Previous changes

August 2024 — minor update. Adverse effects of co-amoxiclav updated in line with manufacturer's SPC.

March 2024 — reviewed. A literature search was conducted in November 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. No major changes to recommendations have been made.

December 2023 — minor update. Information on possible neurological adverse effects of cefalexin added in line with updated SPC.

May 2023 — minor update. Added potential adverse effects of co-amoxiclav to include Kounis syndrome (an allergic reaction which can result in myocardial infarction), aseptic meningitis, linear IgA disease (renal deposition of IgA), and drug-induced enterocolitis syndrome (all of unknown frequency). These adverse effects were noted in an update to the manufacturer’s summary of product characteristics.

February 2023 — minor update. The NICE quality standards have been updated.

March 2021 — minor update. Information on signs and symptoms of acute pyelonephritis have been clarified.

November 2020 — minor update. Cautions for prescribing ciprofloxacin updated in line with revised manufacturer's SPC. 

August 2020 — minor update. Broken URL links updated.

March 2019 — minor update. Prescribing information for quinolones updated in line with MHRA, 2019, Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects.

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

November 2018 — reviewed. A literature search was conducted in November 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. 

November 2018 — minor update. Prescribing information updated to be in line with new NICE guidance pyelonephritis (acute): antimicrobial prescribing. 

September 2017 — minor update. SPC update on quinolones to align all CKS topics prescribing advice. Prostatitis – chronic, Gonorrhoea, Pyelonephritis, Diarrhoea – prevention and advice for travellers, Dyspepsia – unidentified cause, Dyspepsia – proven functional, Dyspepsia – proven peptic ulcer, Diverticular disease, Gastroenteritis and Scrotal pain and swellings. 

December 2016 — minor update. The adverse effects section for ciprofloxacin has been updated to include vision disorders.

June 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.

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

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

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

October 2008 to March 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.

May 2005 — reviewed. Validated in September 2005 and issued in November 2005.

December 2001 — reviewed. Validated in March 2002 and issued in April 2002.

December 1998 — written, replacing guidance on Acute pyelonephritis. Validated in March 1999 and issued in May 1999.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 November 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 November 2023.

Economic appraisals

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

Systematic reviews and meta-analyses

No new systematic review or meta-analyses since 1 November 2023.

Primary evidence

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

New policies

No new national policies or guidelines since 1 November 2023.

New safety alerts

No new safety alerts since 1 November 2023.

Changes in product availability

• New product EXBLIFEP 2 g/0.5 g powder is indicated for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis. See more here.
• New product Emblaveo (aztreonam/avibactam) 1.5 g/0.5 g powder for concentrate for solution for infusion. Licensed for treatment of adults with complicated intra-abdominal infection, hospital-acquired pneumonia, including ventilator-associated pneumonia, complicated UTI including pyelonephritis, and infections due to aerobic Gram-negative organisms when treatment options are limited. See more here.

Basis for recommendation

The recommendations on diagnosing pyelonephritis are based on expert opinion within the UK Health Security Agency (UKHSA) guideline Diagnosis of urinary tract infections: quick reference tool for primary care [UKHSA, 2020], the National Institute for Health and Care Excellence (NICE) guideline Pyelonephritis (acute): antimicrobial prescribing [NICE, 2019a], the BMJ Best Practice guideline Pyelonephritis [BMJ Best Practice, 2023], the European Association of Urology (EAU) guideline Urological infections [EAU, 2018], and narrative reviews  Acute pyelonephritis in adults [Johnson, 2018], and Pyelonephritis can lead to life-threatening complications [Keenan, 2017].  

Diagnosis of pyelonephritis

• Pyelonephritis typically manifests suddenly with signs and symptoms of both systemic inflammation (fever, chills, and malaise) and bladder inflammation (urinary frequency, urgency, and dysuria). However, consensus is lacking regarding diagnostic criteria [Johnson, 2018].  
  • Some people do not have bladder symptoms, and some do not have fever.
• Acute pyelonephritis is suggested by [Keenan, 2017; UKHSA, 2020]: 
  • Temperature ≥ 37.9°C.
  • Flank/renal angle pain — typically unilateral.
  • Nausea and vomiting.
  • Costovertebral angle tenderness.
  • Complaints typical of lower UTI are variably present.

