OTC products

• intravaginal clotrimazole
  • Canesten cream 10% vaginal tablet 
  • Canesten 500mg pessary x 1 
  • Canesten 200mg pessary x 3
  • Canesten 100mg pessary x 6
• oral fluconazole
  • Diflucan 150mg tablet
• topical clotrimazole
  • Canesten 1% or 2% cream

Prescribing

Adult female

Internal symptoms such as discharge

• Clotrimazole 10% cream — insert 5 g into the vagina as a single dose at night
• Fenticonazole 2% cream — insert 5 g into the vagina in the morning and evening for 3 days
• Clotrimazole 200 mg pessaries (3 pessaries) — insert 1 pessary into the vagina once at night for 3 nights 
• Clotrimazole 500 mg single-dose pessary — insert 1 pessary into the vagina once at night as a single dose 
• Econazole nitrate 150 mg single-dose pessary (for adults and children aged over 16 years) — insert 1 pessary into the vagina once at night as a single dose
• Econazole nitrate 150 mg pessaries (3 pessaries) — insert 1 pessary into the vagina once at night for 3 nights
• Miconazole nitrate 1.2 g single-dose vaginal capsules  — insert 1 capsule into the vagina once at night as a single dose
• Fenticonazole 200 mg vaginal capsules (3 capsules) — insert 1 capsule into the vagina once at night for 3 nights
• Fenticonazole 600 mg single-dose vaginal capsules — insert 1 pessary into the vagina once at night as a single dose

if intravaginal not suitable 

• Fluconazole tablets 150 mg as a single dose (see contraindications and interactions below)
• Oral itraconazole 200 mg twice a day for 1 day (link to itraconazole article)
• It is not known whether itraconazole or fluconazole is more effective
• For women aged 60 years and older, oral antifungals may be more acceptable than intravaginal antifungals because of the ease of administration

For external symptoms ie vulval symptoms eg itching

• vaginal applications may be supplemented with a topical antifungal cream
  • Clotrimazole 1% or 2% cream applied 2–3 times a day
  • Ketoconazole 2% cream applied 1–2 times a day (for adults aged 18 years and older)

12–18 year old female

• topical clotrimazole 1% or 2% applied 2–3 times a day
• do not prescribe an intravaginal or oral antifungal

Breastfeeding 

• intravaginal clotrimazole
  • Clotrimazole 10% cream — insert 5 g into the vagina as a single dose at night
  • Clotrimazole 200 mg pessaries (3 pessaries) — insert 1 pessary into the vagina once at night for 3 nights 
  • Clotrimazole 500 mg single-dose pessary — insert 1 pessary into the vagina once at night as a single dose
• intravaginal miconazole
  • Miconazole nitrate 1.2 g single-dose vaginal capsules — insert 1 capsule into the vagina once at night as a single dose
• oral fluconazole
  • Fluconazole tablets 150 mg as a single dose  
  • see contraindications and interactions below

Male

• male partner of a woman with vulvovaginal candidiasis may have candidal balanitis
  • characterized by erythematous areas on the glans of the penis, pruritus, and/or irritation
  • treat with clotrimazole 1% cream 2-3 times daily until symptoms settle or for up to 14 days
    • Advise that topical imidazole preparations may damage latex condoms and diaphragms.
  • or fluconazole 150 mg as a single dose
• Do not routinely treat an asymptomatic sexual partner
• If inflammation is causing discomfort, consider prescribing topical hydrocortisone 1% cream or ointment for up to 14 days in addition
• Recurrent candidal balanitis
  • Consider advising on testing for Candida infection in any sexual partner(s), to reduce the potential reservoir of infection

Recurrent Thrush

Recurrence of vulvovaginal candidiasis is particularly likely if there are predisposing factors, such as antibacterial therapy, pregnancy, diabetes mellitus, or possibly oral contraceptive use (1)

• reservoirs of infection may also lead to recontamination and should be treated; these include other skin sites such as the digits, nail beds, and umbilicus as well as the gastro-intestinal tract and the bladder
• the partner may also be the source of re-infection and, if symptomatic, should be treated with a topical imidazole cream at the same time.

Treatment against candida may need to be extended for 6 months in recurrent vulvovaginal candidiasis.

