Previous changes

March 2024 — minor update. Information on the use of fluoroquinolones was added to the levofloxacin and moxifloxacin prescribing sections in line with a review published by the MHRA. Fixed eruption added as an adverse effect of doxycycline as per the manufacturer's SPC.

January 2024 — minor update. Information on the use of fluoroquinolones and reporting adverse reactions was added in line with the Drug Safety Update published by the MHRA [MHRA, 2023].

October 2023 — reviewed. A literature search was conducted in August 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with current evidence in the literature. The topic has undergone minor restructuring to improve clarity and navigation. A section on the antibiotic Levofloxacin has been added to the Prescribing information section.

July 2023 — minor update. Prescribing information for metronidazole amended to reflect the manufacturer's Summary of Product Characteristics (SPC) which states that QT prolongation has been reported (unknown frequency), particularly when administered with other drugs with potential for QT prolongation.

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

June 2019 — minor update. The recommended dose of ceftriaxone has been increased to 1 g in line with the British Association for Sexual Health and HIV UK national guideline for the management of pelvic inflammatory disease (2019 interim update).

March 2019 — minor update. Prescribing information for quinolones updated in line with the Medicines and Healthcare products Regulatory Agency (MHRA) publication Fluoroquinolone antibiotics: new restrictions and precautions for use due to very rare reports of disabling and potentially long-lasting or irreversible side effects (MHRA 2019).

January 2019 — minor update. Formatting issue corrected.

October 2018 — minor update. The prescribing information section on adverse effects of metronidazole has been updated.

August 2018 — reviewed. A literature search was conducted in August 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The topic has been restructured and the following changes have been made: 

• The role of Mycoplasma genitalium as an important cause of pelvic inflammatory disease (PID) has become clearer, and testing is recommended for women presenting with possible PID and the male partners of women with confirmed M. genitalium infection.
• Moxifloxacin is now recommended as a first-line treatment, especially in women with M. genitalium.
• Doxycycline is now suggested as empirical treatment for male partners of women with PID to reduce exposure to macrolides, which have been associated with increased resistance in M. genitalium.

April 2015 — minor update. Link inserted to the CKS topic on Analgesia - mild-to-moderate pain.

March 2013 — reviewed. A literature search was conducted in March 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. No major changes to clinical 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.

November 2011 — minor update. The dose of intramuscular ceftriaxone has been increased from 250 mg to 500 mg to reflect the reduced sensitivity of Neisseria gonorrhoeae to cephalosporins, and the current UK treatment guidelines for uncomplicated gonorrhoea from the British Association for Sexual Health and HIV (BASHH). 

June 2011 — minor update. Text expanded in the Advice and management of sexual partner nodes to include new recommendations from the British Association for Sexual Health and HIV (BASHH). Also included two new RCTs which suggest that moxifloxacin monotherapy is therapeutically equivalent to other regimens in the treatment of uncomplicated PID (Heystock and Ross, 2009; Judin et al, 2010). The 2010/2011 QIPP options for local implementation have been added to this topic.

February 2011 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that moxifloxacin should be restricted to second-line use for the management of PID because of the increased risk of liver reactions and QT prolongation. 

September 2010 — minor update. Oral cefixime 400 mg as a single dose is included as an alternative treatment option to the intramuscular ceftriaxone component of the recommended antibiotic regimens. The lower age limit for quinolone prescriptions has also been raised from 16 to 18 years. 

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

September 2008 — minor correction to the Changes section. 

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

November 2005 — minor technical update. 

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

December 1999 — written. Validated in March 2000 and issued in May 2000.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 August 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 August 2023.

Economic appraisals

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

Systematic reviews and meta-analyses

No new systematic reviews published since 1 August 2023.

Primary evidence

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

New policies

No new national policies or guidelines since 1 August 2023.

New safety alerts

No new safety alerts since 1 August 2023.

Changes in product availability

No changes in product availability since 1 August 2023.

Basis for recommendation

The recommendations on assessment are largely based on the British Association for Sexual Health and HIV (BASHH) publication United Kingdom national guideline for the management of pelvic inflammatory disease (2019 interim update) [BASHH, 2019], the European publication European guideline for the management of pelvic inflammatory disease [Ross, 2017], and expert opinion in review articles on pelvic inflammatory disease (PID) [Curry, 2019; Hillier, 2021].

Basis for recommendation

The information on the differential diagnosis of pelvic inflammatory disease is based on the British Association for Sexual Health and HIV (BASHH) publication United Kingdom national guideline for the management of pelvic inflammatory disease (2019 interim update) [BASHH, 2019], the European publication European guideline for the management of pelvic inflammatory disease [Ross, 2017], the Faculty of Sexual and Reproductive Healthcare (FSRH) clinical guideline Intrauterine contraception [CoSRH, 2023], and expert opinion in review articles Common questions about the evaluation of acute pelvic pain [Bhavsar, 2016] and Pelvic inflammatory disease: diagnosis, management, and prevention [Curry, 2019]. They are also pragmatic, based on what CKS considers to be good clinical practice.

How should I initially manage suspected PID?

