Consumer medicine information

Ozole 150 mg Capsule

Fluconazole

BRAND INFORMATION

Brand name

Ozole 150 mg

Active ingredient

Fluconazole

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ozole 150 mg Capsule.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about OZOLE (fluconazole 150 mg) capsules.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking OZOLE against the benefits it is expected to have for you.

If you have any concerns about using/taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with this medicine. You may need to read it again.

WHAT OZOLE IS USED FOR

OZOLE contains the active ingredient fluconazole. It is used to treat vaginal thrush in women, when topical treatment has failed. If this is the first time you have had symptoms, talk to your doctor before using any treatment.

Treating vaginal thrush in women

Taken by mouth, OZOLE treats the yeast infection, vaginal thrush, which is caused by a yeast called Candida albicans. Most women have vaginal thrush some time during their lives. Many women have this yeast living harmlessly within their bodies. However, the natural balance that keeps Candida albicans under control can be upset by other factors, e.g. antibiotics, diabetes, the Pill, wearing tight clothing, or using perfumed soaps, bath additives and vaginal deodorants. When the levels of yeast become too high, thrush develops.

You may have one or more of these common symptoms:

  • Vaginal itching
  • Vaginal burning and redness
  • Pain during intercourse
  • A white, curdy, odourless discharge from the vagina (like cottage cheese)

Rubbing and scratching can aggravate the soreness and itching. Also, the salt in urine can sting the sore tissue.

BEFORE YOU TAKE OZOLE

Do not use OZOLE:

  • If you are pregnant, suspect you might be pregnant or are trying to become pregnant or are breast-feeding
  • If you are allergic to any of the ingredients in OZOLE or other thrush treatments such as miconazole, clotrimazole or ketoconazole
  • If you are taking cisapride (a medicine to treat stomach problems), astemizole (used in the treatment of allergy symptoms), erythromycin (an antibiotic used to treat bacterial infections), pimozide (an antipsychotic medication), quinidine (used to treat abnormal heart rhythms) and terfenadine (used to treat allergic conditions).

Do not use OZOLE unless you have spoken to your doctor or pharmacist about the following:

  • If you are taking any medicines. Some medicines and OZOLE may interfere with each other. These include amiodarone, anticoagulants (anticoagulant medicines reduce the blood's natural ability to clot), cyclosporin, oral contraceptives, phenytoin, short acting benzodiazepines, rifabutin, tacrolimus, theophylline, zidovudine, warfarin, gastrointestinal drugs and oral hypoglycaemics (oral hypoglycaemics are medicines to treat diabetes).
  • Tell your doctor or pharmacist before using OZOLE if you are taking warfarin, as bleeding or bruising may occur
  • If you are unsure about the cause of your symptoms
  • 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 any unexplained jaundice
  • If you have had heart problems
  • If you or your partner have had exposure to a sexually transmitted disease
  • If you have had 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 on passing urine

HOW OZOLE IS GIVEN

How much to take

The complete OZOLE course of treatment for thrush is one capsule, once.

How to take it

Take by mouth with a drink of water at any time of day, with or without food.

OZOLE is not recommended for children.

SIDE EFFECTS

Taking this medicine may cause mild side effects such as nausea or feeling sick, headache, stomach pain, indigestion or diarrhoea.

Consult your doctor if you notice anything that is making you feel unwell.

A few people develop allergic reactions to medicines. If you experience difficulty breathing, facial swelling or general itchiness, consult your doctor immediately.

AFTER TAKING OZOLE

You should notice an improvement in your symptoms in a day or two. Consult your doctor if you are no better in 3 days.

How you may avoid thrush in future

  • Wear cotton briefs, stockings and loose fitting clothes rather than tight synthetic clothing
  • Wash regularly but do not wash and dry yourself too harshly
  • Avoid perfumed soaps, bath additives and vaginal deodorants

STORAGE

Keep OZOLE where children cannot reach it.

Keep your capsule in the pack until it is time to take it.

If you take your capsule out of the pack it may not keep as well.

Keep OZOLE in a cool dry place where temperatures stay below 25°C.

Do not store OZOLE or any other medicine in the bathroom or near a sink. Do not leave your medicines on a window sill or in the car. Heat and dampness can destroy some medicines.

Do not use after the expiry date stamped on the pack.