Dipstick tests

UKHSA recommends that people with clinical features of pyelonephritis should start treatment with antibiotics without the need for a dipstick urinalysis test [UKHSA, 2020]. However, some experts suggest that dipstick urinalysis may be useful in excluding other illnesses or assisting in making a diagnosis of pyelonephritis [EAU, 2018; Johnson, 2018; Keenan, 2017]. CKS therefore considers that dipstick urinalysis may be a useful adjunct to aid diagnosis of acute pyelonephritis.

Basis for recommendation

The information on signs and symptoms of pyelonephritis are based on expert opinion within the UK Health Security Agency (UKHSA) guideline Diagnosis of urinary tract infections: quick reference tool for primary care [UKHSA, 2020], the BMJ Best Practice guideline Pyelonephritis [BMJ Best Practice, 2023], the European Association of Urology (EAU) guideline Urological infections [EAU, 2018], and narrative reviews Diagnosis and Treatment of Acute Pyelonephritis in Women [Colgan, 2011] and Acute pyelonephritis in adults [Johnson, 2018].

Basis for recommendation

The advice regarding the differential diagnoses of pyelonephritis is based on expert opinion in the BMJ Best Practice guideline Acute pyelonephritis [BMJ Best Practice, 2023], and a narrative review article Pyelonephritis can lead to life-threatening complications [Keenan, 2017]. 

When should I refer people with acute pyelonephritis?

• Admit people to hospital if they have any symptoms or signs suggesting a more serious illness or condition (for example, sepsis).
• Consider referring or seeking specialist advice for people with acute pyelonephritis if they: 
  • Are significantly dehydrated or unable to take oral fluids and medicines.
  • Are pregnant.
  • Have a higher risk of developing complications — people with known or suspected structural or functional abnormality of the genitourinary tract, underlying disease (such as diabetes mellitus or immunosuppression), or if symptoms persist or worsen despite antibiotic treatment.
  • Have reduced kidney function due to acute kidney injury or chronic kidney disease, severe flank or abdominal pain, or a high fever (>39.4°C).
• Refer or seek specialist advice on further investigation and management for people with recurrent pyelonephritis (two or more episodes in the last 6 months, or three or more in the last 12 months).
• Consider referring men where it is necessary to rule out acute prostatitis.
• Refer urgently using a suspected cancer pathway referral for an appointment within 2 weeks for people: 
  • Aged 45 years and over who have unexplained visible haematuria without urinary tract infection or visible haematuria that persists or recurs after successful treatment of urinary tract infection.
  • Aged 60 years and over who have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test.
• Consider non-urgent referral for bladder cancer in people aged 60 years and over with recurrent or persistent unexplained UTI. 
• For more information on when to suspect urological cancer, see the CKS topic on Urological cancers - recognition and referral. 

How should I manage a person with suspected acute pyelonephritis in primary care?