If a woman has a suspected diagnosis of pelvic inflammatory disease (PID):

• Arrange urgent hospital admission if:
  • The woman is pregnant, or an ectopic pregnancy is suspected. See the CKS topic on Ectopic pregnancy for more information.
  • There are severe systemic symptoms and/or an adnexal mass suggesting a possible complication, such as a tubo-ovarian abscess or pelvic peritonitis.
  • The woman is systemically unwell, and there is an uncertain diagnosis.
  • The woman is unable to follow or tolerate management in primary care.
• Consider seeking advice from an appropriate specialist if:
  • A woman has HIV — liaise with her infectious diseases specialist as needed.
  • A woman has an intrauterine contraceptive (IUC) and actinomyces-like organisms (ALOs) detected on cervical cytology — liaise with the local microbiology and gynaecology teams regarding the need for further investigation and management on a case-by-case basis.
    • Note: if a woman is asymptomatic but has positive ALO on cervical screening, there is no need for further investigation or management.
  • A complication such as perihepatitis is suspected.
  • There is any uncertainty about clinical management.
• If hospital admission or referral is not needed, advise the woman to attend a local specialist sexual health service for sexually transmitted infection (STI) screening, treatment, and contact tracing of current and recent sexual partners (within the last 6 months), depending on clinical judgement and local availability.
  • If the woman is unable or unwilling to attend, see the sections on Antibiotic treatment and Managing sexual partners for more information.
• Advise on the use of over-the-counter medication for symptom relief.
  • Options include paracetamol and/or ibuprofen if there are no contraindications. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for more information.
• Advise to start empirical antibiotic drug treatment as soon as a working diagnosis of PID is made. 
  • Advise the woman to ideally have STI screening before starting antibiotic treatment so that an accurate diagnosis can be made. Do not, however, delay starting drug treatment while awaiting tests to be arranged or the results of laboratory tests.
  • Advise to complete the course of antibiotic treatment, even if vaginal swabs are negative, in order to reduce the risk of long-term complications.
  • See the section on Antibiotic treatment for detailed information on different regimens that may be used.
• If a woman has a copper or levonorgestrel intrauterine device (IUD) in situ:
  • If she has mild-to-moderate symptoms, advise that the IUD can remain in situ, provided she is clinically improving within 48–72 hours of starting antibiotic treatment. If symptoms are not improving, the IUD should be removed. See the CKS topic on Contraception - IUC for more information.
  • If she has severe symptoms at presentation, the IUD should be removed.
  • If the IUD is removed, consider the need for emergency hormonal contraception, follow-up pregnancy testing, and ongoing contraception. See the CKS topics on Contraception - assessment and Contraception - emergency for more information.
• Advise to abstain from all sexual activity until both the woman and any sexual partner(s) have completed antibiotic treatment, are symptom-free, and have had a 'test of cure' if needed, depending on clinical judgement. See the section on Follow-up for more information.
  • Advise that a barrier method of contraception should be used if sexual contact cannot be avoided. Advise that future use of a barrier method of contraception will greatly reduce the risk of reinfection and protect against other STIs. See the CKS topic on Contraception - barrier methods and spermicides for more information.
• Advise on sources of information and support, such as: 
  • NHS (website www.nhs.uk) information Pelvic inflammatory disease.
  • The British Association for Sexual Health and HIV (BASHH website www.bashh.org) information leaflet Pelvic inflammatory disease.
  • The Royal College of Obstetricians and Gynaecologists (RCOG website www.rcog.org.uk) Acute pelvic inflammatory disease (PID): tests and treatment patient information leaflet.
• Arrange to review the woman in primary care, the timescale depends on clinical judgement.
  • See the section on Follow-up for more information.

What antibiotic treatment should be given for suspected PID?

Advise the woman to attend a local specialist sexual health service for sexually transmitted infection (STI) screening, treatment, and contact tracing of current and recent sexual partners, depending on clinical judgement and local availability. If the woman is unable or unwilling to attend, consider prescribing antibiotic treatment in primary care.

• If the risk of gonococcal infection is high:
  • Prescribe ceftriaxone 1 g as a single intramuscular (IM) dose, followed by oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily for 14 days.
  • See the section on Prescribing information for detailed information about contraindications and cautions, adverse effects, and drug interactions of different antibiotics.
  • See the CKS topic on Gonorrhoea for more information about additional risk factors for gonococcal infection.
• If the risk of gonococcal infection is low, prescribe one of the following antibiotic regimens, taking into account drug availability, any contraindications, and local antimicrobial sensitivity patterns.
  • First-line, prescribe ceftriaxone 1 g as a single IM dose, followed by oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily for 14 days.
  • Second-line, consider prescribing one of the following antibiotic regimens: 
    • Oral ofloxacin 400 mg twice daily plus oral metronidazole 400 mg twice daily for 14 days, or
    • Oral levofloxacin 500 mg once daily plus oral metronidazole 400 mg twice daily for 14 days, or
    • Oral moxifloxacin 400mg once daily for 14 days.
    • Note: 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. When prescribing fluoroquinolones, provide the patient information found in the MHRA Drug Safety Update on fluoroquinolone antibiotics.
  • See the section on Prescribing information for detailed information about contraindications and cautions, adverse effects, and drug interactions for different antibiotics.
• If the initial test result for Mycoplasma genitalium is positive:
  • Prescribe oral moxifloxacin 400mg once daily for 14 days. See the section on Prescribing information for detailed information about contraindications and cautions, adverse effects, and drug interactions.
• If all first- and second-line antibiotic regimens are contraindicated or not tolerated, consider prescribing:
  • Ceftriaxone 1 g as a single IM dose, followed by oral azithromycin 1 g per week for 2 weeks.
  • See the section on Prescribing information for detailed information about contraindications and cautions, adverse effects, and drug interactions for different antibiotics.
• If there is a risk of very early pregnancy (too early for a pregnancy test to be positive):
  • Consider starting empirical antibiotic treatment, as the benefits of treatment outweigh the low risks of antibiotic treatment in very early pregnancy.
• Advise to abstain from all sexual activity until both the woman and any sexual partner(s) have completed antibiotic treatment, are symptom-free, and have had a 'test of cure' if needed, depending on clinical judgement. See the section on Follow-up for more information.
  • Advise that a barrier method of contraception should be used if sexual contact cannot be avoided. Advise that future use of a barrier method of contraception will greatly reduce the risk of reinfection and protect against other STIs. See the CKS topic on Contraception - barrier methods and spermicides for more information.