PRODUCT DESCRIPTION

What it looks like

OZOLE 150 mg capsules are hard gelatin capsules, with a blue opaque body and a blue opaque cap. The body and cap have 'RANBAXY' printed in black edible ink. Available in blister packs containing one capsule.

Ingredients

Active ingredient:

Each capsule contains 150 mg fluconazole.

Inactive ingredients:

Other ingredients are lactose, maize starch, colloidal anhydrous silica, magnesium stearate, sodium lauryl sulfate, the colours patent blue V and titanium dioxide, and a gelatin capsule shell.

Australian Registration Number

OZOLE 150 mg: AUST R 122904

Sponsor

OZOLE is supplied in Australia by:

Sun Pharma ANZ Pty Ltd
Suite 2.02, Level 2
12 Waterloo Road
Macquarie Park NSW 2113

This leaflet was prepared in September 2018.

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Ozole 150 mg

Active ingredient

Fluconazole

Schedule

S3

 

1 Name of Medicine

Fluconazole.

2 Qualitative and Quantitative Composition

Each Ozole capsule contains fluconazole 150 mg as the active ingredient.
Other ingredients: lactose. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ozole capsules are a size 1, hard gelatin capsule, with a blue opaque body and a blue opaque cap. The body and the cap has RANBAXY printed in black edible ink.

4 Clinical Particulars

4.1 Therapeutic Indications

Ozole, given orally, is indicated for vaginal candidiasis.

4.2 Dose and Method of Administration

Ozole is administered orally.

Adults.

For vaginal candidiasis, fluconazole 150 mg (Ozole) should be administered as a single oral dose.

Use in renal impairment.

Impaired renal function.

Fluconazole is predominantly excreted in the urine as unchanged drug. No adjustments in single dose therapy are necessary in patients with minor to moderate renal impairment.

Paediatric use.

Children.

Single-dose fluconazole is not recommended for use in children under 18 years of age except under physician supervision.

4.3 Contraindications

Ozole is contraindicated in patients with known sensitivity to fluconazole, related azole compounds or any of the excipients of Ozole.
Co-administration of other drugs known to prolong the QT interval and which are metabolised via the enzyme CYP3A4 such as cisapride, astemizole, erythromycin, pimozide and quinidine are contraindicated (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

In rare cases, as with other azoles, anaphylaxis has been reported.
Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, during treatment with fluconazole. AIDS patients are more prone to the development of serious cutaneous reactions to many drugs.
Fluconazole should not be used again if a rash develops which is attributable to fluconazole.

QT prolongation.

Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. Fluconazole causes QT prolongation via the inhibition of Rectifier Potassium Channel current. The QT prolongation caused by other medicinal products (such as amiodarone) may be amplified via the inhibition of cytochrome P450 (CYP3A4) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). During postmarketing surveillance, there have been very rare causes of QT prolongation and torsades de pointes in patients taking fluconazole. These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant medications that may have been contributory.
Patient with hypokalaemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsades de pointes. Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions (see Section 4.8 Adverse Effects (Undesirable Effects)).
Adrenal insufficiency has been reported in patients receiving other azoles (e.g. ketoconazole).
Cases of adrenal insufficiency were reported in patients receiving fluconazole.

Use in hepatic impairment.

Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities, primarily in patients with serious underlying medical conditions. In cases of fluconazole associated hepatoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed.
Ozole should not be used again if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in renal impairment.

See Section 4.2 Dose and Method of Administration.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The relevance of the following drug interactions to single dose fluconazole is unknown. Patients on other medications should be advised to consult their doctor or pharmacist before starting Ozole.
Fluconazole is an inhibitor of the cytochrome P450 system, particularly the CYP2C and to a lesser extent the CYP3A isoforms. There are possibilities that other drugs may affect the metabolism of fluconazole and that fluconazole may affect the metabolism of other drugs. In vitro studies conducted in human hepatic microsomes demonstrate that the extent of inhibition of CYP3A isoforms is lowest with fluconazole, when compared with ketoconazole and itraconazole.

Hydrochlorothiazide.

Concomitant oral administration of fluconazole 100 mg and hydrochlorothiazide 50 mg for 10 days in normal volunteers resulted in an increase of 41% in Cmax and an increase of 43% in area under the curve (AUC) of fluconazole, compared to fluconazole given alone. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving diuretics, although the prescriber should bear it in mind.

Rifampicin.

