4.1. Therapeutic indications

Canesten Thrush Oral Capsule is indicated for the treatment of candidal vaginitis, acute or recurrent. It should also be used for the treatment of partners with associated candidal balanitis.

Canesten Thrush External Cream is indicated for the treatment of candida vulvitis.

It should be used as an adjunct to treatment of candidal vaginitis.

It can also be used for treatment of the sexual partner's penis to prevent re-infection.

4.2. Posology and method of administration

Adults (16 to 60):

One capsule should be swallowed whole.

The cream should be applied thinly two or three times daily to the vulva and surrounding area and rubbed in gently.

Treatment with the cream should be continued until symptoms of the infection disappear. However, if after concomitant treatment of the vaginitis, the symptoms do not improve within seven days, the patient should consult a doctor.

If the cream is being used for treatment of the sexual partner's penis it should be applied two or three times daily for up to two weeks.

Children (under 16):

Paediatric use is not recommended.

Elderly:

Not recommended in patients over 60.

Renal Impairment:

There is no separate dosage schedule in patients with renal impairment for single dose therapy.

4.3. Contraindications

Hypersensitivity to the active substances (fluconazole and clotrimazole), related azole substances or to any of the excipients listed in section 6.1.

Coadministration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 such as cisapride, astemizole, pimozide, quinidine and erythromycin are contraindicated in patients receiving fluconazole (see sections 4.4 and 4.5).

Coadministration of terfenadine is contraindicated based upon results of a multiple dose interaction study.

4.4. Special warnings and precautions for use

Medical advice should be sought if this is the first time the patient has experienced symptoms of candidal vaginitis.

The product is available from pharmacies without prescription and includes a leaflet that advises the patient - Do not use Canesten Thrush Duo Oral Capsule & External Cream without first consulting your doctor:

If you are under 16 or over 60 years of age

If you are allergic to any of the ingredients in Canesten Thrush Duo Oral Capsule & External Cream or other antifungals and other thrush treatments If you are taking any other medicine other than the Pill.

If you are taking the antihistamine terfenadine or the prescription medicine cisapride

If you have had thrush more than twice in the last six months

If you have any disease or illness affecting your liver or kidneys or have had unexplained jaundice.

If you suffer from any other chronic disease or illness.

If you or your partner have had exposure to a sexually transmitted disease. If you are unsure of the cause of your symptoms.

Women only:

If you are pregnant, suspect you might be pregnant or are breastfeeding. If you have any abnormal or irregular vaginal bleeding or a blood stained discharge

If you have vulval or vaginal sores, ulcers or blisters.

If you are experiencing lower abdominal pain or burning sensation on passing water.

If you are experiencing any adverse events such as redness, irritation or swelling associated with the treatment.

If you are experiencing fever or chills, nausea, vomiting or diarrhoea. If you have foul smelling vaginal discharge.

Men only:

If your sexual partner does not have thrush. If you have penile sores, ulcers or blisters.

If you have an abnormal penile discharge (leakage). If your penis has started to smell.

If you have pain on passing urine.

Recurrent use (men and women): patients should be advised to consult their physician if the symptoms have not been relieved within one week of taking Canesten Oral Capsule. Canesten Oral Capsule can be used if the candidal infection returns after 7 days. However, if the candidal infection recurs more than twice within six months, patients should be advised to consult their physician.

Candidiasis: Studies have shown an increasing prevalence of infections with Candida species other than C. albicans. These are often inherently resistant (e.g. C. krusei and C. auris) or show reduced susceptibility to fluconazole (C. glabrata). Such infections may require alternative antifungal therapy secondary to treatment failure. Therefore, prescribers are advised to take into account the prevalence of resistance in various Candida species to fluconazole.

Renal system

Fluconazole should be administered with caution to patients with renal dysfunction (see section 4.2).

Adrenal insufficiency

Ketoconazole is known to cause adrenal insufficiency and this could also, although rarely seen, be applicable to fluconazole.