How should I follow up a woman with PID?

If a woman has a suspected diagnosis of pelvic inflammatory disease (PID) and has started empirical antibiotic drug treatment as part of initial management:

• Review the woman within 72 hours, depending on clinical judgement.
  • Ask about current symptoms to assess the response to treatment.
    • If she is not clinically improving, check compliance with treatment, reassess for an alternative underlying cause, and consider arranging urgent hospital admission.
  • Check the antibiotic sensitivities from vaginal swab results (if available).
    • Adjust antibiotic drug treatment if necessary. See the section on Antibiotic treatment for more information.
    • Continue antibiotic treatment even if vaginal swabs are negative.
    • If there are mild-to-moderate PID symptoms and the woman is unable to tolerate metronidazole due to adverse effects, advise her to stop metronidazole but continue the other antibiotics in the regimen. See the section on Metronidazole in Prescribing information for more information on the potential adverse effects of metronidazole.
• Consider arranging a further review 2–4 weeks after completion of antibiotic treatment.
  • Check compliance with and response to antibiotic treatment.
  • Check that any sexual partner(s) have been screened and treated. See the section on Managing sexual partners for more information.
  • Advise a repeat pregnancy test and test of cure if clinically indicated.
• Advise on the future use of a barrier method of contraception to reduce the risk of reinfection and protect against other STIs, and advise on options for additional methods of contraception.
  • See the CKS topics on Contraception - assessment and Contraception - barrier methods and spermicides for more information.
• Ensure a 'test of cure' is arranged by the local specialist sexual health service or in primary care if the woman has:
  • A positive initial test result for gonorrhoea.
    • Repeat testing should be routinely arranged 2–4 weeks after completion of treatment.
  • A positive initial test result for chlamydia.
    • Repeat testing should be arranged 3–5 weeks after completion of treatment if there are persisting symptoms or if compliance with oral antibiotics and/or tracing of sexual contacts indicates the possibility of persisting or recurrent infection.
  • A positive initial test result for Mycoplasma genitalium.
    • Repeat testing should be arranged 4 weeks after completion of treatment.
  • Persistent symptoms after completing antibiotic treatment.
  • An initial test result showing unknown antibiotic sensitivity or antibiotic resistance (in cases of gonorrhoea or Mycoplasma genitalium).
  • Suspected poor compliance with antibiotic treatment or treatment has not been tolerated.
  • Possible persisting or recurrent infection, for example, due to repeated sexual contact with untreated partners.

How should I manage sexual partners?

Advise the woman that any current and recent sexual partners (within the last 6 months) should attend a local specialist sexual health service for sexually transmitted infection (STI) screening, treatment, and contact tracing. If a sexual partner is unable or unwilling to attend a specialist clinic:

• Offer screening for chlamydia and gonorrhoea.
  • Whilst awaiting the test results, offer any male partner(s) empirical treatment with a broad-spectrum antibiotic, such as doxycycline 100 mg twice daily for one week.
  • If chlamydia or gonorrhoea infection is confirmed in the partner(s), treat both the partner(s) and the woman appropriately. See the CKS topics on Chlamydia - uncomplicated genital and Gonorrhoea for detailed information on testing and treatment options.
• Offer screening for Mycoplasma genitalium if the woman has confirmed M. genitalium infection (depending on local testing availability).
  • If the test result for M. genitalium is positive, arrange antibiotic treatment for both the partner(s) and the woman. See the section on  Antibiotic treatment for more information.
• Advise to abstain from all sexual activity until both the woman and sexual partner(s) have completed a course of antibiotic treatment, are symptom-free, and have had a 'test of cure' if needed, depending on clinical judgement.
  • See the CKS topics on Chlamydia - uncomplicated genital and Gonorrhoea for detailed information on follow-up.
• Advise on the future use of a barrier method of contraception to reduce the risk of reinfection and protect against other STIs.
  • See the CKS topic on Contraception - barrier methods and spermicides for more information.

What are the contraindications and cautions?

• Do not prescribe azithromycin to people:
  • With severe hepatic impairment.
  • Who are pregnant —  the manufacturer advises to avoid unless no suitable alternative is available.
  • Who are breastfeeding — present in milk, so use only if no suitable alternative is available.
• Prescribe azithromycin with caution to people with:
  • Risk factors for QT interval prolongation, such as:
    • Uncorrected electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, symptomatic arrhythmias, or bradycardia).
    • 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, and antipsychotics).
  • Mild to moderate hepatic impairment.
  • Renal impairment — use with caution if estimated glomerular filtration rate (eGFR) is less than 10 mL/min/1.73 m².
  • Myasthenia gravis — may aggravate symptoms.

