Previous changes

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

December 2021 — minor update. Information that topical imidazole preparations may damage latex condoms and diaphragms has been added to the management section of this topic.

August to September 2021 — reviewed. A literature search was conducted in June 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. The terms 'uncomplicated' and 'complicated' vulvovaginal candidiasis are no longer recommended in the British Association for Sexual Health and HIV (BASHH) national guideline on vulvovaginal candidiasis (2019), and the definition section has been amended accordingly.

The recommended treatment regimens for acute vulvovaginal candidiasis and for women with uncontrolled diabetes or other causes of immunocompromise have been updated, in line with the BASHH national guideline on vulvovaginal candidiasis (2019). The Scenarios on 'Severe infection' and 'Uncontrolled diabetes or immunocompromised' have been deleted, and their content incorporated into other Scenarios, for clarity and ease of navigation. The Prescribing Information section has been updated.

May 2017 — minor update. The prescribing information section has been simplified. Minor typographical errors have been corrected.

December 2016 — minor update. The information on the adverse effects and drug interactions for fluconazole have been updated in line with the manufacturer's Summary of Product Characteristics [ABPI, 2015].

November 2016 — reviewed. A literature search was conducted in October 2016 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 recommendations have been made, but the topic has been restructured.

December 2013 — minor update. Text updated to reflect that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorization for oral ketoconazole. It should no longer be prescribed for the treatment of fungal infections.

August 2013 — minor update to reflect guidance from the EMA regarding the use of oral ketoconazole.

August 2012 — reviewed. A literature search was conducted in July 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of the topic. Changes to clinical recommendations have been made, including management of uncomplicated vulvovaginitis and management of non-albicans Candida infection. Changes to drug regimens for the treatment of Candida infection, including those for induction and maintenance, have been made.

September 2011 — minor update. The Cochrane systematic review Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection [Ray, 2011] is cited regarding the treatment of immunocompromised women, and in the section on recurrent infection. Issued in September 2011.

March 2011 — topic structure revised to ensure consistency across CKS topics. No changes to clinical recommendations have been made.

May 2010 — minor update. The manufacturer of econazole 1% cream (Pevaryl^®) states that it is not recommended for use during pregnancy. The prescription has been removed. Issued in May 2010.

March 2010 — minor update. Results of the updated Cochrane systematic review on oral compared with intra-vaginal imidazole and triazole antifungal treatment of uncomplicated vulvovaginal candidiasis have been updated. Issued in March 2010.

May 2009 — minor update. Econacort-1^®pessaries have been discontinued, so the prescription has been removed. Other intravaginal econazole preparations remain available. Issued in June 2009.

February 2009 — minor update. Nystatin intravaginal cream (Nystan^®) has been discontinued. The prescription has been removed, and the relevant text has been updated. Issued in March 2009.

January 2009 — minor update. Gyno-Daktarin^®pessaries have been discontinued. The prescription has been removed, and the relevant text has been updated. Issued in February 2009.

June to September 2007 — 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.

April 2008 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) guidance regarding oral ketoconazole has been added.

February 2008 — minor update. Late comments from the British Association for Sexual Health and HIV (BASHH) have been included. Gyno-pevaryl 1 combination pack has been discontinued. The prescription has been removed, and the relevant text has been updated. Issued in March 2008.

March 2004 — reviewed. Validated in May 2004 and issued in July 2004.

January 2001 — reviewed. Validated in March 2001 and issued in June 2001.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2021.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 September 2021.

Systematic reviews and meta-analyses

• Cooke, G., Watson, C., Deckx, L., et al. (2022) Treatment for recurrent vaginal candidiasis. Cochrane Library. www.cochranelibrary.com [Free Full-text]

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 September 2021.

New policies

No new national policies or guidelines since 1 September 2021.

New safety alerts

No new safety alerts since 1 September 2021.

Changes in product availability

No changes in product availability since 1 September 2021.

Basis for recommendation

The recommendations on assessment are largely based on the British Association for Sexual Health and HIV (BASHH) publication Guideline for the management of vulvovaginal candidiasis [Saxon, 2019] and Clinical Effectiveness Group (CEG) guidance on tests for sexually transmitted infections [BASHH, 2015], the joint Royal College of General Practitioners (RCGP) and BASHH document Sexually transmitted infections in primary care [RCGP, 2013], the British HIV Association (BHIVA) publication Guidelines on the management of opportunistic infection in people living with HIV: the clinical management of candidiasis 2019 [Dockrell, 2019], the European guideline for the management of vulval conditions [van der Meijden, 2017], a case-control study of self-taken vaginal swabs [Barnes, 2017], and expert opinion in a review article on vaginal discharge [Sim, 2020], on vaginitis [Paladine, 2018], and on recurrent vulvovaginal candidiasis [Sobel, 2016].

