Previous changes

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

February 2024 — minor update. Updated EAU guideline. MHRA warning re fluoroquinolones.

August 2021 — minor update. Adverse effects of co-trimoxazole updated in line with revised manufacturer's SPC relating to the rare problem of severe respiratory toxicity with the potential to progress to Adult Respiratory Distress Syndrome. 

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

March to April 2019 — reviewed. A literature search was conducted in March 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic.

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

November 2018 — minor update. Prescribing information changed to be in line with NICE guidance 110: prostatitis (acute): antimicrobial prescribing. 

August 2014 — reviewed. A literature search was conducted in July 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. This topic now applies to men aged 18 years and older and recommendations have been added regarding testing for sexually transmitted infections and referral to a genito-urinary medicine specialist.

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.

August 2012 — minor update. Minor typographical error corrected.

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

September 2010 — minor update. The lower age limit for quinolone prescriptions has been raised from 16 to 18 years. Issued in September 2010.

October 2008 to February 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. Together with the CKS topic on Prostatitis - chronic, this CKS topic replaces the former topic on Prostatitis.

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

December 2001 — rewritten, replacing guidance on Prostatitis — acute. Validated in March 2002 and issued in April 2002.

January 2000 — reviewed.

December 1998 — written. Validated in March 1999 and issued in May 1999.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 June 2024. 

HTAs (Health Technology Assessments)

No new HTAs since 1 June 2024. 

Economic appraisals

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

Systematic reviews and meta-analyses

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

Primary evidence

No new randomized controlled trials have been published in the major journals since 1 June 2024. 

New policies

No new national policies or guidelines since 1 June 2024. 

New safety alerts

No new safety alerts since 1 June 2024. 

Changes in product availability

No changes in product availability since 1 June 2024. 

Basis for recommendation

These recommendations are based on the European Association of Urology (EAU) guideline Urological infections [EAU, 2023], the British Medical Journal (BMJ) best practice guide Acute prostatitis [BMJ Best Practice, 2022], and expert opinion in narrative reviews Acute bacterial prostatitis: diagnosis and management [Coker, 2016] and Acute bacterial prostatitis [Davis, 2024].

Basis for recommendation

These recommendations are based on the European Association of Urology (EAU) guideline Urological infections [EAU, 2023], the British Medical Journal (BMJ) best practice guide Acute prostatitis [BMJ Best Practice, 2022], and expert opinion in narrative reviews Acute bacterial prostatitis: diagnosis and management [Coker, 2016] and Acute bacterial prostatitis [Davis, 2024].

Basis for recommendation

These recommendations are based on the British Medical Journal best practice guide Acute prostatitis [BMJ Best Practice, 2022] and expert opinion in narrative reviews Acute Bacterial Prostatitis: Diagnosis and Management [Coker, 2016] and Acute bacterial prostatitis [Davis, 2024], and Extremely Elevated Prostate-Specific Antigen in Acute Prostatitis: A Case Report [Nepal, 2023].

How should I manage acute prostatitis?

• Admit the person to hospital if:
  • They are unable to take oral antibiotics. 
  • They have severe symptoms. 
  • They have signs or symptoms of a more serious condition (for example sepsis, acute urinary retention, or prostatic abscess). 
• Consider urgent referral for anyone who:
  • Is immunocompromised or has diabetes mellitus. 
  • Has a pre-existing urological condition (such as benign prostatic hypertrophy or an indwelling catheter) — specialist urological management may be required. 
• Offer oral antibiotic treatment to people with acute prostatitis 
  • Take into account:  
    • The severity of the symptoms.
    • The risk of complications or treatment failure.
    • Previous urine culture results and susceptibilities.
    • Previous antibiotic use, tolerance and possible resistance.
    • The safety issues associated with fluoroquinolones.
  • Offer ciprofloxacin 500 mg twice daily or ofloxacin 200 mg twice daily for 14 days first line, or if a fluoroquinolone is not appropriate, offer trimethoprim 200 mg twice daily for 14 days. 
  • Offer levofloxacin 500 mg once daily, or co-trimoxazole 960 mg twice daily for 14 days second line after taking specialist advice.
    • Co-trimoxazole should only be considered when there is bacteriological evidence of sensitivity and good reasons to prefer this combination to a single antibiotic. 
• Advise them: 
  • To take paracetamol (with or without a low-dose weak opioid, such as codeine) for pain, or ibuprofen if this is preferred and suitable.
  • To drink enough fluids to avoid dehydration. 
  • About the usual course of acute prostatitis (several weeks).
  • About possible adverse effects of the antibiotic — fluoroquinolones can cause long-lasting (up to months or years), disabling, and potentially irreversible adverse effects, sometimes affecting multiple systems, organ classes, and senses. They are estimated to occur in 1-10 people in every 10,000 people taking them.
    
