Previous changes

August 2023 — minor update. A typographical error was corrected.

May to June 2023 — reviewed. A literature search was conducted in May 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with the current literature. The recommendation to treat suspected severe bacterial infection has changed from flucloxacillin to phenoxymethylpenicillin, in line with the updated European consensus publication on balanoposthitis. The Prescribing Information section has been updated accordingly.

July 2022 — minor update. Added drug interaction between clotrimazole and tacrolimus.

October 2018 — minor update. Text on the adverse effects of metronidazole has been updated in the Prescribing Information section.

February 2018 — reviewed. A literature search was conducted in January 2018 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. A section on Complications has been added to the Background information section. A section on Differential diagnosis has been added to the Diagnosis section. The management recommendations have been updated in line with the current literature. The Prescribing Information section has been updated and expanded in line with current CKS style.

July 2015 — minor update. The information on the concurrent use of clarithromycin or erythromycin with statins has been clarified.

January 2014 — minor update. Text amended to include information from the manufacturer's Summary of Product Characteristics (SPC) regarding how much clotrimazole to apply to the skin.

August 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to recommendations have been made.

August 2010 — minor update. Sulconazole 1% cream (Exelderm^®) has been discontinued. The prescription has been removed. 

February to June 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.

January 2009 — correction to a typographical error in the Overview of management section. 

August 2008 — minor update. Nystatin cream and ointment discontinued; prescriptions removed and text amended.

July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007.

November 2005 — minor technical update. 

April 2005 — minor update. Tinaderm-M^® cream (nystatin 100,000 units/g and tolnaftate 1% cream) has been discontinued. The prescription has been removed. 

October 2003 — written. Validated in December 2003 and issued in February 2004.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 May 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2023.

Economic appraisals

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

Systematic reviews and meta-analyses

No new systematic review or meta-analysis published since 1 May 2023.

Primary evidence

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

New policies

No new national policies or guidelines since 1 May 2023.

New safety alerts

No new safety alerts since 1 May 2023.

Changes in product availability

No changes in product availability since 1 May 2023.

Basis for recommendation

The recommendations on the diagnosis of balanitis are based on the European consensus publication 2022 European guideline for the management of balanoposthitis [Edwards, 2023], the British Association of Paediatric Urologists (BAPU) statement Management of foreskin conditions [British Association of Paediatric Urologists, 2013], the British Association of Dermatologists (BAD) publication Guidelines for the management of lichen sclerosus [Lewis, 2018], and expert opinion in a review article on benign male genital skin conditions [Shim, 2016].

Basis for recommendation

The recommendations on assessment are largely based on the European consensus publication 2022 European guideline for the management of balanoposthitis [Edwards, 2023], together with the joint Royal College of General Practitioners and British Association of Sexual Health and HIV (RCGP/BASHH) publication Sexually transmitted infections in primary care [BASHH, 2013], the British Association of Dermatologists (BAD) publication Guidelines for the management of lichen sclerosus [Lewis, 2018], and expert opinion in review articles on benign male genital skin conditions [Shim, 2016] and penile inflammatory skin disorders [Morris, 2017].

• The recommendation to arrange sub-preputial swabs if balanitis is severe is pragmatic, based on the fact that most cases are secondary to non-specific dermatitis with or without candidal or bacterial infection, which usually responds to empirical treatment.
• The European consensus publication states that a sub-preputial swab for candida and bacterial culture and sensitivity may be useful to exclude an infective cause or superinfection of a skin lesion or dermatosis [Edwards, 2023].
  • It also notes that Group B streptococcus and Candida may be commensals or represent opportunistic infection of an underlying skin condition [Edwards, 2023].
• The recommendation to assess for underlying immunosuppression if there is severe or persistent balanitis (or confirmed candidal infection) is based on the European consensus publication [Edwards, 2023] and expert opinion in a review article [Morris, 2017].

Basis for recommendation

The information on the differential diagnosis of balanitis is based on the European consensus publication 2022 European guideline for the management of balanoposthitis [Edwards, 2023], the British Association of Dermatologists (BAD) publication Guidelines for the management of lichen sclerosus [Lewis, 2018], the joint Royal College of General Practitioners and British Association for Sexual Health and HIV (RCGP/BASHH) publication Sexually Transmitted Infections in Primary Care [BASHH, 2013], and expert opinion in a review article on balanitis [Nemirovsky, 2022].

