Ancotil (Flucytosine): Uses, Dosage & Side Effects
An intravenous antifungal medication used to treat serious systemic fungal infections in adults and children, most commonly in combination with amphotericin B
Ancotil (flucytosine, also known as 5-fluorocytosine or 5-FC) is an antifungal medication administered by intravenous infusion to treat serious systemic fungal infections. It is primarily active against Candida species and Cryptococcus neoformans. Flucytosine is most frequently used in combination with amphotericin B, which provides synergistic antifungal activity and helps prevent the development of resistance. Treatment is always administered in a hospital setting under close medical supervision with regular blood monitoring.
Quick Facts: Ancotil (Flucytosine)
Key Takeaways
- Ancotil (flucytosine) is an intravenous antifungal used for serious systemic infections caused by Candida and Cryptococcus neoformans, and is nearly always used in combination with amphotericin B.
- The drug is administered by IV infusion in a hospital setting, typically four times daily over 20–40 minutes, with treatment lasting weeks to months depending on the infection.
- Regular blood monitoring (blood counts, liver and kidney function, drug levels) is essential throughout treatment to detect and prevent serious toxicity.
- Flucytosine must not be used in patients with complete DPD enzyme deficiency, those taking brivudine/sorivudine, or those receiving tegafur/gimeracil/oteracil, as life-threatening toxicity may occur.
- Women of childbearing potential must use effective contraception during treatment and for 6 months after, and the drug is contraindicated during breastfeeding.
What Is Ancotil and What Is It Used For?
Ancotil is the brand name for flucytosine (also called 5-fluorocytosine or 5-FC), a synthetic antifungal agent belonging to the pyrimidine analogue class. Unlike many antifungal medications that target the fungal cell membrane, flucytosine works by interfering with the genetic machinery of fungal cells. Once taken up by the fungal cell via a specific transport protein called cytosine permease, flucytosine is converted into 5-fluorouracil (5-FU) by the enzyme cytosine deaminase. This metabolite disrupts both RNA and DNA synthesis within the fungal cell, ultimately leading to cell death.
Flucytosine has a relatively narrow spectrum of antifungal activity compared to agents such as the azoles or echinocandins. Its primary clinical utility lies in treating infections caused by Candida species (including C. albicans, C. glabrata, and C. tropicalis) and Cryptococcus neoformans. Certain strains of Aspergillus may also show in vitro susceptibility, though clinical evidence for efficacy in aspergillosis is limited.
The most important indication for flucytosine is cryptococcal meningoencephalitis, a life-threatening fungal infection of the brain and its surrounding membranes that predominantly affects immunocompromised patients, particularly those with HIV/AIDS. According to the World Health Organization (WHO) and the Infectious Diseases Society of America (IDSA), the combination of amphotericin B with flucytosine represents the gold standard induction therapy for cryptococcal meningitis. Clinical trials have demonstrated that this combination achieves more rapid fungal clearance from the cerebrospinal fluid compared to amphotericin B alone.
Other clinical indications include systemic candidiasis (invasive Candida infections of the bloodstream and internal organs), Candida endocarditis (fungal infection of the heart valves), and Candida endophthalmitis (fungal infection within the eye). In these settings, flucytosine is valued for its excellent tissue penetration, including the ability to cross the blood-brain barrier and achieve therapeutic concentrations in cerebrospinal fluid (60–90% of serum levels), as well as good penetration into the vitreous humor of the eye and into cardiac vegetations.
One of the key pharmacological advantages of flucytosine is its synergistic interaction with amphotericin B. Amphotericin B creates pores in the fungal cell membrane, which enhances the uptake of flucytosine into the fungal cell, thereby increasing its antifungal effect. This synergy allows for lower doses of amphotericin B to be used, potentially reducing its nephrotoxic effects while maintaining or even improving clinical outcomes.
Resistance to flucytosine develops rapidly when it is used as monotherapy, with resistance rates as high as 30–50% reported during single-agent treatment. Combination with amphotericin B not only provides synergistic killing of fungi but also prevents the emergence of resistant strains. For this reason, flucytosine monotherapy is rarely recommended in modern clinical practice.