• Admit people with acute pyelonephritis to hospital if it is severe or they have any signs or symptoms which suggest a more serious illness or condition, for example, sepsis. 
  • Signs of sepsis include:
    • Significant tachycardia, hypotension, or breathlessness.
    • Marked signs of illness (such as impaired level of consciousness, perfuse sweating, rigors, pallor, and significantly reduced mobility).
    • A temperature greater than 38°C or less than 36°C.
    • For more information, see the CKS topic on Neutropenic sepsis.
• For all other people, offer an antibiotic, taking into account: 
  • The severity of symptoms.
  • The risk of developing complications, which is higher in people with known or suspected structural or functional abnormality of the genitourinary tract or immunosuppression.
  • Previous urine culture and susceptibility results.
  • Previous antibiotic use, which may have led to resistant bacteria.
• For women who are not pregnant, men, and people with indwelling catheters, take account of local antimicrobial resistance data, and prescribe either of the following first line options: 
  • Cefalexin 500 mg twice or three times a day (up to 1– 1.5 g three or four times a day for severe infections) for 7-10 days.
  • Co-amoxiclav (only if appropriate in line with culture and sensitivity results) 500/125 mg three times a day for 7-10 days.
  • Trimethoprim (only if appropriate in line with culture and sensitivity results) 200 mg twice a day for 14 days.
  • Ciprofloxacin 500 mg twice a day for 7 days. Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate.
• For pregnant women who do not require admission, prescribe:
• • • Cefalexin 500 mg twice or three times a day (up to 1– 1.5 g three or four times a day for severe infections) for 7-10 days.
• For people with indwelling urinary catheters:
  • Check that the catheter is correctly positioned, drains correctly and is not blocked.   
  • Consider removing or, if this cannot be done, changing the catheter as soon as possible if it has been in place for more than 7 days.
    • Do not allow catheter removal or change to delay antibiotic treatment. 
    • Do not give antibiotic prophylaxis for catheter changes unless the person has a history of symptomatic UTIs due to catheter change.
• Provide appropriate information and advice.
• Review culture and sensitivity results when available, and change the antibiotic if indicated. If the bacteria are resistant and symptoms are not already improving, use a narrow-spectrum antibiotic wherever possible. 
• Reassess the person if symptoms worsen at any time, or do not start to improve within 48 hours of taking the antibiotic, and consider: 
  • Other possible diagnoses. 
  • Any symptoms or signs suggesting a more serious illness or condition, such as sepsis. 
  • Whether previous antibiotic use may have led to resistant bacteria.
  • Whether referral for specialist urological assessment is needed.

Contraindications and cautions

• Do not prescribe co-amoxiclav in people with:
  • A true penicillin allergy — allergic reactions to penicillins occur in 1–10% of exposed individuals; anaphylactic reactions occur in fewer than 0.05% of treated patients.
  • Gastrointestinal adverse effects alone (for example, nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
  • A history of co-amoxiclav- or penicillin-associated jaundice or hepatic dysfunction.
• Prescribe co-amoxiclav with caution in people with:
  • Hypersensitivity to cephalosporins — there is some evidence of partial cross-allergenicity. 
  • Hepatic impairment — monitor closely.
  • Chronic kidney disease (CKD) — reduce the dose if the estimated glomerular filtration rate (eGFR) is 30 mL/minute/1.73 m² or less.
  • Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection, glandular fever — increased risk of erythematous rashes.

[EMC, 2023a; BNF, 2024]

Adverse effects

• Gastrointestinal — diarrhoea (very common), nausea and vomiting (common), drug-induced enterocolitis syndrome (unknown frequency).
  • Very rarely: antibiotic-associated colitis.
• Nervous system — headache, dizziness (uncommon), aseptic meningitis (unknown frequency).
• Skin — skin rash, urticaria, pruritus (uncommon), drug reaction with eosinophilia and systemic symptoms (DRESS) (unknown frequency).
  • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalized exanthematous pustulosis.
• Other rare or very rare adverse effects include:
  • Hepatitis, cholestatic jaundice.
  • Hyperactivity, convulsions.
  • Hypersensitivity reactions (serious and occasionally fatal).  
  • Interstitial nephritis.
  • Linear IgA disease (renal deposition of IgA).  
  • Leucopenia, thrombocytopenia, haemolytic anaemia.
  • Kounis syndrome (an allergic reaction which can cause myocardial infarction).
• Symmetrical Drug-related Intertriginous and Flexural Exanthema (SDRIFE) are adverse effects of unknown frequency.

[EMC, 2023a; BNF, 2024; EMC, 2024]

Drug interactions

• Allopurinol — concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes.
• Methotrexate — co-amoxiclav may reduce methotrexate clearance, causing an increased risk of toxicity.
  • Monitor methotrexate levels more closely. One recommendation is to carry out twice weekly platelet and white cell counts for 2 weeks initially, with the measurement of methotrexate levels if toxicity is suspected.
• Mycophenolate mofetil — reduction in the level of active metabolite may occur when given with co-amoxiclav.
• Oral anticoagulants (warfarin, phenindione) — prolongation of prothrombin time has been reported in people taking penicillins and warfarin concurrently.
  • Monitor the prothrombin time or international normalized ratio (INR) more closely with the addition or withdrawal of penicillin. Adjustment of the anticoagulant dose may be necessary.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of co-amoxiclav.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods. 
• Probenecid — concomitant administration may result in increased levels of amoxicillin but not clavulanic acid.