Clinical features on history-taking

• The recommendation on symptoms to ask about is based on the BASHH guideline [Saxon, 2019], the joint RCGP/BASHH document [RCGP, 2013], and expert opinion in review articles [Sobel, 2016; Paladine, 2018; Sim, 2020].
  • Expert opinion in a review article notes that a curd-like white non-odourous vaginal discharge is a suggestive but very non-specific finding of vulvovaginal candidiasis [Sobel, 2016].
• The recommendation to ask about risk factors for a sexually transmitted infection (STI) is based on the BASHH guideline [Saxon, 2019],  the joint RCGP/BASHH document [RCGP, 2013], the BASHH CEG guidance [BASHH, 2015], and the European guideline [van der Meijden, 2017].
• The recommendation to ask about treatments tried is based on the joint RCGP/BASHH document [RCGP, 2013].
• The recommendation to ask about pregnancy and contraceptive use is based on the joint RCGP/BASHH document [RCGP, 2013] and expert opinion in a review article [Sim, 2020].
  • The joint document notes that oral azoles are contraindicated in pregnancy and risk of pregnancy.
• The recommendation to ask about additional symptoms is based on the BASHH guideline [Saxon, 2019] and the joint RCGP/BASHH document [RCGP, 2013].

Clinical features on examination

• The recommendations on when to offer or arrange an examination of the external genitalia are based on the BASHH guideline [Saxon, 2019] and the joint RCGP/BASHH document [RCGP, 2013].
  • The joint document notes that external examination may be normal, and advises that empirical treatment may be given without external examination if there is suspected acute infection based on history alone.
• The information on the signs of severe infection is based on the BASHH guideline [Saxon, 2019], the joint RCGP/BASHH document [RCGP, 2013], and expert opinion in a review article [Sim, 2020].

Investigations to consider

• The information that investigations are not routinely needed if there is suspected acute infection is based on the BASHH guideline [Saxon, 2019].
• The recommendation on when to consider arranging additional investigations to confirm the diagnosis and/or exclude an alternative diagnosis is based on the BASHH guideline [Saxon, 2019] and the joint RCGP/BASHH document [RCGP, 2013].
• The information that a self-taken low vulvovaginal swab (LVS) may be appropriate is based on the BASHH guideline [Saxon, 2019], the BHIVA publication [Dockrell, 2019], a case-control study [Barnes, 2017], and expert opinion in a review article [Paladine, 2018].
  • The BHIVA publication notes that self-swab is an effective method of collecting a sample with high acceptance rates.
  • A primary care-based case control study of self-taken LVS compared with clinician-taken high vaginal swab (HVS, n = 104) found that self-taken samples were a valid alternative for detecting vulvovaginal candidiasis [Barnes, 2017].
• The recommendation to arrange a HVS for microscopy first-line if there is suspected acute infection is based on the BASHH guideline [Saxon, 2019].
  • This notes that fungal culture is no longer considered a cost-effective or reliable addition to microscopy for acute infection, due to its inability to differentiate colonisation from infection.
• The recommendation to arrange a HVS for culture if there is suspected recurrent infection is based on the BASHH guideline [Saxon, 2019] and the joint RCGP/BASHH document [RCGP, 2013].
  • The information on the possible micro-organisms that may be cultured is based on the BASHH guideline [Saxon, 2019].
  • The recommendation to arrange culture with full speciation and sensitivity testing if there is a poor or partial response to maintenance therapy is based on the BASHH guideline [Saxon, 2019]. In addition, the BHIVA publication notes that culture and susceptibility testing is needed for recurrent or persistent symptoms following antifungal therapy, to identify an azole resistant strain or alternative diagnosis [Dockrell, 2019].
  • The recommendation to consider arranging a self-collected swab if initial results are negative is based on the BASHH guideline [Saxon, 2019].
• The information that vaginal pH testing of secretions is not essential to make a diagnosis is largely based on the BASHH guideline [Saxon, 2019].
  • The joint RCGP/BASHH document also notes that pH testing is a sensitive but not specific test, as Candida infection can present with a normal pH, as can non-infective vaginal discharge [RCGP, 2013].
  • Of note, the BASHH guideline states that 'interpretation of antifungal susceptibility testing should take into account the acid pH of the vagina compared with the neutral pH at which testing is usually performed. The activity of azole antifungals is reduced in acidic environment and clinical resistance may occur despite the isolate being microbiologically susceptible'.

