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Drug Details

Ancotil 2.5g/250ml Solution for Infusion

• Presentation
  Infusion bottles containing 2.5g flucytosine Ph. Eur. in 250 ml isotonic sodium chloride solution.
• Description
  Flucytosine Ph. Eur. 2.5g in 250 ml.
• 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.

• Adult Dosage
  

  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 body-weight divided into four doses over the 24 hours. In patients harboring extremely sensitive organisms a total daily dose of 100 to 150 mg/kg body-weight 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 infection 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 four 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 interval should remain the same.

  Elderly

  Although no specific studies have been performed to establish the use of Ancotil in the elderly, documented use indicated 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 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
  

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

• Special 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.

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

• 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.

• Adverse Drug 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. This is 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 may be irreversible and could lead to death in patients with pre-existing immuno-suppression. Local irritation or phlebitis does not appear to be a problem with Ancotil for Infusion.