Previous changes

January 2024 — minor update. Changes made to the section on Prescribing information.

October 2023 — reviewed. A literature search was conducted in September 2023 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.

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

September 2020 — minor update. Reference to a branded barrier preparation has been removed from this topic.

June to July 2018 — reviewed. A literature search was conducted in June 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. The topic has undergone minor restructuring. Sections on Complications and Prognosis have been added to the section on Background information, and the section on Differential diagnosis has been expanded. The recommendations in the section on Management have been updated in line with current literature. A section on Prescribing information has been added to this topic.

July 2013 — reviewed. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made. There have been minor changes to the recommendations on topical treatments in the sections on Treatment and Treatment failure.

February 2013 — minor update. The 2013 Quality, Innovation, Productivity, and Prevention (QIPP) options for local implementation have been added to this topic.

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

Febriary 2012 — typographical error corrected in the section on Treatment. 

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

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

August 2009 — minor update. Advice to apply barrier preparations thinly has been added. 

March 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.

September 2008 — minor correction to the Changes section. Issued September 2008.

August 2008 — minor update. Nystatin cream and ointment have been discontinued. The prescriptions have been removed and relevant text amended. 

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

July 2005 — minor update to drug rationales. 

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. Issued in February 2004.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2023. 

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2023. 

Economic appraisals

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

Systematic reviews and meta-analyses

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

Primary evidence

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

New policies

No new national policies or guidelines since 1 September 2023. 

New safety alerts

No new safety alerts since 1 September 2023. 

Changes in product availability

No changes to product availability since 1 September 2023. 

Basis for recommendation

These recommendations are based on expert opinion in review articles Diaper dermatitis: a review and update [Ravanfar, 2012], Diaper dermatitis: clinical characteristics and differential diagnosis [Coughlin, 2014], Diaper dermatitis: etiology, manifestations, prevention, and management [Stamatas, 2014], Prevention, treatment and parent education for diaper dermatitis [Merrill, 2015], Infections and skin diseases mimicking diaper dermatitis [Van Gysel, 2016], Differential diagnosis of diaper dermatitis [Cohen, 2017], and the British Medical Journal (BMJ) Best Practice guide Nappy rash [BMJ Best Practice, 2023].

When to arrange skin swabs

• Skin swabs are not generally recommended for the management of nappy rash as the results are difficult to interpret. In addition, both Candida and bacteria (such as Staphylococcus aureus and streptococcus) colonize healthy skin, and a skin swab may be positive when infection is not present.
• However, a skin swab for culture and sensitivity may be helpful if an underlying infection is suspected, to confirm the diagnosis and guide management [Merrill, 2015; Van Gysel, 2016; BMJ Best Practice, 2023]. The same culture swab can be used for culturing both fungus and bacteria [BMJ Best Practice, 2023].

Basis for recommendation

The information on differential diagnoses of nappy rash is based on expert opinion in the narrative review articles Diaper dermatitis: a review and update [Ravanfar, 2012], Neonatal skin care: a concise review [Ness, 2013], Diaper dermatitis: clinical characteristics and differential diagnosis [Coughlin, 2014], Prevention, treatment and parent education for diaper dermatitis [Merrill, 2015], Infections and skin diseases mimicking diaper dermatitis [Van Gysel, 2016], Differential diagnosis of diaper dermatitis [Cohen, 2017], and the British Medical Journal (BMJ) Best Practice guide Nappy rash [BMJ Best Practice, 2023].

How should I initially manage a child with nappy rash?

• Advise parents/carers on the following self-management strategies: 
  • Consider using nappies with high absorbency (for example disposable gel matrix nappies).
    • Ensure the nappy fits properly (too tight increases skin occlusion, too loose minimizes absorption of fluids).
    • Parental/carer choice will depend on issues such as convenience, cost, and environmental impact.
  • Leave nappies off for as long as possible to reduce skin contact with urine, faeces, moisture, and other irritants, and frictional damage from nappies.
  • Change nappies every 2–3 hours, or as soon as possible after wetting or soiling, to reduce skin exposure to urine and faeces.
    • Clean the skin with water, or fragrance and alcohol-free baby wipes.
    • Dry the skin gently after cleaning — avoid vigorous rubbing.
    • Bath the child daily — avoid excessive bathing (such as more than twice a day) as this may dry the skin excessively.
    • Avoid using soap, bubble baths, lotions, talcum powder, or topical antibiotics, which can have an irritant effect.
    • Avoid the use of plastic underpants over the nappy.
• Advise on sources of written information and support.
  • NHS A-Z has an information leaflet on Nappy rash.
• If there is mild erythema and the child is asymptomatic:
  • Advise on the use of a barrier preparation to protect the skin. 
    