Basis for recommendation

The information on the differential diagnoses of vulvovaginal candidiasis is based on the British Association of Sexual Health and HIV (BASHH) publications Guideline for the management of vulvovaginal candidiasis [Saxon, 2019] and Guideline on the management of vulval conditions [BASHH, 2014], the joint Royal College of General Practitioners (RCGP) and BASHH publication Sexually transmitted infections in primary care [RCGP, 2013], the European guideline for the management of vulval conditions [van der Meijden, 2017], and expert opinion in review articles on vaginal discharge [Sim, 2020] and on vaginitis [Paladine, 2018]. It is also pragmatic, based on what CKS considers to be good clinical practice.

How should I manage acute vulvovaginal candidiasis?

If a woman presents with an episode of acute vulvovaginal candidiasis:

• Offer advice on sources of information and support, such as the NHS leaflet Thrush in men and women.
• Advise on self-management measures to provide symptom relief:
  • Use simple emollients as a soap substitute to wash and/or moisturize the vulval area.
  • Avoid contact with potentially irritant soap, shampoo, bubblebath, or shower gels, wipes, and daily or intermenstrual 'feminine hygiene' pad products.
  • Avoid vaginal douching.
  • Avoid wearing tight-fitting and/or non-absorbent clothing, which may irritate the area.
  • Avoid use of complementary therapies such as application of yoghurt, topical or oral probiotics, and tea tree or other essential oils.
• If a woman has uncontrolled diabetes mellitus or is otherwise immuncompromised:
  • Optimize management of any underlying conditions causing immunocompromise if possible. See the CKS topics on Diabetes - type 1, Diabetes - type 2, and HIV infection and AIDS for more information.
• Advise on antifungal drug treatment options and preparations, depending on the woman's age, co-morbidities, personal preference, and drug cautions and contraindications.
  • Advise fluconazole 150 mg oral capsule as a single dose first-line.
  • Advise clotrimazole 500 mg intravaginal pessary as a single dose if oral therapy is contraindicated. See the section on Oral fluconazole in Prescribing information for more information on drug contraindications and cautions.
    • Advise that topical imidazole preparations may damage latex condoms and diaphragms.
  • Note: if these treatment options are not tolerated or contraindicated, see the section on Alternative treatment regimens for more information.
  • See the section on Prescribing information for detailed information on oral, intravaginal, and topical antifungals, including contraindications and cautions, adverse effects, and drug interactions.
• If there are vulval symptoms, consider advising on use of a topical imidazole in addition to an oral or intravaginal antifungal. 
  • Options include clotrimazole 1% or 2% cream applied 2–3 times a day.
  • Advise that oral fluconazole, intravaginal clotrimazole, and topical clotrimazole can be bought over-the-counter.
    • Advise that topical imidazole preparations may damage latex condoms and diaphragms.
• If there are signs of severe infection, advise to repeat antifungal drug treatment after 72 hours:
  • Prescribe fluconazole 150 mg oral capsule on day 1 and 4 first-line.
  • Note: if this treatment option is not tolerated or contraindicated, see the section on Alternative treatment regimens for more information. 
  • See the section on Prescribing information for detailed information on oral, intravaginal, and topical antifungals, including contraindications and cautions, adverse effects, and drug interactions.
• Arrange follow-up if symptoms have not resolved within 7–14 days or if symptoms are recurrent. See the section on Management of treatment failure and the Scenario on Recurrent infection for more information.
  • Advise that follow-up and test of cure are not necessary if symptoms have resolved.
  • Do not routinely treat an asymptomatic male sexual partner. If a woman's male partner has suspected balanitis, see the CKS topic on Balanitis for more information on diagnosis and management.

How should I manage treatment failure of acute vulvovaginal candidiasis?

