Ancotil

Package leaflet: Information for the user

ANCOTIL 2.5 g/250 ml infusion solution

flucytosine
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What ANCOTIL is and what it is used for
2. What you need to know before using ANCOTIL
3. How to use ANCOTIL
4. Possible side effects
5. How to store ANCOTIL
6. Contents of the pack and other information

1. What ANCOTIL is and what it is used for

Ancotil contains the active substance flucytosine, which belongs to a group of medicines called
antifungal agents, used to treat infections caused by fungi.
Ancotil is indicated for the treatment of the following serious fungal infections:

• generalized candidiasis, an infection caused by a fungus of the genus Candida;
• cryptococcosis, an infection affecting the lungs, caused by Cryptococcus neoformans;
• chromoblastomycosis, a skin and subcutaneous tissue infection caused by several types of fungi.

2. What you should know before using ANCOTIL

Do not use ANCOTIL

• if you are allergic to flucytosine or to any of the other ingredients of this medicine (listed in section 6);
• if you are being treated with irreversible inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD), e.g. brivudine, sorivudine and their analogues (see sections “Warnings and precautions” and “Other medicines and ANCOTIL”);
• if you are taking tegafur/gimeracil/oteracil (an anticancer medicine) at the same time;
• if you know you have no activity of the enzyme dihydropyrimidine dehydrogenase (DPD) (complete absence of DPD activity);
• if you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor or nurse before using Ancotil.
This medicine will be administered with extreme caution if:

• you have kidney problems or are undergoing haemodialysis. Your doctor will determine the dose of this medicine based on your kidney function (see sections “Use in patients with kidney problems” and “If you take more ANCOTIL than you should”);
• you have liver problems, as you will need medical monitoring before and during treatment (see section “Use in patients with liver problems”);
• you have severe bone marrow problems (bone marrow depression) or are at risk of bone marrow problems;
• you have a deficiency of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism and elimination from the body of certain substances.

Children and adolescents
The safety and efficacy of Ancotil in children and adolescents have not yet been established.
Other medicines and ANCOTIL
Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
This medicine should be administered with caution, especially if you are taking the following medicines:

• amphotericin B, a medicine used to treat fungal infections;
• cytarabine, a medicine used to treat certain cancers;
• phenytoin, a medicine for epilepsy;
• brivudine, sorivudine and similar medicines, used to treat viral infections (see sections “Do not use ANCOTIL” and “Warnings and precautions”);
• tegafur/gimeracil/oteracil (an anticancer medicine);
• myelosuppressive agents, medicines that impair blood cell production in the bone marrow.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or nurse before using this medicine.
Your doctor will decide whether you should take Ancotil during pregnancy. If Ancotil is administered during pregnancy, there is a teratogenic risk (risk of fetal malformations), and careful prenatal and postnatal monitoring must be performed. Do not take Ancotil if you are breastfeeding.
Contraception in men and women
Women of childbearing potential undergoing treatment must use effective contraception during treatment and for 6 months after the end of treatment. Male patients (or their female partners of childbearing potential) must use effective contraception during treatment and for three months after the end of treatment. If renal function is reduced, the contraception period should be extended by an additional 2 months.
Driving and using machines
This medicine does not impair the ability to drive or operate machinery.
ANCOTIL contains sodium
This medicine contains 792 mg of sodium (the main component of table salt) per vial.
This corresponds to 40% of the maximum daily dietary intake recommended for an adult.
The maximum daily recommended dose of this product (14 g of flucytosine) contains 4.4 g of sodium (the main component of table salt). This corresponds to 220% of the maximum daily dietary intake recommended for an adult.
Talk to your doctor or pharmacist if you need to use Ancotil daily for a prolonged period, especially if you have been advised to follow a low-sodium diet.