How should I manage a child with balanitis?

If a child presents with suspected balanitis:

• Advise on the importance of good daily hygiene.
  • Advise to wash daily with lukewarm water and to keep the foreskin retracted until the glans penis is dry, where possible.
  • Do not attempt to retract the foreskin to clean under it, if it is still fixed.
  • Avoid irritants such as soap, bubble bath, or baby wipes.
  • Consider use of an emollient as a soap substitute.
  • For infants and toddlers, advise to change nappies frequently. See the CKS topic on Nappy rash for more information.
• Advise on sources of information and support, such as:
  • The NHS information leaflet on Balanitis.
• Advise on management options depending on the likely underlying cause:
  • If there is suspected non-specific dermatitis:
    • Prescribe topical hydrocortisone 1% cream or ointment once a day, until symptoms settle or for up to 14 days. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
    • Prescribe an imidazole cream, the frequency depending on the preparation used, until symptoms settle or for up to 14 days. See the section on Topical imidazoles in the section on Prescribing information for more information.
  • If there is suspected irritant or allergic contact dermatitis:
    • Avoid any suspected triggers (such as soap, bubble bath, or creams).
    • Prescribe topical hydrocortisone 1% cream or ointment once a day until symptoms settle, or for up to 14 days. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
    • Advise on the use of a regular emollient to moisturise and use as a soap substitute. See the CKS topic on Dermatitis - contact for more information.
  • If there is suspected or confirmed candidal balanitis:
    • Prescribe an imidazole cream, the frequency depending on the preparation used, until symptoms settle or for up to 14 days. See the section on Topical imidazoles in the section on Prescribing information for more information.
    • If inflammation is causing discomfort, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
  • If there is suspected or confirmed bacterial balanitis:
    • If there is mild infection, consider use of a topical antibiotic preparation such as mupirocin 2% ointment 2–3 times a day for 7–10 days.
    • If there is severe infection, consider prescribing oral phenoxymethylpenicillin for 10 days while awaiting swab results. If there is a true penicillin allergy, prescribe oral clarithromycin for seven days. See the sections on Phenoxymethylpenicillin and Clarithromycin in the section on Prescribing information for more information including dosage regimens.
    • If inflammation is causing discomfort, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
  • If there is suspected seborrhoeic dermatitis, see the CKS topic on Seborrhoeic dermatitis for more information on management.
  • If there is another possible underlying cause or diagnostic uncertainty, arrange specialist referral. See the section on Referral for more information.
• Arrange to review the child if symptoms are severe, or have not improved following initial treatment.
  
  • Stop treatment with topical hydrocortisone if this has been used.
  • Take a sub-preputial swab to exclude or confirm a fungal or bacterial infection, and treat accordingly. Be aware that:
    • Group B streptococcus is usually a commensal and may not need treatment.
    • Candida may be a superadded infection and its presence does not exclude an underlying skin condition.
• Consider blood testing for HbA1c to assess for underlying diabetes mellitus or other causes of immunocompromise if balanitis is severe, persistent, or recurrent (especially if candida infection is present). See the CKS topics on Diabetes - type 1 for more information.

When should I refer a child with balanitis?

• Arrange referral to a paediatrician, paediatric dermatologist, or paediatric urologist or surgeon, depending on the most likely underlying cause, if:
  • The diagnosis is uncertain — biopsy may be needed.
  • There is persistent or recurrent balanitis which is not responding to management in primary care.
  • There is suspected allergic contact dermatitis — arrange referral to a dermatologist for consideration of patch testing. See the CKS topic on Dermatitis - contact for more information.
  • There is suspected lichen sclerosus and/or persistent phimosis — arrange referral to a paediatric urologist or surgeon for consideration of circumcision.

How should I manage an adult with balanitis?

