin may be markedly increased by macrolides. Consider increasing INR monitoring. 
• Drugs that cause hypokalaemia (such as beta2-agonists, corticosteroids, thiazide and loop diuretics) — increased risk of torsades de pointes. Monitor potassium levels closely.
• Drugs that prolong the QT interval (such as amiodarone, hydroxyzine, domperidone, sotalol) — all macrolides can prolong the QT interval, and concomitant use of drugs that prolong the QT interval is not contraindicated
  • Use an alternative antibiotic and/or seek advice from a microbiologist.
• Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, receiving live cholera vaccines.
• Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]

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 ofloxacin to people:
  • With glucose-6-phosphate dehydrogenase deficiency.
  • With a history of tendon disorders related to quinolone use. 
  • With a history of epilepsy or an existing central nervous system disorder with a lowered seizure threshold.
  • Taking corticosteroids — co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture. 
• Do not prescribe ofloxacin to:
  • Children or growing adolescents.
• Prescribe ofloxacin with caution to:
  • People aged over 60 years. 
  • People who have had solid organ transplants. 
• Prescribe ofloxacin with caution to people with:
  • A predisposition to seizures, and in people taking other medication that may predispose to seizures (such as nonsteroidal anti-inflammatory drugs), as quinolones can lower the seizure threshold.
  • Diabetes mellitus — may affect blood glucose. Blood glucose should be monitored closely.
  • A history of tendonitis — quinolones can very rarely cause tendon damage, and the risk of tendon rupture is increased by co-administration of corticosteroid.
  • Renal impairment — give usual initial dose, then use half normal dose if creatinine clearance 20–50 mL/minute; 100 mg once daily if creatinine clearance less than 20 mL/minute. 
  • A family history of aneurysm disease or congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic 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.
  • Hepatic impairment.  
  • Conditions which predispose to QT interval prolongation:
    • Congenital long QT syndrome. 
    • Concomitant use of drugs that are known to prolong the QT interval (for example Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics). 
    • Uncorrected electrolyte imbalance (for example hypokalaemia, or hypomagnesaemia). 
    • Cardiac disease (for example, heart failure, myocardial infarction, arrhythmias or bradycardia).
    • Electrolyte disturbances.
  • A 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. 

[MHRA, 2018; MHRA, 2019; MHRA, 2020; EMC, 2022; MHRA, 2023b; BNF, 2024; MHRA, 2024]

Adverse effects

Possible adverse effects of ofloxacin include:

• Cardiovascular
  • Rare: tachycardia.
  • Unknown frequency: ventricular arrhythmias, torsades de pointes, QT interval prolongation.
  • Aortic aneurysm and dissection — there is an increased risk with fluoroquinolones (rare). Advise people to seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops.
  • Heart valve regurgitation — advise to seek immediate medical attention if there is rapid-onset breathlessness (especially if lying flat); ankle, foot, or abdominal swelling; or new-onset heart palpitations.
• Gastrointestinal
  • Uncommon: abdominal pain, diarrhoea, nausea, vomiting.
• Musculoskeletal
  • Rare or very rare: arthralgia, myalgia, tendon damage including tendonitis and tendon rupture.
    • Tendon rupture may occur within 48 hours of starting treatment or months after stopping a quinolone. Risk of tendon rupture is increased by concomitant corticosteroids and in people aged over 60 years. If tendonitis or tendon rupture is suspected, advise to stop ofloxacin immediately and seek medical advice.
• Central nervous system 
  • Uncommon: headache, dizziness.
  • Rare: sleep disorders, taste disorders, paraesthesia, memory impairment. 
  • If peripheral neuropathy, muscle weakness, or serious CNS adverse effects are suspected, advise to stop ofloxacin immediately and seek medical advice.
• Psychiatric
  • Uncommon: agitation, sleep disorder, insomnia.
  • Rare: confusion, anxiety, depression, nightmares.
• Skin and subcutaneous tissue
  • Uncommon: rash, pruritus. 
• Other adverse effects
  • Anaphylaxis,
  • Dyspnoea
  • Fever.
  • Increased risk of infection.
• Fluoroquinolones can very rarely cause long-lasting, disabling, and potentially irreversible adverse effects, sometimes affecting multiple organ systems.
• People should be advised to stop fluoroquinolone 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 or central nervous system effects. 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; EMC, 2022; MHRA, 2023b; BNF, 2024; MHRA, 2024]

Drug interactions

Possible drug interactions include:

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these may reduce the absorption of ofloxacin if taken concurrently. Ofloxacin should be taken at least 2 hours before and not less than 4 to 6 hours after these preparations.
• Corticosteroids — the risk of tendonitis and tendon rupture is increased in people taking a fluoroquinolone and a corticosteroid. Avoid concurrent use. 
• Ergometrine — quinolones may increase levels of ergot derivatives, which may cause ergotism. Avoid concurrent use. 
• Mycophenolate — levels may be reduced if taken concurrently with ofloxacin. Monitor for efficacy. 
• 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.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate. Temporarily stop strontium treatment if ofloxacin is necessary. 
• Coumarin anticoagulants (such as warfarin) — quinolones may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalised ratio (INR) within 3 to 5 days of starting ofloxacin and adjust the dose if necessary. 
• Zolmitriptan — quinolones increase the plasma concentration of zolmitriptan. The manufacturer recommends a maximum dose of 5 mg in 24 hours in people taking a quinolone.
• Drugs that prolong the QT interval (such as Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) — very rare cases of QT interval prolongation have been reported in people taking quinolones and they should therefore be prescribed with caution alongside drugs known to prolong the QT interval.
• Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, receiving live cholera vaccines.
• Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]

Contraindications and cautions

• Prescribe metronidazole with caution to people with:
  • Cockayne syndrome.
  • Active or chronic severe peripheral and central nervous system disease.
  • Severe liver disease or hepatic encephalopathy — prescribe one-third of the daily dosage once daily.

[BNF, 2024; EMC, 2024]

Adverse effects

• Blood disorders 
  • Very rare: agranulocytosis, neutropenia, thrombocytopenia, and pancytopenia.
  • Unknown: leucopenia and bone marrow depression disorders such as aplastic anaemia.
• Gastrointestinal 
  • Unknown: nausea, vomiting, anorexia, epigastric pain, taste disturbances, furred tongue, and oral mucositis.
• Hepatobiliary
  • Very rare: abnormal liver function tests, cholestatic hepatitis, jaundice, and pancreatitis.
• Nervous system
  • Very rare: drowsiness, dizziness, convulsions, headaches, and encephalopathy.
  • Unknown: depression, paraesthesia, and peripheral sensory neuropathy.
• Psychiatric 
  • Very rare: psychotic disorders and hallucinations.
• Skin
  • Very rare: rash, pruritus, and flushing.
  • Unknown: erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, and fixed drug eruption.
• Other rare, or very rare adverse effects include:
  • Anaphylaxis and angioedema.
  • Darkening of urine.
  • Diplopia or myopia.
  • Hearing impairment and tinnitus.
  • Liver enzyme increases, jaundice, and pancreatitis.
  • Myalgia and arthralgia.

[BNF, 2024; EMC, 2024]

Drug interactions

Possible drug interactions include:

• Alcohol — some people taking metronidazole experience a disulfiram-like reaction with alcohol.
  • Warn the person that they might experience this reaction if they drink alcohol whilst on metronidazole and for at least 48 hours afterwards. 
• Busulfan — plasma levels of busulfan increased potentially leading to toxicity. Avoid high doses of busulfan. If conventional doses of busulfan are given, monitor blood count weekly.
• Ciclosporin — levels of ciclosporin may be increased. If co-administration of metronidazole and ciclosporin is necessary, monitor serum ciclosporin and serum creatinine levels closely.
• Ergot alkaloids — levels may be increased, which may lead to ergotism. If concurrent use is unavoidable, advise the person to be alert for symptoms of ergotism (coldness, numbness, or tingling of the hands and feet), and advise them to stop treatment and seek medical advice.
• Fluorouracil — metronidazole reduces the clearance of fluorouracil, increasing the risk of toxicity. Monitor the person for increased toxicity.
• Lithium — seek specialist advice regarding the use of metronidazole with lithium, as metronidazole increases the risk of lithium toxicity. Lithium dose reduction may be required due to the risk of renal damage with concurrent use. Plasma concentrations of lithium, creatinine, and electrolytes should be monitored if metronidazole and lithium are used simultaneously.
• Phenobarbital — the metabolism of metronidazole is increased significantly. The dose of metronidazole may need to be increased.
• Coumarin anticoagulants (for example, warfarin) — the anticoagulant effects of warfarin are increased by metronidazole. 
  • Monitor the international normalized ratio (INR) and adjust the warfarin dose accordingly. 
• Live cholera vaccine — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, receiving live cholera vaccines.
• Live typhoid vaccine — immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]