    • The barrier preparation should be applied thinly at each nappy change.
    • A range of options are available to buy over-the-counter, including Zinc and Castor Oil ointment and white soft paraffin BP ointment.
• If the rash appears inflamed and is causing discomfort in a child aged 1 month or over:
  • Consider prescribing hydrocortisone 1% cream in addition to the barrier preparation.
    • A thin layer of topical corticosteroid should be applied once a day until symptoms settle or for a maximum of 7 days.
    • The barrier preparation should be applied a few minutes after applying the topical corticosteroid
    • See the CKS topic on Corticosteroids - topical (skin), nose, and eyes for prescribing information on hydrocortisone cream.
• If the rash persists and candidal infection is suspected or confirmed on swab:
  • Prescribe a topical imidazole cream (clotrimazole, econazole, or miconazole).
    • Advise against the use of a barrier preparation until the candidal infection has settled. 
    • See the section on Topical imidazoles for prescribing information.
• If the rash persists and bacterial infection is suspected or confirmed by swab:
  • Prescribe an oral antibiotic.
    • Prescribe flucloxacillin solution for 7 days.
    • If the child is allergic to penicillin, prescribe clarithromycin suspension for 7 days.
    • Adjust the choice of antibiotic if indicated, depending on swab results.
    • See the sections on Flucloxacillin and Clarithromycin for prescribing information.
• Review the child to assess the response to treatment (with time interval dependent on clinical judgement).
  • If symptoms are not settling, see the section on Treatment failure and referral for management information.

How should I manage treatment failure?

• If the nappy rash is not improving following initial management:
  • Consider and, if possible, manage any underlying cause of treatment failure, including:
    • Non-adherence to self-care advice or the treatment regimen.
    • Candidal or bacterial secondary infection — take a skin swab for culture and sensitivity, and manage accordingly. 
    • An alternative cause for the rash.
    • An immunocompromised host.
  • If the rash persists following treatment for secondary infection:
    • Adjust the choice of topical imidazole or oral antibiotic if indicated, depending on swab results.
    • Seek specialist advice from a medical microbiologist if the rash has not responded to appropriate treatment.
  • Consider referral to a paediatric dermatologist if:
    • There is uncertainty about the diagnosis.
    • The rash persists despite optimal treatment in primary care.
    • There are recurrent, severe unexplained episodes.

Dosages

Topical imidazoles should be applied thinly and evenly to prevent moisture entrapment.

• Topical clotrimazole 1% is licensed for treating candidal nappy rash.
  • The cream should be applied 2–3 times daily and rubbed in gently. 
  • Treatment should be continued for at least 2 weeks.
• Topical miconazole 2% is licensed for treating fungal skin infections.
  • The cream should be applied twice daily and rubbed in gently. 
  • The duration of treatment varies from 2–6 weeks depending on the localization and the severity of the lesion.
  • Treatment should be continued for at least 1 week after the disappearance of all signs and symptoms.
• Topical econazole 1% is licensed for treating fungal skin infections.
  • The cream should be applied twice daily and rubbed in gently.
  • The usual treatment duration is 2–4 weeks. If no improvement in symptoms is experienced after 4 weeks, the treatment should be reassessed.

[EMC, 2020; EMC, 2021; EMC, 2022a]

Cautions

• Advise parents/carers:
  • To avoid contact with the eyes and mucous membranes during the use of topical imidazoles.
  • That they should not smoke or go near naked flames whilst applying clotrimazole cream.
    • The manufacturer advises that fabric (such as clothing, bedding, and dressings) that has been in contact with the product burns more easily and is a serious fire hazard.
    • Washing may reduce product build-up but not totally remove it.

[EMC, 2020; EMC, 2021; EMC, 2022a]

Adverse effects

• Topical imidazoles are generally well tolerated. 
• Rash, erythema, itch, mild burning sensation, and hypersensitivity reactions may occur. Treatment should be discontinued if these are severe.