What Should You Know Before Taking Ancotil?
Flucytosine is a potent medication that requires careful patient selection and monitoring. Because it is metabolized in part to 5-fluorouracil (the same compound used as a cancer chemotherapy agent), flucytosine carries risks of bone marrow suppression, liver toxicity, and gastrointestinal side effects that must be carefully managed. Understanding who should and should not receive this medication, and what precautions are necessary, is critical for safe treatment.
Contraindications
- You have a known allergy to flucytosine or any of its excipients (sodium chloride, trometamol, hydrochloric acid, water for injections)
- You have a confirmed complete deficiency of dihydropyrimidine dehydrogenase (DPD) — this enzyme is essential for metabolizing 5-fluorouracil, and its absence can lead to life-threatening accumulation of toxic metabolites
- You are currently being treated with brivudine, sorivudine, or similar antiviral agents
- You are receiving tegafur/gimeracil/oteracil (a combination cancer chemotherapy drug) — at least 7 days must elapse after stopping this medication before flucytosine can be started
- You are breastfeeding
Warnings and Precautions
Before starting treatment with Ancotil, it is essential that your healthcare team is aware of your complete medical history. Several conditions require special caution and more intensive monitoring during flucytosine therapy.
Impaired kidney function: Flucytosine is primarily eliminated by the kidneys, with approximately 90% of the drug excreted unchanged in the urine. Patients with reduced kidney function are at significantly higher risk of drug accumulation and toxicity. Dose adjustments are necessary, and serum drug levels must be monitored frequently. Target trough levels should be maintained between 25 and 50 mg/L to balance efficacy and safety.
Impaired liver function: Because flucytosine can cause hepatotoxicity, patients with pre-existing liver disease require close monitoring of liver function tests (including ALT, AST, alkaline phosphatase, and bilirubin) throughout treatment. Treatment may need to be interrupted or discontinued if liver enzymes rise significantly.
Blood disorders: Flucytosine can suppress bone marrow function, leading to decreased production of white blood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia). Patients with pre-existing bone marrow suppression or blood dyscrasias are at particularly high risk. Complete blood counts should be performed at least twice weekly during treatment.
Immunosuppressive therapy: Patients already receiving immunosuppressive medications (such as those following organ transplantation or those with autoimmune conditions) may be at increased risk of bone marrow toxicity when flucytosine is added to their regimen. Enhanced monitoring is required in these patients.
DPD partial deficiency: Even a partial deficiency of the DPD enzyme can increase the risk of severe toxicity from flucytosine. Your doctor may order blood tests (including DPD genotyping or phenotyping) to assess your DPD status before initiating treatment.
Each 250 ml bottle of Ancotil infusion solution contains 792 mg of sodium, equivalent to approximately 40% of the WHO recommended maximum daily intake for adults. This is particularly important for patients on sodium-restricted diets, those with heart failure, or patients with kidney disease. Your healthcare team will factor this sodium load into your overall fluid and electrolyte management plan.
Pregnancy and Breastfeeding
Flucytosine poses significant risks during pregnancy. Animal studies have demonstrated teratogenic effects (the potential to cause birth defects), and the drug's mechanism of action — interfering with nucleic acid synthesis — inherently carries a risk of harm to the developing fetus. Flucytosine should only be used during pregnancy when the infection is life-threatening and no safer alternative exists. If Ancotil is administered during pregnancy, close monitoring of both the mother and the fetus before and after delivery is essential.
Contraception requirements: Women of childbearing potential who receive Ancotil must use effective contraception throughout the duration of treatment and for 6 months after the last dose. Male patients receiving Ancotil, and their female partners of childbearing potential, must use effective contraception during treatment and for 3 months after the last dose. In patients with impaired kidney function, the contraception period should be extended by an additional 2 months due to slower drug clearance.