Hepatobiliary system

Fluconazole should be administered with caution to patients with liver dysfunction.

Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions.

The patient should be informed of suggestive symptoms of serious hepatic effect (important asthenia, anorexia, persistent nausea, vomiting and jaundice) and be advised to consult a doctor.

Cardiovascular system

Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram.

The QT prolongation caused by other medicinal products may be amplified via the inhibition of cytochrome P450(CYP)3A4 (see sections 4.3 and 4.5).

Patients with hypokalaemia and advanced cardiac failure are at an increased risk for the occurrence of life threatening ventricular arrhythmias and torsades de pointes.

Fluconazole must be administered with caution in patients with congenital or acquired QT prolongation, known cardiomyopathy, sinus bradycardia, cardiac arrhythmia, or history of torsades de pointes or other proarrhythmic conditions.

Dermatological reactions

Patients have rarely developed exfoliative cutaneous reactions such as Stevens Johnson syndrome and toxic epidermal necrolysis during treatment with fluconazole. Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported. The patient should be advised to consult a doctor if a rash, which is considered attributable to fluconazole, develops.

Hypersensitivity

The product should never be used again if the patient experiences a rash or anaphylaxis following the use of the drug.

Cytochrome P450

Fluconazole should be administered with caution to patients who are taking medicinal products with a narrow therapeutic window metabolized through CYP2C9, CYP2C19 and CYP3A4 (see section 4.5).

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The cream contains cetostearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis). The cream also contains benzyl alcohol which may cause allergic reactions and mild local irritation.

4.5. Interaction with other medicinal products and other forms of interaction

Fluconazole is a moderate inhibitor of cytochrome P450 (CYP) isoenzyme 2C9 and 3A4. Fluconazole is also a strong inhibitor of the isozyme CYP2C19. In addition to the observed/documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolized by CYP2C9, CYP2C19 and CYP3A4 coadministered with fluconazole. Therefore caution should be exercised when using these combinations and the patients should be carefully monitored.

The vast majority of formal interaction studies and case reports are related to multiple dose fluconazole use, therefore, the magnitude of the effect of this inhibition on an individual patient after a single dose of fluconazole is hard to predict, particularly in light of the individual variability in the activity of the isoenzymes. Nonetheless, single dose pharmacokinetic studies have demonstrated that the inhibitory action of fluconazole is immediate and leads, dose-dependently, to increased plasma concentrations of the interacting agents.

The enzyme inhibiting effect of fluconazole persists 4-5 days after discontinuation of fluconazole treatment due to fluconazole's long plasma elimination half-life of approximately 30 hours and substantially longer tissue bioavailability (see section 5.2 Pharmacokinetic Properties), therefore these interactions may be clinically relevant following coadministration with drugs that have both a narrow therapeutic window and also act on vital organ systems like the heart and brain or are involved with glucose metabolism.

Oral Anticoagulants (Coumarin-type / Warfarin, Indanedione):

Bleeding events (bruising, epistaxis, gastro-intestinal bleeding, haematuria, and melena) have been reported, in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. During concomitant treatment with fluconazole and warfarin the prothrombin time was prolonged up to 2-fold, probably due to an inhibition of the warfarin metabolism through CYP2C9. In patients receiving coumarin-type or indanedione anticoagulants concurrently with fluconazole the prothrombin time should be carefully monitored. Dose adjustment of the anticoagulant may be necessary.

Sulphonylureas (Chlorpropamide, Glibenclamide, Glipizide, Tolbutamide): Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulphonylureas (e.g. chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy volunteers.

Frequent monitoring of blood glucose and appropriate reduction of sulfonylurea dose is recommended during coadministration.

Diuretics (Hydrochlorothiazide):

Co-administration of fluconazole and multiple dose hydrochlorothiazide to healthy volunteers during a kinetic interaction study, increased plasma concentrations of fluconazole by 40%. However, although the prescriber should bear this in mind, the fluconazole dose in patients receiving concomitant diuretics should not need to be altered.