[EMC, 2020; EMC, 2021; EMC, 2022a]

Drug interactions

• Oral anticoagulants (such as warfarin) — oral miconazole and econazole are known to inhibit CYP450 enzymes. Due to the limited systemic availability after topical application, clinically relevant interactions are rare. However, the effect of oral anticoagulants (such as warfarin) may be enhanced by topical miconazole or econazole. 
  • Monitor the international normalised ratio (INR) during concurrent use of topical miconazole or econazole with an oral anticoagulant, and adjust the warfarin dose accordingly.

[EMC, 2020; EMC, 2021] 

Dosages

• The recommended dosages of flucloxacillin for children with infected nappy rash are: 
  
  • Age 1 month to 1 year — 62.5 mg to 125 mg four times daily for 7 days.
  • Age 2–9 years — 125 mg to 250 mg four times daily for 7 days.
• In children with severe renal impairment (creatinine clearance less than 10 ml/minute):
  • Consider a dose reduction or an extension of the dosing interval due to the risk of neurotoxicity.
• Flucloxacillin should be taken 1 hour before food or on an empty stomach.

[BNFC, 2023]

Contraindications and cautions

• Do not prescribe flucloxacillin to children with:
  • A true penicillin hypersensitivity — gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute a true penicillin allergy.
  • History of urticaria or rash immediately after penicillin administration — risk of immediate hypersensitivity to penicillins.
  • History of a severe immediate hypersensitivity reaction (for example, anaphylaxis) to cephalosporins — there is some evidence of partial cross-allergenicity between cephalosporins and penicillins. 
  • History of flucloxacillin-associated jaundice/hepatic dysfunction.
• Prescribe flucloxacillin with caution to children with:
  • History of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after administration of a penicillin — possibility of an allergic reaction to penicillins.
  • History of allergy to cephalosporins or other medications.
  • History of atopic allergy (including asthma, eczema, or hay fever) — high risk of anaphylactic reactions to penicillins.
  • Hepatic impairment, especially if they have a serious underlying disease.
  • Severe renal impairment (creatinine clearance less than 10 ml/minute) — consider a dose reduction or an extension of the dosing interval due to the risk of neurotoxicity.

[BNFC, 2023; EMC, 2023a]

Adverse effects

• For all penicillins
  • The most common adverse effects are:
    • Gastrointestinal adverse effects, such as diarrhoea, nausea, and vomiting.
    • Skin reactions.
    • Thrombocytopenia.
  • The most significant adverse effect is hypersensitivity, which causes rashes and anaphylaxis and can be fatal.
    
    • Allergic reactions occur in 1–10% of people treated with a penicillin; anaphylactic reactions occur in fewer than 0.05% of people. 
    • People with a history of atopic allergy (for example, asthma, eczema, and hay fever) are at a higher risk of anaphylactic reactions to penicillins.
    • People with a history of anaphylaxis, urticaria, or rash immediately after penicillin administration are at risk of immediate hypersensitivity and should not take flucloxacillin.
    • People with a history of a minor rash (non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration are probably not allergic to penicillin. Flucloxacillin should not be withheld unnecessarily for serious infections, but the possibility of an allergic reaction should be noted. Other beta-lactam antibiotics (including cephalosporins) can be used.
    • People allergic to one penicillin will be allergic to all because the hypersensitivity is related to the basic penicillin structure.
    • People with a history of immediate hypersensitivity to penicillins may also react to cephalosporins and other beta-lactam antibiotics and so should not receive these antibiotics. There is some evidence of partial cross-allergenicity of penicillins and cephalosporins. 
    • If a penicillin (or another beta-lactam) antibiotic is essential in a person with immediate hypersensitivity to penicillins, specialist advice should be sought on hypersensitivity testing or using a beta-lactam antibiotic with a different structure to the penicillin that caused the hypersensitivity.
  • Antibiotic-associated colitis has been reported and may range in severity from mild to life-threatening.
    • Consider this diagnosis in children who present with diarrhoea during or after treatment with any antibiotic.
    • The risk is increased with longer durations of antibiotic treatments, multiple antibiotics prescribed concurrently, or multiple courses of antibiotics.
    • See the CKS topic on Diarrhoea - antibiotic associated for more information. 
  • Other possible adverse effects include:
    • Uncommon — arthralgia and leucopenia.
    • Rare or very rare — agranulocytosis, angioedema, haemolytic anaemia, hepatic disorders, nephritis tubulointerstitial, neutropenia, seizure, and severe cutaneous adverse reactions (SCARs).
• For flucloxacillin
  • Hepatitis and cholestatic jaundice have been reported.
    • These reactions are unrelated to the dose or route of administration of flucloxacillin.
    • The onset of these hepatic effects may be delayed for up to two months post-treatment; in several cases, the course of the reactions has been protracted and lasted for some months.
    • In very rare cases, a fatal outcome has been reported. Most reports of deaths have been in people aged 50 years and older and people with serious underlying disease.
  • Other possible adverse effects include:
    