[CoSRH, 2022; EMC, 2023a; BNF, 2024; Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

• Co-amoxiclav is not known to be harmful in pregnancy.

Breastfeeding

• Trace amounts of co-amoxiclav are found in breastmilk — this is not known to be harmful.

[SPS, 2020a; BNF, 2024]

Contraindications and cautions

• Do not prescribe cefalexin in people with:
  • A known allergy to the cephalosporin group of antibiotics or a history of immediate hypersensitivity to penicillin and other beta-lactams.
• Prescribe cefalexin with caution in people with:
  • Sensitivity to penicillin and other beta-lactams. About 0.5–6.5% of penicillin-sensitive people will also be allergic to cephalosporins.

[EMC, 2023b; BNF, 2024]

Adverse effects

• Gastrointestinal — diarrhoea (most common), nausea, vomiting, abdominal discomfort.
• Nervous system — headache, dizziness.
  • Tremor, myoclonia, convulsions, and encephalopathy have also been reported — most cases occurred in patients with renal impairment on doses above the recommended maximum and resolved following discontinuation. 
• Psychiatric — hallucinations, confusion, agitation.
• Skin — rash urticaria, angioedema.
  • Rarely: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (exanthematic necrolysis)
• Other adverse effects include: 
  • Anaphylaxis.
  • Arthralgia and myalgia.
  • Eosinophilia, neutropenia, thrombocytopenia, haemolytic anaemia. 
  • Genital and anal pruritus.
  • Hepatitis, cholestatic jaundice.
  • Interstitial nephritis (rarely).
  • Pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated. 

[EMC, 2023b; BNF, 2024]

Drug interactions

• Aminoglycosides (for example, gentamicin) — possible increased risk of nephrotoxicity. Routine renal monitoring for the aminoglycoside is usually adequate.
• Oral anticoagulants (warfarin and phenindione) — cefalexin may enhance the anticoagulant effect. Monitor the international normalized ratio (INR) closely during concomitant use. 
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of cefalexin.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods. 
• Probenecid — renal excretion of cefalexin is inhibited. However, no dose adjustment is normally required.

[CoSRH, 2022; EMC, 2023b; BNF, 2024; Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

• Cefalexin is not known to be harmful in pregnancy.

Breastfeeding

• Trace amounts of cefalexin are found in breastmilk — this is not known to be harmful.

[SPS, 2020b; EMC, 2023b; BNF, 2024]

Contraindications and cautions

• Do not prescribe trimethoprim in:
  • People with severe hepatic insufficiency or severe renal insufficiency.
  • People with megaloblastic anaemia or other blood dyscrasias.
  • Premature infants or children aged under 4 months.
  • Women in the first trimester of pregnancy.
• Prescribe trimethoprim with caution in people:
  • With impaired renal function.
  • With hyperkalaemia or taking medication that is known to cause hyperkalaemia.
  • With acute porphyria.
  • Predisposed to folate deficiency — because of the potential anti-folate effect of trimethoprim, there is a risk of further exacerbating folate deficiency in people who are folate deficient or who are predisposed to folate deficiency (for example, elderly people) or who are taking folate antagonists.

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

Adverse effects

• Blood disorders — leukopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, hyperkalaemia (particularly in the elderly and in HIV patients), methaemoglobinaemia.
• Gastrointestinal — nausea, diarrhoea, vomiting (common). 
• Nervous system — aseptic meningitis (frequency unknown).
• Skin — Pruritus and skin rashes (common).
  • Rarely: Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodosum, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura, angioedema.
• Other adverse effects include:
  • Anaphylaxis.
  • Liver enzyme disturbances, cholestatic jaundice.
  • Myalgia.
  • Raised serum creatinine.

