Ancobon 500mg Capsules
WARNING: If you have kidney disease, talk to your doctor.Your doctor must closely watch your blood cells and kidney and liver function. @ COMMON USES: It is used to treat fungal infections.
Drug Class
Antifungal
Pharmacologic Class
Antimetabolite Antifungal
Pregnancy Category
C
FDA Approved
Aug 1971
DEA Schedule
Not Controlled
Overview
What is this medicine?
Flucytosine is an antifungal medicine used to treat serious fungal infections, especially those caused by yeast-like fungi. It works by stopping the growth of the fungus. It is often used with another antifungal medicine called amphotericin B.
How to Use This Medicine
Taking Your Medication
To take this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To minimize stomach upset or nausea, consider taking a few capsules at a time over a 15-minute period.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry location, avoiding the bathroom. Keep all medications in a safe place, out of reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, consult with your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses.
To take this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed by your doctor or healthcare provider, even if you start to feel better.
To minimize stomach upset or nausea, consider taking a few capsules at a time over a 15-minute period.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry location, avoiding the bathroom. Keep all medications in a safe place, out of reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, consult with your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take the capsules with food to help reduce nausea and vomiting.
- Take doses exactly as prescribed, usually every 6 hours, to maintain steady levels of the medicine in your body.
- Do not miss doses. If you miss a dose, take it as soon as you remember, unless it's almost time for your next dose. Do not double doses.
- Complete the full course of treatment, even if you start feeling better, to prevent the infection from returning.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
100 to 150 mg/kg/day orally in divided doses every 6 hours
Dose Range:
100 - 150 mg
Condition-Specific Dosing:
Cryptococcal Meningitis:
100 mg/kg/day in divided doses every 6 hours, often in combination with amphotericin B.
Severe Candidiasis:
100 to 150 mg/kg/day in divided doses every 6 hours.
Pediatric Dosing
Neonatal:
Not established (limited data, use with extreme caution and close monitoring)
Infant:
50 to 150 mg/kg/day orally in divided doses every 6 hours (based on limited data, similar to adult dosing, but requires careful monitoring)
Child:
50 to 150 mg/kg/day orally in divided doses every 6 hours
Adolescent:
100 to 150 mg/kg/day orally in divided doses every 6 hours
Dose Adjustments
Renal Impairment:
Mild:
CrCl > 40 mL/min: No adjustment needed. Administer standard dose every 6 hours.
Moderate:
CrCl 20-40 mL/min: Administer standard dose every 12 hours.
Severe:
CrCl 10-20 mL/min: Administer standard dose every 24 hours. CrCl < 10 mL/min: Administer standard dose every 24-48 hours or based on serum levels.
Dialysis:
Hemodialysis: Administer a single dose after each dialysis session. Peritoneal Dialysis: Dose adjustment required, often 25-50 mg/kg once daily or based on serum levels.
Confidence:
High
Hepatic Impairment:
Mild:
No specific adjustment recommended, but monitor liver function closely.
Moderate:
No specific adjustment recommended, but monitor liver function closely.
Severe:
No specific adjustment recommended, but monitor liver function closely.
Confidence:
Medium
Pharmacology
Mechanism of Action
Flucytosine is an antifungal agent that is converted to 5-fluorouracil (5-FU) inside susceptible fungal cells by the enzyme cytosine deaminase. 5-FU is then metabolized to 5-fluorouridine triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine monophosphate (FdUMP). FUTP is incorporated into fungal RNA, disrupting protein synthesis, while FdUMP inhibits thymidylate synthetase, thereby interfering with fungal DNA synthesis. This dual mechanism leads to fungistatic or fungicidal effects depending on concentration and organism.
Pharmacokinetics
Absorption:
Bioavailability:
80-90%
Tmax:
2-6 hours
FoodEffect:
Minimal effect on absorption; can be taken with food to reduce gastrointestinal upset.
Distribution:
Vd:
0.6-0.7 L/kg
ProteinBinding:
<5%
CnssPenetration:
Yes (achieves therapeutic concentrations in CSF, aqueous humor, joint fluid, and peritoneal fluid)
Elimination:
HalfLife:
3-6 hours (normal renal function); significantly prolonged in renal impairment (up to 200 hours in anuric patients)
Clearance:
Primarily renal clearance, proportional to creatinine clearance.
ExcretionRoute:
Renal (glomerular filtration)
Unchanged:
Approximately 90% of the dose is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Variable, depends on fungal burden and susceptibility. Clinical improvement typically seen within days to weeks.
PeakEffect:
Not directly applicable as it's an antimicrobial; peak serum concentrations are achieved within 2-6 hours.
DurationOfAction:
Dependent on dosing interval and half-life; maintained by q6h dosing.
Confidence:
High
Safety & Warnings
BLACK BOX WARNING
WARNING: Flucytosine is a highly potent antineoplastic-like compound. It is essential to monitor hematologic, renal, and hepatic status frequently during therapy. Severe hematologic toxicity (bone marrow depression) may occur. This toxicity is more likely to occur in patients with impaired renal function, pre-existing bone marrow depression, or in those receiving concomitant myelosuppressive drugs. Fatalities have occurred.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ Abnormal heartbeat
Signs of low blood sugar, such as:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Rapid heartbeat
+ Confusion
+ Hunger
+ Sweating
Chest pain or pressure
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Confusion
Hallucinations (seeing or hearing things that are not there)
Seizures
Mood changes
Mouth irritation or mouth sores
Hearing loss
Changes in balance
Abnormal burning, numbness, or tingling sensations
Shakiness, difficulty moving, or stiffness
Severe and potentially life-threatening liver problems, characterized by:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to consult your doctor if you notice any of the following:
Drowsiness
Dry mouth
Stomach pain or diarrhea
Nausea or vomiting
Decreased appetite
Headache
Fatigue or weakness
If you experience any of these side effects or any other unusual symptoms, contact your doctor for guidance. They can help you manage your symptoms and provide advice on how to proceed.
