drug-medicine : ancotil solution for infusion

ancotil

PATIENT INFORMATION LEAFLET

Ancotil® 2.5g/250mL

(1g in 100mL)

Solution for Infusion

Flucytosine

Please read this leaflet carefully. If you have any questions or are not sure about anything, ask your doctor, nurse or pharmacist.

What is Ancotil Solution for Infusion?

Ancotil Solution for Infusion contains an active ingredient called flucytosine which is an anti-fungal agent. The other ingredients are sodium chloride, tromethamine, hydrochloric acid and water for injections.

Ancotil Solution for Infusion is available in packs of 5 bottles of 250 mL. Each 250 mL contains 2.5 g of flucytosine.

What is Ancotil Solution for Infusion used for?

It is a medicine used to treat certain yeast and fungal infections.

When must Ancotil Solution for Infusion not be used?

The product must not be used:

If you are allergic to Ancotil or any of the other ingredients it contains.
If you are breast-feeding.

When should you be extra careful while having Ancotil Solution for Infusion?

Make sure your doctor knows if you are taking other medicines e.g. cytarabine (which is used to treat certain leukaemias).
If you have a liver, kidney or blood problem, your doctor will need to carry out blood tests during your treatment.

May Ancotil Solution for Infusion be used during pregnancy or while breast-feeding?

You must tell your doctor if you are pregnant, if you think you may get pregnant or if you are breast-feeding.

You should not take Ancotil if you are breast-feeding.

Your doctor will assess the benefits against any risk to you and your baby.

How should Ancotil Solution for Infusion be used?

It is usually given into a vein or by a procedure called "intraperitoneal infusion" while you are in hospital.
The usual total daily dose is 100 to 150 mg/kg bodyweight in divided doses. In some instances, you may be given up to a total daily dose of 200 mg/kg bodyweight in divided doses.
Smaller doses may be given to patients with kidney problems.
Ancotil should not be injected in the same solution as other medicines (except glucose and/or saline infusion).

What are the possible unwanted effects of Ancotil Solution for Infusion?

Your reaction to the medicine will be monitored by your doctor.

Nausea, vomiting, diarrhoea and skin rashes may occur but these usually do not last long.
Allergies, skin inflammation that may lead to severe blistering, effects on the heart muscle and its pumping, confusion, effects on your senses (e.g. seeing or hearing things), convulsions (fits), headache, sleepiness and dizziness are less common.
Tests on your blood may show changes to your liver or certain factors in your blood.
Allergic reaction (rash, palpitations, swelling of eyelids, face, lips, mouth or tongue, sudden wheeziness, chest tightness, lumpy skin rash).

If you are concerned about these or any other unwanted effects, talk to your doctor or nurse.

How should Ancotil Solution for Infusion be stored?

Keep this medicine out of the reach and sight of children.
The product will have been stored between 18°C and 25°C.
This medicine must not be used after the date (EXP) printed on the carton and bottle label.
The product should only be handled by experienced health care professionals.

Information for health professionals

Ancotil® 2.5g/250mL

(1g in 100 mL)

Solution for Infusion

Flucytosine

This leaflet provides technical information about Ancotil for the healthcare professional.

The tear-off portion attached is intended for the patient.

Presentation

Infusion bottles containing 2.5g flucytosine in 250 mL isotonic sodium chloride solution. Other excipients are sodium chloride, tromethamine, hydrochloric acid and water for injections. The solution is colourless to slightly yellow.

Uses

Properties

Ancotil is a fluorinated pyrimidine effective in the treatment of certain systemic fungal infections.

In fungi sensitive to the preparation, it acts as a competitive inhibitor of uracil metabolism.

Pharmacokinetics

Ancotil is widely distributed in body tissues and fluids (including cerebrospinal fluid). Binding to plasma proteins is minimal. Half-life of elimination is 3 to 6 hours in patients with normal renal function but this value increases in renal failure. About 90% of the dose administered is excreted unchanged in the urine. Flucytosine is metabolised to 5-fluorouracil. The area under the curves (AUC) ratio of 5-fluorouracil to flucytosine is 4%. Flucytosine can be removed by haemodialysis.

Indications

Ancotil is indicated for the treatment of systemic yeast and fungal infections due to sensitive organisms: such infections include cryptococcosis, candidiasis, chromomycosis and infections due to Torulopsis glabrata and Hansenula.

In the treatment of cryptococcal meningitis and severe systemic candidiasis it is recommended that Ancotil should be given in combination with amphotericin-B. Amphotericin- B may also be given in combination with Ancotil in severe or long-standing infections due to other organisms. In cases of cryptococcal meningitis, where toxicity of amphotericin B, or a combination of flucytosine with amphotericin B is dose limiting, a combination of flucytosine with fluconazole has demonstrated successful cure, but at a lower rate than in combination with amphotericin B.

Dosage and administration

Adults and children

Ancotil for Infusion should be administered using a giving set. It may be administered directly into a vein, through a central venous catheter, or by intra-peritoneal infusion. The recommended daily dosage in adults and children is 200 mg/kg bodyweight divided into four doses over the 24 hours. In patients harbouring extremely sensitive organisms, a total daily dose of 100 to 150 mg/kg bodyweight may be sufficient. Adequate effects can, however, often be obtained with a lower dose.

It is suggested that the duration of the infusion should be of the order of 20 to 40 minutes, provided this is balanced with the fluid requirements of the patient. As a rule, treatment with Ancotil for Infusion should rarely be required for periods of more than one week.

