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.

SUMMARY CMI

Chemists' Own Femazole One

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Chemists' Own Femazole One?

Chemists' Own Femazole One contains the active ingredient Fluconazole. Chemists' Own Femazole One is used to treat a fungal infection known as vaginal thrush (vaginal candidiasis).

For more information, see Section 1. Why am I using Chemists' Own Femazole One? in the full CMI.

2. What should I know before I use Chemists' Own Femazole One?

Do not use if you have ever had an allergic reaction to Fluconazole or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Chemists' Own Femazole One? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Chemists' Own Femazole One and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Chemists' Own Femazole One?

  • Chemists' Own Femazole One should be taken as single dose of one capsule. The whole capsule is to be swallowed with one glass of water.

More instructions can be found in Section 4. How do I use Chemists' Own Femazole One? in the full CMI.

5. What should I know while using Chemists' Own Femazole One?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Chemists' Own Femazole One.
  • Are about to be started on any new medicine, remind your doctor or pharmacist that your have taken this medicine.
  • If you become pregnant while taking this medicine, tell your doctor immediately
  • If the symptoms of your infections do not improve after 03 days, or if they become worse, tell your doctor or pharmacist
Things you should not do
  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not take this medicine to treat any other complaint unless your doctor pr pharmacist tells you to do.
Driving or using machines
  • No effects on driving or using machines
Drinking alcohol
  • No effects on drinking alcohol
Looking after your medicine
  • Keep your medicine in its pack until it is time to take it.
  • If you take your medicine out of its pack it may not keep well.

For more information, see Section 5. What should I know while using Chemists' Own Femazole One? in the full CMI.

6. Are there any side effects?

The common side effects include nausea, vomiting, stomach pain, indigestion, wind, diarrhoea, muscle or back pain and head ache

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Chemists' Own Femazole One

Active ingredient(s): Fluconazole

Consumer Medicine Information (CMI)

This leaflet provides important information about using Chemists' Own Femazole One. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Chemists' Own Femazole One.

Where to find information in this leaflet:

1. Why am I using Chemists' Own Femazole One?
2. What should I know before I use Chemists' Own Femazole One?
3. What if I am taking other medicines?
4. How do I use Chemists' Own Femazole One?
5. What should I know while using Chemists' Own Femazole One?
6. Are there any side effects?
7. Product details

1. Why am I using Chemists' Own Femazole One?

Chemists' Own Femazole One contains the active ingredient Fluconazole. Fluconazole belongs to a group of medicines known as azole antifungals.

Chemists' Own Femazole One is used to treat a fungal infection known as vaginal thrush (vaginal candidiasis).

2. What should I know before I use Chemists' Own Femazole One?

Warnings

Do not use Chemists' Own Femazole One if:

  • you are allergic to Fluconazole, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • Any other azole antifungals e.g., clotrimazole

Some of the symptoms of an allergic reaction may include

  • Shortness of breath
  • Wheezing or breathing difficulty
  • Swelling of the face, lips, tongue, throat, or other parts of the body
  • Rash, itching or hives on the skin.

Check with your doctor if you:

  • have any other medical conditions
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Fluconazole may affect your developing baby if you take it during pregnancy. Your pharmacist will discuss with you the risks and benefits involved.

Do not use this medicine if you are a female of childbearing age unless you are using adequate contraception.

Effective contraception should be taken during treatment and for about 1 week after the final dose.

Do not take this medicine if you are breast-feeding.

Fluconazole may pass into breast milk and affect your baby.

3. What if I am taking other medicines?

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

Some medicines may interfere with Fluconazole and affect how it works.

  • Astemizole, used for allergies.
  • Cisapride, used to treat stomach problems.
  • Quinidine, used to treat heart problems.
  • Erythromycin, as an antibiotic
  • Pimozide, used to treat mood disorders.
  • Voriconazole, used as an anti-fungal medicine.

Medicines to be taken with care with Fluconazole.

  • Terfenadine (do not take this medicineif you are receiving fluconazole at multiple doses of 400mg/day)
  • Amiodarone, used for heart problems
  • Some medicines used to treat diabetes (e.g., glipizide, chlorpropamide, tolbutamide, glibenclamide, glimepiride, gliclazide, pioglitazone, rosiglitazone
  • Some antibiotics and antiviral drugs (e.g., erythromycin, amphotericin B, rifampicin, rifabutin, zidovudine, saquinavir)
  • Some medicine used to impress the immune system (e.g., ciclosporine, tacrolimus, sirolimus, prednisone)
  • Some medicines used to treat cancer (e.g., cyclophosphamide, ibrutinib, Olaparib, vincristine, vinblastine)
  • Vitamin A
  • Antidepressants (e.g., amitriptyline, nortriptyline
  • Warfarine or ticlopidine, used to stop blood clots.
  • Phenytoin and carbamazepine used to treat epilepsy.
  • Theophylline, used to treat asthma.
  • Medicine used during anaesthetics (e.g., alfentanil, midazolam, fentanyl)
  • Benzodiazepines (e.g., triazolam)
  • Hydrochlorothiazide, used for treating fluid problems.
  • Medicines used to treat high blood pressure (e.g. losartan, amlodipine, felodipine)
  • Medicines used to treat high cholesterol (e.g., simvastatin, Fluvastatin, atorvastatin)
  • Medicines to treat low levels of sodium in the blood (e.g., tolvaptan)
  • Some medicines used for pain relief (e.g., methadone, celecoxib)
  • Halofantrine, used to treat malaria.
  • the contraceptive pill