Administration of a single oral dose of fluconazole 200 mg after chronic rifampicin administration resulted in a 25% decrease in AUC and a 20% shorter half-life of fluconazole in normal volunteers. Depending on clinical circumstances, an increase of the dose of fluconazole should be considered when it is administered with rifampicin.

Concomitant use of the following agents with fluconazole is contraindicated.

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 four times a day yielded a significant increase in cisapride plasma levels and prolongation of QT interval.

Astemizole.

Concomitant administration of fluconazole with astemizole may decrease the clearance of astemizole. Resulting increased plasma concentrations of astemizole can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and astemizole is contraindicated (see Section 4.3 Contraindications).

Erythromycin.

Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsade de pointes) and consequently sudden heart death. Co-administration of fluconazole and erythromycin is contraindicated.

Pimozide.

Although not studied in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Co-administration of fluconazole and pimozide is contraindicated (see Section 4.3 Contraindications).

Quinidine.

Although not stated in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Co-administration of fluconazole and pimozide is contraindicated (see Section 4.3 Contraindications).

Terfenadine.

Because of the occurrence of serious cardiac dysrhythmias secondary to prolongation of the QTc interval in patients receiving azole antifungals in conjunction with terfenadine, interaction studies have been performed. One study at a 200 mg daily dose of fluconazole failed to demonstrate a prolongation in QTc interval. Another study at a 400 mg and 800 mg daily dose of fluconazole demonstrated that fluconazole taken in doses of 400 mg per day or greater significantly increases plasma levels of terfenadine when taken concomitantly. The combined use of fluconazole at doses of 400 mg or greater with terfenadine is contraindicated (see Section 4.3 Contraindications). The co-administration of fluconazole at doses lower that 400 mg per day with terfenadine should be carefully monitored.

Concomitant use that should be used with caution.

Amiodarone.

Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Caution must be exercised if the concomitant use of fluconazole and amiodarone is necessary, notably with high-dose fluconazole (800 mg).

Anticoagulants.

Careful monitoring of prothrombin time in patients receiving fluconazole and indanedione anticoagulants is recommended.

Cyclosporin.

A kinetic study in renal transplant patients found fluconazole 200 mg daily slowly increased cyclosporin concentrations. However, in another multiple dose study with 100 mg daily, fluconazole did not affect cyclosporin levels in patients with bone marrow transplants. Cyclosporin plasma concentration monitoring in patients, with or without impaired renal function, receiving fluconazole is recommended.

Oral contraceptives.

Fluconazole at a dose of 50 mg for 10 days decreased the AUC for ethinyloestradiol by 16%, but values for levonorgestrel were unchanged.

Oral hypoglycaemic agents.

The effects of fluconazole on the pharmacokinetics of the sulfonylurea oral hypoglycaemic agents tolbutamide, glipizide and glibenclamide were examined in three placebo controlled crossover studies in normal volunteers. All subjects received the sulfonylurea alone and following treatment with fluconazole 100 mg as a single daily oral dose for 7 days. Fluconazole administration resulted in significant increases in Cmax and AUC of the sulfonylurea. Several subjects in these three studies experienced symptoms consistent with hypoglycaemia. In the glibenclamide study, several volunteers required oral glucose treatment. As fluconazole is a potent inhibitor CYP2C8 and CYP2C9, it may also interact with other sulfonylureas (e.g. glimepiride and gliclazide) and the thiazolidinediones (e.g. pioglitazone and rosiglitazone), which are metabolised by these enzymes. When fluconazole and sulfonylureas or thiazolidinediones are coadministered, blood glucose concentrations should be monitored carefully. The possibility of a hypoglycaemic episode should be borne in mind.

Phenytoin.

Concomitant administration of oral fluconazole 200 mg with phenytoin at steady state resulted in average increase of 75% of phenytoin AUC values in normal volunteers. Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended.

Short acting benzodiazepines.

Studies in human subjects have reported changes in midazolam pharmacokinetics and clinical effects that are dependent on dosage and route of administration. Single doses of fluconazole 150 mg resulted in modest increases in midazolam concentrations and psychomotor effects following oral administration of 10 mg that may not be clinically significant. At doses used to treat systemic mycoses, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects following oral administration of midazolam 7.5 mg, but only modest increases that are not likely to be clinically significant following intravenous infusion of midazolam 0.05 mg/kg.
If concomitant benzodiazepine therapy is necessary in patients being treated with fluconazole, consideration should be given to decreasing the benzodiazepine dosage and the patients should be appropriately monitored.