Ancotil is contraindicated during breastfeeding. It is not known whether flucytosine passes into human breast milk, but given the drug's pharmacological properties and potential for serious adverse effects in the nursing infant, breastfeeding must be discontinued during treatment.
Driving and Operating Machinery
Flucytosine treatment may cause confusion, hallucinations, and drowsiness. These neurological side effects can impair your ability to drive or operate machinery safely. Patients should be advised not to drive or perform tasks requiring alertness until they know how the medication affects them. Given that Ancotil is administered in a hospital setting, this precaution is most relevant during the recovery period and after discharge.
How Does Ancotil Interact with Other Drugs?
Because flucytosine is converted to 5-fluorouracil (5-FU) within the body, any drug that interferes with the metabolism or elimination of 5-FU can dramatically increase the risk of toxicity. Additionally, drugs that independently suppress bone marrow function or affect kidney function can compound the adverse effects of flucytosine. It is critical that your healthcare team has a complete list of all medications you are taking, including prescription drugs, over-the-counter medicines, and herbal supplements.
Major Interactions (Contraindicated)
| Drug | Interaction Type | Clinical Significance |
|---|---|---|
| Brivudine / Sorivudine | Irreversible inhibition of DPD enzyme | Can cause fatal 5-FU toxicity. Absolutely contraindicated. Must wait at least 4 weeks after stopping brivudine before starting flucytosine. |
| Tegafur / Gimeracil / Oteracil | Inhibition of 5-FU metabolism | Massively increased 5-FU levels and risk of fatal toxicity. Must wait at least 7 days after discontinuation before starting flucytosine. |
Significant Interactions (Require Monitoring)
| Drug | Interaction Type | Management |
|---|---|---|
| Amphotericin B | Synergistic antifungal activity; amphotericin B enhances flucytosine uptake. However, amphotericin B-induced nephrotoxicity can impair flucytosine clearance. | Intentional combination. Monitor renal function closely and adjust flucytosine dose based on creatinine clearance and serum drug levels. Do not co-administer in the same IV line (precipitation occurs). |
| Cytarabine (Ara-C) | Competitive inhibition — cytarabine can reduce the antifungal efficacy of flucytosine | Avoid concurrent use if possible. If both drugs are necessary, monitor flucytosine serum levels and clinical response closely. |
| Phenytoin | Flucytosine may alter phenytoin metabolism, potentially increasing phenytoin levels | Monitor phenytoin serum levels and adjust dose as needed. Watch for signs of phenytoin toxicity (nystagmus, ataxia, drowsiness). |
| Myelosuppressive agents (e.g., chemotherapy, immunosuppressants) | Additive bone marrow suppression | Increased risk of severe neutropenia, thrombocytopenia, and anemia. Perform frequent complete blood counts. Dose adjustment may be required. |
| Nephrotoxic drugs (e.g., aminoglycosides, vancomycin, NSAIDs) | Reduced renal clearance of flucytosine leading to drug accumulation | Monitor renal function and flucytosine serum levels. Adjust flucytosine dose according to creatinine clearance. |
Ancotil infusion solution can be administered together with 0.9% sodium chloride solution, 5% glucose solution, or sodium chloride/glucose combination infusion solutions. However, it must not be mixed with or administered simultaneously in the same IV line as amphotericin B, as precipitation will occur. If the same infusion set is used for both drugs, the line must be thoroughly flushed with glucose solution between infusions.
What Is the Correct Dosage of Ancotil?
Ancotil is always administered in a hospital setting by qualified healthcare professionals. The dosage is individualized based on the patient's body weight, the type and severity of the fungal infection, kidney function, and serum drug level monitoring. The treating physician determines the dose, duration, and any necessary adjustments.
Adults
Standard Adult Dosage
The usual dose is 100–200 mg/kg body weight per day, divided into four equal doses administered at 6-hour intervals. Each dose is given by intravenous infusion over 20 to 40 minutes.
For a 70 kg adult, this equates to approximately 1,750–3,500 mg (7–14 ml of the 10 mg/ml solution) per dose, given four times daily.