If a woman has acute vulvovaginal candidiasis which has not responded to initial treatment within 7–14 days:

• Check that initial treatment was used as recommended.
  • Be aware that topical treatments can cause vulvovaginal irritation, which may be mistaken for treatment failure. See the section on Topical antifungals in Prescribing information for more information.
• Reassess for risk factors for persistent or recurrent infection, and manage appropriately.
• Arrange an examination of the external genitalia (if not already performed) with high vaginal swab (HVS), and arrange other investigations to assess for an alternative or additional diagnosis, depending on clinical judgement.
  • See the section on Assessment for more information.
• Treat any ongoing infection, depending on the HVS result.
  • If there has been poor compliance with initial treatment, prescribe an alternative preparation (for example, prescribe oral treatment instead of intravaginal treatment).
• Reinforce self-management advice for symptom relief. See the section on Initial management for more information.
• Arrange specialist referral or seek specialist advice, depending on clinical judgement, if:
  • An affected young person is aged 12–15 years.
  • There is uncertainty about the diagnosis.
  • Symptoms are not improving and treatment failure is unexplained.
  • Symptoms persist after a second course of antifungal treatment.
  • The woman has uncontrolled diabetes and treatment failure.

How should I manage recurrent vulvovaginal candidiasis?

If a woman presents with recurrent vulvovaginal candidiasis:

• Offer advice on sources of information and support, such as the NHS leaflet Thrush in men and women.
• Reinforce advice on self-management measures to provide symptom relief.
  • See the section on Initial management in the Scenario on Acute infection for more information.
• Reassess for risk factors for persistent or recurrent infection, and manage appropriately.
• Arrange an examination of the external genitalia with high vaginal swab (HVS), and arrange other investigations to assess for an alternative or additional diagnosis, depending on clinical judgement.
  • See the section on Assessment for more information.
• Offer an induction regimen immediately followed by maintenance treatment, the drug treatment and preparation depending on the woman's age, co-morbidities, and personal preference, and drug cautions and contraindications.
  
  • For induction, prescribe three doses of oral fluconazole 150 mg (to be taken every 72 hours) first-line.
  • For maintenance, prescribe oral fluconazole 150 mg once a week for six months first-line.
  • Note: if these treatment options are not tolerated or contraindicated, see the section on Alternative treatment regimens for more information.
  • Note: routine use of a topical imidazole in addition to an oral or intravaginal antifungal for vulval symptoms is not recommended.
  • See the section on Prescribing information for detailed information on oral, intravaginal, and topical antifungals, including contraindications and cautions, adverse effects, and drug interactions.
• Arrange follow-up if there is a poor or partial response to maintenance treatment. See the section on Follow-up for more information.
  • Do not routinely treat an asymptomatic male sexual partner. If a woman's male partner has suspected balanitis, see the CKS topic on Balanitis for more information on diagnosis and management.

How should I follow-up recurrent vulvovaginal candidiasis?

If a woman has completed an induction and maintenance regimen of treatment for recurrent vulvovaginal candidiasis:

• If there are recurrent symptoms between maintenance treatment doses, options include:
  • Oral fluconazole 150 mg twice-weekly instead of once a week, or
  • Considering the use of cetirizine 10 mg once daily for six months, particularly if there is a history of allergy (off-label indication).
• If there is a poor or partial response to maintenance therapy: 
  • Check concordance with therapy.
  • Arrange a high vaginal swab (HVS) and request culture with full speciation and sensitivity testing (if not already requested), and treat accordingly. See the section on Assessment for more information.
    
    • If HVS culture is negative and symptoms persist, consider assessment for an alternative diagnosis.
    • If a non-albicans Candida species or azole resistant Candida is identified, seek specialist advice.
• If there are infrequent further sporadic episodes of vulvovaginal candidiasis, treat each episode as an acute infection.
  • See the Scenario on Acute infection for more information.
• If there is further recurrent vulvovaginal candidiasis, consider the use of a repeat induction and maintenance treatment regimen if clinically indicated.
  • See the sections on Initial management and Alternative treatment regimens for more information.
• Arrange specialist referral or seek specialist advice, depending on clinical judgement, if:
  • An affected young person is aged 12–15 years.
  • There is uncertainty about the diagnosis.
  • A non-albicans Candida species or azole resistant Candida is identified.
  • A woman has uncontrolled diabetes and recurrent infection.

How should I manage vulvovaginal candidiasis in pregnancy?