3. How to use ANCOTIL

Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your
doctor or nurse.
This medicine is administered intravenously (into a vein). The recommended dose for each
injection is 37.5–50 mg per kg of body weight. The administration should be repeated every 6 hours via
a slow intravenous infusion (20–40 minutes).
Duration of treatment
Your doctor will determine the duration of treatment based on the type of fungus, the site and severity
of the infection, and your response to treatment.
Use in patients with kidney problems
If you have kidney problems, the time interval between Ancotil injections should be longer than in patients with normal kidney function. Your doctor will adjust the dose according to your kidney function (see sections “Warnings and precautions” and “If you use more ANCOTIL than you should”).
If you are undergoing a blood purification procedure (haemodialysis or peritoneal dialysis), Ancotil
will be administered after each session.
Use in patients with liver problems
If you have liver problems, your doctor will need to monitor your health condition particularly closely during treatment (see section “Warnings and precautions”).
Use in children
Although some clinical data are available in children, these data are insufficient to establish precise dosing recommendations for this age group. If this medicine is prescribed for your child, the doctor will choose the most appropriate dose.
Due to prolonged elimination of flucytosine in paediatric patients, especially in younger children, administration of flucytosine may lead to excessive blood concentrations. Therefore, flucytosine blood levels in your child will be regularly monitored during treatment.
If you use more ANCOTIL than you should
Cases of overdose with this medicine are not known. If overdose occurs due to impaired kidney function, effects are usually temporary and resolve with dose adjustment or discontinuation of treatment.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Frequency is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), not known (frequency cannot be estimated from the available data).
The following side effects have been reported with this medicine at a frequency not known:

• blood disorders, especially reduced number of red blood cells (anaemia), reduced number of white blood cells (leucopenia), and reduced number of platelets (thrombocytopenia);
• allergic reactions (hypersensitivity);
• confusion, hallucination;
• headache (cephalalgia), stupor;
• dizziness;
• nausea, vomiting, diarrhoea;
• liver problems (increased liver enzymes);
• skin rash.

Reporting of side effects
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ANCOTIL

Keep this medicine out of the sight and reach of children.
Store this medicine at a temperature between 18 and 25°C.
Do not use this medicine after the expiry date stated on the packaging after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice the presence of solid particles in the solution. This may occur if Ancotil is stored at temperatures below 18°C.
If stored above 25°C, flucytosine may be converted imperceptibly into 5-fluorouracil, a cytostatic agent.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ANCOTIL contains

• The active substance is flucytosine. Each 250 ml vial contains 2.5 g of flucytosine.
• The other components are: tromethamine, sodium chloride, hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of ANCOTIL and package contents
ANCOTIL is available in packs containing 5 glass vials, each closed with a pierceable stopper and screw cap, containing 250 ml of solution for intravenous infusion.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Viatris Italia S.r.l.
Via Vittor Pisani, 20
20124 Milano, Italy

Manufacturer
Meda Pharma GmbH & Co. KG
Benzstrasse 1
D-61352 Bad Homburg
Germany

The following information is intended exclusively for healthcare professionals:

Intravenous infusion
The recommended daily dose is 37.5–50 mg/kg, repeated every 6 hours, with an infusion duration of 20 to 40 minutes.

Duration of treatment
The duration of treatment should be determined on an individual basis. The outcome of therapy will depend on the susceptibility of the infecting microorganism, its accessibility, its sensitivity to Ancotil, and individual patient responses.

Special populations

Patients with renal impairment
Since Ancotil is primarily excreted by the kidneys, in patients with impaired renal function, doses should be administered at longer intervals based on creatinine clearance values according to the following schedule:

Ancotil must not be used in patients with impaired renal function if plasma concentration monitoring is not possible.
Patients undergoing dialysis
Ancotil is largely eliminated during hemodialysis and peritoneal dialysis. Therefore, in patients undergoing dialytic treatment, administration of Ancotil must be repeated after each dialysis session.
Laboratory tests
Creatinine measurement:
flucytosine may interfere with the two-stage enzymatic determination of creatinine, leading to a false-positive azotemia. Alternative methods should be used for creatinine determination. Flucytosine does not interfere with the Jaffe test.
Antimicrobial susceptibility testing
It is recommended that cultures for strain identification and susceptibility testing be performed before starting treatment and repeated at regular intervals during therapy.
For susceptibility testing, it is essential that culture media be free of flucytosine antagonists.
Serum flucytosine levels
5-FC levels should be monitored to adjust dosing.
Dosing should ensure maintenance of serum levels above 25 µg/ml due to the increased risk of resistance development at lower concentrations.
Prolonged existence of serum levels above 100 µg/ml should be avoided due to increased hematological toxicity.
It is recommended to collect blood samples for monitoring Ancotil serum levels 2 hours after administration.
Drug toxicity
In case of suspected drug toxicity, treatment interruption and appropriate measures should be considered.
Serum phenytoin level
Patients concurrently receiving phenytoin and Ancotil should be monitored regularly for increased plasma phenytoin concentrations (see section 4.5 of the Summary of Product Characteristics).