Therapeutic drug monitoring: Target trough serum flucytosine levels should be maintained between 25–50 mg/L. Peak levels above 100 mg/L are associated with increased toxicity, particularly bone marrow suppression.
Treatment duration varies considerably depending on the type and location of the fungal infection. For cryptococcal meningitis, the induction phase with amphotericin B plus flucytosine typically lasts 2 weeks, followed by consolidation therapy with fluconazole. For other deep-seated fungal infections such as Candida endocarditis or osteomyelitis, treatment may extend to several months.
Patients with Kidney Impairment
Renal Dose Adjustment
Because flucytosine is primarily eliminated by the kidneys, dose reduction is critical in patients with impaired renal function. Dose adjustments are guided by creatinine clearance (CrCl) and serum flucytosine levels:
- CrCl > 40 ml/min: Standard dose (100–200 mg/kg/day in 4 divided doses)
- CrCl 20–40 ml/min: Reduce dose and/or extend dosing interval. Frequent drug level monitoring is essential.
- CrCl < 20 ml/min: Significant dose reduction required. Individual doses may be given every 12–24 hours rather than every 6 hours. Serum levels must be checked before each dose.
- Haemodialysis patients: Flucytosine is efficiently removed by dialysis. A supplemental dose should be given after each dialysis session, guided by post-dialysis drug levels.
Children
Paediatric Dosage
Clinical data on the use of flucytosine in children are limited, and there are no established paediatric dosing guidelines with the same level of evidence as for adults. When prescribed for children, the dose is generally based on body weight using the same mg/kg range as for adults, with the specific dose determined by the treating physician.
Special caution in neonates and young infants: Very young children have delayed renal excretion of flucytosine, which can lead to unexpectedly high drug levels even at standard weight-based doses. Serum flucytosine concentrations must be measured regularly throughout treatment in all paediatric patients, with particular vigilance in neonates and infants.
Elderly Patients
Older adults frequently have reduced kidney function, even when serum creatinine levels appear within normal range. Age-related decline in glomerular filtration rate means that elderly patients may require lower doses and more frequent drug level monitoring. Creatinine clearance (rather than serum creatinine alone) should be used to guide dosing.
Missed Dose
Since Ancotil is administered in a hospital setting by healthcare professionals, missed doses are unlikely. If a dose is missed, the healthcare team will determine whether to administer the dose as soon as possible or to adjust the dosing schedule. Patients should not receive a double dose to compensate for a missed infusion.
Overdose
Overdose with flucytosine may lead to severe bone marrow suppression, hepatotoxicity, and gastrointestinal toxicity. Because the drug is administered in a controlled hospital setting, overdose is uncommon but can occur due to accumulation in patients with deteriorating kidney function. Management includes immediate discontinuation of the drug, supportive care, and haemodialysis, which effectively removes flucytosine from the bloodstream. If you are concerned that too much Ancotil has been administered, alert your healthcare team immediately.
What Are the Side Effects of Ancotil?
Like all medicines, flucytosine can cause side effects, although not everybody experiences them. Many of the adverse effects of flucytosine are related to its conversion to 5-fluorouracil and are dose-dependent, meaning they are more likely to occur when serum drug levels exceed the recommended therapeutic range (above 100 mg/L). This is why regular drug level monitoring is so important during treatment.
The risk of side effects is higher in patients with impaired kidney function (due to drug accumulation), those receiving concurrent myelosuppressive therapy, and those with pre-existing liver disease. Most side effects occur during the first two to three weeks of treatment, and many resolve upon dose reduction or discontinuation of the drug.