If an adult presents with suspected balanitis:

• Advise on the importance of good daily hygiene.
  • Advise to wash daily with lukewarm water and to keep the foreskin retracted until the glans penis is dry, where possible.
  • Avoid irritants such as soap, bubble bath, or baby wipes.
  • Consider use of an emollient as a soap substitute.
• Advise on sources of information and support, such as:
  • The NHS information leaflet on Balanitis.
• Advise on management options depending on the likely underlying cause:
  • If there is suspected non-specific dermatitis:
    • Prescribe topical hydrocortisone 1% cream or ointment once a day, until symptoms settle or for up to 14 days. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
    • Prescribe an imidazole cream, the frequency depending on the preparation used, until symptoms settle or for up to 14 days. See the section on Topical imidazoles in the section on Prescribing information for more information.
  • If there is suspected irritant or allergic contact dermatitis:
    • Advise to avoid any suspected triggers (such as soap, bubble bath, latex condoms, lubricants, or creams).
    • Prescribe topical hydrocortisone 1% cream or ointment once a day until symptoms settle, or for up to 14 days. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
    • Advise on the use of a regular emollient to moisturise and use as a soap substitute. See the CKS topic on Dermatitis - contact for more information.
  • If there is suspected or confirmed candidal balanitis:
    • Prescribe an imidazole cream, the frequency depending on the preparation used, until symptoms settle or for up to 14 days, or oral fluconazole 150 mg as a single dose if there are severe symptoms. See the sections on Topical imidazoles and Oral fluconazole in the section on Prescribing information for more information.
    • If marked inflammation is present, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
  • If there is suspected or confirmed bacterial balanitis:
    • If there is mild infection, consider use of a topical antibiotic preparation such as mupirocin 2% ointment 2–3 times a day for 7–10 days.
    • If there is severe infection, consider prescribing oral phenoxymethylpenicillin 500 mg four times a day for 10 days while awaiting swab results. If there is a true penicillin allergy, prescribe oral clarithromycin 250 mg twice daily for seven days. See the sections on Phenoxymethylpenicillin and Clarithromycin in the section on Prescribing information for more information.
    • If inflammation is causing discomfort, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
    • If there is confirmed recurrent streptococcal balanitis, consider testing for and treating streptococcal infection in any sexual partner(s), to reduce the potential reservoir of infection.
  • If there is suspected or confirmed anaerobic (Gardnerella) balanitis:
    • Prescribe oral metronidazole 400 mg twice a day for one week. Consider prescribing co-amoxiclav 375 mg three times a day for one week as an alternative option if needed. See the sections on Metronidazole and Co-amoxiclav in the section on Prescribing information for more information.
    • If inflammation is causing discomfort, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition. See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for more information.
  • If there is suspected seborrhoeic dermatitis, see the CKS topic on Seborrhoeic dermatitis for more information on management.
  • If there is suspected genital psoriasis, see the CKS topic on Psoriasis for more information on management.
  • If there is a suspected or confirmed sexually transmitted infection, advise referral to a local sexual health clinic or manage in primary care, depending on clinical judgement.
  • If there is another possible underlying cause or diagnostic uncertainty, arrange specialist referral. See the section on Referral for more information.
• Arrange to review the person if symptoms are severe, or have not improved following initial treatment.
  • Stop treatment with topical hydrocortisone if this has been used.
  • Take a sub-preputial swab to exclude or confirm a fungal or bacterial infection, and treat accordingly. Be aware that:
    • Group B streptococcus is usually a commensal and may not need treatment.
    • Candida may be a superadded infection and its presence does not exclude an underlying skin condition.
• Consider blood testing for HbA1c, HIV, or other causes of immunocomprise, if balanitis is severe, persistent, or recurrent (especially if candida infection is present). See the CKS topics on Diabetes - type 1, Diabetes - type 2, and HIV infection and AIDS for more information.

When should I refer an adult with balanitis?