If a woman is pregnant or at risk of pregnancy and presents with vulvovaginal candidiasis:

• Offer advice on sources of information and support, such as the NHS leaflet Thrush in pregnancy.
• Advise on self-management measures to provide symptom relief:
  • Use simple emollients as a soap substitute to wash and/or moisturize the vulval area.
  • Avoid contact with potentially irritant soap, shampoo, bubblebath, or shower gels, wipes, and daily or intermenstrual 'feminine hygiene' pad products.
  • Avoid vaginal douching.
  • Avoid wearing tight-fitting and/or non-absorbent clothing, which may irritate the area.
  • Avoid use of complementary therapies such as application of yoghurt, topical or oral probiotics, and tea tree or other essential oils.
• Advise on antifungal drug treatment options and preparations for symptomatic acute infection, depending on the woman's age, co-morbidities, personal preference, and drug cautions and contraindications.
  
  • Prescribe clotrimazole pessary 500 mg intravaginally at night for up to 7 consecutive nights first-line (if aged 16 years and older).
  • Note: if this treatment is not tolerated or is contraindicated, see the section on Alternative treatment regimens for more information.
  • See the section on Prescribing information for detailed information on intravaginal and topical antifungals, including contraindications and cautions, adverse effects, and drug interactions.
• Offer an induction regimen immediately followed by maintenance treatment for recurrent infection.
  • For induction, prescribe topical imidazole therapy (such as clotrimazole pessary 500 mg intravaginally at night, if aged 16 years and older) for 10–14 days according to symptom response. 
  • For maintenance, prescribe one clotrimazole pessary 500 mg intravaginally at night once a week for six months (if aged 16 years and older).
• If there are vulval symptoms, consider prescribing a topical imidazole in addition to an intravaginal antifungal. 
  • Options include clotrimazole 1% or 2% cream applied 2–3 times a day.
• Arrange follow-up if symptoms have not resolved within 7–14 days for acute infection. See the section on Management of treatment failure for more information.
  • Advise that follow-up and test of cure are not necessary if symptoms have resolved.
  • Do not routinely treat an asymptomatic male sexual partner. If a woman's male partner has suspected balanitis, see the CKS topic on Balanitis for more information on diagnosis and management.

How should I manage treatment failure in pregnancy?

If a pregnant woman has acute vulvovaginal candidiasis which has not responded to initial treatment within 7–14 days:

• Check that initial treatment was used as recommended.
  • Be aware that topical treatments can cause vulvovaginal irritation, which may be mistaken for treatment failure. See the section on Topical antifungals in Prescribing information for more information.
• Reassess for risk factors for persistent or recurrent infection, and manage appropriately.
• Arrange an examination of the external genitalia (if not already performed) with high vaginal swab (HVS), and arrange other investigations to assess for an alternative or additional diagnosis, depending on clinical judgement.
  • See the section on Assessment for more information.
• Treat any ongoing infection, depending on the HVS result.
• Reinforce self-management advice for symptom relief.
  • See the section on Initial management for more information.
• Arrange specialist referral or seek specialist advice, depending on clinical judgement, if:
  • An affected young person is aged 13–15 years.
  • There is uncertainty about the diagnosis.
  • Symptoms are not improving and treatment failure is unexplained.
  • Symptoms persist after a second course of antifungal treatment.
  • A non-albicans Candida species or treatment-resistant Candida is identified.

Contraindications and cautions

• Do not prescribe oral fluconazole to women:
  • With acute porphyria.
  • Who are pregnant — multiple congenital abnormalities reported with long-term high doses.
    • The manufacturer recommends a washout period of approximately 1 week (corresponding to 5-6 half-lives) after a single-dose or discontinuation of a course of treatment for women before they become pregnant.
  • Who are breastfeeding (particularly high or repeated doses).
• Prescribe oral fluconazole with caution to women:
  • Who are at risk of QT interval prolongation — including women with cardiomyopathy, sinus bradycardia, arrhythmias, hypokalaemia, hypomagnesaemia, hypocalcaemia, and taking drugs known to cause QT interval prolongation (such as tricyclic antidepressants, antipsychotics, or antiarrhythmics).
  • With hepatic impairment or taking concurrent hepatotoxic drugs (risk of hepatic necrosis) — discontinue if clinical features of acute liver disease, such as severe abdominal pain, vomiting, jaundice.
  • With renal impairment (estimated glomerular filtration rate [eGFR] less than 50mL/min/1.73m²) — use the usual initial dose then halve any subsequent doses.