Common
May affect up to 1 in 10 patients
- Changes in blood cell counts (decreased white blood cells, red blood cells, or platelets)
- Nausea and vomiting
- Diarrhea
- Abnormal liver function tests (elevated transaminases)
- Impaired liver function
Uncommon
May affect up to 1 in 100 patients
- Confusion and disorientation
- Skin rash
Rare
May affect up to 1 in 1,000 patients
- Bone marrow failure (agranulocytosis, pancytopenia)
- Severe skin reactions (toxic epidermal necrolysis — widespread skin peeling and mucous membrane damage)
- Hallucinations
- Seizures (convulsions)
- Peripheral neuropathy (tingling, numbness in hands and feet)
- Drowsiness and fatigue
- Cardiac damage (myocardial toxicity)
- Intestinal damage (ulceration, perforation)
- Severe liver disease (hepatic necrosis)
Contact your healthcare team immediately if you experience any of the following: unexplained bruising or bleeding, signs of infection (fever, sore throat, mouth ulcers), severe skin rash or skin peeling, chest pain or palpitations, severe abdominal pain, confusion or hallucinations, or seizures. These may indicate serious side effects requiring urgent medical intervention.
The relationship between serum flucytosine levels and toxicity is well established. Peak levels above 100 mg/L are associated with a significantly increased risk of bone marrow suppression and hepatotoxicity. This dose-dependent toxicity underscores the critical importance of therapeutic drug monitoring throughout the course of treatment. Most centres aim for trough levels between 25 and 50 mg/L, which provides an optimal balance of efficacy and safety.
In patients receiving combination therapy with amphotericin B, the nephrotoxic effects of amphotericin B can reduce flucytosine clearance, leading to rising serum levels and an increased risk of toxicity. Close coordination between monitoring of kidney function, amphotericin B dosing, and flucytosine levels is therefore essential.
How Should You Store Ancotil?
Proper storage of Ancotil is critical to maintaining the drug's safety and efficacy. As a hospital-administered intravenous medication, storage is primarily the responsibility of the pharmacy and ward staff, but patients and caregivers should be aware of these requirements.
- Temperature: Store at 18–25°C (64–77°F). This narrow temperature range is important because of the drug's physical and chemical properties.
- Below 18°C: Flucytosine may crystallize out of solution (precipitation). If this occurs, the solution must not be used.
- Above 25°C: The drug may undergo chemical degradation, converting to 5-fluorouracil, which would change the drug's toxicity profile.
- Expiry date: Do not use after the date printed on the carton (marked EXP). The expiry date refers to the last day of that month.
- Keep out of sight and reach of children.
- Disposal: Unused medication should not be disposed of via wastewater or household waste. Healthcare facilities follow established protocols for safe disposal of pharmaceutical waste to protect the environment.
What Does Ancotil Contain?
Understanding the full composition of Ancotil is important for identifying potential allergies to excipients and for calculating the sodium load from infusions, which is clinically relevant for patients on fluid or sodium-restricted regimens.
Active Ingredient
- Flucytosine 10 mg/ml (each 250 ml bottle contains 2,500 mg of flucytosine)
Inactive Ingredients (Excipients)
- Sodium chloride — provides isotonicity; contributes 792 mg sodium per bottle (approximately 40% of the recommended daily adult intake)
- Trometamol (tromethamine) — buffer to maintain pH stability
- Hydrochloric acid — pH adjustment
- Water for injections — solvent
Packaging
Ancotil is supplied as a clear, colourless to slightly yellow solution for infusion in 250 ml glass bottles. Each carton contains 5 bottles. The solution should be visually inspected before use — do not use if it appears cloudy, discoloured, or contains visible particles.
The marketing authorisation holder is Viatris (formerly Mylan/MEDA Pharmaceuticals). Ancotil is also available in some markets under the brand name Ancobon (oral capsule formulation, not available in all countries).
Frequently Asked Questions About Ancotil
Ancotil (flucytosine) is an intravenous antifungal medication used to treat serious systemic fungal infections. Its primary indications include cryptococcal meningitis (a life-threatening fungal infection of the brain), systemic candidiasis (invasive Candida bloodstream infections), Candida endocarditis, and Candida infections of the eye (endophthalmitis). It is almost always used in combination with amphotericin B, as the two drugs work synergistically and combination therapy helps prevent the development of drug resistance.