Rifabutin.

There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.

Tacrolimus.

There have been reports that an interaction exists when fluconazole is administered concomitantly with tacrolimus, leading to increased serum levels of tacrolimus. There have been reports of nephrotoxicity in patients to whom fluconazole and tacrolimus were coadministered. Patients receiving tacrolimus and fluconazole concomitantly should be carefully monitored.

Theophylline.

In a placebo controlled interaction study, the administration of fluconazole 200 mg for 14 days resulted in an 18% decrease in the mean plasma clearance of theophylline. Patients who are receiving high doses of theophylline or who are otherwise at increased risk of theophylline toxicity should be observed for signs of theophylline toxicity while receiving fluconazole and therapy modified appropriately if signs of toxicity develop.

Warfarin.

A single dose of warfarin 15 mg given to normal volunteers following 14 days of orally administered fluconazole 200 mg resulted in a 12% increase in the prothrombin time response (area under the prothrombin time-time curve). One in 13 subjects experienced a twofold increase in prothrombin time response. In postmarketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, haematuria and melaena) have been reported in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. Careful monitoring of prothrombin time in patients receiving fluconazole and coumarin type anticoagulants is recommended.

Zidovudine.

The AUC of zidovudine significantly increased (74%) during coadministration with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine related adverse reactions.

Gastrointestinal drugs.

In fasted normal volunteers, absorption of orally administered fluconazole does not appear to be affected by agents that increase gastric pH. Single dose administration of fluconazole 100 mg with cimetidine 400 mg resulted in a 13% reduction in AUC and 21% reduction in Cmax of fluconazole. Administration of an antacid containing aluminium and magnesium hydroxides immediately prior to a single dose of fluconazole 100 mg had no effect on the absorption or elimination of fluconazole.

Other.

Physicians should be alert to the potential for drug-drug interactions with other drugs for which pharmacokinetic drug-drug interaction studies have not been conducted.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fluconazole did not affect the fertility of male or female rats treated orally with daily doses of 5, 10 or 20 mg/kg or with parenteral doses of 5, 25 or 75 mg/kg, although the onset of parturition was slightly delayed at 20 mg/kg given orally. In an intravenous perinatal study in rats at 5, 20 and 40 mg/kg, dystocia and prolongation of parturition were observed in a few dams at 20 and 40 mg/kg, but not at 5 mg/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.
(Category D)
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
There have been reports of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester.
There are no adequate and well controlled studies in pregnant women. There have been reports of multiple congenital abnormalities in infants whose mothers were being treated for three or more months with high dose fluconazole therapy (400 to 800 mg/day) for coccidiomycosis. The relationship between fluconazole use and these events is unclear.
Fluconazole should not be used in women who are pregnant, or in women of childbearing potential unless adequate contraception is employed. Effective contraceptive measures should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose.
 Fluconazole has been found in human breast milk at concentrations similar to those in plasma, hence its use in breastfeeding women is not recommended.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicines on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Fluconazole is generally well tolerated.

Common adverse events (> 1%) observed during vaginal candidiasis clinical trials and associated with fluconazole.

Nervous system.

Headache.

Gastrointestinal.

Nausea, abdominal pain, diarrhoea, dyspepsia.

Uncommon adverse events (> 0.1% and < 1%) observed during vaginal candidiasis clinical trials associated with fluconazole.

Dermatological.

Pruritus, genital pruritus, rash, erythematous rash, dry skin, abnormal skin odour, urticaria.

Nervous system.

Dizziness, flushing, dry mouth, vertigo, hyperkinesia, hypertonia, taste perversion.

Gastrointestinal.

Constipation, anorexia, flatulence, vomiting, loose stools.

Metabolic.

Thirst.

Psychiatric.

Insomnia, nervousness, female sexual dysfunction.

Reproductive.

Intermenstrual bleeding, dysmenorrhoea, leucorrhoea, menorrhagia, uterine spasm, vaginal disorder.

Respiratory.

Pharyngitis.

Special senses.

Abnormal vision, visual field defect.

Urinary.

Polyuria, renal pain.

General.

Fatigue, hot flushes, malaise, back pain, herpes simplex, pain, rigors.

The following adverse events have occurred during experience with overall fluconazole use.

Blood and lymphatic system.

Leukopenia including neutropenia and agranulocytosis, thrombocytopenia.

