Antifungal Drug Flucytosine (Ancobon) PDF

Overview of the Drug Class **Prototype: flucytosine (Ancobon) ** - **Category**: Pyrimidine Analog Antifungal Agent  - **Primary Function**: Flucytosine is a narrow-spectrum antifungal agent. Flucytosine fungicidal activity is highest against susceptible strains of Candida and C. neof...

Overview of the Drug Class **Prototype: flucytosine (Ancobon) ** - **Category**: Pyrimidine Analog Antifungal Agent  - **Primary Function**: Flucytosine is a narrow-spectrum antifungal agent. Flucytosine fungicidal activity is highest against susceptible strains of Candida and C. neoformans. Most other fungi are resistant to flucytosine.  - **Unique Features**: Flucytosine is almost always used in combination with amphotericin b due to commonly developed resistance.   Mechanism of Action - Flucytosine is taken up by fungal cells and converted to the powerful antimetabolite 5-fluorouracil (5-FU). These metabolites disrupt fungal DNA and RNA synthesis. Flucytosine is relatively harmless to humans because mammalian cells lack cytosine deaminase (an enzyme that converts flucytosine to 5-FU).  **Image Title: Mechanism of antifungal drugs** - Cell wall - Cell membrane - DNA - Proteins - Echinocandins, triterpenoids - Azoles, polyenes, allylamines - 5-fluorocytosine - Sordarins Indications and Therapeutic Uses - **Systemic Fungal Infections**: Flucytosine is indicated for treating candidiasis and cryptococcosis. In treating severe infections such as systemic candidiasis and cryptococcal meningitis, flucytosine should be combined with amphotericin b. Side Effects and Adverse Reactions **Side Effect** **Description** --------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Hematologic Effects Bone marrow suppression is the most severe complication of therapy. This includes the risk of reversible neutropenia or thrombocytopenia and a rare risk of fatal agranulocytosis. Hepatotoxicity Mild and reversible hepatic dysfunction is common with flucytosine use, but severe hepatic injury is rare. Precautions and Contraindications **Precautions** - Use caution in clients with renal impairment due to this drug's prolonged half-life. Dosage must be reduced in clients with renal insufficiency.  - Use caution in clients with hematologic disorders and bone marrow suppression.  **Black Box Warning** - Use extreme caution in clients with renal impairment due to its long half-life.  Drug Interactions - **\[Amphotericin b\]** can cause nephrotoxicity, and although it is frequently combined with flucytosine, flucytosine excretion necessitates adequate **\[kidney function\]**, without which flucytosine **\[toxicity\]** can occur.   - Since flucytosine can inhibit CYP450 enzymes, concomitant use of **\[cisapride, pimozide, dofetilide, or quinidine\]** can raise their plasma levels and increase the risk of fatal dysrhythmias.  Dosing, Administration, & Client Teaching **Dosing** - Dosing varies based on the condition, severity, and client response.  - Check drug dosing guidelines for individualized dosing.  - Often administered combined with amphotericin b.  - Flucytosine is available in 250 mg and 500 mg capsules for oral administration.  - Dosing for clients with normal renal function is 50 -- 150 mg/kg/day administered in four divided doses at 6-hour intervals.    - Dosage must be reduced for clients with renal insufficiency.  **Administration** - Oral administration. **Client Teaching** - Educate clients to monitor for hematologic or hepatic adverse effects.  Labs to Monitor **Basic Metabolic Panel (BMP)** - Monitor renal function during therapy, including BUN/Creatine and Creatine Clearance.  **Complete Blood Count (CBC)** Monitor platelet and leukocyte counts weekly.  **Liver Function Tests (LFTs)** - Monitor LFTs weekly to monitor for hepatotoxicity.  **Serum Drug Levels** - Monitor flucytosine levels in clients concomitantly using amphotericin b.