Some alternative recommended regimens include (1):

• initially, fluconazole by mouth 150 mg every 72 hours for 3 doses, then 150 mg once every week for 6 months;
  
  
• initially, intravaginal application of a topical imidazole for 10-14 days, then clotrimazole vaginally 500-mg pessary once every week for 6 months;
  
  
• initially, intravaginal application of a topical imidazole for 10-14 days, then itraconazole by mouth 50-100 mg daily for 6 months.

Public Health England guidance states:

If recurrent vaginal candidiasis

• fluconazole (induction/maintenance)
  • 150mg every 72 hours for 3 doses THEN 150mg once a week

A systematic review showed that weekly treatment with fluconazole (150 mg) for six months was effective against recurrent vulvovaginal candidiasis (2).

Patients with recurrent vaginal thrush can be advised on self-help measures. These may include:

• if there is any bowel reservoir of organisms then consider treatment with oral antifungals will treat bowel infection
• treatment of male sexual partner (treatment is simultaneous)
• avoid precipitating factors e.g. tight fitting clothes,
• the use of natural yoghurt (taken orally or given intravaginally) - the bacteria in the yoghurt apparently produce pH changes in the vagina that discourage the growth of candida
• diabetes must be excluded
  • a large proportion of vulvovaginal candidiasis in diabetes is due to non-albicans Candida species such as C. glabrata (3)
  • observational studies indicate that diabetic patients with C. glabrata vulvovaginal candidiasis respond poorly to azole drugs

Additional info

• Return if symptoms have not resolved within 7–14 days
• Follow-up and test of cure are not necessary if symptoms resolve
• Topical anti-fungals may affect the effectiveness of latex contraceptives
• Advise for women:
  • Wash the vulval area with a soap substitute — this should be used externally and not more than once a day
  • Use a simple emollient to moisturise the vulval area
  • Consider using probiotics (such as live yoghurts) orally or topically to relieve symptoms
  • Avoid the following potential predisposing factors:
    • Washing and cleaning the vulval area with soap or shower gels (including those containing perfume and antiseptics [such as tea tree oil]), wipes, and 'feminine hygiene' products
    • Cleaning the vulval area more than once a day
    • Washing underwear in biological washing powder and using fabric conditioners
    • Vaginal douching
    • Wearing tight-fitting and/or non-absorbent clothing

Fluconazole

Do not prescribe to

• Women with acute porphyria
• Pregnant women

Do not prescribe high or repeated doses to

• Breastfeeding women

Prescribe with caution to women

• at risk of QT interval prolongation
  • women with cardiomyopathy, sinus bradycardia, arrhythmias, hypokalaemia, hypomagnesaemia, hypocalcaemia, and those taking other drugs known to cause QT interval prolongation (such as tricyclic antidepressants, antipsychotics, or antiarrhythmics)
• with hepatic impairment or taking concurrent hepatotoxic drugs
  • due to the risk of hepatic necrosis
  • discontinue if signs or symptoms of hepatic disease develop (such as severe abdominal pain, jaundice, or weakness)
• with renal impairment
  • eGFR<50mL/min/1.73m2
  • use the usual initial dose then halve any subsequent doses

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 enzyme-inhibiting effect of fluconazole persists 4–5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole
• In general, fluconazole interactions relate to multiple-dose treatments
• The following drugs are contraindicated (or should be avoided) during treatment with fluconazole
  • Ergotamine — there is an increased risk of ergotism
  • Erythromycin — concurrent use with fluconazole has the potential to increase the risk of cardiotoxicity (prolonged QT interval and Torsades de Pointes) and consequently sudden heart death
  • Pimozide — concurrent use with fluconazole may lead to QT prolongation and rare occurrences of Torsade de Pointes.
  • Quetiapine
  • Reboxetine
• Concurrent treatment with fluconazole and the following drugs should be done with caution (concurrent use should be monitored; dose adjustments may be indicated)
  • Aminophylline and theophylline
  • Avanafil
  • Ciclosporin
  • Coumarins
    • such as warfarin
  • Diazepam
    • risk of prolonged sedation
  • Fentanyl
  • Midazolam
    • risk of prolonged sedation
  • Phenytoin
  • Rifabutin
    • increased risk of uveitis
  • Statins
    • the risk of myopathy and rhabdomyolysis increases when fluconazole is given with atorvastatin, simvastatin and 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 and glipizide
    • if concurrent use is indicated, advise the person to seek medical advice if they have symptoms of hypoglycaemia (for example nervousness, sweating, and/or trembling)
  • Tacrolimus and sirolimus
  • Tretinoin
    • fluconazole possibly increases the risk of tretinoin toxicity
  • Zidovudine
    • fluconazole increases the risk of zidovudine toxicity