[BNF, 2023; EMC, 2023]

What are the adverse effects?

• Possible adverse effects of azithromycin include:
  • Common or very common — abdominal discomfort, anorexia, diarrhoea, disturbances in taste, arthralgia, disturbances in vision, dizziness, dyspepsia, flatulence, headache, malaise, nausea and vomiting, pancreatitis, paraesthesia, and reversible hearing loss.
  • Uncommon — anxiety, chest pain, cholestatic jaundice, constipation, gastritis, hypoaesthesia, leucopenia, oedema, photosensitivity, rash, and sleep disturbance.
  • Rare — agitation.
  • Frequency not known — acute renal failure, convulsions, haemolytic anaemia, interstitial nephritis, smell disturbances, syncope, thrombocytopenia, and tongue discolouration.

[BNF, 2023; EMC, 2023]

What are the drug interactions?

• Possible drug interactions of azithromycin include:
  • Antacids — plasma concentrations of azithromycin may be reduced by antacids.
    • Advise that azithromycin should be taken at least two hours before or one hour after antacids.
  • Chloroquine and hydroxychloroquine — the manufacturer advises that clinicians carefully consider the balance of benefits and risks of co-administration due to increased risk of cardiovascular events and mortality.
  • Ciclosporin — azithromycin can affect clearance of ciclosporin.
    • If co-administration of these drugs is necessary, monitor ciclosporin levels and adjust the dose accordingly.
  • Colchicine — azithromycin slightly increases the levels of colchicine.
    • Monitor for signs of colchicine toxicity (for example, nausea, vomiting, diarrhoea, myopathy, and pancytopenia).
  • Digoxin — macrolides increase digoxin levels. 
    • Monitor and reduce the digoxin dose if required.
  • Edoxaban — levels may be increased by azithromycin.
    • Dose adjustment of edoxaban may be required.
  • Ergot derivatives — there is a theoretical possibility of ergot toxicity if taken concomitantly with azithromycin.
    • The manufacturer of azithromycin recommends to avoid.
  • Rifabutin — azithromycin increases the risk of neutropenia when given with rifabutin.
    • Monitor closely.
  • Statins — there is a possible increased risk of myopathy.
    • Advise the person to report any muscle pain, tenderness, or weakness.
  • Warfarin — occasionally and unpredictably, the effects of warfarin may be markedly increased by macrolides.
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
  • Drugs that prolong the QT interval (such as amiodarone, sotalol, or hydroxyzine) — all macrolides can prolong the QT interval, and concomitant use of drugs that prolong the QT interval is not recommended.
    • Use an alternative antibiotic and/or seek advice from a microbiologist.
  • Drugs that cause hypokalaemia (such as diuretics, corticosteroids, and short-acting beta-2 agonists) — hypokalaemia is a risk factor for QT prolongation.

 [BNF, 2023; EMC, 2023]

What are the contraindications and cautions?

• Do not prescribe ceftriaxone to people with:
  • Known hypersensitivity to any cephalosporins or a history of immediate hypersensitivity to penicillin and other beta-lactams.
    • Cross-reactivity between penicillins and first- and early second-generation cephalosporins has been reported to occur in up to 10% of people and for third-generation cephalosporins in 2–3% of people with a penicillin allergy. 
    • Note that gastrointestinal adverse effects alone (for example, nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
• Prescribe ceftriaxone with caution to people with:
  • A gastrointestinal disorder such as colitis.
  • Hypercalciuria.
  • Kidney stones.
  • Severe hepatic impairment (no information available).
  • Severe renal impairment in combination with hepatic impairment — reduce dose and monitor efficacy of treatment. In adults, reduce the dose if creatinine clearance is less than 10 mL/min (maximum of 2 g daily). 

[BNF, 2023]

What are the adverse effects?

• Possible adverse effects of ceftriaxone include:
  • Common or very common
    • Abdominal pain, diarrhoea, dizziness, eosinophilia, headache, leucopenia, nausea, neutropenia, antibiotic-associated colitis, skin reactions, thrombocytopenia, vomiting, vulvovaginal candidiasis.
  • Uncommon
    • Anaemia, coagulation disorder, fungal infection.
  • Rare
    • Bronchospasm, glycosuria, haematuria, and oedema.
    • Precipitation of calcium ceftriaxone in gall bladder — consider discontinuation if symptomatic.
    • Precipitation of calcium ceftriaxone in urine (particularly if dehydrated or immobilized) —consider discontinuation if symptomatic.

[BNF, 2023]

What are the drug interactions?

• Possible drug interactions associated with ceftriaxone include:
  • Warfarin — ceftriaxone may enhance the anticoagulant effect of warfarin.
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.
  • Calcium chloride and calcium gluconate — ceftriaxone increases the risk of cardio-respiratory arrest when given with calcium chloride or calcium gluconate.
    • The manufacturer advises that concurrent use should be avoided.

[BNF, 2023] 

What are the contraindications and cautions?