Cardiovascular.

QT prolongation, torsades de pointes (see Section 4.4 Special Warnings and Precautions for Use).

Nervous system.

Seizures.

Immune system disorders.

Anaphylaxis (including face oedema, angioedema, urticaria and pruritus).

Metabolic.

Hypercholesterolaemia, hypertriglyceridaemia and hypokalaemia.

Hepatobiliary disorders.

Hepatic failure, hepatitis, hepatocellular necrosis, jaundice.

Skin and subcutaneous tissue disorders.

Alopecia, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal products 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

There have been reports of overdosage with fluconazole, and in one case a 42 year old patient infected with HIV developed hallucinations and exhibited paranoid behaviour after reportedly ingesting 8,200 mg of fluconazole. The patient was admitted to hospital and his condition resolved within 48 hours.
In the event of overdosage, symptomatic treatment (with supportive measures and gastric lavage if necessary) should be undertaken.
Fluconazole is largely excreted in the urine; forced volume diuresis would probably increase the elimination rate. A three hour haemodialysis session decreases plasma levels by approximately 50%.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Fluconazole administered orally or intravenously was active in a variety of animal models of fungal infections using standard laboratory strains of fungi.
Fluconazole exhibits in vitro activity against Cryptococcus neoformans and Candida species. Activity has been demonstrated in vivo in normal and immunocompromised animals against infections with Candida spp. including systemic candidiasis, and in normal animals with Cryptococcus neoformans, including intracranial infections. One case of cross-resistance of Candida to fluconazole in a patient [not infected with human immunodeficiency virus (HIV)] previously treated with ketoconazole has been reported. The efficacy of fluconazole in vivo is greater than would be apparent from in vitro testing against the above mentioned fungi.
Concurrent administration of fluconazole and amphotericin B in infected normal and immunocompromised mice showed antagonism of the two drugs in systemic infection with Aspergillus fumigatus. The clinical significance of results obtained in these studies is unknown.
Fluconazole is a member of the bis-triazole class of antifungal agents. Fluconazole is a highly selective inhibitor of fungal cytochrome P450 sterol C-14 alpha-demethylation. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. The subsequent loss of normal sterols correlates with the accumulation of 14 alpha-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg do not affect its metabolism.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. Oral administration is not affected by concomitant food intake. In fasted normal volunteers, peak plasma concentrations occur between 1 and 2 hours postdose with a terminal plasma elimination half-life of approximately 30 hours (range 20 to 50 hours). The apparent volume of distribution approximates to total body water. Plasma protein binding is low (11 to 12%).

Distribution.

Fluconazole has been found to achieve good penetration into all tissues and body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels.

Excretion.

The major route of excretion is renal, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites. The pharmacokinetics of fluconazole are markedly affected by reduction in renal function, however, no adjustments in single dose therapy are necessary. There is an inverse relationship between the elimination half-life and creatinine clearance.
The long plasma elimination half-life provides the basis for single dose therapy for vaginal candidiasis.
There are differences in the pharmacokinetics between adults and children, with children after the neonatal period generally having faster elimination rate and larger volume of distribution than adults.

5.3 Preclinical Safety Data

Genotoxicity.

Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in four strains of Salmonella typhimurium and in the mouse lymphoma system. Cytogenetic studies in vivo and in vitro showed no evidence of chromosomal mutations.

Carcinogenicity.

Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5, 5 or 10 mg/kg/day (approximately two to seven times the recommended human dose). Male rats treated with 5 and 10 mg/kg/day had an increased incidence of hepatocellular adenomas.

6 Pharmaceutical Particulars

6.1 List of Excipients

Other ingredients: gelatin, lactose, pregelatinised maize starch, colloidal anhydrous silica, magnesium stearate, sodium lauryl sulfate, patent blue V, titanium dioxide, TekPrint SW-9008 black printing ink.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

PVC/PVDC/Aluminium blister pack of 1 capsule.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Fluconazole is a white to off white crystalline powder which is sparingly soluble in water and saline. Its chemical name is 2-(2,4-difluoro phenyl)-1,3-bis (1H-1,2,4-triazol- 1-yl)-2-propanol.
Molecular formula: C13H12F2N6O.
Molecular weight: 306.3.

CAS number.

CAS Registry No.: 86386-73-4.

7 Medicine Schedule (Poisons Standard)

All States and A.C.T. - S.3.

Summary Table of Changes