• Arrange referral to a dermatologist, sexual health specialist, or urologist, depending on the most likely underlying cause, if:
  • The diagnosis is uncertain — biopsy may be needed.
  • Balanitis is persistent or recurrent and does not respond to initial management in primary care.
  • Balanitis is recurrent and associated with phimosis — arrange referral to a urologist for consideration of circumcision.
  • There is suspected allergic contact dermatitis — arrange referral to a dermatologist for consideration of patch testing. See the CKS topic on Dermatitis - contact for more information.
  • There is suspected Zoon's balanitis — a penile biopsy may be needed to exclude a penile intraepithelial neoplasia which may present similarly.
  • There is suspected lichen sclerosus — a penile biopsy may be needed to exclude a penile intraepithelial neoplasia or malignancy.
  • There is a penile mass or persistent penile lesion (if a sexually transmitted infection has been excluded or treated) — arrange urgent referral using a two-week pathway to exclude penile intraepithelial neoplasia or malignancy. See the CKS topic on Urological cancers - recognition and referral for more information.

Contraindications and cautions

Inform the person that when using topical imidazoles:

• Avoid contact with the eyes and mucous membranes.
• Clotrimazole may cause damage to latex condoms, reducing their effectiveness. Advise the use of alternative contraception for at least five days after using this preparation. See the CKS topic on Contraception - assessment for more information.

[BNF, 2023]

Adverse effects

Topical imidazoles are generally well tolerated. Possible adverse effects include:

• Local skin irritation, rash, erythema, itch, mild burning sensation, and hypersensitivity reactions. Treatment should be discontinued if these are severe.

[BNF, 2023]

Drug interactions

Possible drug interactions with topical imidazoles include:

• Oral anticoagulants — the effect of oral anticoagulants (such as warfarin) may be enhanced by topical miconazole. Monitor the person’s international normalised ratio (INR) during concurrent use, and adjust the warfarin dose accordingly.
• Amlodipine — miconazole is predicted to increase the exposure to Amlodipine. Manufacturer advises use with caution and adjust dose.
• Atorvastatin — miconazole might increase the exposure to Atorvastatin. Manufacturer makes no recommendation.
• Carbamazepine — miconazole increases the risk of carbamazepine toxicity. Manufacturer advises monitor and adjust dose.
• Disopyramide — miconazole is predicted to increase the exposure to disopyramide. Manufacturer advises use with caution and adjust dose.
• Felodipine, lercanidipine, and nifedipine — miconazole is predicted to increase the exposure to felodipine, lercanidipine, and nifedipine. Manufacturer advises use with caution and adjust dose.
• Fluvastatin — miconazole is predicted to increase the exposure to fluvastatin. Manufacturer advises caution.
• Gliclazide and glimepiride — miconazole is predicted to increase the exposure to gliclazide and glimepiride. Manufacturer advises use with caution and adjust dose.
• Mizolastine — miconazole is predicted to increase the exposure to mizolastine. Manufacturer advises avoid.
• Phenytoin — miconazole increases the risk of phenytoin toxicity when given with phenytoin. Manufacturer advises monitor and adjust dose.
• Simvastatin — miconazole is predicted to increase the exposure to simvastatin. Manufacturer advises avoid.
• Tacrolimus — miconazole is predicted to increase the concentration of tacrolimus. Manufacturer advises monitor and adjust dose.

[BNF, 2023]

Application regimens

• Topical clotrimazole 1% is licensed for the treatment of balanitis.
  • Advise the person to apply topical clotrimazole to the affected area 2 to 3 times daily for at least two weeks.
• Topical miconazole 2% is licensed for treatment of mycotic infections of the skin and nails.
  • Advise the person to apply topical miconazole to the affected area twice daily. Treatment should be continued for 10 days after lesions have healed.
• Topical econazole 1% is licensed for the treatment of mycotic balanitis.
  • Advise the person to apply topical econazole to the affected area twice daily for at least two weeks.
• Topical ketoconazole 2% is licensed for the treatment of fungal infections of the skin.
  • Advise the person to apply topical ketoconazole to the affected area once or twice daily. Treatment should be continued for a few days after the lesions have disappeared.

[BNF, 2023]

Contraindications and cautions

Do not prescribe oral fluconazole to people:

• With acute porphyria.
• Taking other drugs known to cause QT interval prolongation (such as tricyclic antidepressants, antipsychotics, or antiarrhythmics) and drugs that are extensively metabolized by the liver, such as warfarin, statins, or some immunosuppressant drugs (such as ciclosporin).

