Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about Ancotil. 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 using Ancotil against the benefits they expect it will have for you.

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

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

What Ancotil is used for

This medicine is used to treat:

• fungal or yeast infections in your body, which are also known as candidiasis, cryptococcosis or chromoblastomycosis.

Ask your doctor if you have any questions about why Ancotil has been prescribed for you. Your doctor may have prescribed Ancotil for another purpose.

Ancotil is not addictive.

Ancotil is available only with a doctor's prescription.

Before you have Ancotil

When you must not have it

Do not have Ancotil if you have an allergy to:

• any medicine containing flucytosine
• 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.

Do not have Ancotil if you know that you do not have any activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete DPD deficiency).

Do not have this medicine if you are pregnant. It may affect your developing baby if you take it during pregnancy.

Do not breast-feed if you are having this medicine. It is not known if the active ingredient in Ancotil passes into breast milk and there is a possibility that your baby may be affected.

Do not have Ancotil after the expiry date (EXP) printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, your pharmacist will dispose of it for you.

Before you start to have it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you have kidney problems. Your doctor will discuss the risks and benefits of using Ancotil and the need to monitor your kidney function. The dose of Ancotil may be adjusted according to your kidney function

Tell your doctor if you have bone marrow depression or a blood disorder. Your doctor will discuss the risks and benefits of using Ancotil and the need to monitor your blood picture, kidney and liver function.

If you have not told your doctor about any of the above, tell them before you use Ancotil.

Taking other medicines

Tell your doctor if you are taking any other medicines including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop. Some medicines and Ancotil may interfere with each other.

These include:

• cytostatics
• cytosine arabinoside
• amphotericin B
• phenytoin
• cytarabine

These medicines may be affected by Ancotil 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 Ancotil.

How Ancotil is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

How much is administered

The dose of Ancotil may be different for each person and ranges between 37.5 to 50 mg per kilogram body weight. Your doctor will decide the right dose for you.

How is it administered

Ancotil is administered by slow intravenous infusion for 20 to 40 minutes. If your kidney function is normal this dose is repeated every six hours.

If your kidney function is impaired the intervals between administrations of the doses could vary up to 24 hours. Your doctor will decide the appropriate dosing for you.

How long use it

Your doctor will determine how long Ancotil should be used.

While you are using Ancotil

Things you must do

If you are about to be started on a new medicine, remind your doctor and pharmacist that you are taking Ancotil.

Tell any other doctors, dentists and pharmacists who are treating you that you are using Ancotil.

If you feel that Ancotil is not helping your condition, tell your doctor or pharmacist.

Ask your doctor or pharmacist if you are concerned about the length of time you have been given Ancotil. While you are being treated with Ancotil, your doctor will monitor your kidney function, liver function and blood picture.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given Ancotil.

Ancotil helps to clear the fungal or yeast infection, but it may have unwanted side effects in some people.

All medicines may 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 lists of side effects. You may not experience any of them.

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

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

• nausea
• vomiting
• diarrhoea
• skin rashes

These side effects are usually mild and do not last long.

The following are less frequent side effects:

• fits
• headache
• sleepiness
• dizziness
• blood tests may show changes to your liver or certain factors in your blood.

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

• an allergic reaction

If you have an allergic reaction you may experience swelling of eyelids, face, lips, mouth or tongue, sudden wheeziness, chest tightness, lumpy skin rash

• skin inflammation that may lead to severe blistering
• changes in the way your heart beats

Other side effects not listed above may occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell when you are undergoing, or soon after Ancotil treatment.

Ask your doctor or pharmacist if you don't understand anything in this list.

After having Ancotil

Storage

Ancotil will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place where the temperature stays below 25°C.

Disposal

Since Ancotil is usually given in a hospital setting your pharmacist will dispose of any left over Ancotil.

Product description

What Ancotil looks like

Ancotil is an isotonic infusion solution containing flucytosine (1%) and 0.805% NaCl. It comes in a 250 mL glass bottle.

Ingredients

Ancotil also contains sodium chloride, trometamol, hydrochloric acid and water for injections.

Sponsor

Ancotil is supplied in Australia by:

iNova Pharmaceuticals (Australia) Pty Limited
ABN: 13 617 871 539
Level 10, 12 Help Street
Chatswood NSW 2067
Tel: 1800 630 056

®= Registered Trademark

AUST R 13705

Date of Preparation: July 2021

Published by MIMS August 2021

1 Name of Medicine

Flucytosine.

2 Qualitative and Quantitative Composition

The active ingredient of Ancotil is 5-flucytosine (5-FC), a fluorinated pyrimidine. Ancotil is available as an isotonic infusion solution (1%) containing 0.805% sodium chloride. Ancotil also contains the excipients hydrochloric acid, trometamol and water for injections.