Other possible drug interactions of fluconazole include

• Clopidogrel
  • fluconazole possibly reduces the antiplatelet effect of clopidogrel
• Hydrochlorothiazide
  • the plasma levels of fluconazole may be increased by 40%; however, no adjustment in dosage of fluconazole is required
• Rifampicin
  • metabolism of fluconazole may be accelerated by rifampicin, leading to reduced plasma concentrations

Itraconazole 

Do not prescribe to

• Women with ventricular dysfunction or a history of heart failure
• Women with acute porphyria
• Pregnant or breastfeeding women
• Children and young people (age not specified by the manufacturer)
• Women taking certain drugs

Avoid oral itraconazole or use with caution in

• Women with hepatic impairment, a history of hepatotoxicity with other drugs, or active liver disease
  • Potentially life-threatening hepatotoxicity may occur with itraconazole
  • Advise the woman to report signs of liver disease (such as anorexia, nausea and vomiting, fatigue, abdominal pain, or dark urine). Discontinue treatment if this occurs
  • Monitor liver function
    • if treatment continues for longer than one month
    • if the woman is receiving other hepatotoxic drugs
    • if there is a history of hepatotoxicity with other drugs
    • if there is hepatic impairment

Use oral itraconazole with caution in women

• At high risk of heart failure
  • Those receiving high doses and longer treatment courses
  • Older women and those with cardiac disease
• Those with chronic lung disease/COPD associated with pulmonary hypertension
• Those receiving treatment with negative inotropic drugs, for example calcium channel blockers

Itraconazole inhibits the metabolism of drugs metabolized by the cytochrome P450 enzyme CYP3A4 (as it is a potent inhibitor of this enzyme). This may result in a higher and/or prolonged effect of these drugs, including adverse effects.The following drugs are contraindicated (or should be avoided) during treatment with itraconazole

• Aliskiren
• Apixaban
• Avanafil
• Colchicine
  • suspend or reduce dose of colchicine
• Domperidone
  • possible increased risk of ventricular arrhythmias
• Eletriptan
• Eplerenone
• Ergot alkaloids
  • such as ergotamine and ergometrine
  • increased risk of ergotism
• Ivabradine
• Midazolam
• 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
• Ranolazine
• Reboxetine
• Rivaroxaban
• Sirolimus
• Statins
  • 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
• Vardenafil

Concurrent treatment with itraconazole and the following drugs should be done with caution (concurrent use should be monitored; dose adjustments may be indicated)

• Aripiprazole
• Budesonide
• Ciclosporin
• Cilostazol
• 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
• Digoxin
• Disopyramide
• Felodipine
• Fentanyl
• HIV protease inhibitors
  • increases plasma concentrations of indinavir
  • possibly increases plasma concentrations of saquinavir
  • Concurrent treatment with ritonavir may increase plasma concentrations of either drug (or both)
• Methadone
  • increased risk of ventricular arrhythmias
• Rosuvastatin
• Solifenacin
• Tacrolimus

Other possible drug interactions of itraconazole include

• Clopidogrel
  • itraconazole possibly reduces the antiplatelet effect of clopidogrel
• CYP3A4 inducers — itraconazole is mainly metabolized by CYP3A4. The plasma concentrations of itraconazole are therefore reduced by potent CYP3A4 inducers, such as 
  • rifampicin
  • rifabutin
  • phenytoin
• Similar effects are expected for other enzyme inducers such as
  • carbamazepine
  • St John's wort
  • phenobarbital
  • Itraconazole should not be used during treatment with (and within 2 weeks of stopping) these drugs