• Do not prescribe doxycycline to people:
  • With known hypersensitivity to any of the tetracyclines.
  • With acute porphyria.
  • Who are pregnant or breastfeeding women — doxycycline is deposited in the teeth and bones of unborn or developing children and may have effects on skeletal development and cause teeth discolouration.
• Prescribe doxycycline with caution to people: 
  • With myasthenia gravis — tetracyclines may increase muscle weakness.
  • With systemic lupus erythematous — tetracyclines may exacerbate symptoms.
  • With hepatic impairment — avoid if possible.
  • With renal impairment — avoid excessive doses.
  • With alcohol dependency.
  • Likely to be exposed to direct sunlight or ultraviolet light — may cause photosensitivity and an exaggerated sunburn reaction in some people.

[BNF, 2023]

What are the adverse effects?

• Possible adverse effects of doxycycline include:
  • Angioedema, diarrhoea, dizziness, dyspnoea, headache, hypersensitivity, hypotension, nausea, pancreatitis, pericarditis, peripheral oedema, photosensitivity reaction, skin reaction, tachycardia and vomiting.
  • Anorexia, anxiety, benign intracranial hypertension, dry mouth, dysphagia, fixed eruption, flushing, fungal superinfection (when used for periodontitis), glossitis, hepatic disorders, increased risk of infection, neutropenia, antibiotic-associated colitis, Stevens-Johnson syndrome, thrombocytopenia (rare).

[BNF, 2023; EMC, 2024a]

What are the drug interactions?

• Possible drug interactions associated with doxycycline include:

  • Antacids (containing aluminium, bismuth, calcium, or magnesium) and other medications containing iron or zinc — these reduce the absorption of tetracyclines if taken concurrently.
    • Avoid taking antacids and other medications containing iron or zinc 2 hours before or after taking tetracyclines.
  • CYP3A enzyme inducers (phenobarbital, carbamazepine, or phenytoin) — these may reduce the serum half-life of doxycycline. Monitor and adjust the dose if necessary.
  • Flucloxacillin — concurrent use increases risk of hepatotoxicity.
  • Fluconazole — concurrent use increases risk of hepatotoxicity.
  • Insulin — the blood-glucose lowering effect may be increased if taken with doxycycline. Monitor blood glucose levels.
  • Lithium — lithium levels may be increased by doxycycline. Manufacturer advises to avoid or adjust dose.
  • Methotrexate — concurrent use increases risk of hepatotoxicity.
  • Paracetamol — concurrent use increases risk of hepatotoxicity.
  • Retinoids — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with retinoids (such as isotretinoin). Avoid the concurrent use of tetracyclines and retinoids.
  • Rifampicin — doxycycline levels are markedly reduced, which may lead to treatment failure. Monitor the effects and increase doxycycline dose if necessary.
  • Statins — concurrent use increases risk of hepatotoxicity.
  • Sulfasalazine — concurrent use increases risk of hepatotoxicity.
  • Valproate — concurrent use increases risk of hepatotoxicity. 
  • Warfarin — the concurrent use of warfarin with tetracyclines may increase the anticoagulant effect. Consider monitoring the person's international normalised ratio (INR) regularly and within 3 days of starting the tetracycline. Adjust the warfarin dose accordingly.

[BNF, 2023]

Contraindications and cautions

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.
• Do not prescribe levofloxacin to people:
  • With a history of serious adverse reactions with a quinolone antibiotic (for example, nalidixic acid) or a fluoroquinolone antibiotic.
  • Who are pregnant — shown to cause arthropathy in animal studies; safer alternatives are available.
  • Who are breastfeeding — manufacturer advises to avoid, as present in milk in animal studies.
• Prescribe levofloxacin with caution to people:
  • Aged over 60 years — increased risk of tendon damage and aortic aneurysm and dissection in older people.
• Also prescribe levofloxacin with caution to people with:
  • Aortic aneurysm and/or aortic dissection, a family history of aneurysm, or other risk factors or conditions predisposing to aortic aneurysm and dissection (such as Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, atherosclerosis) — small increased risk of aortic aneurysm and dissection.
  • Congenital or pre-existing heart valve disease, or with risk factors or conditions predisposing to heart valve regurgitation (such as Turner's syndrome, Behcet's disease, rheumatoid arthritis, and infective endocarditis) — small increased risk of heart valve regurgitation.
  • Conditions which predispose to QT interval prolongation:
    • Concurrent use of drugs that are known to prolong the QT interval (for example, Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
    • Electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, bradycardia, congenital long QT syndrome, history of arrhythmias).
  • Solid-organ transplant — increased risk of tendon damage.
  • Diabetes mellitus — may affect blood glucose.
  • A history of tendonitis — quinolones can very rarely cause tendon damage.
  • Conditions which predispose to seizures; history of epilepsy — quinolones may induce convulsions in people with a history of convulsions, and the risk is increased in people taking a nonsteroidal anti-inflammatory drug (NSAID). Concurrent NSAID use should be avoided in people with epilepsy or with conditions that predispose to seizures.
  • Renal impairment — usual initial dose, then use half normal dose if creatinine clearance is 20–50 mL/min. Consult product literature if creatinine clearance is less than 20 mL/min.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Psychiatric disorders — reports of suicidal thoughts or self-endangering behaviour after quinolone use.
  • Myasthenia gravis — may exacerbate symptoms.