Since Ancotil is excreted primarily by the kidneys, patients with renal impairment should be given smaller doses. The following is suggested as a guide for dosage in patients with severe infection associated with renal impairment:

In patients with:

creatinine clearance < 40 to > 20 mL/min: 50 mg/kg every 12 hours.
creatinine clearance < 20 to > 10 mL/min: 50 mg/kg every 24 hours.
creatinine clearance < 10 mL/min: an initial single dose of 50 mg/kg; subsequent doses should be calculated according to the results of regular monitoring of the serum concentration of the drug, which should not be allowed to exceed 80 micrograms/mL. Blood levels of 25 to 50 micrograms/mL are normally effective.

The duration of treatment should be determined on an individual basis.

The outcome of therapy will be affected by variations in the sensitivity of the infecting organism, its accessibility and its susceptibility to Ancotil, as well as by differences in the response of individual patients. In cases of cryptococcal meningitis, treatment should last for at least 4 months.

Neonates

The dose in neonates should be calculated in the same way as for adults and children, but the high possibility of renal impairment should be considered in this group either as intrinsic to their age or as a result of other nephrotoxic therapies. It is advised to closely monitor the serum levels of flucytosine in this group and adjust the dose according to levels. In cases where renal impairment is present the dose interval should be extended (as with adults and children).Where renal impairment is not a feature but serum levels are above those recommended, the dose should be reduced but the dosing intervals should remain the same.

Use in the elderly

Although no specific studies have been performed to establish the use of Ancotil in the elderly, documented use indicates that the dosage requirements and side effects profile are similar to those of younger patients. Particular attention should be paid to renal function in this group.

Ancotil for Infusion is for intravenous or intraperitoneal administration.

Ancotil for Infusion may be given concurrently with other infusions of normal saline, glucose or glucose/saline. No other agent should be added to or mixed with Ancotil for Infusion.

Contra-indications and warnings

Contra-indications

Ancotil is contra-indicated in patients who have shown hypersensitivity to flucytosine or any of the excipients.

Use in pregnancy and lactation

Teratogenic effects have been seen in rats. In this species flucytosine is metabolised to fluorouracil. The metabolism may differ in man: nevertheless, the use of Ancotil in pregnancy and in women of childbearing age requires that the potential benefits of therapy be weighed against its possible hazards. The drug should not be given to women breast-feeding infants.

Precautions

The product should be used with great caution in patients with depression of bone marrow function or blood dyscrasias. Blood counts and tests of renal and hepatic function should be performed before and during treatment. This should occur at least weekly in patients with renal insufficiency or blood dyscrasias.

Ancotil should not be used in patients with impaired renal function in the absence of facilities for monitoring blood levels of the drug.

When measuring drug serum levels, it should be noted that levels of the drug in blood samples, taken during or immediately after administration of Ancotil for Infusion, are not a reliable guide to subsequent levels; it is advisable to remove blood for monitoring of blood levels of Ancotil shortly before starting the next infusion.

In calculating the fluid and electrolyte intake of patients with impaired renal function, cardiac failure or electrolyte imbalance, due allowance should be made for the volume and sodium content (138 millimole/litre) of Ancotil for Infusion.

Side effects and adverse reactions

Nausea, vomiting, diarrhoea and skin rashes may occur but are usually of a transient nature.

Less frequently observed side effects include allergic reactions, Lyell's Syndrome, myocardial toxicity and ventricular dysfunction, confusion, hallucinations, convulsions, headache, sedation and vertigo. Alterations in tests of liver function are generally dose-related and reversible but hepatitis and hepatic necrosis have been reported. Acute liver injury with possible fatal outcome in debilitated patients may occur in isolated cases.

Haematological changes, mainly leucopenia, thrombocytopenia, agranulocytosis or aplastic anaemia have been reported. These are more common when serum levels of flucytosine are high in patients with renal impairment and when amphotericin-B has been co-prescribed. In isolated cases, bone marrow toxicity has been reported. This toxicity may be irreversible and could lead to death in patients with pre-existing immunosuppression.

Local irritation or phlebitis does not appear to be a problem with Ancotil for Infusion.

Drug interactions

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.

Treatment of overdosage

Haemodialysis produces a rapid fall in the serum concentration of Ancotil.

Pharmaceutical precautions

Storage

Ancotil for Infusion should be stored between 18°C and 25°C. If stored below 18°C, precipitation of Ancotil substance may occur, which should be redissolved by heating to 80°C for not more than 30 minutes.

Prolonged storage above 25°C could lead to the decomposition of Ancotil resulting in the formation of 5-fluorouracil.

Additives

Ancotil for Infusion may be given concurrently with other infusions of sodium chloride intravenous infusion (0.9% w/v) BP, glucose intravenous infusion 5% w/v) BP, or sodium chloride (0.18% w/v) and glucose (4% w/v), intravenous BP. No other agent should be added to or mixed with Ancotil for Infusion.

Legal category

UK: POM

Ireland: Restricted to sale or supply on prescription only.

Package quantities

Ancotil for Infusion 2.5g in 250 mL in packs of 5.

Further information

Availability

Ancotil for Infusion is available to hospitals only.

Sensitivity testing

It is recommended that cultures for sensitivity testing be taken before treatment and repeated at regular intervals during therapy. However, it is not necessary to delay treatment until results of these tests are known.

To determine sensitivities, the methods of Shadomy (Appl Microbiol, 1969, 17, 871) and Scholer (Mykosen, 1970, 13, 179) are recommended.

For sensitivity testing it is essential that culture media are free of antagonists to flucytosine.

Creatinine measurement

Flucytosine may interfere with the dual-slide enzymatic measurement of creatinine used with the manual, desk-top Vitros DT 60 analyser, giving the false impression of azotemia.

Other suitable methods should be used for creatinine assessment. The current creatinine method used with automated Vitros analysers is not affected by flucytosine.