Consumer medicine information

Chemists’ Own Femazole One

Fluconazole

BRAND INFORMATION

Brand name

Chemists' Own Femazole One

Active ingredient

Fluconazole

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Chemists’ Own Femazole One.

What is in this leaflet

This leaflet answers some common questions about CHEMISTS’ OWN FEMAZOLE ONE.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor or pharmacist has weighed the risks of you using CHEMISTS’ OWN FEMAZOLE ONE against the benefits expected for you.

If you have any concerns about using this medicine, talk to your doctor or pharmacist.

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

This information in this leaflet relates only to CHEMISTS’ OWN FEMAZOLE ONE. It is not to be used in relation to any other product, which may contain the same active ingredient.

What CHEMISTS’ OWN FEMAZOLE ONE is used for

CHEMISTS’ OWN FEMAZOLE ONE is used to treat a fungal infection known as vaginal thrush.

The active ingredient in CHEMISTS’ OWN FEMAZOLE ONE is fluconazole, which is classified with medicines know as azole antifungals. This group of antifungal medicines work by preventing the growth of fungi causing your infection.

Ask your doctor or pharmacist if you have any questions about why CHEMISTS’ OWN FEMAZOLE ONE has been recommended for you.

Your doctor or pharmacist may have recommended CHEMISTS’ OWN FEMAZOLE ONE for another reason.

CHEMISTS’ OWN FEMAZOLE ONE is not recommended for children under 18 years of age except under doctor supervision.

There is no evidence that either component in CHEMISTS’ OWN FEMAZOLE ONE is addictive.

CHEMISTS’ OWN FEMAZOLE ONE is a "Pharmacist Only Medicine". It is available without a doctor's prescription, but your pharmacist's advice is required.

What is vaginal thrush
Vaginal candidiasis, and infection caused by a yeast-like fungus Candida, is commonly referred to as “vaginal thrush”.

Candida is one of many organisms that live in the vagina and its growth is normally balanced by your body’s natural defence mechanism know as the ‘immune system’. However, when this natural balancing is upset, Candida can multiply in the vagina to cause the symptoms of thrush.

Common symptoms of vaginal thrush include:

  • itching, burning or soreness around the vagina
  • cottage-cheese like discharge
  • swelling or irritation of the infected area.

What you can do to avoid thrush in the future:

  • avoid wearing synthetic clothing
  • wear loose-fitting cotton briefs, stockings
  • wash the area regularly, but not wash and dry yourself harshly
  • avoid vaginal deodorants, perfumed soaps and bath additives

Ask your doctor or pharmacist for more information on things you can do to avoid thrush in the future.

Before you take CHEMISTS’ OWN FEMAZOLE ONE

When you must not take it

Do not take CHEMISTS’ OWN FEMAZOLE ONE if you have and allergy to:

  • medicines containing fluconazole
  • medicines related to fluconazole such as miconazole (eg Daktarin), ketoconazole (eg. Nizoral) or clotrimazole ( eg. Canestan, Clonea), itraconazole (Sporanox)
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives, shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

  • Do not take CHEMISTS’ OWN FEMAZOLE ONE if you are taking cisapride (Prepulsid), a medicine used to treat stomach problems.
  • Astemizole
  • Pimozide
  • quinidine

Combining CHEMISTS’ OWN FEMAZOLE ONE with cisapride may cause serious side effects such as an abnormal heart rhythm.

Do not take CHEMISTS’ OWN FEMAZOLE ONE if you are pregnant, suspect you may be pregnant or if you may become pregnant during treatment. CHEMISTS’ OWN FEMAZOLE ONE should not be used during pregnancy as it may affect your developing baby.

Do not take CHEMISTS’ OWN FEMAZOLE ONE if you are breastfeeding. CHEMISTS’ OWN FEMAZOLE ONE passes into breast milk and may affect your baby.

Do not take CHEMISTS’ OWN FEMAZOLE ONE if the expiry date (EXP) printed on the packaging has passed.

Do not take CHEMISTS’ OWN FEMAZOLE ONE if the packaging shows signs of tampering or the capsule does not look quite right.

If you are not sure whether you should start using this medicine, talk to your doctor or pharmacist.

Before you start to use it

Tell your doctor or pharmacist if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor or pharmacist if you have any of the following medical conditions:

  • thrush more than twice in the last six months
  • any liver problems
  • any kidney problems
  • any heart problems
  • diabetes
  • HIV infection or AIDS

Your doctor or pharmacist may want to take special care if you have any of these conditions.