Prescribe oral fluconazole with caution to people:

• At risk of QT interval prolongation — including people with cardiomyopathy, sinus bradycardia, arrhythmias, hypokalaemia, hypomagnesaemia, and hypocalcaemia.
• With hepatic impairment or taking concurrent hepatotoxic drugs, due to the risk of hepatic necrosis — discontinue if signs or symptoms of hepatic disease develop (such as severe abdominal pain or jaundice).  
• With renal impairment (estimated glomerular filtration rate [eGFR] less than 50mL/min/1.73m²) — use the usual initial dose then halve any subsequent doses.

[BNF, 2023]

Adverse effects

Adverse effects of oral fluconazole include:

• Common or very common
  • Abdominal discomfort, bloating, diarrhoea, nausea, flatulence, headache, rash.
• Uncommon
  • Alopecia, adrenal insufficiency, hyperlipidaemia, dizziness, seizures, dyspepsia, vomiting, and taste disturbance, hepatic disorders, pruritus, anaphylaxis, hypersensitivity reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
• Rare or very rare
  • Hypokalaemia, leucopenia, and thrombocytopenia.

[BNF, 2023]

Drug interactions

• Fluconazole inhibits the metabolism of drugs metabolized by the cytochrome P450 enzymes CYP2C9 (potently), CYP3A4 (moderately), and CYP2C19. This may result in a higher and/or prolonged action of these drugs, including adverse effects. In general, fluconazole drug interactions relate to multiple-dose treatments.
  • The following drugs are contraindicated during treatment with fluconazole:
    • Ergotamine — there is an increased risk of ergotism.
    • Erythromycin — concurrent use with fluconazole has the potential to increase the risk of cardiotoxicity (prolonged QT interval and torsades de pointes) and sudden death.
    • Pimozide — concurrent use with fluconazole may lead to QT prolongation and rare occurrences of torsade de pointes.
    • Quetiapine.
    • Reboxetine.
  • The following drugs should be used with caution when prescribed with fluconazole:
    • Aminophylline and theophylline.
    • Ciclosporin.
    • Coumarins, such as warfarin. 
    • Diazepam (risk of prolonged sedation).
    • Fentanyl.
    • Midazolam (risk of prolonged sedation).
    • Phenytoin.
    • Rifabutin (increased risk of uveitis).
    • Statins — the risk of myopathy and rhabdomyolysis increases when fluconazole is given with statins metabolized through CYP3A4 (atorvastatin and simvastatin) or through CYP2C9 (fluvastatin). If concurrent treatment is necessary, monitor for symptoms of myopathy and rhabdomyolysis, and monitor creatine kinase. Discontinue the statin if a marked increase in creatine kinase occurs or if myopathy or rhabdomyolysis is suspected.
    • Sulfonylureas (such as gliclazide and glipizide) — if concurrent use is indicated, advise the person to seek medical advice if they have symptoms of hypoglycaemia (for example anxiety, sweating, and/or trembling). The manufacturer advises frequent monitoring of blood glucose and appropriate reduction in sulphonylurea dose with co-administration.
    • Tacrolimus.
    • Tretinoin — fluconazole possibly increases the risk of tretinoin toxicity.
• Other possible drug interactions of fluconazole include:
  • Clopidogrel — fluconazole possibly reduces the antiplatelet effect of clopidogrel.
  • Rifampicin — metabolism of fluconazole may be accelerated by rifampicin, leading to reduced plasma concentrations.

[BNF, 2023; Preston, 2019]

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 an allergy to penicillin.
• A history of penicillin-associated jaundice or hepatic dysfunction.

Prescribe phenoxymethylpenicillin with caution to people with:

• Hypersensitivity to cephalosporins — there is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and cephalosporins, and people have been known to have severe reactions (including anaphylaxis) to both drugs.

[BNF, 2023]

Adverse effects

• Common adverse effects of phenoxymethylpenicillin include:
  • Diarrhoea, nausea, vomiting.
  • Skin rash, joint pains.
• Other adverse effects include:
  • Antibiotic-associated colitis. See the CKS topic on Diarrhoea - antibiotic associated for more information.
  • Hepatic disorders.
  • Neurotoxicity, coagulation disorders, agranulocytosis, leukopenia, haemolytic anaemia, neutropenia, interstitial nephritis.