    • Rare or very rare — eosinophilia, fever, and myalgia.
    • Frequency not known  — hypokalaemia, oesophageal disorder, oral pain, oropharyngeal pain, and throat irritation.

[BNFC, 2023; EMC, 2023a]

Drug interactions

• Drug interactions of flucloxacillin include:
  • Live cholera vaccine — efficacy of the vaccine may be reduced.
    • Avoid flucloxacillin from 14 days before to 10 days after receiving live cholera vaccine.
  • Live typhoid vaccine — immune response to the vaccine may be reduced.
    • Avoid flucloxacillin from 3 days before to 3 days after receiving live typhoid vaccine.
  • Methotrexate — reduced clearance and acute methotrexate toxicity have been attributed to concurrent use with some penicillins. Serious interactions are uncommon, but risk factors are as yet unknown. People taking low-dose methotrexate have been affected.
    • High-dose methotrexate: standard routine monitoring will identify any decreases in elimination, which should be managed according to local guidelines.
    • Low-dose methotrexate: consult local or national guidelines for recommendations on appropriate monitoring and management.
  • Paracetamol — paracetamol has been reported to cause high anion gap metabolic acidosis (HAGMA) when given with flucloxacillin.
    • Be alert for signs and symptoms of HAGMA.
    • Risk factors include severe renal impairment, sepsis, or malnutrition, especially if the maximum daily doses of paracetamol are used.
    • On stopping paracetamol, HAGMA may persist with flucloxacillin alone.
  • Phenidione — flucloxacillin is predicted to increase the risk of bleeding when given with phenindione.
    • Consider increased monitoring of the international normalized ratio (INR) if flucloxacillin is started or stopped.
  • Posaconazole and voriconazole — flucloxacillin (particularly high doses) appears to greatly decrease the concentrations of these antifungals.
    • If concurrent use is unavoidable, monitor for decreased efficacy and consider increasing the dose of the azole (although this may not resolve the issue). 
  • Probenecid — probenecid reduces the excretion of penicillins and usually increases their concentrations.
    • Concurrent use with flucloxacillin can be beneficial. However, consider any detrimental effect elevated flucloxacillin concentrations may have on the child.
  • Warfarin — flucloxacillin decreases the INR in people taking warfarin.
    • Consider an interaction if otherwise unexplained decreases in INR occur.
    • Monitor and adjust the warfarin dose accordingly.

[BNFC, 2024; Preston, 2024]

Dosages

• The recommended dosages of clarithromycin for infected nappy rash in children aged 1 month to 11 years are:
  • Body weight up to 8 kg — 7.5 mg/kg twice daily for 7 days.
  • Body weight 8–11 kg — 62.5 mg twice daily for 7 days.
  • Body weight 12–19 kg — 125 mg twice daily for 7 days.
  • Body weight 20–29 kg — 187.5 mg twice daily for 7 days.
  • Body weight 30–40 kg —  250 mg twice daily for 7 days.
• In children with renal impairment:
  • Use half the usual dosage if creatinine clearance (CrCl) is less than 30 mL/minute.

[BNFC, 2023]

Contraindications and cautions

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

[EMC, 2022b; BNFC, 2023]

Adverse effects

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

[EMC, 2022b; BNFC, 2023] 

Drug interactions

• Drug interactions of clarithromycin include:
  • Antidiabetic drugs — concurrent use with oral hypoglycaemic drugs (such as sulfonylureas) or insulin can result in significant hypoglycaemia.
    