    • Advise them to stop treatment with a fluoroquinolone antibiotic at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately. Give them the patient information sheet Fluoroquinolone antibiotics (-oxacins): what you need to know about side effects of tendons, muscles, joints, and nerves.
  • To seek medical help if:
    • Symptoms worsen at any time.
    • Symptoms do not start to improve within 48 hours of taking the antibiotic.
    • They become systemically very unwell.
• Arrange follow up after 48 hours to check their response to treatment and the urine culture results.
  • Review the choice of antibiotic and change it according to susceptibility results if the bacteria are resistant — use a narrow-spectrum antibiotic wherever possible.
  • Admit to hospital if symptoms have not improved 48 hours after starting antibiotic treatment.
  • If a sexually transmitted infection (STI) is identified, refer urgently to a genito-urinary medicine (GUM) clinic. If there is likely to be a delay before the person is seen, seek advice from a GUM specialist regarding interim treatment.
• Reassess the person if symptoms worsen at any time, taking account of: 
  • Other possible diagnoses.
  • Any symptoms or signs suggesting a more serious illness or condition, such as acute urinary retention, prostatic abscess or sepsis.
  • Previous antibiotic use, which may have led to resistant bacteria.
• Review antibiotic treatment after 14 days and either stop treatment, or continue for an additional 14 days based on an assessment of history, symptoms, clinical examination, urine and blood tests. Treatment may be required for up to 6 weeks.
• Following recovery, refer for investigation to exclude structural abnormality of the urinary tract. 

Cautions and contraindications

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.

• Do not prescribe ciprofloxacin to people:

  • With a history of tendon disorders related to quinolone use.
  • Who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic.
  • Taking a corticosteroid — coadministration could exacerbate fluoroquinolone-induced tendonitis and tendon rupture.
• 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 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 corticosteroid.
  • 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 anti-arrhythmics, tricyclic antidepressants, macrolides, 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 use quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
• Also 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, 2023a; BNF, 2024; MHRA, 2024]

Adverse effects

• Gastrointestinal — diarrhoea, nausea (common), vomiting, dyspepsia, flatulence, and gastrointestinal and abdominal pains (uncommon).
  • Rarely: pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated).
• Musculoskeletal — pain and arthralgia (uncommon).
  • Rarely: myalgia and arthritis.
  • Very rarely: muscle weakness, tendonitis, and 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, and taste disorders (uncommon).
  • Rarely: tremor, vertigo, and convulsions in people with or without a history of convulsions (taking NSAIDs at the same time may also induce them).
• Psychiatric — hyperactivity, and agitation (uncommon).
  • Rarely: confusion, anxiety, depression, and hallucinations.
• Skin — rash, pruritus, and urticaria.
  • Rarely: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis anaphylaxis, drug rash with eosinophilia, systemic symptoms (DRESS), and 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, 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 and hepatitis.
  • Renal impairment.
  • Tachycardia.
  • Tinnitus.
  • Visual disturbances.
• NOTE: fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses. People should be advised to stop treatment at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice.

[EMC, 2023a; MHRA, 2023a; BNF, 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.
• 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. Manufacturer recommends a maximum dose of 5 mg in 24 hours in people taking a quinolone.
• Drugs that prolong the QT interval (such as Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) — very rare cases of QT interval prolongation have been reported in people taking quinolones and they should therefore be prescribed with caution alongside drugs known to prolong the QT interval.

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

Cautions and contraindications

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.