[EMC, 2023; Joint Formulary Committee, 2021] 

Adverse effects

Possible adverse effects of oral fluconazole include:

• • Abdominal discomfort, diarrhoea, nausea, vomiting, headache, and skin reactions (common).
  • Dizziness, flatulence, hepatic disorders, taste disturbance, seizure (uncommon).
  • Agranulocytosis, alopecia, dyslipidaemia, hypokalaemia, leucopenia, neutropenia, QT prolongation, thrombocytopenia, torsades de pointes (rare).

 [Joint Formulary Committee, 2021]

Drug interactions

• Fluconazole inhibits the metabolism of drugs metabolized by the cytochrome P450 enzymes CYP2C9 (potently), CYP3A4 (moderately), and CYP2C19. This may result in a higher and/or prolonged action of these drugs, including adverse effects.
  • The following drugs are contraindicated during treatment with fluconazole:
    • Amiodarone — both amiodarone and fluconazole increase the QT interval.
    • Amisulpride and silpiride  — both amisulpride/sulpiride and fluconazole increase the QT interval.
    • Citalopram — both citalopram and fluconazole increase the QT interval.
    • Clarithromycin — both clarithromycin and fluconazole increase the QT interval.
    • Domperidone — fluconazole is predicted to increase the exposure to domperidone; domperidone increases the risk of QT prolongation.
    • Erythromycin — concurrent use with fluconazole has the potential to increase the risk of cardiotoxicity (prolonged QT interval and torsades de pointes) and sudden cardiac death.
    • Escitalopram — both escitalopram and fluconazole increase the QT interval.
    • Flecainide — both flecainide and fluconazole increase the QT interval.
    • Haloperidol — both haloperidol and fluconazole increase the QT interval.
    • Hydroxyzine — both hydroxyzine and fluconazole increase the QT interval.
    • Lithium — both lithium and fluconazole increase the QT interval.
    • Ondansetron — both ondansetron and fluconazole increase the QT interval.
    • Pimozide — concurrent use with fluconazole may lead to QT prolongation and torsade de pointes.
    • Quinine — both quinine and fluconazole increase the QT interval.
    • Ranolazine — both ranolazine and fluconazole increase the QT interval.
    • Risperidone — both risperidone and fluconazole increase the QT interval.
    • Sildenafil — both sildenafil and fluconazole increase the QT interval.
    • Sotalol — both sotalol and fluconazole increase the QT interval.
    • Tolterodine — both tolterodine and fluconazole increase the QT interval.
    • Venlafaxine — both venlafazine and fluconazole increase the QT interval.
  • The following drugs should be used with caution with fluconazole:
    • Aminophylline and theophylline — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Bendroflumethiazide — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Bumetanide — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Carbamazepine — carbamazepine is predicted to decrease the efficacy of fluconazole, and fluconazole increases the concentration of carbamazepine. Manufacturer advises avoid or monitor the concentration of carbamazepine, and adjust dose accordingly.
    • Ciclosporin — fluconazole is predicted to increase the concentration of ciclosporin.
    • Clopidogrel — fluconazole possibly reduces the antiplatelet effect of clopidogrel.
    • Colchicine — fluconazole is predicted to increase the exposure to colchicine.
    • Dabigatran — fluconzole is predicted to increase the exposure to dabigatran.
    • Dexamethasone, hydrocortisone, prednisolone, and methylprednisolone — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Coumarins, such as warfarin — fluconazole increases the anticoagulant effect. Manufacturer advises monitor the international normalized ration (INR) and adjust dose accordingly.
    • Diazepam (risk of prolonged sedation).
    • Ergotamine — there is an increased risk of ergotism.
    • Fludrocortisone — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Furosemide — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Indapamide — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Mefloquine — mefloquine is predicted to increase the risk of QT prolongation.
    • Metolazone — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Rifabutin (increased risk of uveitis).
    • Rifampicin — metabolism of fluconazole may be accelerated by rifampicin, leading to reduced plasma concentrations.
    • Salbutamol, salmeterol, and terbutaline — may cause hypokalaemia which increases the risk of torsades de pointes.
    • Statins — the risk of myopathy and rhabdomyolysis increases when fluconazole is given with statins metabolized through CYP3A4 (atorvastatin and simvastatin) or through CYP2C9 (fluvastatin). If concurrent treatment is necessary, monitor for symptoms of myopathy and rhabdomyolysis, and monitor creatine kinase. Discontinue the statin if a marked increase in creatine kinase is observed or if myopathy/rhabdomyolysis is diagnosed or suspected.
    • Sulfonylureas (such as gliclazide) — advise the person to seek medical advice if they have symptoms of hypoglycaemia (such as agitiation, sweating, and/or tremor).
    • Tacrolimus — fluconazole is predicted to increase the concentration of tacrolimus.
    • Tadalafil — fluconazole is predicted to increase the exposure to tadalafil.
    • Torasemide — may cause hypokalaemia which increases the risk of torsades de pointes. 
    • Tretinoin — fluconazole possibly increases the risk of tretinoin toxicity.