[EMC, 2019; BNF, 2024]

Drug interactions

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists AIIRAs — there may be an increased risk of hyperkalaemia with the concurrent use of these drugs and trimethoprim. Monitor potassium concentrations. 
• Azathioprine and mercaptopurine — increased risk of haematological toxicity in people who have had a renal transplant. However, the combination is commonly used in practice. Monitor the full blood count routinely.
• Ciclosporin — serum creatinine levels may be increased. Possible increased risk of nephrotoxicity. Monitor renal function closely.
• Coumarins (warfarin) — the anticoagulant effect of coumarins may be potentiated. Monitor international normalised ratio (INR) and adjust dose accordingly.
• Digoxin — digoxin levels may be increased in the elderly if taken with trimethoprim. Monitor for digoxin adverse effects, and adjust dose accordingly.
• Diuretics — hyperkalaemia may be exacerbated by concomitant administration of diuretics, particularly potassium-sparing diuretics and/or thiazide diuretics and eplerenone.
• Methotrexate (a folate antagonist) — there is an increased risk of haematologic adverse effects. Several cases of bone marrow suppression have been reported (some fatal). Full blood count should be monitored routinely.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of trimethoprim.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods. 
• Phenytoin — phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust dose accordingly

[EMC, 2019; CoSRH, 2022; BNF, 2024; Preston, 2024]

Pregnancy and breastfeeding

• Pregnancy
  • There is a possible teratogenic risk in the first trimester of pregnancy due to the folate antagonistic effects of trimethoprim.
    • The manufacturer therefore advises that use in pregnant women should be avoided.
  • The UK Teratology Information Service (UKTIS) states that if trimethoprim use is clinically necessary during the first trimester:
    • Ensure the woman is taking a folic acid supplement.
    • Prescribe folic acid 5 mg daily.
  • UKTIS states that there is no evidence that trimethoprim causes harm beyond the first trimester and can be used at this stage of pregnancy if indicated.
• Breastfeeding
  • Trimethoprim is excreted in breast milk in small amounts that are not expected to cause adverse effects.

[EMC, 2019; Lactmed, 2021; BNF, 2024; UKTIS, 2024]

Contraindications and cautions

• Systemic fluoroquinolones must only be prescribed when other commonly recommended antibiotics are inappropriate.

• Do not prescribe ciprofloxacin to people:
  • With a history of adverse reactions with a quinolone antibiotic (for example, nalidixic acid) or a fluoroquinolone antibiotic.
• Prescribe ciprofloxacin with caution to people with:
  • Positive family history of aneurysm disease or congenital heart valve disease.
  • Pre-existing aortic aneurysm and/or dissection or heart valve disease, or in the presence of other risk factors or conditions predisposing for:
    • Both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis) or additionally
    • Aortic aneurysm and dissection (such as vascular disorders including Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome) or additionally
    • Heart valve regurgitation/incompetence (such as infective endocarditis).
  • Epilepsy, or conditions that predispose to seizures, and in people taking other medication that may predispose to seizures, as quinolones can lower the seizure threshold.
    • Quinolones may induce convulsions in patients with or without a history of convulsions, and taking NSAIDs at the same time may also induce them.
  • Diabetes mellitus — may affect blood glucose. Blood glucose should be monitored closely.
  • Glucose-6-phosphate dehydrogenase deficiency —haemolytic reactions have been reported.
  • A history of tendonitis — quinolones can very rarely cause tendon damage, and the risk of tendon rupture is increased by co-administration of corticosteroids.
  • 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, and antipsychotics).
    • Uncorrected electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, or bradycardia).
    • Electrolyte disturbances.
  • History of a psychotic disorder — there have been reports of suicidal thoughts or self-endangering behaviour after the use of quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
• Prescribe with caution in people aged over 60 years, people with renal impairment or solid-organ transplants, as they are at a higher risk of tendon injury.

