flucytosine

Action and Spectrum

Actions and Spectrum: 

flucytosine is an antifungal medication that disrupts DNA and RNA synthesis within fungal cells. It is primarily used to treat systemic fungal infections, particularly those caused by Candida and Cryptococcus species. 

The spectrum of activity of flucytosine is limited to fungal species, as it is not effective against bacteria, viruses, or other types of microorganisms. flucytosine is not used to treat superficial fungal infections such as athlete’s foot or ringworm. 

The action of flucytosine is to inhibit the synthesis of fungal nucleic acids by interfering with the fungal-specific enzyme cytosine deaminase. This results in the inhibition of DNA and RNA synthesis, ultimately leading to the death of the fungal cell. 

Drug Interaction

Adverse Reaction

Frequency not Defined 

Confusion 

Headache 

Drowsiness 

Psychosis 

Hallucinations 

Dizziness 

Parkinsonism 

Ataxia 

Photosensitivity 

Pruritus 

Sedation 

Rash 

Urticaria 

Temporary growth failure 

Nausea 

Vomiting 

Hypoglycemia 

Hypokalemia 

Diarrhea 

Abdominal pain 

Loss of appetite 

Leukopenia 

Thrombocytopenia 

Increased level of liver enzymes 

Bone marrow suppression 

Anemia 

Hepatitis 

Azotemia 

Weakness 

Hearing loss 

Peripheral neuropathy 

Paresthesia 

Anaphylaxis 

Renal failure 

Respiratory arrest 

Black Box Warning

Black Box Warning: 

Use cautiously in patients with renal impairment 

Monitor renal, hepatic, and hematologic function 

Before administration, review the instructions thoroughly 

Contraindication / Caution

Contraindication/Caution: 

flucytosine is an antifungal medication that disrupts DNA and RNA synthesis within fungal cells. It is primarily used to treat systemic fungal infections, particularly those caused by Candida and Cryptococcus species. 

The spectrum of activity of flucytosine is limited to fungal species, as it is not effective against bacteria, viruses, or other types of microorganisms. flucytosine is not used to treat superficial fungal infections such as athlete’s foot or ringworm. 

The action of flucytosine is to inhibit the synthesis of fungal nucleic acids by interfering with the fungal-specific enzyme cytosine deaminase. This results in the inhibition of DNA and RNA synthesis, ultimately leading to the death of the fungal cell. 

flucytosine is usually administered orally and is often used with other antifungal medications such as amphotericin B or fluconazole. It is important to note that flucytosine can have significant side effects, including bone marrow suppression, gastrointestinal disturbances, and liver toxicity, so it should only be used under close medical supervision. 

Pregnancy / Lactation

Pregnancy consideration:  

Administer this drug during pregnancy only if the potential benefits outweigh the potential fetal risks. 

Breastfeeding warnings:  

Unknown  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology

Pharmacology: 

flucytosine is an antifungal medication that belongs to the class of antimetabolites. It works by disrupting the synthesis of DNA and RNA within fungal cells, ultimately leading to the death of the fungal cell. 

flucytosine is taken up by fungal cells through a specific transporter protein and is converted to its active form, 5-fluorouracil (5-FU), by the enzyme cytosine deaminase. 5-FU then interferes with the synthesis of fungal nucleic acids by inhibiting the enzyme thymidylate synthase, which is necessary for the synthesis of DNA. It also interferes with RNA synthesis by inhibiting the enzyme RNA synthase. 

flucytosine has a narrow spectrum of activity, primarily targeting fungal species such as Candida and Cryptococcus. It is ineffective against bacteria, viruses, or other microorganisms. 

Pharmacodynamics: 

The pharmacodynamics of flucytosine involves the drug’s effects on the fungal cells it targets. flucytosine is an antimetabolite that is selectively taken up by fungal cells and converted to its active form, 5-fluorouracil (5-FU), by the enzyme cytosine deaminase. 

Once inside the fungal cell, 5-FU interferes with the synthesis of nucleic acids by inhibiting the enzyme thymidylate synthase, which is necessary for the synthesis of DNA. It also interferes with RNA synthesis by inhibiting the enzyme RNA synthase. These actions ultimately lead to the death of the fungal cell. 

flucytosine has a narrow spectrum of activity, primarily targeting fungal species such as Candida and Cryptococcus. It is ineffective against bacteria, viruses, or other microorganisms. 

The efficacy of flucytosine depends on several factors, including the concentration of the drug at the site of infection, the susceptibility of the fungal species to the drug, and the duration of treatment. flucytosine is often used with other antifungal medications, such as amphotericin B or fluconazole, to increase its efficacy and reduce the risk of resistance. 

Pharmacokinetics: 

Absorption 

The drug is 75-90% absorbed 

Distribution 

The drug is distributed into the cerebrospinal fluid, joints, peritoneal fluid, aqueous humor, & bronchial secretions. 

Protein Bound is 2-4% 

The half-life elimination is 3-8 hours; for anuria, it is up to 200 hours; and for end-stage renal disease, it is 75-200 hours. 

Peak Plasma Time: 2-6 hours 

Metabolism 

The drug undergoes minimum hepatic metabolism  

Elimination and Excretion 

The drug is excreted 75-90% unchanged in the urine

Adminstartion

Administration: 

flucytosine is typically administered orally, as a capsule or tablet, with or without food. The usual recommended dose for adults is 25-50 mg/kg daily, given in 4 divided doses. The maximum daily dose should be at most 150 mg/kg. 

The dose of flucytosine may need to be adjusted in patients with renal impairment, as the kidneys primarily excrete the drug. The dosage should be reduced in patients with moderate to severe renal impairment to avoid drug accumulation and potential toxicity. 

flucytosine should be used cautiously in patients with hepatic impairment or pre-existing liver disease, as it can cause liver toxicity. Liver function tests should be monitored during treatment with flucytosine, and the drug should be discontinued if significant liver dysfunction occurs. 

flucytosine should be used cautiously in pregnant and breastfeeding women, as the drug’s safety during pregnancy and lactation has not been established. The potential benefits of treatment must be weighed against the potential risks to the fetus or infant. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: flucytosine  

Pronounced: floo-SYE-toe-seen  

Why do we use flucytosine? 

flucytosine is used to treat fungal infections, particularly those caused by Candida and Cryptococcus species. It is often used with other antifungal medications, such as amphotericin B or fluconazole, to increase its efficacy and reduce the risk of resistance. 

flucytosine is particularly useful in treating systemic fungal infections, such as cryptococcal meningitis, as it can penetrate the blood-brain barrier and achieve therapeutic concentrations in the central nervous system. It is also effective against Candida bloodstream infections, urinary tract infections, and other organs. 

In addition to its antifungal properties, flucytosine has also been studied for its potential anticancer effects. However, its use as an anticancer agent is currently limited, and more research is needed to determine its efficacy and safety in this context.