Tell your doctor or pharmacist before using CHEMISTS’ OWN FEMAZOLE ONE if you are taking warfarin (eg. Marevan, Coumadin) as bleeding or bruising may occur.

Tell your doctor or pharmacist if you are experiencing any of the following:

  • abdominal or irregular vaginal bleeding or blood-stained discharge
  • Foul smelling or unusual coloured discharge
  • Vulval or vaginal sores, ulcers or blisters
  • Lower abdominal pain or burning when passing urine
  • Fever or chills.

If you have not told your doctor about any of the above, tell them before you start taking CHEMISTS’ OWN FEMAZOLE ONE.

Taking other medicines

Do not take CHEMISTS’ OWN FEMAZOLE ONE if you are taking:

  • cisapride (Prepulsid), a medicine used to treat stomach problems
  • astemizole
  • pimozide
  • quinidine.

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and CHEMISTS’ OWN FEMAZOLE ONE may interfere with each other. These include:

  • warfarin (eg. Marevan, Coumadin), a medicine used to prevent blood clots
  • phenytoin (eg. Dilantin) or carbamazepine (eg. Tegretol), medicines used to treat epilepsy
  • cyclosporin (eg. Neoral), sirolimus (eg. Rapamune) or tacrolimus (eg. Prograf), medicines used to prevent organ transplant rejection or to treat certain problems with the immune system
  • certain medicines use to treat diabetes such as:
    - glibenclamide (eg. Daonil, Glimel), glipizide (eg. Minidiab, Melizide), glimepiride (eg. Amaryl), gliclazide (eg. Diamicron, Glyade)
    - pioglitazone (eg. Actos), rosiglitazone (eg. Avandia)
  • rifampicin (eg. Rifadin, Rimycin) or rifabutin (eg. Mycobutin), antibiotics used to treat infections
  • theophylline (eg. Nuelin), a medicine used to treat asthma
  • midazolam (eg. Hypnovel) and triazolam (eg. Halcion), medicines used as sedatives or to treat anxiety
  • zidovudine (eg. Retrovir), saquinavir (eg. Invirase), medicines used to treat AIDS patients
  • hydrochlorothiazide (eg. Dithiazide), a medicine used for treating fluid problems and high blood pressure
  • the contraceptive pill (birth control pill)
  • amphotericin B (eg. Fungilin), a medicine used to treat fungal infection
  • erythromycin (eg. E-Mycin) and azithromycin (eg. Zithromax), antibiotics used to treat certain types of bacterial infections
  • anticancer drugs such as cyclophosphamide, vincristine and vinblastine, medicines used to treat certain types of cancers
  • carbamazepine (eg. Tegretol), a medicine used in the treatment of epilepsy and bipolar disorder
  • NSAIDs such as naproxen, diclofenac and celecoxib (eg. Celebrex)
  • opioid pain killers such as alfentanil, fentanyl and methadone
  • losartan, a medicine used to treat high blood pressure
  • calcium channel blockers, such as nifedipine, amlodipine and felodipine used in relieving high blood pressure and certain heart conditions
  • statins such as atorvastatin, simvastatin and fluvastatin, used to control high cholesterol levels
  • antidepressants such as amitriptyline (eg. Endep) and nortriptyline.

Talk to your doctor about the need for an additional method of contraception while taking CHEMISTS’ OWN FEMAZOLE ONE. It may decrease the effectiveness of some birth control pills.

Your doctor can tell you what to do if you are taking any of these medicines.

These medicines may be affected by CHEMISTS’ OWN FEMAZOLE ONE or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take Chemists' Own FEMAZOLE ONE.

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Adults
For vaginal thrush in adults, only a single dose (1 capsule) of CHEMISTS’ OWN FEMAZOLE ONE is needed.

CHEMISTS’ OWN FEMAZOLE ONE in not recommended for children under 18 years of age except under doctor supervision.

How to take it

Swallow the capsule whole with a glass of water.

When to take it

CHEMISTS’ OWN FEMAZOLE ONE can be taken any time before, with or after food.

If you take too much CHEMISTS’ OWN FEMAZOLE ONE (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26 IN Australia or 0800 764 766 in New Zealand) or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have used too much CHEMISTS’ OWN FEMAZOLE ONE.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking CHEMISTS’ OWN FEMAZOLE ONE

Things you must do

  • Before starting any new medicine, tell your doctor or pharmacist that you are taking or have taken CHEMISTS’ OWN FEMAZOLE ONE.
  • Tell any other doctors, dentists and pharmacists who treat you that you are taking CHEMISTS’ OWN FEMAZOLE ONE.
  • Use effective contraception to prevent pregnancy while taking CHEMISTS’ OWN FEMAZOLE ONE.
  • Immediately tell your doctor if you do become pregnant while taking CHEMISTS’ OWN FEMAZOLE ONE.
  • If your symptoms of your infection do not improve after 3 days, or if they become worse, tell your doctor or pharmacist.