• Do not prescribe ofloxacin in people:
  • With glucose-6-phosphate dehydrogenase deficiency.
  • With a history of tendon disorders related to fluoroquinolone administration, or who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic.
  • Taking a corticosteroid — coadministration could exacerbate fluoroquinolone-induced tendonitis and tendon rupture.
• Prescribe ofloxacin with caution in people with:
  • Aortic aneurysm and/or aortic dissection, a family history of aneurysm disease, or with 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).
  • Diabetes mellitus — may affect blood glucose. Blood glucose should be monitored closely.
  • A history of tendonitis — quinolones can very rarely cause tendon damage, and the risk of tendon rupture is increased by co-administration of corticosteroid.
  • Impaired liver function — liver damage can occur. 
  • Conditions which predispose to QT interval prolongation:
    • Congenital long QT syndrome.
    • Concurrent use of drugs that are known to prolong the QT interval (for example Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
    • 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 use quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
• Also 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, 2022; BNF, 2024; MHRA, 2024]

Adverse effects

• Cardiovascular system — tachycardia (rarely); ventricular arrhythmias, torsades de pointes, and QT interval prolongation (frequency unknown).
  • 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 a positive family history of aneurysm disease, 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).
• Gastrointestinal — diarrhoea, nausea, vomiting, and abdominal pains (uncommon).
  • Very rarely: pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Musculoskeletal — tendonitis (rare).
  • Very rarely: arthralgia, myalgia, and tendon rupture — 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 and dizziness (uncommon),
  • Rarely: sleep disorders, taste disorders, tremor, vertigo, and convulsions in people with or without a history of convulsions (taking NSAIDs at the same time may also induce them).
• Psychiatric — agitation, sleep disorder, and insomnia (uncommon).
  • Rarely: confusion, anxiety, depression, and nightmares.
• Skin — rash and pruritus (uncommon)
  • Rarely: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis anaphylaxis, drug rash with eosinophilia, systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP).
• Other adverse effects include:
  • Anaphylaxis.
  • Dyspnoea and bronchospasm.
  • Hepatic impairment and hepatitis.
  • Renal impairment.
  • Tachycardia.
  • Tinnitus.
  • Visual disturbances.
• NOTE: fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses. People should be advised to stop treatment at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice.

[EMC, 2022; MHRA, 2023a; BNF, 2024]

Drug interactions

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these may reduce the absorption of ofloxacin if taken concurrently.
  • Ofloxacin should be taken at least 2 hours before these preparations, and not less than 4–6 hours after them.
• 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. 
• Ergometrine — levels may be increased, leading to ergotism. Concurrent use is contraindicated. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — possible increased risk of seizures when quinolones are given with NSAIDs. Avoid concurrent use in people with epilepsy or people predisposed to seizures, or monitor them very closely.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate so they should not be given together.
• Theophylline — ciprofloxacin increases the plasma concentration of theophylline, leading to possible increased risk of convulsions. There is the possibility of a similar effect with ofloxacin. Monitor theophylline concentration closely.
• Warfarin — rarely, ofloxacin may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalised ratio (INR) within 3 to 5 days of starting ofloxacin, 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.

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

Cautions and contraindications

• Do not prescribe trimethoprim to people with:
  • Severe hepatic insufficiency or severe renal insufficiency.
  • Megaloblastic anaemia or other blood dyscrasias.
• Prescribe trimethoprim with caution to people:
  • With impaired renal function.
  • With hyperkalaemia or taking medication that is known to cause hyperkalaemia.
  • With acute porphyrias.
  • 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.

[MHRA, 2023b; BNF, 2024]

Adverse effects

• Blood disorders — leucopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, hyperkalaemia (particularly in the elderly and in HIV patients), and methaemoglobinaemia.
• Gastrointestinal — diarrhoea, nausea, vomiting, and glossitis.
• Nervous system — headache (common).
  • Very rarely: dyskinesias, tremor, ataxia, dizziness, lethargy, and aseptic meningitis (frequency unknown).
• Skin — urticaria and skin rashes (common).
  • Rarely: photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodusum, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura, and angioedema.
• Other adverse effects include:
  • Anaphylaxis.
  • Hypoglycaemia.
  • Liver enzyme disturbances and cholestatic jaundice.
  • Myalgia.
  • Raised serum creatinine.