    • Monitor blood glucose levels closely, and adjust the antidiabetic dose accordingly.
  • Calcium channel blockers — clarithromycin possibly inhibits the metabolism of calcium channel blockers, such as verapamil and amlodipine, increasing the risk of hypotension and other adverse effects.
    • Monitor for hypotension and other adverse effects, and adjust the dose of the calcium channel blocker if necessary.
  • Digoxin — clarithromycin increases the plasma concentration of digoxin.  
    • Monitor for signs of digoxin adverse effects (bradycardia).
    • Measure digoxin concentrations, and adjust the dose if problems develop.
  • Direct oral anticoagulants (DOACs) — clarithromycin increases the exposure to dabigatran, slightly increases the exposure to apixaban, and is predicted to increase the exposure to edoxaban.
    
    • Monitor for signs and symptoms of bleeding or anaemia, especially in children with renal impairment.
  • Drugs that prolong the QT interval — clarithromycin can prolong the QT interval. Concurrent use with other drugs that prolong QT intervals can increase the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
    • Concurrent use with domperidone, ivabradine, or pimozide is contraindicated. Seek advice from a medical microbiologist regarding a suitable alternative antibiotic.
    • Most manufacturers advise avoiding the use of two or more drugs that are associated with QT prolongation.
    • Increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation.
  • Drugs that cause hypokalaemia (such as diuretics) — concurrent use with clarithromycin can predispose to QT prolongation.
    
    • Monitor potassium concentrations closely.
  • Drugs that induce cytochrome P450 (CYP3A4) enzyme — concurrent use may decrease plasma concentrations of clarithromycin, leading to sub-therapeutic levels and reduced efficacy.  
    • Monitor concurrent use of clarithromycin and CYP3A4 enzyme inducers, such as rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort.
    • It may also be necessary to monitor the plasma levels of the CYP3A4 inducer, which could be increased due to the inhibition of CYP3A4 by clarithromycin. For example, concurrent treatment with rifabutin and clarithromycin increases rifabutin levels and decreases clarithromycin levels.
  • Edoxaban — manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
  • Ivabradine — concomitant treatment is contraindicated, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
  • Statins — clarithromycin is a CYP3A4 enzyme inhibitor. Concurrent use with a statin metabolized by CYP3A4 will increase the plasma concentration of the statin, leading to an increased risk of myopathy (including rhabdomyolysis) [MHRA, 2014]. 
    • Simvastatin is extensively metabolized by CYP3A4. Concurrent use with clarithromycin is contraindicated. If clarithromycin treatment cannot be avoided, withhold simvastatin for the duration of the clarithromycin course.
    • Atorvastatin is moderately metabolized by CYP3A4. Avoid concurrent use with clarithromycin. If concurrent use cannot be avoided, do not exceed 20 mg of atorvastatin daily. Advise parents/carers to report any muscle pain, tenderness, or weakness.
    • Pravastatin is not associated with cytochrome P450 interactions. However, the Medicines and Healthcare products Regulatory Agency (MHRA) advises caution with clarithromycin. Advise parents/carers to report any muscle pain, tenderness, or weakness.
    • Rosuvastatin is not associated with cytochrome P450 interactions. Nevertheless, advise parents/carers to report any muscle pain, tenderness, or weakness.
    • Fluvastatin is not dependent on CYP3A metabolism. Nevertheless, advise parents/carers to report any muscle pain, tenderness, or weakness [EMC, 2023b]. 
  • Other drugs metabolized by CYP3A4 — concurrent use with clarithromycin may increase plasma concentrations of the concurrent drug, leading to increased or prolonged therapeutic and adverse effects of the concurrent drug.
    • Concurrent use with domperidone, pimozide, or terfenadine is contraindicated due to the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
    • Concurrent use with ergot alkaloids, oral midazolam, colchicine, ticagrelor, or ranolazine is contraindicated.
    • Concurrent use of clarithromycin with other drugs metabolized by CYP3A4 should be done with caution, especially if the other drug has a narrow safety margin (such as carbamazepine) or is extensively metabolized by CYP3A4. Dosage adjustments may be considered, and when possible, serum concentrations of the CYP3A4 substrate should be monitored closely.
  • Warfarin — clarithromycin may enhance the anticoagulant effect of warfarin.
    • Monitor the international normalized ratio (INR) closely, and adjust the warfarin dose accordingly.
• For further information on drug interactions of clarithromycin, see the electronic Medicines Compendium (eMC) or the British National Formulary for Children (BNFc).

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