[BNF, 2023]

Drug interactions

Possible drug interactions with phenoxymethylpenicillin include:

• Anticoagulants (such as warfarin) — monitor the person’s international normalised ratio (INR) during concurrent use and adjust the warfarin dose accordingly. Prolongation of prothrombin time has been reported in people taking penicillins and warfarin concurrently.
• Methotrexate — phenoxymethylpenicillin is predicted to increase the risk of toxicity when given with methotrexate. Manufacturer advises monitor.

[BNF, 2023]

Dosage regimens

The dosage regimens for oral phenoxymethylpenicillin are:

• 1–11 months — 62.5 mg every 6 hours for 10 days.
• 1–5 years — 125 mg every 6 hours for 10 days.
• 6–11 years — 250 mg every 6 hours for 10 days.
• 12–17 years — 250–500 mg every 6 hours for 10 days.

[BNFC, 2023]

Contraindications and cautions

• Do not prescribe clarithromycin to people with:
  • Severe hepatic impairment in combination with renal impairment.
  • Hypokalaemia — risk of QT interval prolongation.
  • A history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes arrhythmias.
• Prescribe clarithromycin with caution to people with:
  • Hepatic impairment (or people concomitantly taking potentially hepatotoxic drugs) — clarithromycin is principally excreted by the liver.
  • Renal impairment — if the creatinine clearance is less than 30 mL/min, prescribe half the normal dose for immediate-release preparations, and avoid modified-release preparations. If the creatinine clearance is 30–60 mL/min, use half the normal dose for modified-release preparations.
  • Conditions which predispose to QT interval prolongation — such as electrolyte disturbances and people taking drugs that prolong the QT interval, for example amiodarone, sotalol, terfenadine, and amisulpride.
  • Myasthenia gravis — may aggravate symptoms.

[BNF, 2023]

Adverse effects

Common adverse effects of clarithromycin include:

• Nausea, vomiting, abdominal discomfort, and diarrhoea.
• Antibiotic-associated colitis. See the CKS topic on Diarrhoea - antibiotic associated for more information.

Other adverse effects include:

• Taste disturbance, headache, insomnia, paraesthesia, drowsiness, leucopenia, neutropenia, tinnitus, vertigo.
• Hepatotoxicity (including cholestatic jaundice), pancreatitis, rash, QT interval prolongation, arrhythmias, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

[BNF, 2023]

Drug interactions

Possible drug interactions with clarithromycin include:

• Antidiabetic drugs — the concurrent use of clarithromycin and antidiabetic drugs (such as nateglinide and repaglinide) can result in significant hypoglycaemia. Monitor blood glucose levels more regularly and adjust the antidiabetic drug dose accordingly.
• Apixaban, edoxaban — clarithromycin slightly increases the exposure to apixaban and edoxaban. Manufacturer makes no recommendation.
• Calcium channel blockers (CCBs) — clarithromycin is predicted to increase the exposure to CCBs. Manufacturer advises monitor and adjust dose. Clarithromycin is predicted to markedly increase the exposure to lercanidipine. Manufacturer advises avoid.
• Carbamazepine — clarithromycin slightly increases the concentration of carbamazepine. Manufacturer advises monitor concentration and adjust dose. Advise the person to report symptoms of carbamazepine toxicity (such as dizziness, diplopia, ataxia, or confusion).
• Colchicine — clarithromycin is predicted to increase the exposure to colchicine. Manufacturer advises avoid potent CYP3A4 inhibitors or adjust colchicine dose.
• Digoxin — clarithromycin increases the concentration of digoxin. Manufacturer advises monitor digoxin concentration.
• Drugs that prolong the QT interval (such as anti-arrhythmics like amiodarone and sotalol, antipsychotics like amisulpride, lithium, tricyclic and selective serotonin reuptake inhibitor antidepressants, venlafaxine, macrolide antibiotics, domperidone, fluconazole) — most manufacturers advise avoiding the use of two or more drugs that are associated with QT prolongation.
• Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta₂-agonists) — increased risk of QT prolongation and torsade de pointes. Seek advice from a medical microbiologist regarding a suitable alternative antibiotic.
• Edoxaban — manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
• Itraconazole — clarithromycin increases the plasma concentration of itraconazole, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
• Ivabradine — concomitant treatment is contraindicated, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
• Ketoconazole — the manufacturer advises to avoid the use of concomitant clarithromycin in severe renal impairment.
• Mirabegron — clarithromycin is predicted to increase the exposure to mirabegron. Manufacturer advises adjust mirabegron dose in hepatic and renal impairment.
• Mirtazapine — clarithromycin is predicted to increase the exposure to mirtazapine. Manufacturer advises caution.
• Omeprazole — the plasma concentrations of both drugs are increased when clarithromycin is given with omeprazole.
• Phenytoin — clarithromycin inhibits the metabolism of phenytoin, leading to increased plasma concentrations. If there are signs of phenytoin toxicity, such as blurred vision, nystagmus, ataxia, or drowsiness, stop clarithromycin and seek specialist advice if needed.
• Oxybutynin — clarithromycin is predicted to increase the exposure to oxybutynin. Manufacturer makes no recommendation.
• Sildenafil — clarithromycin increases the plasma concentration of sildenafil. Consider reducing the initial dose for sildenafil.
• Statins — there is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) if clarithromycin is taken with atorvastatin or simvastatin.
  • Atorvastatin — clarithromycin is predicted to increase the exposure to atorvastatin. Manufacturer advises avoid or adjust dose and monitor rhabdomyolysis.
  • Fluvastatin — is not dependent on CYP3A metabolism, therefore interaction with clarithromycin is unlikely. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness.
  • Pravastatin — clarithromycin moderately increases the exposure to pravastatin. Manufacturer advises caution.
  • Simvastatin — clarithromycin is predicted to increase the exposure to simvastatin. Manufacturer advises avoid.
• Theophylline — clarithromycin possibly increases the plasma concentration of theophylline. Consider a dose reduction of theophylline if toxicity is suspected (for example headache, nausea, or palpitations occur).
• Quetiapine — clarithromycin possibly increases the plasma concentration of quetiapine. The manufacturer of quetiapine advises to avoid concomitant use.
• Warfarin and acenocoumarol — clarithromycin enhances the anticoagulant effect of warfarin and acenocoumarol. Monitor the international normalized ratio (INR), and adjust the anticoagulant dose accordingly.

[BNF, 2023; Preston, 2019; EMC, 2024]

Dosage regimens

• The dosage regimens for oral clarithromycin are:
  • Children 1 month to 11 years
    • Body weight up to 8 kg — 7.5 mg/kg twice daily.
    • Body weight 8–11 kg — 62.5 mg twice daily.
    • Body weight 12–19 kg — 125 mg twice daily.
    • Body weight 20–29 kg — 187.5 mg twice daily.
    • Body weight 30–40 kg —  250 mg twice daily.
  • Children 12–17 years
    • 250 mg twice daily.

[BNFC, 2023]

Contraindications and cautions

Do not prescribe metronidazole to people with:

• Known metronidazole or nitroimidazole hypersensitivity.
• Cockayne syndrome — cases of severe hepatotoxicity or acute hepatic failure, including risk of death, have been reported. This may have rapid onset after treatment with products containing metronidazole for systemic use. Only use if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout, and after treatment until liver function is within normal ranges, or until the baseline values are reached. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.

Prescribe metronidazole with caution to people with:

• Hepatic impairment — manufacturer advises caution in hepatic encephalopathy (risk of decreased clearance). Manufacturer advises dose reduction to one-third of the daily dose in hepatic encephalopathy (dose may be given once daily).
• Alcohol dependency — may be a disulfiram-like reaction if taken with alcohol.