Ancotil is given as an intravenous infusion (drip) in a hospital setting, always under the supervision of healthcare professionals. The infusion is typically given four times a day at six-hour intervals, with each infusion lasting 20 to 40 minutes. It cannot be taken by mouth (as an infusion formulation) and must be administered directly into a vein. Treatment duration varies from a few weeks for cryptococcal meningitis induction therapy to several months for deep-seated infections.
The most common side effects include changes in blood cell counts (low white cells, red cells, or platelets), nausea, vomiting, diarrhea, and abnormal liver function tests. These typically occur during the first two to three weeks of treatment and are often related to high drug levels in the blood. Regular blood tests are performed to detect these effects early. Less common effects include confusion, skin rash, and rarely, severe reactions such as bone marrow failure, hallucinations, seizures, and liver damage.
Flucytosine should only be used during pregnancy when the infection is life-threatening and no safer alternative is available, as it carries a risk of fetal harm. Women of childbearing potential must use effective contraception during treatment and for six months after the last dose. Male patients and their female partners should also use contraception during treatment and for three months afterward. Breastfeeding is completely contraindicated during Ancotil therapy.
Flucytosine and amphotericin B are used together because they produce a synergistic effect — meaning their combined antifungal action is greater than the sum of their individual effects. Amphotericin B creates pores in the fungal cell membrane, which enhances the entry of flucytosine into the fungal cell. Additionally, using flucytosine alone leads to rapid development of drug resistance (as high as 30–50% during monotherapy), whereas combination therapy significantly reduces this risk. The WHO and IDSA both recommend this combination as the gold standard treatment for cryptococcal meningitis.
Several blood tests are required before and during treatment. These include: complete blood counts (to monitor white cells, red cells, and platelets for signs of bone marrow suppression), liver function tests (ALT, AST, bilirubin, alkaline phosphatase), kidney function tests (serum creatinine, blood urea nitrogen), and serum flucytosine drug levels. Drug levels are particularly important — trough levels should be maintained between 25–50 mg/L, and peak levels above 100 mg/L are associated with increased toxicity. Blood tests are typically performed at least twice weekly during the course of treatment.
References
- World Health Organization. Guidelines for the Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children. Geneva: WHO; 2018.
- Perfect JR, Dismukes WE, Dromer F, et al. Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2010;50(3):291–322.
- Day JN, Chau TTH, Wolbers M, et al. Combination Antifungal Therapy for Cryptococcal Meningitis. New England Journal of Medicine. 2013;368(14):1291–1302.
- European Medicines Agency. Ancotil (Flucytosine) Summary of Product Characteristics. EMA; 2023.
- British National Formulary. Flucytosine Monograph. BNF; 2024.
- Vermes A, Guchelaar H-J, Dankert J. Flucytosine: A Review of its Pharmacology, Clinical Indications, Pharmacokinetics, Toxicity and Drug Interactions. Journal of Antimicrobial Chemotherapy. 2000;46(2):171–179.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2016;62(4):e1–e50.
- Molloy SF, Kanyama C, Heyderman RS, et al. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. New England Journal of Medicine. 2018;378(11):1004–1017.
- World Health Organization. WHO Model List of Essential Medicines — 23rd List. Geneva: WHO; 2023.
- Francis P, Walsh TJ. Evolving Role of Flucytosine in Immunocompromised Patients: New Insights into Safety, Pharmacokinetics, and Antifungal Therapy. Clinical Infectious Diseases. 1992;15(6):1003–1018.
Editorial Team
This article was written by the iMedic Medical Editorial Team, comprising licensed specialist physicians in clinical pharmacology, infectious disease medicine, and mycology. All content is independently reviewed and follows the GRADE evidence framework.
iMedic Medical Editorial Team — Specialists in Clinical Pharmacology and Infectious Disease
iMedic Medical Review Board — Independent expert panel following WHO, EMA, FDA and IDSA guidelines
Level 1A — Based on systematic reviews, randomized controlled trials, and international clinical practice guidelines
No pharmaceutical company funding or sponsorship. All content is independent and free from commercial influence.