 [Joint Formulary Committee, 2021]

Contraindications and cautions

• Do not prescribe oral itraconazole to women:
  • With acute porphyria.
  • With heart failure or a history of heart failure.
  • Who are pregnant or at risk of pregnancy.
  • Who are breastfeeding.
• Prescribe oral itraconazole with caution to women: 
  • With hepatic impairment, a history of hepatotoxicity with other drugs, or active liver disease — risk of life-threatening hepatotoxicity. Discontinue if clinical features of acute liver disease, such as severe abdominal pain, vomiting, jaundice.
  • At high risk of heart failure.
  • With renal impairment — increased risk of heart failure.
  • Who are elderly.

[ABPI, 2018; Joint Formulary Committee, 2021]

Adverse effects

Possible adverse effects of oral itraconazole include:

• Alopecia, constipation, diarrhoea, dyspnoea, headache, heart failure, hepatic disorders, hyperbilirubinaemia, nausea, oedema, pulmonary oedema, skin reactions, vision disorders, vomiting (common).
• Hearing loss, altered taste (uncommon).
• Angioedema, hypersensitivity vasculitis, hypertriglyceridaemia, pancreatitis, photosensitivity reaction (rare).

 [Joint Formulary Committee, 2021]

Drug interactions

• Itraconazole inhibits the metabolism of drugs metabolized by the cytochrome P450 enzyme CYP3A4. This may result in a higher and/or prolonged effect of these drugs, including adverse effects.
  • The following drugs are contraindicated during treatment with itraconazole:
    • Apixaban — itraconzole is predicted to increase the exposure to apixaban.
    • Colchicine — avoid or reduce dose of colchicine (avoid concurrent use in hepatic or renal impairment).
    • Dabigatran — itraconazole is predicted to increase the exposure to dabigatran.
    • Domperidone — possible increased risk of ventricular arrhythmias when itraconazole is given with domperidone.
    • Eplerenone — itraconzole is predicted to increase the exposure to eplenerone.
    • Ergot alkaloids (such as ergotamine and ergometrine) — increased risk of ergotism.
    • Ivabradine — itraconazole is predicted to increase the exposure to ivabradine.
    • Lercanidipine — itraconazole is predicted to increase the exposure to lercanidipine.
    • Mizolastine — concurrent use with itraconazole may lead to QT prolongation and rare occurrences of torsade de pointes.
    • Pimozide — concurrent use with itraconazole may lead to QT prolongation and rare occurrences of torsade de pointes.
    • Quetiapine — itraconazole is predicted to increase the exposure to quetiapine.
    • Ranolazine — itraconazole is predicted to increase the exposure to ranolazine.
    • Rifabutin — itraconzole increases the concentration of rifabutin, and rifabutin decreases the concentration of itraconazole.
    • Rivaroxaban — itraconazole is predicted to increase the exposure to rivaroxaban.
    • Salmeterol —  itraconazole is predicted to increase the exposure to salmeterol.
    • Statins metabolized via cytochrome P450 3A4 (atorvastatin and simvastatin) — possible increased risk of myopathy and rhabdomyolysis. If treatment with itraconazole is unavoidable, stop statin treatment during the course of treatment with itraconazole.
    • Ticagrelor — itraconazole is predicted to increase the exposure to ticagrelor.
    • Tolterodine — itraconazole is predicted to increase the exposure to tolterodine.
    • Verapamil — itraconazole is predicted to increase the exposure to verapamil.
    • Vardenafil — itraconazole is predicted to increase the exposure to vardenafil.
  • The following drug should be used with caution with itraconazole:
    