Pimozide, Quinidine, Erythromycin:

Coadministration of fluconazole and other drugs such as pimozide, quinidine and erythromycin is contraindicated. Fluconazole can cause changes in the metabolism of these drugs, which can lead to increased plasma levels with potential risk of cardiotoxicity (QT prolongation and torsades de pointes).

Antiarrhythmics (Amiodarone):

Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Therefore, caution should be taken when both drugs are combined, notably with high doses fluconazole (800 mg).

Hypnotic (Lemborexant):

Fluconazole increases Lemborexant Cmax and AUC by approximately 1.6 and 4.2-fold respectively which is expected to increase risk of adverse reactions, such as somnolence. Therefore concomitant use of Lemborexant should be avoided.

Antimalarials (Halofantrine):

Fluconazole can also lead to increased levels of halofantrine (via inhibitory effect on CYP3A4) with potential risk of cardiotoxicity. This combination should be avoided (see section 4.4).

Antipsychotics (Lurasidone):

Moderate inhibitors of CYP3A4 such as fluconazole may increase lurasidone plasma concentrations and so concomitant use should be avoided. If concomitant use cannot be avoided, a reduced dose of lurasidone as instructed in the lurasidone prescribing information should be used.

Benzodiazepines (Midazolam, Triazolam):

Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. Concomitant intake of fluconazole 200 mg and midazolam 7.5 mg orally increased the midazolam AUC and half-life 3.7-fold and 2.2-fold, respectively. Fluconazole 200 mg daily given concurrently with triazolam 0.25 mg orally increased the triazolam AUC and half-life 4.4-fold and 2.3-fold, respectively. Potentiated and prolonged effects of triazolam have been observed at concomitant treatment with fluconazole.

If concomitant benzodiazepine therapy is necessary in patients being treated with fluconazole, consideration should be given to decreasing the benzodiazepine dose, and the patients should be appropriately monitored.

Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator (Ivacaftor):

A reduction of the ivacaftor (alone or combined with drugs in the same therapeutic class) dose is necessary as instructed in the ivacaftor prescribing information due to increased exposure when co-administered with fluconazole.

HMG CoA reductase inhibitors (Atorvastatin, Simvastatin, Fluvastatin): The risk of myopathy and rhabdomyolysis increases (dose-dependent) when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolised through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin (decreased hepatic metabolism of the statin). If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected. Lower doses of HMG-CoA reductase inhibitors may be necessary as instructed in the statins prescribing information.

Antiepileptics (Phenytoin, Carbamazepine):

Levels of phenytoin may increase to a clinically significant degree during co- administration with fluconazole. Phenytoin levels should be monitored and the phenytoin dose adjusted to maintain therapeutic levels if co-administration is necessary.

Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed. There is a risk of developing carbamazepine toxicity, therefore dose adjustment of carbamazepine may be necessary.

Oral Contraceptives (Ethinylestradiol, Levonorgestrel):

Studies on the use of combined oral contraceptives with multiple doses of fluconazole have been performed. No relevant effects on hormone levels occurred during a study with fluconazole 50mg, whilst the AUCs of ethinylestradiol and levonorgestrel were increased by 40% and 24% respectively during a study with fluconazole 200mg. It is therefore considered that multiple dose fluconazole is unlikely to affect the efficacy of the combined oral contraceptive.

Anti-infectives (Rifampicin, Rifabutin):

A 25% decrease in the AUC and 20% shorter half-life of fluconazole occurred when fluconazole and rifampicin were administered concomitantly. An increase in the fluconazole dose should be considered in patients receiving concomitant rifampicin.

Fluconazole increases serum concentrations of rifabutin, leading to increase in the AUC of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. In combination therapy, symptoms of rifabutin toxicity should be taken into consideration.

Angiotensin II Antagonists (Losartan):

CYP2C9 and CYP3A4 are involved in the metabolism of losartan to its active carboxylic acid metabolite E-3174 that is responsible for most of the angiotensin II receptor antagonism that occurs with losartan therapy.