Talk to your doctor or pharmacist about the need for an additional method of contraception while taking fluconazole.

If you are taking any of these, you may need a different dose, or you may need to take different medicines.

Other medicines not listed above may interact with Fluconazole.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Chemists' Own Femazole One.

4. How do I use Chemists' Own Femazole One?

How much to take / use

  • Follow all directions given to you by your pharmacist carefully.
  • They may differ to this information contained in this leaflet.
  • Follow the instructions provided and use Chemists' Own Femazole One until your doctor tells you to stop.

When to take / use Chemists' Own Femazole

  • Chemists' Own Femazole One should be taken as single dose of one capsule.
  • The whole capsule is to be swallowed with one glass of water.
  • It does not matter whether you take this medicine with or without food.

If you forget to use Chemists' Own Femazole One

Chemists' Own Femazole One should be used regularly at the same time each day. If you miss your dose at the usual time, take immediately before the next dose.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much Chemists' Own Femazole One

If you think that you have used too much Chemists' Own Femazole One, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Chemists' Own Femazole One?

Things you should do

Call your doctor straight away if you:

  • Are about to be started on any new medicine, remind your doctor or pharmacist that your have taken this medicine.
  • Tell any other doctors, dentists and pharmacists who are treating you that you have taken this medicine.
  • If you become pregnant while taking this medicine, tell your doctor immediately.
  • If the symptoms of your infections do not improve after 03 days, or if they become worse, tell your doctor or pharmacist.

Remind any doctor, dentist, or pharmacist you visit that you are using Chemists' Own Femazole One.

Things you should not do

  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not take this medicine to treat any other complaint unless your doctor pr pharmacist tells you to do.

Things to be careful of

Tell your doctor or pharmacist immediately if you develop rash soon after taking this medicine.

  • People with AIDS or weak immune system may be prone to more serious side effects of the skin.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Chemists' Own Femazole One affects you.

No effects on driving or using machines.

Drinking alcohol

Tell your doctor if you drink alcohol.

No information on alcohol consumption with Chemists' Own Femazole One.

Looking after your medicine

  • Keep your medicine in its pack until it is time to take it.
  • If you take your medicine out of its pack it may not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and -a half meters above the ground is a good place to store medicines.

When to discard your medicine

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • Nausea or vomiting
  • Stomach pain, indigestion, wind
  • Diarrhoea
  • Muscle or back pain
  • headache
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • skin reactions or rash
  • unusual muscle stiffness causing poor control of movement.
  • Frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • Bleeding or bruising more easily than normal.
  • Passing more urine than normal, kidney pain (pain on the sides of the body)
  • Yellowing of the skin or eyes (jaundice); dark urine, pale stools; loss of appetite; unusual tiredness (signs of liver disease)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Very Serious side effects

Very Serious side effectsWhat to do
  • Shortness of breath, wheezing or difficulty breathing; swelling of face lips, tongue, throat, or other parts of the body; rash itching or hives on the skin (signs of an allergic reaction)
  • Fast, slow, or irregular heartbeat or palpitation and/or fainting
  • Severe blisters and bleeding of the lips, eyes, mouth, nose, and genitals.
  • A severe rash with skin peeling, fever, chills, and aching muscles.
These are very serious side effects which are very rare.
You may need urgent medical attention or hospitalization.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Chemists' Own Femazole One contains

Active ingredient
(main ingredient)		Fluconazole
Other ingredients
(inactive ingredients)		Lactose monohydrate
Maize starch
Colloidal anhydrous silica
Purified talc
Sodium lauryl sulphate
Gelatin
Titanium dioxide
Paten blue V
Potential allergensN/A

This medicine does not contain gluten, sucrose, tartrazine, or any other azo dyes.

This medicine contains sugars (as lactose) and sulfites.

Do not take this medicine if you are allergic to any of these ingredients.

What Chemists' Own Femazole One looks like

Chemists' Own Femazole One is hard gelatin capsule of size “1” with sky blue body and cap (Aust R 152959).

Who distributes Chemists' Own Femazole One

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121
Australia
Web: www.arrotex.com.au

This leaflet was prepared in November 2024.

Published by MIMS January 2025

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