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CANESTEN THRUSH ORAL CAPSULE 150MG CAPSULES

Active substance(s): FLUCONAZOLE / FLUCONAZOLE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Canesten Thrush Oral Capsule 150mg capsule

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Fluconazole 150mg
For excipients, see 6.1

3

PHARMACEUTICAL FORM
Hard capsule
Opaque light blue capsule (size 1) with “Canesten®” printed in black between
two black lines.

4

CLINICAL PARTICULARS

4.1

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

4.2

Posology and method of administration
Adults (16 to 60):
One capsule should be swallowed whole.
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
Known hypersensitivity to fluconazole, related azole compounds or any of the
excipients in this product.

Fluconazole should not be administered concomitantly with terfenadine, cisapride or
ergot-derivatives (see 4.5).

4.4

Special warnings and precautions for use
The product available from pharmacies without prescription will include a
leaflet that advises the patient - Do not use Canesten Thrush Oral Capsule
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 Oral Capsule
or other antifungals and other thrush treatments (see section “After Taking
Canesten Thrush Oral Capsule”).
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 breast-feeding.
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.
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.

The product should never be used again if the patient experiences a rash or
anaphylaxis following the use of the drug.
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 Thrush Oral Capsule. Canesten Thrush 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.
Fluconazole has been associated with rare cases of serious hepatic toxicity,
including fatalities primarily in patients with serious underlying medical
conditions.
Fluconazole must be taken with particular care in patients with congenital or
acquired QT prolongation and torsades de pointes or a history thereof, known
cardiomyopathy, sinus bradycardia, cardiac arrhythmia, or are treated with a
co-medication potentially leading to QT prolongation (see 4.5).
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
medicine.
4.5

Interaction with other medicinal products and other forms of interaction
Fluconazole, like other azoles, may interfere with the metabolism of some drugs if
given concomitantly, mainly through inhibition of the cytochrome P450 isoenzymes
CYP3A4 and CYP2C9. 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. Given fluconazole’s long
plasma elimination half-life of approximately 30 hours and substantially longer tissue
bioavailability (see section 5.2 Pharmacokinetic Properties), 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.
Anticoagulants:
Fluconazole increased the prothrombin time after warfarin administration in healthy
males during an interaction study. The change was small (12%) but bleeding events
such as bruising, epistaxis, gastrointestinal bleeding, hematuria and melena have been
reported in association with increases in prothrombin time in patients receiving
fluconazole and warfarin concomitantly. Careful monitoring of prothrombin time in
patients receiving coumarin type anticoagulants is recommended.
Sulphonylureas:
In healthy volunteers, fluconazole prolonged the serum half-life of oral
sulphonylureas such as chlorpropamide, glibenclamide, glipizide and tolbutamide,
when co-administered. Fluconazole and oral sulphonylureas may be concomitantly

administered to diabetics but the possibility of an hypoglycaemic episode should be
considered.
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.
Anti-arrhythmic drugs
Cases of QTc prolongation and/or torsades de pointes may occur after concomitant
use of fluconazole with Class I, Class Ia, and all Class III anti-arrhythmic agents.
Even though no formal drug interaction studies have been done, concomitant use of
these anti-arrhythmic agents and drugs known to prolong the QT interval is not
recommended.
Pharmacodynamic interactions
Medicinal products that prolong QT interval: Case reports indicate that fluconazole
might have the potential to induce QT prolongation leading to serious cardiac
arrhythmia. Patients treated concomitantly with fluconazole and other drugs that
prolong QT interval should be carefully monitored, since an additive effect cannot be
excluded.
Benzodiazepines:
Substantial increases in midazolam concentrations and psychomotor effects are
observed when oral midazolam and fluconazole (oral or intravenous) are coadministered. The effect on midazolam appears to be greater when fluconazole is
administered orally than when fluconazole is administered intravenously. If
concomitant administration of benzodiazepines and fluconazole is required then the
prescriber should consider reducing the benzodiazepine dose and appropriate
monitoring of the patient should be undertaken.
Phenytoin:
Levels of phenytoin may increase to a clinically significant degree during coadministration with fluconazole. Phenytoin levels should be monitored and the
phenytoin dose adjusted to maintain therapeutic levels if co-administration is
necessary.
Carbamazepine, Phenobarbital, Phenytoin, Rifapentine
Concurrent administration of fluconazole and
carbamazepine, phenobarbital,
phenytoin or rifapentine results in enhanced metabolism of fluconazole, potentially
reducing fluconazole effective inhibitory serum concentrations. An increase in the
fluconazole dose should be considered in patients receiving concomitant
carbamazepine, phenobarbital, phenytoin or rifapentine.
Oral Contraceptives:
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.
Rifampicin:

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.
Endogenous Steroid:
No effect on endogenous steroid levels was observed in females when treated with
fluconazole 50mg daily. No significant effect on endogenous steroid levels or on
ACTH stimulated response was observed in healthy male volunteers when treated
with fluconazole 200 to 400mg daily.
Ergot derivatives
Because of the potential for serious toxicity including vasospasm that can occur with
increased plasma concentrations of ergot derivatives (dihydroergotamine, ergoloid
mesylates, ergonovine, ergotamine, methylergonovine, methysergide) the concurrent
use of fluconazole and ergot derivatives is contraindicated (see Contraindications).
Fluconazole and ergot derivatives are both metabolized by cytochrome P450 3A4
enzymes, and the competition for metabolism could result in a rapid onset of
increased plasma concentration of the ergot derivative.
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.
Ciclosporin:
In a kinetic study it was found that fluconazole 200mg daily slowly increases
ciclosporin concentrations in renal transplant patients, but a multiple dose study with
fluconazole 100mg daily showed no effect on ciclosporin levels in patients with bone
marrow transplants. It is therefore recommended that ciclosporin plasma
concentration is monitored in patients receiving fluconazole.
Fentanyl, Methadone
Coadministration of fluconazole may cause decreased clearance of fentanyl or
methadone and subsequent increased or prolonged opioid effects (CNS depression,
respiratory depression) Dosage adjustment of the opioid may be necessary.
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.
Terfenadine:
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 4.3).

Cisapride:
Cardiac events including torsades de pointes have been reported in patients receiving
fluconazole and cisapride concomitantly. Most of these patients appear to have been
predisposed to arrhythmias or had serious underlying medical conditions, and the
relationship of the reported events to a possible drug interaction is uncertain. Coadministration of cisapride is contra-indicated in patients receiving fluconazole. (See
4.3).
Zidovudine:
Zidovudine levels in AIDS or ARC patients were determined before and after daily
treatment with fluconazole 200mg for 15 days. A significant increase in zidovudine
AUC was observed (20%). A second study in HIV infected patients also showed a
significant increase in zidovudine AUC (74%) when fluconazole was administered
concomitantly. Patients received zidovudine 200mg every eight hours either with or
without fluconazole 400mg for seven days on two occasions, 21 days apart. The
increased zidovudine levels are most likely caused by a decrease in the conversion of
zidovudine to its major metabolite. It is recommended that patients receiving
fluconazole and zidovudine be monitored for zidovudine related adverse reactions.
Rifabutin:
Increased serum levels of rifabutin have been reported in patients receiving
fluconazole and rifabutin concomitantly, suggesting a possible interaction. Uveitis has
also been reported in patients receiving this combination. It is therefore recommended
that patients are carefully monitored.
Tacrolimus, Sirolimus:
Increased serum levels of tacrolimus have been reported in patients receiving
fluconazole and tacrolimus concomitantly, suggesting a possible interaction. There
have also been reports of nephrotoxicity in patients receiving this combination.
Patients receiving tacrolimus or sirolimus and fluconazole concomitantly should be
carefully monitored.
Astemizole or other drugs metabolised by the cytochrome P450 system taken
concomitantly with fluconazole may be associated with elevations in serum levels of
these drugs in patients. Fluconazole should be co-administered with caution in these
circumstances and careful monitoring of patients should be undertaken.
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.
Drug – drug interaction studies with other medications have not been conducted but
prescribers should be aware that such interactions may occur.

4.6

Fertility, pregnancy and lactation
An observational study has suggested an increased risk of spontaneous abortion in
women treated with fluconazole during the first trimester.
Fluconazole should not be used during pregnancy or in women of childbearing
potential unless adequate contraception is being used. Fluconazole is found in breast
milk so it should not be used whilst breast-feeding.