Fluconazole was shown to significantly inhibit the conversion of losartan to this metabolite. Monitoring of patients for continued control of their hypertension is recommended.

Antidepressants (Amitriptyline and Nortriptyline):

Fluconazole increases the effect of amitriptyline and nortriptyline. Dose of amitriptyline/ nortriptyline should be adjusted, if necessary.

Analgesics/Anaesthetics (Alfentanil, Fentanyl, Methadone): Coadministration of fluconazole may cause decreased clearance of alfentanil, fentanyl or methadone and subsequent increased or prolonged opioid effects (CNS depression, respiratory depression). Dose adjustment may be required.

Xanthines (Theophylline):

Use of fluconazole 200mg for 14 days showed an 18% decrease in the mean plasma clearance of theophylline. Patients who require high doses of theophylline or who may be at increased risk of theophylline toxicity should be monitored for signs of theophylline toxicity when fluconazole is co- administered. The therapy should be modified if signs of toxicity occur.

Antihistamines (Terfenadine, Astemizole):

One study with terfenadine and fluconazole 200mg daily did not show a prolongation in the QTc interval. Use of fluconazole (taken in multiple doses of 400mg and 800mg per day) and terfenadine concomitantly, significantly increased plasma levels of terfenadine. Spontaneous reports of palpitations, tachycardia, dizziness and chest pains have occurred in patients taking fluconazole and terfenadine concomitantly where the relationship of the reported adverse events to drug therapy or underlying medical condition is uncertain. It is recommended that terfenadine and fluconazole should not be administered concomitantly due to the potential seriousness of such an interaction (see section 4.3).

Astemizole taken concomitantly with fluconazole may be associated with elevations in serum levels of this drug in patients, which can lead to QT prolongation and torsades de pointes. Coadministration of fluconazole and astemizole is contraindicated (see section 4.3).

Propulsives (Cisapride):

Cardiac events including torsades de pointes have been reported in patients receiving fluconazole and cisapride concomitantly. A controlled study found that concomitant fluconazole 200 mg once daily and cisapride 20 mg four times a day yielded a significant increase in cisapride plasma levels and prolongation of QTc interval. Co-administration of cisapride is contra- indicated in patients receiving fluconazole (see section 4.3).

Antivirals (Zidovudine, Saquinavir):

Fluconazole increases Cmax and AUC of zidovudine by 84% and 74%, respectively, due to an approx. 45% decrease in oral zidovudine clearance. The half-life of zidovudine was likewise prolonged by approximately 128% following combination therapy with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.

Fluconazole increases the AUC and Cmax of saquinavir with approximately 50% and 55% respectively, due to inhibition of saquinavir's hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein.

Dose adjustment of these drugs may be required.

Non-Steroidal Anti-inflammatory drugs (Celecoxib, Flurbiprofen, Ibuprofen, Naproxen, Lornoxicam, Meloxicam, Diclofenac):

Fluconazole may increase the systemic exposure of non-steroidal anti- inflammatory drugs. Adjustment of dose during concomitant treatment may be required.

Immuno-suppressants (Ciclosporin, Tacrolimus, Sirolimus, Tofacitinib):

Fluconazole significantly increases the concentration and AUC of ciclosporin. During concomitant treatment with fluconazole 200 mg daily and ciclosporin (2.7 mg/kg/day) there was a 1.8 fold increase in ciclosporin AUC. This combination may be used by reducing the dose of ciclosporin depending on ciclosporin concentration.

Increased serum levels of tacrolimus (when orally administered) and sirolimus have been reported in patients receiving fluconazole and these drugs concomitantly, potentially due to inhibition of their metabolism. Increased levels of tacrolimus have been associated with nephrotoxicity. Dose of tacrolimus or sirolimus should be adjusted.

Exposure of tofacitinib is increased when tofacitinib is co-administered with fluconazole therefore, it is recommended to reduce tofacitinib dose to 5 mg once daily.