Things you must not do

  • Do not use CHEMISTS’ OWN FEMAZOLE ONE to treat any other medical complaints unless your doctor or pharmacist tells you to.
  • Do not give CHEMISTS’ OWN FEMAZOLE ONE to anyone else, even if they have the same condition as you.

Things to be careful of

  • Tell your doctor immediately if you develop a rash while taking CHEMISTS’ OWN FEMAZOLE ONE
  • People with AIDS or a weak immune system may be more prone to serious side effects of the skin.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking CHEMISTS’ OWN FEMAZOLE ONE.

This medicine helps most people and is generally well tolerated. However it may have unwanted side effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • nausea (feeling sick), vomiting
  • stomach pain, indigestion
  • diarrhoea
  • acne
  • headache.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • unusual muscle stiffness causing poor control of movement
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • asthma, wheezing, shortness of breath
  • sudden or severe itching, skin rash, hives
  • fainting, seizures or fits
  • flaking of the skin
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • passing more urine than normal, kidney pain (pain on the sides of the body)
  • symptoms of liver disease such as yellowing of the skin or eyes; dark urine, pale stools; loss of appetite; unusual tiredness
  • irregular heart beat or palpitations
  • increased sweating.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking CHEMISTS’ OWN FEMAZOLE ONE

Storage

Keep CHEMISTS’ OWN FEMAZOLE ONE where young children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your medicine in its original pack until it is time to take it.

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

Keep CHEMISTS’ OWN FEMAZOLE ONE capsules in a cool, dry place where the temperature stays below 25°C.

Do not store CHEMISTS’ OWN FEMAZOLE ONE in the bathroom or near a sink

Do not leave CHEMISTS’ OWN FEMAZOLE ONE on a window sill or in the car. Heat and dampness can destroy some medicines.

Disposal

If your doctor or pharmacist tells you to stop taking this medicine, or it has passed its expiry date, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

CHEMISTS’ OWN FEMAZOLE ONE capsule is a hard gelatin capsule with sky blue opaque body and cap.

Each pack contains 1 capsule.

Ingredients

The active ingredient in the CHEMISTS’ OWN FEMAZOLE ONE is fluconazole 150 mg/capsule.

Each capsule also contains the following inactive ingredients:

lactose monohydrate
starch maize
gelatin
silica colloidal anhydrous
sodium lauryl sulfate
titanium dioxide
talc purified
patent blue V

This medicine contains sugars (as lactose) and sulfites.

Supplier:

CHEMISTS’ OWN FEMAZOLE ONE is supplied in Australia by:

Arrow Pharma Pty Ltd
15 – 17 Chapel Street,
Cremorne, VIC 3121

Australian Registration Number: AUST R 299349

This leaflet was last updated in October 2020

Published by MIMS December 2020

BRAND INFORMATION

Brand name

Chemists' Own Femazole One

Active ingredient

Fluconazole

Schedule

S3

 

1 Name of Medicine

Fluconazole.

2 Qualitative and Quantitative Composition

Chemists' Own Femazole One capsule contains 150 mg of fluconazole as the active ingredient.

Excipients with known effect.

Lactose monohydrate and sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hard gelatin capsules of size '1' with sky blue opaque body and cap.

4 Clinical Particulars

4.1 Therapeutic Indications

Chemists' Own Femazole One, given orally, is indicated for the treatment of vaginal candidiasis.

4.2 Dose and Method of Administration

Adults.

Chemists' Own Femazole One capsule should be administered as a single oral dose.

Use in renal impairment.

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

Children.

Chemists' Own Femazole One capsule is not recommended in children under 18 years of age.

4.3 Contraindications

Chemists' Own Femazole One should not be used in patients with known sensitivity to fluconazole; to related azole compounds or to any of its excipients. Concomitant administration with cisapride is contraindicated (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
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

Anaphylaxis has been reported in rare instances. 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 hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patient has been observed.
Fluconazole 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)).
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. If rash which is attributable to fluconazole develops in a patient treated for a superficial fungal infection, fluconazole should not be used again. 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 post-marketing surveillance, there have been very rare cases of QT prolongation and torsade 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 (see Section 4.8 Adverse Effects (Undesirable Effects)). 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 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.

No data available.

Use in renal impairment.

See Section 4.2 Dose and Method of Administration, Use in renal impairment.