3 Pharmaceutical Form

Ancotil is a clear, colourless liquid. It is a 2.5 g/250 mL (1% w/v) injection administered intravenously.

4 Clinical Particulars

4.1 Therapeutic Indications

Ancotil is indicated in the treatment of generalised candidiasis, cryptococcosis and chromoblastomycosis.

4.2 Dose and Method of Administration

Intravenous administration of Ancotil using the infusion solution (37.5-50 mg per kg) is given as infusions of short duration (20 to 40 minutes). In patients whose renal function is normal, this dose is repeated at six hourly intervals.

Special dosage instructions.

4.3 Contraindications

Ancotil should not be administered to patients with: known hypersensitivity to the medicine or any of the excipients; known complete dihydropyrimidine dehydrogenase (DPD) deficiency (see Section 4.4).

4.4 Special Warnings and Precautions for Use

Before and during treatment with Ancotil the patient's kidney function should be monitored, preferably by determination of endogenous creatinine clearance. If necessary, the dose should be adapted accordingly (see Section 4.2 Dose and Method of Administration, Special dosage instructions). Ancotil should not be used in patients with impaired renal function in the absence of facilities for monitoring blood levels of the drug.
Ancotil should be given with extreme caution to patients with bone marrow depression or blood dyscrasias. The blood picture, renal and liver function should also be monitored daily at the start of treatment and later twice weekly.
The risk of severe drug toxicity is increased when Ancotil is used in individuals with deficiency in dihydropyrimidine dehydrogenase (DPD). Determination of DPD activity may be considered where drug toxicity is confirmed or suspected. In the event of suspected drug toxicity, consideration should be given to stopping Ancotil treatment.

Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Since there is a risk of leucopoenia (particularly neutropenia often accompanied by thrombocytopenia) when undergoing treatment with Ancotil, daily monitoring of the blood picture may be necessary where cytostatics are administered simultaneously.
Because excretion is almost exclusively renal, drugs which inhibit glomerular filtration automatically cause prolongation of the half-life of the active ingredient of Ancotil. In such cases it is essential that creatinine clearance be monitored regularly and the dose adapted accordingly.
The antimycotic effect of Ancotil is inhibited by the cytostatic cytosine arabinoside. Infusion solutions of Ancotil and amphotericin B should be administered separately.
There is contradictory evidence concerning a drug interaction between Ancotil and cytarabine. Strict monitoring of blood levels is required if the two medicines are given concurrently.
Increased phenytoin plasma levels have been reported with concomitant administration of phenytoin and intravenous fluorouracil, leading to symptoms of phenytoin intoxication. Patients receiving phenytoin and Ancotil concomitantly should be checked regularly for increased phenytoin plasma levels.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

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)

At the recommended dosage Ancotil is usually well tolerated. Nausea, vomiting, diarrhoea and skin rashes may occur. Allergic reactions, Lyell's syndrome, convulsions, headache, sedation, vertigo and myocardial toxicity and ventricular dysfunction have been reported.
Haematological changes, mainly leucopenia, thrombocytopenia, agranulocytosis or aplastic anaemia have been reported. In isolated cases, bone marrow toxicity has been reported. The toxicity may be irreversible and could lead to death in patients with pre-existing immunosuppression.
An increase of hepatic enzymes in the serum, hepatitis and hepatic necrosis have been reported. Acute liver injury with possible fatal outcome in debilitated patients may occur in isolated cases.
Gastrointestinal bleeding (haemorrhage) has been observed when Ancotil was given in combination with amphotericin B and/or corticosteroids.

Reporting suspected adverse effects.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
No cases of intentional overdose are known. In cases of relative overdosage resulting from impaired renal function, there is an increased risk of undesirable effects, both in incidence and severity, in patients with a tendency to renal disorders (see Section 4.8 Adverse Effects (Undesirable Effects)). These side effects are generally rapidly reversible on adjustment of the dosage or withdrawal of the drug.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

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

6.3 Shelf Life

18 months.

6.4 Special Precautions for Storage

Store below 25°C.
Precipitate occurs at prolonged storage below 15°C. The precipitate can be redissolved by heating at a temperature of no higher than 80°C for not longer than thirty minutes.
Storage above 25°C may result in the formation of 5-fluorouracil, a cytostatic whose presence cannot be detected visibly.

6.5 Nature and Contents of Container

Ancotil 2.5 g/250 mL (1% w/v) Injection comes in packs of 5 bottles.
It is contained in a glass bottle of hydrolytic class II glass with fluoresin coated rubber stopper.

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.

CAS number.

References

1. Scholer H.J.: Mykosen (1970); 13, 179-188.
2. Shadomy S.: Appl. Microbiol. (1969); 17, 871-877.
3. Schoenebeck J. et.al: Chemotherapy (1973); 18, 321-336.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine.

Summary Table of Changes