[BNF, 2023; MHRA, 2023]

Adverse effects

Possible adverse effects of levofloxacin include:

• Cardiovascular
  • Tachycardia, ventricular arrhythmias, torsades de pointes, QT interval prolongation.
  • There is an increased risk of aortic aneurysm and dissection with fluoroquinolones (rare). Advise to seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops.
  • Heart valve regurgitation — advise to seek immediate medical attention if there is rapid-onset breathlessness (especially if lying flat); ankle, foot, or abdominal swelling; or new-onset heart palpitations.
• Gastrointestinal
  • Diarrhoea, constipation, nausea, vomiting, reduced appetite, abdominal pain.
• Musculoskeletal
  • Arthralgia, myalgia, tendon damage including tendonitis and tendon rupture (rare).
    • Tendon rupture may occur within 48 hours of starting treatment or months after stopping a quinolone. Risk of tendon rupture is increased by concomitant corticosteroids and in people aged over 60 years. If tendonitis or tendon rupture is suspected, advise to stop levofloxacin immediately and seek medical advice.
• Central nervous system (CNS)
  • Headache, dizziness, sleep disorders, taste disorders, tinnitus, tremor, vertigo, visual disturbances.
    • If peripheral neuropathy, muscle weakness, or serious CNS adverse effects are suspected, advise to stop levofloxacin immediately and seek medical advice.
• Psychiatric
  • Agitation, sleep disorder, confusion, anxiety, depression, nightmares.
• Skin
  • Rash, pruritus (uncommon).
• Other
  • Anaphylaxis, fever, increased risk of infection, dyspnoea.
  • Fluoroquinolones can very rarely cause long-lasting, disabling, and potentially irreversible adverse effects, sometimes affecting multiple organ systems.
• People should be advised to stop fluoroquinolone treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy or central nervous system effects. Remain alert to the risk of suicidal thoughts and behaviours with use of fluoroquinolone antibiotics. 

Report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website: https://yellowcard.mhra.gov.uk/.

[BNF, 2023; MHRA, 2023]

Drug interactions

Possible drug interactions associated with levofloxacin include:

• 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.
• Celecoxib and other COX-2 inhibitors — celecoxib potentially increases the risk of seizures when given with levofloxacin. Manufacturer advises caution.
• Corticosteroids — the risk of tendonitis and tendon rupture is increased in people taking a fluoroquinolone and a corticosteroid. Concurrent use should be avoided. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — potentially increased risk of seizures when quinolones are given with NSAIDs. Manufacturer advises caution.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate. Manufacturer advises to avoid.
• Warfarin — levofloxacin increases the anticoagulant effect of warfarin. The manufacturer advises to monitor the international normalized ratio (INR).
• 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.

[BNF, 2023; MHRA, 2023]

What are the contraindications and cautions?

• Do not prescribe metronidazole to people with:
  • Known metronidazole or nitroimidazole hypersensitivity.
  • Cockayne syndrome — cases of severe hepatotoxicity or acute hepatic failure, including risk of death, have been reported. This may have rapid onset after treatment with products containing metronidazole for systemic use. Only use if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout, and after treatment until liver function is within normal ranges or until the baseline values are reached. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.
• Prescribe metronidazole with caution to people with:
  • Hepatic impairment — manufacturer advises caution in hepatic encephalopathy (risk of decreased clearance). Manufacturer advises dose reduction to one-third of the daily dose in hepatic encephalopathy (dose may be given once daily).
  • Alcohol dependency — may be a disulfiram-like reaction if taken with alcohol.

[EMC, 2022; BNF, 2023]

What are the adverse effects?

• Possible adverse effects of metronidazole include:

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

[EMC, 2022; BNF, 2023]

What are the drug interactions?

Possible drug interactions associated with metronidazole include:

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

 [BNF, 2023]

What are the contraindications and cautions?

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.
• Do not prescribe moxifloxacin to people:
  • With a history of tendon disorders related to quinolone use or previous serious adverse reactions to a quinolone or fluoroquinolone antibiotic.
  • With concomitant corticosteroid use — may exacerbate risk of quinolone-induced tendonitis and tendon rupture.
  • With conditions which predispose to QT interval prolongation:
    • Concurrent use of drugs that are known to prolong the QT interval (for example, Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics).
    • Electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, acute myocardial infarction, bradycardia, congenital long QT syndrome, history of symptomatic arrhythmias).
  • Who are pregnant — shown to cause arthropathy in animal studies; safer alternatives are available.
  • Who are breastfeeding — manufacturer advises avoid, as present in milk in animal studies.
• Prescribe moxifloxacin with caution to people:
  • Aged over 60 years — increased risk of tendon damage and aortic aneurysm and dissection in older people.
• Also prescribe moxifloxacin with caution to people with:
  • Aortic aneurysm and/or aortic dissection, a family history of aneurysm, or other risk factors or conditions predisposing to aortic aneurysm and dissection (such as Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, atherosclerosis) — small increased risk of aortic aneurysm and dissection.
  • Congenital or pre-existing heart valve disease, or with risk factors or conditions predisposing to heart valve regurgitation (such as Turner's syndrome, Behcet's disease, rheumatoid arthritis, and infective endocarditis) — small increased risk of heart valve regurgitation.
  • Diabetes mellitus — may affect blood glucose.
  • A history of tendonitis — quinolones can very rarely cause tendon damage.
  • Conditions which predispose to seizures; history of epilepsy — quinolones may induce convulsions in people with a history of convulsions, and the risk is increased in people taking a nonsteroidal anti-inflammatory drug (NSAID). Concurrent NSAID use should be avoided in people with epilepsy or with conditions that predispose to seizures.
  • Exposure to excessive sunlight and ultraviolet radiation — should be avoided during treatment and for 48 hours after stopping treatment.
  • Hepatic impairment — manufacturer advises avoid in severe impairment or increased transaminases (5 times upper limit of normal).
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Psychiatric disorders — reports of suicidal thoughts or self-endangering behaviour after quinolone use.
  • Myasthenia gravis — may exacerbate symptoms.
  • Solid-organ transplant — increased risk of tendon damage.
  • Renal impairment — increased risk of tendon damage.