Use in the elderly.

No data available.

Paediatric use.

Insufficient evidence is available to establish safety and efficacy of fluconazole in the above indications in children.
See Section 4.2 Dose and Method of Administration, Children.

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 Chemists' Own Femazole One.
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.

Concomitant use of the following agents with fluconazole is contraindicated.

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 coadministration of fluconazole at doses lower than 400 mg per day with terfenadine should be carefully monitored.

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).

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 administraton of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsades de pointes. Coadminsitration of fluconazole and quinidine is contraindicated.

Anticoagulants.

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

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).

Hydrochlorothiazide.

Concomitant oral administration of fluconazole 100 mg and hydrochlorothiazide 50 mg for ten 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.

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 QTc interval.
Coadministration of cisapride is contraindicated in patients receiving fluconazole (see Section 4.3 Contraindications).

Cyclosporin.

A pharmacokinetic 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 ten 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 seven 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 two-fold 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 p.o. 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 mg/kg 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 the dose levels. The effects of parturition in rats are consistent with the species specific oestrogen-lowering properties produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole (see Section 5.1 Pharmacodynamic Properties).
(Category D)
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 3 or more months with high dose (400-800 mg/day) fluconazole therapy for coccidiomycosis. The relationship between fluconazole use and these events is unclear.
Adverse foetal effects have been seen in animals only at high dose levels associated with maternal toxicity. These findings are not considered relevant to Chemists' Own Femazole One used at therapeutic doses. 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.
Australian categorization definition of 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.
 Fluconazole has been found in human breast milk at concentrations similar to plasma, hence its use in nursing mothers is not recommended.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine 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.

Leucopenia including neutropenia and agranulocytosis, thrombocytopenia.

Cardiovascular.

QT prolongation, torsade 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 Steven-Johnson syndrome and toxic epidermal necrolysis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://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.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Fluconazole is a member of the bis-triazole class of antifungal agents. Fluconazole is a highly selective inhibitor of fungal cytochrome P-450 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. Fluconazole 50 mg daily given up to 28 days has been shown not to affect corticosteroid levels or ACTH stimulated response in healthy female volunteers. Plasma oestradiol levels and urinary free cortisol levels were decreased with little effect on plasma testosterone levels. Interaction studies with antipyrine indicate that single or multiple doses of fluconazole 50 mg do not affect its metabolism.

Mechanism of action.

Fluconazole administered orally or intravenously was active in a variety of animal models of fungal infections using standard laboratory stains of fungi. Fluconazole exhibits in vitro activity against Candida spp. Activity has been demonstrated in vivo in normal and immunocompromised animals against infections with Candida spp, including systemic candidiasis. One case of cross-resistance of Candida to fluconazole in a patient (non-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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Adults.

The pharmacokinetic properties of fluconazole are similar following administration by intravenous or oral routes.

Distribution.

In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. In fasted normal volunteers, peak plasma concentrations occur between 1 and 2 hours post dose with a terminal plasma elimination half-life of approximately 30 hours (range 20 - 50 hours). Plasma concentrations are proportional to dose and steady-state levels are reached within 5-10 days with oral doses of 50-400 mg once daily. Steady-state levels are approximately 2.5 times the level achieved with single doses. The apparent volume of distribution approximates to total body water. Plasma protein binding is low (11-12%).
Fluconazole has been found to achieve good penetration into all tissues and body fluids studies. See Table 1.

Metabolism and 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 is markedly affected by reduction in renal function. There is an inverse relationship between the elimination half-life and creatinine clearance. The long plasma elimination half-life provides the basis for a single dose therapy for vaginal candidiasis, once daily and once week if required.

5.3 Preclinical Safety Data

Genotoxicity.

Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in 4 strains of Salmonella typhimurium and in 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 2-7 x 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

The inactive ingredients are: lactose monohydrate, starch maize, silica-colloidal anhydrous, talc-purified and sodium lauryl sulfate, gelatin, titanium dioxide, patent blue V.

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/PE/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 by taking to your local pharmacy.

6.7 Physicochemical Properties

Fluconazole is a bis-triazole antifungal, with a chemical name 2-(2,4- difluorophenyl)-1,3-bis (1H-1,2,4-triazol-1-yl)-2-propanol. It is a white to off-white crystalline powder, which is sparingly soluble in water and saline.
The molecular formula of fluconazole is C13H12F2N6O.
The molecular weight of fluconazole is 306.3.

Chemical structure.


CAS number.

86386-73-4.

7 Medicine Schedule (Poisons Standard)

Pharmacist Only Medicine (S3).

Summary Table of Changes