 [EMC, 2023c; BNF, 2024; MHRA, 2024]

Adverse effects

• Gastrointestinal — diarrhoea, nausea (common), vomiting, dyspepsia, flatulence, gastrointestinal and abdominal pains (uncommon).
  • Rarely: pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated).
• Musculoskeletal — pain, arthralgia (uncommon).
  • Rarely: myalgia, arthritis.
  • Very rarely: muscle weakness, tendonitis, tendon damage — this may occur within 48 hours of starting treatment, or months after stopping. Risk of tendon rupture is increased by co-administration of corticosteroids and in people aged over 60 years. If tendonitis is suspected, ciprofloxacin should be discontinued immediately.
• Nervous system — headache, dizziness, sleep disorders, taste disorders (uncommon).
  • Rarely: tremor, vertigo, lowering of the seizure threshold – this may trigger seizures. 
• Psychiatric — hyperactivity, agitation (uncommon).
  • Rarely: confusion, anxiety, depression, suicidal ideation, hallucinations.
• Skin — rash, pruritus, urticaria.
  • Rarely: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis anaphylaxis, drug rash with eosinophilia, systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP).
• Cardiovascular system — there is an increased risk of aortic aneurysm and dissection with fluoroquinolones, particularly in the older population. Fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in people with positive family history of aneurysm disease, or in people diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in the presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (for example, Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s disease, hypertension, known atherosclerosis).
• Other adverse effects include:
  • Anaphylaxis.
  • Hepatic impairment, hepatitis.
  • Renal impairment.
  • Tachycardia.
  • Tinnitus.
  • Visual disturbances.
• 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 the use of fluoroquinolone antibiotics. 
• Report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website: https://yellowcard.mhra.gov.uk/

 [EMC, 2023c; BNF, 2024; MHRA, 2024]

Drug interactions

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these reduce the absorption of ciprofloxacin if taken concurrently.
  • Ciprofloxacin should be taken at least 2 hours before these preparations and not less than 4 to 6 hours after them.
• Ciclosporin — increased concentrations and nephrotoxicity might occur in a small number of patients.
• Corticosteroids — the risk of tendonitis and tendon rupture is increased in people taking a fluoroquinolone and a corticosteroid. The MHRA advises that concurrent should be avoided. 
• Domperidone — the manufacturer advises that concurrent use with ciprofloxacin should be avoided as it may lead to QT interval prolongation.
• Ergometrine — levels may be increased, leading to ergotism. Concurrent use is contraindicated. 
• Mizolastine — the manufacturer advises that concurrent use should be avoided. Mizolastine has a weak potential to cause QT interval prolongation in some people and this may be additive to the effects of ciprofloxacin.
• Methotrexate — plasma levels of methotrexate may be increased. The manufacturer recommends that concurrent use is avoided.
  • If concurrent use is necessary, monitor methotrexate levels.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — possible increased risk of seizures when quinolones are given with NSAIDs. Avoid concurrent use in people with epilepsy or people predisposed to seizures, or monitor them very closely.
• Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of ciprofloxacin.
  • However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
• Phenytoin — concurrent administration of ciprofloxacin can cause an increase or decrease in serum phenytoin levels. Monitor phenytoin levels.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate so they should not be given together.
• Theophylline — ciprofloxacin increases the plasma concentration of theophylline, leading to possible increased risk of convulsions. Monitor theophylline concentration closely.
• Tizanidine — ciprofloxacin increases the plasma concentration of tizanidine (increased risk of toxicity). Avoid concurrent use.
• Warfarin — rarely, ciprofloxacin may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalised ratio (INR) within 3 to 5 days of starting ciprofloxacin, frequently during and shortly after administration.
• Zolmitriptan — quinolones increase the plasma concentration of zolmitriptan by inhibiting its metabolism. 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 antiarrhythmics, 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.

 [CoSRH, 2022; EMC, 2023c; BNF, 2024; MHRA, 2024; Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

• Ciprofloxacin should be avoided in women who are pregnant.

Breastfeeding

• Ciprofloxacin is excreted in breast milk in quantities too small to be harmful. However, the manufacturer advises that it should be avoided due to the risk of articular damage.
  • However, studies indicate there is little risk, and quinolones are generally accepted for use during breastfeeding.
  • Avoiding breastfeeding for 3 to 4 hours after a dose should decrease the exposure of the infant to ciprofloxacin in breast milk.

 [EMC, 2023c; Lactmed, 2023; BNF, 2024]