[BNF, 2023; MHRA, 2023]

What are the adverse effects?

Possible adverse effects of moxifloxacin include:

• Cardiovascular
  • Tachycardia, ventricular arrhythmias, torsades de pointes, QT interval prolongation.
  • There is an increased risk of aortic aneurysm and dissection with fluoroquinolones (rare). Advise to seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops.
  • Heart valve regurgitation — advise to seek immediate medical attention if there is rapid-onset breathlessness (especially if lying flat); ankle, foot, or abdominal swelling; or new-onset heart palpitations.
• Gastrointestinal
  • Diarrhoea, constipation, nausea, vomiting, reduced appetite, abdominal pain.
• Musculoskeletal
  • Arthralgia, myalgia, tendon damage including tendonitis and tendon rupture (rare).
    • Tendon rupture may occur within 48 hours of starting treatment or months after stopping a quinolone. Risk of tendon rupture is increased by concomitant corticosteroids and in people aged over 60 years. If tendonitis or tendon rupture is suspected, advise to stop moxifloxacin immediately and seek medical advice.
• Central nervous system (CNS)
  • Headache, dizziness, sleep disorders, taste disorders, tinnitus, tremor, vertigo, visual disturbances.
    • If peripheral neuropathy, muscle weakness, or serious CNS adverse effects are suspected, advise to stop moxifloxacin immediately and seek medical advice.
• Psychiatric
  • Agitation, sleep disorder, confusion, anxiety, depression, nightmares.
• Skin
  • Rash, pruritus (uncommon).
• Other
  • Anaphylaxis, fever, increased risk of infection, dyspnoea.
  • Fluoroquinolones can very rarely cause long-lasting, disabling, and potentially irreversible adverse effects, sometimes affecting multiple organ systems.
  • Photosensitivity reactions and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have all been reported with unknown frequency.
• People should be advised to stop fluoroquinolone treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy or central nervous system effects. Remain alert to the risk of suicidal thoughts and behaviours with use of fluoroquinolone antibiotics. 

Report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website: https://yellowcard.mhra.gov.uk/.

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

What are the drug interactions?

• Possible drug interactions associated with moxifloxacin include:
  • Aluminium hydroxide — decreases the absorption of moxifloxacin.
    • Manufacturer advises that moxifloxacin should be taken 2 hours before or 4 hours after aluminium hydroxide.
  • Corticosteroids — Avoid co-administration of a corticosteroid with a fluoroquinolone since this could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.
  • Drugs that prolong the QT interval — moxifloxacin can also prolong the QT interval. 
    • Avoid moxifloxacin in people taking drugs that are associated with QT prolongation, such as class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics.
  • Drugs that can cause hypokalaemia — hypokalaemia is a risk factor for torsade de pointes arrhythmia and QT prolongation. 
    • Avoid moxifloxacin in people taking drugs that can cause hypokalaemia, such as diuretics (bendroflumethiazide, furosemide), indapamide, prednisolone, salmeterol, salbutamol, terbutaline, aminophylline, and theophylline.
  • Iron salts (sulfate, fumarate, and gluconate) — decrease the exposure to moxifloxacin.
    • Manufacturer advises that administration should be separated by at least 2 hours.
  • Magnesium carbonate and magnesium trisilicate — decrease the absorption of moxifloxacin. 
    • Manufacturer advises that moxifloxacin should be taken 2 hours before or 4 hours after magnesium carbonate or magnesium trisilicate.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — NSAIDs potentially increase the risk of seizures when given with moxifloxacin.
    • Discontinue treatment with moxifloxacin if seizures occur following concurrent treatment with NSAIDs.
  • Sucralfate — decreases the exposure to moxifloxacin.
    • Manufacturer advises separate administration by 2 hours.
  • Warfarin — moxifloxacin increases the anticoagulant effect of warfarin.
    • Monitor the international normalized ratio (INR) if concurrent treatment is indicated and adjust the warfarin dose accordingly.
    • Warn the person of the possible risk of increased bruising and bleeding, and advise them on when to seek medical help.
  • Zinc — predicted to decrease the exposure to moxifloxacin.
    • Manufacturer advises that administration should be separated by at least 2 hours.

[BNF, 2023; MHRA, 2023]

What are the contraindications and cautions?