Kinase Inhibitors (Ibrutinib, Abrocitinib)

Moderate inhibitors of CYP3A4 such as fluconazole increase plasma ibrutinib concentrations and may increase risk of toxicity. If the combination cannot be avoided, reduce the dose of ibrutinib to 280 mg once daily (two capsules) for the duration of the inhibitor use and provide close clinical monitoring.

Fluconazole (inhibitor of CYP2C19, 2C9, 3A4) increased exposure of abrocitinib active moiety by 155%. If co-administered with fluconazole, adjust the dose of abrocitinib as instructed in the abrocitinib prescribing information.

Poly(ADP-ribose) polymerase (PARP) Inhibitor (Olaparib)

Fluconazole increases olaparib plasma concentrations therefore, concomitant use is not recommended. If the combination cannot be avoided limit the dose of olaparib to 200 mg twice daily.

Studies show that when fluconazole is taken orally with food, cimetidine, antacids or following total body irradiation for bone marrow transplantation, the absorption of fluconazole is not significantly impaired.

Laboratory tests have suggested that, when used together, the cream may cause damage to latex contraceptives. Consequently the effectiveness of such contraceptives may be reduced. Patients should be advised to use alternative precautions for at least five days after using this product.

Selective Vasopressin V2-Receptor Antagonist (Tolvaptan)

Exposure to tolvaptan is significantly increased (200% in AUC; 80% in Cmax) when tolvaptan, a CYP3A4 substrate, is co-administered with fluconazole, a moderate CYP3A4 inhibitor, with risk of significant increase in adverse reactions particularly significant diuresis, dehydration and acute renal failure. In case of concomitant use, the tolvaptan dose should be reduced as instructed in the tolvaptan prescribing information and the patient should be frequently monitored for any adverse reactions associated with tolvaptan.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

Before initiating treatment, the patient should be informed of the potential risk to the foetus.

After single dose treatment, a washout period of 1 week (corresponding to 5-6 half-lives) is recommended before becoming pregnant (see section 5.2).

For longer courses of treatment, contraception may be considered, as appropriate, in women of childbearing potential throughout the treatment period and for 1 week after the final dose.

Pregnancy

Observational studies suggest an increased risk of spontaneous abortion in women treated with fluconazole during the first and/or second trimester compared to women not treated with fluconazole or treated with topical azoles during the same period.

Data from several thousand pregnant women treated with a cumulative dose of ≤ 150 mg of fluconazole, administered in the first trimester, show no increase in the overall risk of malformations in the foetus. In one large observational cohort study, first trimester exposure to oral fluconazole was associated with a small increased risk of musculoskeletal malformations, corresponding to approximately 1 additional case per 1000 women treated with cumulative doses ≤450 mg compared with women treated with topical azoles and to approximately 4 additional cases per 1000 women treated with cumulative doses over 450 mg. The adjusted relative risk was 1.29 (95% CI 1.05 to 1.58) for 150 mg oral fluconazole and 1.98 (95% CI 1.23 to 3.17) for doses over 450 mg fluconazole.

Available epidemiological studies on cardiac malformations with use of fluconazole during pregnancy provide inconsistent results. However, a meta-analysis of 5 observational studies including several thousand pregnant women exposed to fluconazole during the first trimester finds a 1.8-2 fold increased risk of cardiac malformations when compared to no fluconazole use and/or topical azoles use.

Case reports describe a pattern of birth defects among infants whose mothers received high-dose (400 to 800 mg/day) fluconazole during pregnancy for 3 months or more, in the treatment of coccidioidomycosis. The birth defects seen in these infants include brachycephaly, ears dysplasia, giant anterior fontanelles, femoral bowing and radio-humeral synostosis. A causal relationship between fluconazole use and these birth defects is uncertain.

Fluconazole in standard doses and short-term treatments should not be used during pregnancy or in women of childbearing potential unless clearly necessary or as recommended by a doctor. Fluconazole in high dose and/or in prolonged regimens should not be used during pregnancy except for potentially life-threatening infections.