[MHRA, 2023b; 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 ciclosporin concentrations and the effect on renal function closely.
• Coumarins (warfarin) — the anticoagulant effect of coumarins may be potentiated. Monitor the international normalised ratio (INR) and adjust the 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 concurrent 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.
• Phenytoin — phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust the dose accordingly.

 [MHRA, 2023b; BNF, 2024; Preston, 2024]

Cautions and contraindications

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.

• Do not prescribe levofloxacin to people:
  • With epilepsy.
  • With a history of tendon disorders related to fluoroquinolone administration, or who have previously had serious adverse reactions with a quinolone or fluoroquinolone antibiotic.
  • Taking a corticosteroid — coadministration could exacerbate fluoroquinolone-induced tendonitis and tendon rupture.
• Prescribe levofloxacin with caution to people with:
  • A history of tendonitis.
  • Aortic aneurysm and/or aortic dissection, a family history of aneurysm disease, or with 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, and known atherosclerosis).
  • A predisposition to seizures, or taking medicines that lower the seizure threshold (for example, theophylline). 
  • 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.
  • Diabetes mellitus — may affect blood glucose. Blood glucose should be monitored closely.
  • Glucose-6-phosphate dehydrogenase deficiency — haemolytic reactions have been reported.
  • History of a psychotic disorder — there have been reports of suicidal thoughts or self-endangering behaviour after use quinolones. 
  • Myasthenia gravis — symptoms can be exacerbated.
• Also prescribe with caution in people aged over 60 years, people with renal impairment (dose adjustments may be required) or solid-organ transplants, as they are at a higher risk of tendon injury.

[EMC, 2021; MHRA, 2023a; BNF, 2024]

Adverse effects

• Cardiovascular — 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 a positive family history of aneurysm disease, 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).
• Gastrointestinal — diarrhoea, nausea, vomiting (common), abdominal pain, dyspepsia, and flatulence (uncommon).
  • Very rarely: pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Hepatobiliary — hepatic enzyme increases (common), blood bilirubin increase (uncommon), jaundice, severe liver failure, and hepatitis (frequency unknown).
• Musculoskeletal — arthralgia and myalgia (uncommon). 
  • Rarely: tendon disorders (including tendonitis), muscular weakness — 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 treatment should be stopped immediately. 
  • Frequency unknown: rhabdomyolysis, tendon rupture, ligament rupture. 
• Nervous system — headache, dizziness (uncommon), somnolence, tremor, dysgeusia (uncommon), and convulsions in people with or without a history of convulsions (taking NSAIDs at the same time may also induce them).
  • Rarely: peripheral neuropathy, dyskinesia, syncope. 
• Psychiatric — insomnia (common), anxiety, confusional state, and nervousness (uncommon)
  • Rarely: psychotic disorder with self-endangering behaviour including suicidal ideation or suicide attempt.
• Skin — rash, pruritus, urticaria, and hyperhidrosis (uncommon).
  • Rarely: Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis anaphylaxis.
• Other adverse effects include:
  • Anaphylaxis.
  • Dyspnoea and bronchospasm.
  • Renal impairment.
  • Tachycardia and palpitations.
  • Vertigo and tinnitus.
  • Visual disturbances.
• NOTE: fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses. People should be advised to stop treatment at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice.

[EMC, 2021; MHRA, 2023a; BNF, 2024]

Drug interactions

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these may reduce the absorption of levofloxacin if taken concurrently.
  • Levofloxacin should be taken at least 2 hours before these preparations and not less than 4–6 hours after them. 
• 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 levofloxacin should be avoided as it may lead to QT interval prolongation.
• 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 levofloxacin.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — possible increased risk of seizures when quinolones are given with NSAIDs. Avoid concurrent use in people with epilepsy or people predisposed to seizures, or monitor them very closely.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate so they should not be given together.
• Tacrolimus — levels are increased slightly when taken concurrently with levofloxacin. Consider increased monitoring if levofloxacin is started or stopped.
• Theophylline — levofloxacin does not affect plasma levels of theophylline, however, there has been a report of theophylline toxicity and reports of seizures in people given theophylline and a quinolone. Theophylline can cause hypokalaemia increasing the risk of torsade de pointes which may be additive with the effects of levofloxacin. Monitor potassium concentration closely.
• Warfarin — rarely, levofloxacin may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalised ratio (INR) within 3 to 5 days of starting levofloxacin, 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.