• Note that systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate. This follows a review by the MHRA which looked at the effectiveness of current measures to reduce the identified risk of disabling and potentially long-lasting or irreversible side effects.
• Do not prescribe ofloxacin to people:
  • With a history of tendon disorders related to quinolone use or previous serious adverse reactions to a quinolone or fluoroquinolone antibiotic.
  • Taking corticosteroids concomitantly — may exacerbate risk of quinolone-induced tendonitis and tendon rupture.
  • Who are pregnant — shown to cause arthropathy in animal studies; safer alternatives are available.
  • Who are breastfeeding — manufacturer advises avoid, as present in milk in animal studies.
• Prescribe ofloxacin with caution to people:
  • Aged over 60 years — increased risk of tendon damage and aortic aneurysm and dissection in older people.
• Also prescribe ofloxacin with caution to people with:
  • Aortic aneurysm and/or aortic dissection, a family history of aneurysm, or other risk factors or conditions predisposing to aortic aneurysm and dissection (such as Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, atherosclerosis) — small increased risk of aortic aneurysm and dissection.
  • Congenital or pre-existing heart valve disease, or with risk factors or conditions predisposing to heart valve regurgitation (such as Turner's syndrome, Behcet's disease, rheumatoid arthritis, and infective endocarditis) — small increased risk of heart valve regurgitation.
  • Conditions which predispose to QT interval prolongation:
    • Concurrent use of drugs that are known to prolong the QT interval (for example, Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics).
    • Electrolyte imbalance (for example, hypokalaemia or hypomagnesaemia).
    • Cardiac disease (for example, heart failure, myocardial infarction, bradycardia, congenital long QT syndrome, history of arrhythmias).
  • Solid-organ transplant — increased risk of tendon damage.
  • Diabetes mellitus — may affect blood glucose.
  • A history of tendonitis — quinolones can very rarely cause tendon damage.
  • Conditions which predispose to seizures; history of epilepsy — quinolones may induce convulsions in people with a history of convulsions, and the risk is increased in people taking a nonsteroidal anti-inflammatory drug (NSAID). Concurrent NSAID use should be avoided in people with epilepsy or with conditions that predispose to seizures.
  • Hepatic impairment — liver damage can occur (risk of decreased elimination).
  • Renal impairment — usual initial dose, then use half normal dose if creatinine clearance is 20–50 mL/min; 100 mg every 24 hours if creatinine clearance is less than 20 mL/min.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Psychiatric disorders — reports of suicidal thoughts or self-endangering behaviour after quinolone use.
  • Myasthenia gravis — may exacerbate symptoms.

[BNF, 2023; MHRA, 2023]

What are the adverse effects?

Possible adverse effects of ofloxacin include:

• Cardiovascular
  • Tachycardia, ventricular arrhythmias, torsades de pointes, QT interval prolongation.
  • There is an increased risk of aortic aneurysm and dissection with fluoroquinolones (rare). Advise to seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops.
  • Heart valve regurgitation — advise to seek immediate medical attention if there is rapid-onset breathlessness (especially if lying flat); ankle, foot, or abdominal swelling; or new-onset heart palpitations.
• Gastrointestinal
  • Diarrhoea, constipation, nausea, vomiting, reduced appetite, abdominal pain.
• Musculoskeletal
  • Arthralgia, myalgia, tendon damage including tendonitis and tendon rupture (rare).
    • Tendon rupture may occur within 48 hours of starting treatment or months after stopping a quinolone. Risk of tendon rupture is increased by concomitant corticosteroids and in people aged over 60 years. If tendonitis or tendon rupture is suspected, advise to stop ofloxacin immediately and seek medical advice.
• Central nervous system (CNS)
  • Headache, dizziness, sleep disorders, taste disorders, tinnitus, tremor, vertigo, visual disturbances.
    • If peripheral neuropathy, muscle weakness, or serious CNS adverse effects are suspected, advise to stop ofloxacin immediately and seek medical advice.
• Psychiatric
  • Agitation, sleep disorder, confusion, anxiety, depression, nightmares.
• Skin
  • Rash, pruritus (uncommon).
• Other
  • Anaphylaxis, fever, increased risk of infection, dyspnoea.
  • Fluoroquinolones can very rarely cause long-lasting, disabling, and potentially irreversible adverse effects, sometimes affecting multiple organ systems.
• People should be advised to stop fluoroquinolone treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy or central nervous system effects. Remain alert to the risk of suicidal thoughts and behaviours with use of fluoroquinolone antibiotics. 

Report suspected adverse drug reactions to fluoroquinolone antibiotics on the Yellow Card website: https://yellowcard.mhra.gov.uk/.

[BNF, 2023; MHRA, 2023]

What are the drug interactions?

Possible drug interactions associated with ofloxacin include:

• Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc — these may reduce the absorption of ofloxacin if taken concurrently.
  • Ofloxacin should be taken at least 2 hours before these preparations and not less than 4–6 hours after them.
• Celecoxib and other COX-2 inhibitors — celecoxib potentially increases the risk of seizures when given with ofloxacin. Manufacturer advises caution.
• Corticosteroids — the risk of tendonitis and tendon rupture is increased in people taking a fluoroquinolone and a corticosteroid. Concurrent use should be avoided. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs) — potentially increased risk of seizures when quinolones are given with NSAIDs. Manufacturer advises caution.
• Strontium ranelate — the absorption of quinolones is reduced by strontium ranelate. Manufacturer advises avoid.
• Warfarin — ofloxacin increases the anticoagulant effect of warfarin. The manufacturer advises monitoring the international normalized ratio (INR).
• 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.

[BNF, 2023]