Fluconazole passes into breast milk to reach concentrations similar to those in plasma (see section 5.2). Breastfeeding may be maintained after a single dose of 150 mg fluconazole but is not recommended after repeated use. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fluconazole 150 mg and any potential adverse effects on the breastfed child from fluconazole 150 mg or from the underlying maternal condition. There are no data on the excretion of clotrimazole into human milk. However, systemic absorption is minimal after administration and is unlikely to lead to systemic effects. Clotrimazole may be used during lactation.

4.7. Effects on ability to drive and use machines

No studies on the effect on the ability to drive and use machines have been performed. However, undesirable effects such as dizziness have been observed. If dizziness occurs, patients should not drive or operate machines.

4.8. Undesirable effects

The listed undesirable effects are based on spontaneous reports, thus assigning accurate frequency of occurrence for each is not possible.

Canesten Thrush Oral Capsule

Summary of safety profile:

Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in association with fluconazole treatment (see section 4.4).

The most frequently (>1/10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased and rash.

The following adverse reactions have been observed and reported during treatment with Fluconazole with the following frequencies: Common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Uncommon: Anaemia.

Rare: Agranulocytosis, leukopenia, thrombocytopenia, neutropenia.

Immune System Disorders

Rare: Anaphylaxis.

Not known: Hypersensitivity.

Metabolism and nutrition disorders

Uncommon: Decreased appetite.

Rare: Hypercholesterolaemia, hypertriglyceridaemia, hypokalaemia.

Psychiatric disorders

Uncommon: Somnolence, insomnia.

Nervous system disorders

Common: Headache.

Uncommon: Seizures, paraesthesia, dizziness, dysgeusia.

Rare: Tremor.

Ear and labyrinth disorders

Uncommon: Vertigo.

Cardiac disorders

Rare: Torsades de pointes (see section 4.4), QT prolongation (see section 4.4).

Gastrointestinal disorders

Common: Abdominal pain, vomiting, diarrhoea, nausea.

Uncommon: Constipation, dyspepsia, flatulence, dry mouth.

Hepatobiliary disorders

Common: Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased (see section 4.4).

Uncommon: Jaundice, cholestasis, bilirubin increased.

Rare: Hepatic failure, hepatocellular necrosis, hepatitis, hepatocellular damage (see section 4.4).

Skin and subcutaneous tissue disorders

Common: Rash (see section 4.4).

Uncommon: Drug eruption* (see section 4.4), urticaria (see section 4.4), pruritus, hyperhidrosis.

Rare: Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalised exanthematous-pustulosis, dermatitis exfoliative, angioedema, face oedema, alopecia.

Not Known: Drug reaction with eosinophilia and systemic symptoms (DRESS).

*including Fixed Drug Eruption.

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia.

General disorders and administration site conditions

Uncommon: Fatigue, malaise, asthenia, pyrexia.

Canesten Thrush External Cream

Immune System Disorders

Anaphylactic reaction, angioedema, hypersensitivity.

Skin and subcutaneous tissue disorders

Blister, dermatitis contact,, erythema, paraesthesia, skin exfoliation, pruritus, rash, urticaria, stinging skin/burning sensation skin.

General disorders and administration site conditions:

Application site irritation, application site reaction, oedema, pain.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Canesten Thrush Oral Capsule

There have been reports of overdose with fluconazole and hallucination and paranoid behaviour have been concomitantly reported.

In the event of overdose, supportive measures and symptomatic treatment, with gastric lavage if necessary, may be adequate.

Fluconazole is largely excreted in the urine and therefore, forced volume diuresis would probably increase the elimination rate. Plasma levels are decreased by approximately 50% during a 3-hour haemodialysis session.

Canesten Thrush External Cream

No risk of acute intoxication is seen as it is unlikely to occur following a single dermal application of an overdose (application over a large area under conditions favourable to absorption) or inadvertent oral ingestion. There is no specific antidote.

However, in the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting). Gastric lavage should be carried out only if the airway can be protected adequately.