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 an
organisation according to CIOMS III categories of frequency is not possible.
Blood and lymphatic system disorders
Leukopenia, neutropenia, agranulocytosis, thrombocytopenia.
Cardiac disorders
Torsades de pointes/QT prolongation.
Gastrointestinal disorders
Nausea, diarrhea, vomiting, gastrointestinal and abdominal pains, abdominal
distension, flatulence.
Hepatobiliary disorders
Most events were observed when a multiple treatment was used: mild transient
elevations in transaminases, hepatitis (non infective), jaundice, cholestasis and
acute hepatic failure, including fatalities.
Immune System Disorders
Allergic reaction, anaphylactic reaction, anaphylactic shock.
Hypersensitivity reactions including symptoms such as rash, urticaria, oedema,
pruritus, cardio-respiratory distress.
Investigations
Electrocardiogram QT prolonged, electrocardiogram QT corrected interval
prolonged, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Nervous system disorders
Seizures, dizziness, headache, dysgeusia.
Skin and subcutaneous tissue disorders
Rash, pruritus, alopecia, exfoliative skin reactions including Stevens-Johnson
syndrome, toxic epidermal necrolysis.
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.

4.9

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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Fluconazole is a triazole antifungal, ATC-Code:
J02AC01
Fluconazole is a triazole antifungal. It is a potent and selective inhibitor of
fungal enzymes necessary for the synthesis of ergosterol.
Fluconazole shows little pharmacological activity in a wide range of animal
studies. Some prolongation of pentabarbitone sleeping times in mice (p.o.),
increased mean arterial and left ventricular blood pressure and increased heart
rate in anaesthetised cats (i.v.) occurred. Inhibition of rat ovarian aromatase
was observed at high concentrations.
Fluconazole was active in a variety of animal fungal infection models.
Activity has been demonstrated against opportunistic mycoses, such as
infections with Candida spp. including systemic candidiasis in immunocompromised animals; with Cryptococcus neoformans, including intracranial
infections; with Microsporum spp. and with Trichophyton spp. Fluconazole
has also been shown to be active in animal models of endemic mycoses,
including infections with Blastomyces dermatitides; with Coccidoides immitis,
including intracranial infection and with Histoplasma capsulatum in normal
and immuno-compromised animals.
There have been reports of cases of superinfection with Candida species other
than C. albicans, which are often inherently not susceptible to fluconazole
(e.g. Candida krusei). Such cases may require alternative antifungal therapy.
Fluconazole is highly specific for fungal cytochrome P-450 dependent
enzymes. Fluconazole has been shown not to affect testosterone plasma
concentrations in males or steroid concentrations in females of childbearing
age when given 50mg daily for up to 28 days. No clinically significant effect
has been seen on endogenous steroid levels or on ACTH stimulated response
in healthy male volunteers taking fluconazole 200 – 400mg daily. Interaction
studies with antipyrine indicate that single or multiple doses of fluconazole
50mg do not affect its metabolism.

5.2

Pharmacokinetic properties
The pharmacokinetic properties of fluconazole are similar whether
administered orally or by the intravenous route. After oral administration,
fluconazole is well absorbed and plasma levels (and systemic bioavailability)