    • Clopidogrel — itraconazole possibly reduces the antiplatelet effect of clopidogrel.
    • Ciclosporin — itraconzole increases the concentration of ciclosporin.
    • Coumarins — there are case reports of increased international normalized ratio (INR) and bleeding when itraconazole and coumarins (such as warfarin) are used concurrently. Monitor the INR closely.
    • Dexamethasone, fluticasone, hydrocortisone, prednisolone, methylprednisolone — itraconzole is predicted to increase the exposure to corticosteroids. Manufacturer advises avoid or monitor for adverse effects.
    • Digoxin — itraconazole is predicted to increase the concentration of digoxin. Manufacturer advises monitor and adjust dose.
    • Diltiazem — itraconazole is predicted to increase the exposure to diltiazem.
    • Fesoterodine — itraconazole is predicted to increase the exposure to fesoterodine. Manufacturer advises adjust dose, and avoid in hepatic and renal impairment.
    • Fludrocortisone — itraconazole is predicted to increase exposure to fludrocortisone. Manufacturer advises avoid or monitor for adverse effects.
    • HIV protease inhibitors — itraconazole increases plasma concentrations of indinavir and possibly increases plasma concentrations of saquinavir. Concurrent treatment with ritonavir may increase plasma concentrations of either drug (or both).
    • Oxycodone — itraconazole is predicted to increase the exposure to oxycodone.
    • Sildenafil and tadalafil — itraconzole is predicted to increase the exposure to sildenafil and tadalafil. Manufacturer advises avoid or adjust sildenafil dose; use with caution with tadalafil or avoid.
    • Solifenacin — itraconazole is predicted to increase the exposure to solifenacin. Manufacturer advises adjust dose, avoid in hepatic and renal impairment.
    • Tacrolimus — itraconazole is predicted to increase the concentration of tacrolimus. Manufacturer advises monitor and adjust dose.

 [Joint Formulary Committee, 2021]

Contraindications and cautions

• Do not prescribe an imidazole intravaginal preparation to young girls:
  • Clotrimazole and econazole intravaginal preparations are licensed for use in women and girls aged 16 years and older.
  • Miconazole intravaginal preparations are licensed for use in women aged 18 years and older. 
  • Fenticonazole intravaginal preparations are not licensed for use in children (age not specified by the manufacturer).

 [Joint Formulary Committee, 2021]

Adverse effects

• Possible adverse effects of intravaginal imidazoles include:
  • Local mild burning or irritation.
  • Damage to latex contraceptives and can inactivate spermicidal contraceptives.

[Saxon, 2019; Joint Formulary Committee, 2021]

Drug interactions

• Drug interactions with intravaginal imidazoles are unlikely, due to the limited systemic availability after vaginal application. However, the following interactions are possible:
  • Oral anticoagulants (such as warfarin) — miconazole is a known inhibitor of cytochrome P450 enzymes CYP3A4 and CYP2C9. The Medicines and Healthcare products Regulatory Agency (MHRA) advises that miconazole (including possibly vaginal and topical formulations) can enhance the anticoagulant effect of warfarin. If concurrent treatment is necessary, monitor for adverse effects such as unexplained bruising or nosebleeds [MHRA, 2016].
  • Other drugs metabolized by CYP3A4 and CYP2C9 — during concurrent treatment with miconazole, the effects and adverse effects of other drugs metabolized by CYP3A4 (such as statins and calcium channel blockers and CYP2C9 (such as oral antidiabetic drugs and phenytoin) may be increased.
  • Oral tacrolimus — concurrent use with vaginal clotrimazole may lead to increased tacrolimus plasma levels. Manufacturer advises monitor and adjust dose.

 [Joint Formulary Committee, 2021]

Contraindications and cautions

• There are no contraindications for use of topical clotrimazole 1% or 2% cream to be applied to the anogenital area.
• Contact with eyes and mucous membranes should be avoided.

 [Joint Formulary Committee, 2021]

Adverse effects

• Possible adverse effects of clotrimazole 1% or 2% cream include:
  • Local skin irritation and pain.
  • Damage to latex contraceptives and can inactivate spermicidal contraceptives.

[Saxon, 2019; Joint Formulary Committee, 2021]

Drug interactions

• Although drug interactions with topical clotrimazole 1% or 2% cream are unlikely, due to the limited systemic availability after topical application it has been noted with tacrolimus leading to increased levels of plasma tacrolimus [ABPI, 2022].