[EMC, 2021; MHRA, 2023a; BNF, 2024; Preston, 2024]

Cautions and contraindications

• Do not prescribe co-trimoxazole to people with:
  • Acute porphyrias.
  • A history of drug-induced immune thrombocytopenia with the use of trimethoprim and/or sulphonamides.
  • Haematological disorders (unless under specialist supervision).
  • Marked liver parenchymal damage.
  • Severe hepatic impairment.
  • Severe kidney impairment.
• Prescribe co-trimoxazole with caution to people with:
  • Asthma. 
  • Renal impairment — use half the normal dose if the estimated glomerular filtration rate (eGFR) is 15–30 mL/minute/1.73 m².
  • Hyperkalaemia or taking medication that is known to cause hyperkalaemia.
  • Glucose-6-phosphate dehydrogenase deficiency.
  • Severe allergy.
• Also prescribe with caution in: 
  • People predisposed to folate deficiency.
  • The elderly.

[EMC, 2023b; BNF, 2024]

Adverse effects

• Gastrointestinal — nausea, diarrhoea, (common), and vomiting (uncommon).
  • Very rarely: glossitis, stomatitis, pseudomembranous colitis, and pancreatitis.
• Metabolism and nutrition — hyperkalaemia (very common).
  • Very rarely: hypoglycaemia, hyponatraemia, and anorexia.
• Nervous system — headache (common),
  • Very rarely: aseptic meningitis, convulsions, ataxia, vertigo, tinnitus, and dizziness.
• Skin and subcutaneous tissue — rash (common) and drug reaction with eosinophilia and systemic symptoms (DRESS) (frequency unknown).
  • Very rarely: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, and exfoliative dermatitis.
• Other adverse effects include: 
  • Anaphylaxis.
  • Aplastic anaemia and haemolytic anaemia (older people, people with hepatic or renal failure, and people with poor folate status are more susceptible).
  • Arthralgia and myalgia.
  • Fungal overgrowth.
  • Renal impairment.
  • Liver enzyme disturbances and cholestatic jaundice
  • Severe respiratory toxicity including potential progression to Adult Respiratory Distress Syndrome.

[EMC, 2023b; BNF, 2024]

Drug interactions

• Angiotensin-converting enzyme (ACE) inhibitors — risk of severe hyperkalaemia.
• Antiarrhythmics — increased risk of ventricular arrhythmias with amiodarone.
• Coumarins (warfarin) — effect of warfarin enhanced.
  • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
• Antidiabetics — effect of sulfonylureas enhanced.
• Antifolates — if considered appropriate, a folate supplement should be considered for people taking antifolate drugs such as methotrexate or proguanil.
• Antivirals — plasma concentrations of lamivudine increased, avoid concurrent high-dose co-trimoxazole. Concurrent treatment with zidovudine may increase the risk of haematological adverse effects. Zalcitabine plasma concentrations possibly increased by co-trimoxazole.
• 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.
• Clozapine — increased risk of fatal agranulocytosis. Concurrent use is contraindicated.
• Ciclosporin — serum creatinine levels may be increased. Possible increased risk of nephrotoxicity, monitor renal function closely. Reversible deterioration in renal function has been reported in people following renal transplantation.
• Digoxin —digoxin levels may be increased in the elderly if taken with trimethoprim. Monitor for digoxin adverse effects, and adjust the dose accordingly.
• Diuretics — for older people concurrently receiving diuretics (mainly thiazides) there is an increased risk of thrombocytopenia. Hyperkalaemia may be exacerbated by concurrent administration of diuretics, particularly potassium-sparing diuretics and/or thiazide diuretics and eplerenone.
• Methotrexate — plasma levels may be increased.
• Phenytoin — phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust the dose accordingly.

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