Flucytosine is the name given to a pyrimidine antifungal drug. The drug is used for the therapy of fungal diseases.
What is flucytosine?
In medicine, flucytosine is also known as 5-fluorocytosine, 5-FC, or flucytosinum. This refers to a heterocyclic organic compound that has a pyrimidine backbone. The active ingredient is considered a derivative of the nucleic base cytosine. Flucytosine is used as a systemic antifungal agent for various fungal diseases (mycoses) under the trade name Ancotil. Flucytosine is considered a so-called prodrug. This is understood to mean a little active drug that develops into an active drug in the course of metabolization (metabolization).
Pharmacological action
Flucytosine exhibits a chemical relationship of the heterocyclic organic compound pyrimidine. The pyrimidine forms the basis for building blocks from the genetic material (DNA) as well as the transporting substance (RNA), which has a share in the production of proteins (proteins). The uptake of flucytosine in fungi takes place through a special enzyme. In the further course, the active substance is converted into 5-fluorouracil, which is incorporated into the cell RNA. At this point, the substance can exert its effect as a “false building block” and ensures that the production of protein in the fungi proceeds incorrectly. Furthermore, the antimycotic is responsible for inhibiting the production of genetic material. Flucytosine achieves a growth-inhibiting and killing effect in yeast infections such as chromomycosis and cryptococcosis. In Aspergillus fungi, the effect is limited to inhibition of fungal growth. In principle, flucytosine can act only in the cells of fungi. In humans and mammals, on the other hand, an enzyme that transmits the active ingredient into the body’s cells is missing. The half-life of flucytosine is three to five hours. Elimination of the antifungal drug from the body occurs 90 percent through the kidneys.
Medicinal use and application
Flucytosine is suitable for the treatment of fungal diseases in adults, children, and babies. It is used to combat fungal genera such as cryptococcus and candida, as well as fungi that cause chromoblastomycosis. The most frequent areas of application of the antifungal drug are systemic candidiasis, in which the entire body, urinary tract and blood are attacked by fungi, causing scattered infections. The yeast fungi invade the organism of the affected person from the outside. Particular danger exists for high-risk patients whose immune system is weakened. In the worst case, the fungal infection even takes a fatal outcome. Other indications for flucytosine are meningitis caused by cryptococci (cryptococcal meningitis) and aspergillosis. In the case of therapy with flucytosine alone, physicians always administer the antifungal agent together with the agent amphotericin B. This allows resistance to develop. In this way, resistance of the pathogens to the active substance can be avoided. If the patient suffers from cryptococcal meningitis and reacts intolerantly to amphotericin B, a combination with fluconazole can take place as an alternative. Flucytosine is administered either as an infusion solution or orally. The recommended amount of the active ingredient is 150 milligrams, which is distributed in four doses. Tolerability of the antifungal drug is considered good.
Risks and side effects
By taking flucytosine, the occurrence of side effects is possible, but they do not automatically occur in every patient. The most common are changes in the blood count, such as a deficiency of white blood cells, platelets, and granulocytes, anemia, nausea, vomiting, diarrhea, a temporary increase in liver enzymes, and liver dysfunction. In addition, headache, dizziness, weakness, dry mouth, fatigue, drowsiness, breathing problems, chest pain, abdominal pain, hives, skin rash, itching, fever, concentration problems or confusion are conceivable. In rare cases, Lyell syndrome, movement disorders, convulsions, psychosis, hearing loss, and hallucinations occur. Even life-threatening death of liver cells is within the realm of possibility. Administration of flucytosine must not take place if the patient suffers from hypersensitivity to the antifungal drug.The same applies if the patient is undergoing therapy with antiviral agents at the same time, as they have an inhibitory effect on the metabolism of flucytosine, which in turn can lead to poisoning. These drugs include sorivudine, ganciclovir, brivudine, and valganciclovir. A thorough weighing of risks and benefits by the physician must be done in patients who are being treated with immunosuppressants or cytostatic drugs, who suffer from liver or kidney dysfunction, or who are deficient in the enzyme dihydropyrimidine dehydrogenase. Due to the enzyme deficiency, flucytosine cannot be properly broken down. Due to the partial degradation of flucytosine into 5-fluorouracil, changes in the human genome are possible, as a result of which malformations may occur. For this reason, women of childbearing potential must use a reliable method of contraception during treatment. Protective measures also apply to males treated with the antifungal agent. Flucytosine must not be used under any circumstances during pregnancy, as it can penetrate the placenta and harm or even kill the unborn child. Administration during breastfeeding is also not recommended. The simultaneous administration of flucytosine and certain other drugs may result in interactions. This is especially true for substances that may have a negative effect on the filtration properties of the kidney. In this case, the physician must closely monitor renal functions. A weakening of the effect of the antifungal drug is attributed to the cytostatic drug cytarabine. In principle, concomitant administration of flucytosine and cytostatic drugs may result in a deficiency of platelets (thrombocytes) and white blood cells (leukocytes).