are over 90% of the levels achieved after intravenous administration.
Concomitant food intake does not affect oral absorption. In the fasting state
peak plasma concentrations occur between 0.5 and 1.5 hours post-dose with a
plasma elimination half-life of approximately 30 hours. Plasma concentrations
are proportional to dose. Ninety- percent steady state levels are reached by day
4 to 5 with multiple once daily dosing.
Administration of a loading dose (on day 1) of twice the usual daily dose
enables plasma levels to approximate to 90% steady state levels by day 2. The
apparent volume of distribution approximates to total body water. Plasma
protein binding is low (11-12%).
Fluconazole achieves good penetration in all body fluids studied. The levels of
fluconazole in saliva and sputum are similar to plasma levels. In patients with
fungal meningitis, fluconazole levels in the CSF are approximately 80% of the
corresponding plasma levels.
High skin concentrations of fluconazole, above serum concentrations, are
achieved in the stratum corneum, epidermis-dermis and eccrine sweat.
Fluconazole accumulates in the stratum corneum. At a dose of 50mg once
daily, the concentration of fluconazole after 12 days was 73 mg/g and 7 days
after cessation of treatment the concentration was still 5.8 mg/g.
Excretion is mainly renal, with approximately 80% of the administered dose
appearing in the urine as unchanged drug. Fluconazole clearance is
proportional to creatine clearance. There is no evidence of circulating
metabolites.
The long plasma elimination half-life provides the basis for single dose
therapy for genital candidiasis.
A study compared the saliva and plasma concentrations of a single fluconazole
100mg dose administration in a capsule or in an oral suspension by rinsing and
retaining in the mouth for 2 minutes and swallowing. The maximum
concentration of fluconazole in saliva after the suspension was observed five
minutes after ingestion and was 182 times higher than maximum saliva
concentration after the capsule which occurred four hours after ingestion.
After about four hours, the saliva concentrations of fluconazole were similar.
The mean AUC (0-96) in saliva was significantly greater after the suspension
compared to the capsule. There was no significant difference in the
elimination rate from the saliva or the plasma pharmacokinetic parameters for
the two formulations.

5.3

Preclinical safety data
Reproductive Toxicity:
At 25 and 50mg/kg and higher doses, increases in foetal anatomical variants
(supernumerary ribs, renal pelvis dilation) and delays in ossification were observed.
At doses ranging from 80mg/kg to 320mg/kg embryolethality in rats was increased
and foetal abnormalities included wavy ribs, cleft palate and abnormal cranio-facial
ossification. This may be a result of known effects of lowered oestrogen on

pregnancy, organogenesis and parturition as it is consistent with the inhibition of
oestrogen synthesis in rats.
Carcinogenesis:
No evidence of carcinogenic potential was observed in mice and rats treated orally
with fluconazole for 24 months at doses of 2.5, 5 or 10mg/kg/day. The incidence of
hepatocellular adenomas was increased in male rats treated with 5 and 10mg/kg/day.
Mutagenesis:
Fluconazole, with or without metabolic activation, was negative in tests for
mutagenicity in 4 strains of S. typhimurium and in the mouse lymphoma L5178Y
system. No evidence of chromosomal mutations was observed in cytogenetic studies
in vivo (murine bone marrow cells, following oral administration of fluconazole).
Data derived from in vitro studies (human lymphocytes exposed to fluconazole) are
not consistent.
Impairment of Fertility:
The fertility of male or female rats treated orally with daily doses of fluconazole at
doses of 5, 10 or 20mg/kg or with parenteral doses of 5, 25 or 75mg/kg was not
affected, although the onset of parturition was slightly delayed at 20mg/kg p.o. In an
intravenous perinatal study in rats at 5, 20 and 40mg/kg, dystocia and prolongation of
parturition were observed in a few dams at 20mg/kg and 40mg/kg, but not at 5mg/kg.
The disturbances in parturition were reflected by a slight increase in the number of
stillborn pups and decrease of neonatal survival at these dose levels. The effects on
parturition in rats are consistent with the species specific oestrogen-lowering property
produced by high doses of fluconazole. Such a hormone change has not been
observed in women treated with fluconazole.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose monohydrate
Maize starch
Colloidal silicon dioxide
Magnesium stearate
Sodium lauryl sulphate
Capsule shells contain:
Brilliant blue FCF (E133)
Titanium dioxide (E171)
Gelatin
Printing ink contains:
Shellac
Black iron oxide (E172)
Propylene glycol

6.2

Incompatibilities
Not applicable

6.3

Shelf life
3 years

6.4

Special precautions for storage
No special precautions for storage

6.5

Nature and contents of container
Opaque, white PVC/PVdC (60g/m2) blister with 20µm aluminium foil backing
containing one capsule.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Bayer plc
Bayer House
Strawberry Hill
Newbury
Berkshire
RG14 1JA
United Kingdom
Trading as Bayer plc, Consumer Care Division

8

MARKETING AUTHORISATION NUMBER
PL 00010/0282

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/03/2009

10

DATE OF REVISION OF THE TEXT
09/08/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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