[EMC, 2022; BNF, 2023]

Adverse effects

Adverse effects of metronidazole include:

• Nausea and vomiting, anorexia, and very rarely hepatitis, jaundice, or pancreatitis.
• Taste disturbances, oral mucositis, headache, ataxia, myalgia, arthralgia, darkening of urine.
• Thrombocytopenia, pancytopenia, rash, pruritus, erythema multiforme. Severe bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or acute generalised exanthematous pustulosis (AGEP) have been reported. If symptoms/signs are present, stop treatment immediately.
• Drowsiness, dizziness, confusion, hallucinations, convulsions, or transient visual disorders. Advise the person not to drive or operate machinery if these symptoms occur.

[EMC, 2022; BNF, 2023]

Drug interactions

Possible drug interactions with metronidazole include:

• Alcohol — some people taking metronidazole experience a disulfiram-like reaction with alcohol (flushing, increased respiratory rate, increased pulse rate). Warn the person that they might experience this reaction if they drink alcohol whilst on metronidazole and for at least 48 hours afterwards. 
• Anticoagulants — the anticoagulant effects of warfarin can be markedly increased by metronidazole. Monitor the international normalized ratio (INR) and adjust the warfarin dose accordingly. 
• Cimetidine — metabolism of metronidazole inhibited by cimetidine, resulting in an increased plasma concentration.
• Lithium — metronidazole is predicted to increase the concentration of lithium. Manufacturer advises avoid or adjust dose.
• Phenytoin — Both metronidazole and phenytoin can increase the risk of peripheral neuropathy.
• Nitrofurantoin — both metronidazole and nitrofurantoin can increase the risk of peripheral neuropathy.
• The manufacturers SPC also notes that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

[BNF, 2023; EMC, 2023]

Contraindications and cautions

Do not prescribe co-amoxiclav to people with:

• A history of co-amoxiclav-associated jaundice or hepatic dysfunction.
• A history of penicillin-associated jaundice or hepatic dysfunction.

Prescribe co-amoxiclav with caution to people with:

• Hypersensitivity to cephalosporins — there is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and cephalosporins, and people have been known to have severe reactions (including anaphylaxis) to both drugs.
• Hepatic impairment — monitor liver function.
• Renal impairment — reduce the dose of co-amoxiclav based on the estimated glomerular filtration rate (eGFR):
  • If the eGFR is 10–30 mL/min/1.73 m², prescribe one 250/125 strength tablet every 12 hours or one 500/125 strength tablet every 12 hours.
  • If the eGFR is less than 10 mL/min/1.73 m², prescribe one 250/125 strength tablet every 24 hours or one 500/125 strength tablet every 24 hours.
• Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection, and glandular fever — increased risk of erythematous rashes.

[BNF, 2023]

Adverse effects

Adverse effects of co-amoxiclav include:

• Diarrhoea, nausea, vomiting, dyspepsia.
• Skin rash, joint pains, dizziness, headache.
• Increased risk of infection.
• Antibiotic-associated colitis. See the CKS topic on Diarrhoea - antibiotic associated for more information.
• Hepatic disorders.
• Neurotoxicity, coagulation disorders, agranulocytosis, leukopenia, haemolytic anaemia, neutropenia, interstitial nephritis.
• Akathisia, black hairy tongue, cholangitis, Kounis syndrome (an allergic reaction which can cause cardiovascular symptoms).

[BNF, 2023]

Drug interactions

• Possible drug interactions of co-amoxiclav include:
  • Allopurinol — concomitant use of allopurinol and co-amoxiclav may increase the incidence of skin rash. Manufacturer advises to consider alternatives.
  • Anticoagulants (for example warfarin) — penicillins potentially alter the anticoagulant effect of warfarin. Monitor the prothrombin time or international normalized ratio (INR) more closely with the addition or withdrawal of a penicillin. Adjustment of the anticoagulant dose may be necessary.
  • Other antibiotics and antifungals — increased risk of hepatotoxicity with doxycycline, flucloxacillin, fluconazole, itraconazole, lymecycline, oxytetracycline, and tetracycline.
  • Methotrexate — amoxicillin is predicted to increase the risk of toxicity when given with methotrexate. Clavulanate and methotrexate can increase the risk of hepatotoxicity. Manufacturer advises monitor.
  • Statins — both clavulanate and pravastatin, rosuvastatin, and simvastatin can increase the risk of hepatotoxicity.

[BNF, 2023]