Reporting Side Effects
If you have questions or concerns about side effects, you can contact your doctor or report them to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ Abnormal heartbeat
Signs of low blood sugar, such as:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Rapid heartbeat
+ Confusion
+ Hunger
+ Sweating
Chest pain or pressure
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Confusion
Hallucinations (seeing or hearing things that are not there)
Seizures
Mood changes
Mouth irritation or mouth sores
Hearing loss
Changes in balance
Abnormal burning, numbness, or tingling sensations
Shakiness, difficulty moving, or stiffness
Severe and potentially life-threatening liver problems, characterized by:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it is essential to consult your doctor if you notice any of the following:
Drowsiness
Dry mouth
Stomach pain or diarrhea
Nausea or vomiting
Decreased appetite
Headache
Fatigue or weakness
If you experience any of these side effects or any other unusual symptoms, contact your doctor for guidance. They can help you manage your symptoms and provide advice on how to proceed.
Reporting Side Effects
If you have questions or concerns about side effects, you can contact your doctor or report them to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Unusual bleeding or bruising
- Fever, chills, or sore throat (signs of infection due to low white blood cells)
- Unusual tiredness or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Skin rash or itching
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have a dihydropyrimidine dehydrogenase (DPD) deficiency, a condition that affects the body's ability to break down certain medications.
This is not an exhaustive list of all potential interactions with this medication. Therefore, it is crucial to discuss all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Health problems
with your doctor and pharmacist to ensure safe use. Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to confirm it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have a dihydropyrimidine dehydrogenase (DPD) deficiency, a condition that affects the body's ability to break down certain medications.
This is not an exhaustive list of all potential interactions with this medication. Therefore, it is crucial to discuss all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Health problems
with your doctor and pharmacist to ensure safe use. Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to confirm it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to discuss any concerns or questions with your doctor.
This medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
One of the potential risks associated with this medication is that it may impair the bone marrow's ability to produce essential blood cells, leading to severe and potentially life-threatening bleeding problems or infections. If you experience any symptoms of infection, such as fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that does not heal, or if you notice any bruising or bleeding, or feel extremely tired or weak, notify your doctor immediately.
As this medication may increase your risk of bleeding, it is essential to take precautions to avoid injury. Use a soft-bristled toothbrush and an electric razor to minimize the risk of bleeding.
Additionally, you may be more susceptible to infections while taking this medication. To reduce this risk, wash your hands frequently and avoid close contact with people who have infections, colds, or flu.
This medication may also increase your sensitivity to the sun, making you more prone to sunburn. Take necessary precautions when spending time outdoors, and inform your doctor if you experience any unusual sunburn or sensitivity.
Do not take this medication for longer than prescribed, as this may increase the risk of developing a secondary infection.
If you are pregnant, planning to become pregnant, or breastfeeding, it is essential to discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
This medication may interfere with certain laboratory tests, so it is crucial to notify all your healthcare providers and laboratory personnel that you are taking this drug.
One of the potential risks associated with this medication is that it may impair the bone marrow's ability to produce essential blood cells, leading to severe and potentially life-threatening bleeding problems or infections. If you experience any symptoms of infection, such as fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that does not heal, or if you notice any bruising or bleeding, or feel extremely tired or weak, notify your doctor immediately.
As this medication may increase your risk of bleeding, it is essential to take precautions to avoid injury. Use a soft-bristled toothbrush and an electric razor to minimize the risk of bleeding.
Additionally, you may be more susceptible to infections while taking this medication. To reduce this risk, wash your hands frequently and avoid close contact with people who have infections, colds, or flu.
This medication may also increase your sensitivity to the sun, making you more prone to sunburn. Take necessary precautions when spending time outdoors, and inform your doctor if you experience any unusual sunburn or sensitivity.
Do not take this medication for longer than prescribed, as this may increase the risk of developing a secondary infection.
If you are pregnant, planning to become pregnant, or breastfeeding, it is essential to discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- Severe bone marrow depression (e.g., severe neutropenia, thrombocytopenia, anemia)
- Severe gastrointestinal disturbances (e.g., nausea, vomiting, diarrhea)
- Liver dysfunction
What to Do:
Seek immediate medical attention. There is no specific antidote. Management is supportive. Hemodialysis can effectively remove flucytosine from the body. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Major Interactions
- Cytarabine: Antagonizes the antifungal activity of flucytosine.
- Amphotericin B: While often used synergistically, amphotericin B can increase flucytosine toxicity by impairing renal clearance of flucytosine. Close monitoring of flucytosine levels and renal function is crucial.
Moderate Interactions
- Myelosuppressive agents (e.g., chemotherapy, zidovudine): Increased risk of severe bone marrow depression.
- Drugs that impair renal function (e.g., NSAIDs, aminoglycosides): May increase flucytosine levels and toxicity due to reduced renal clearance.
Confidence Interactions
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic status due to risk of bone marrow depression.
Timing: Prior to initiation of therapy.
Renal Function (Serum Creatinine, BUN, Creatinine Clearance)
Rationale: Flucytosine is primarily renally eliminated; renal impairment necessitates dose adjustment and increases risk of toxicity.
Timing: Prior to initiation of therapy.
Liver Function Tests (AST, ALT, ALP, Bilirubin)
Rationale: To establish baseline hepatic status and monitor for potential hepatotoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with differential
Frequency: At least twice weekly, especially during the first 2 weeks of therapy, then weekly.
Target: Maintain WBC > 3000/mm³, Platelets > 75,000/mm³.
Action Threshold: Discontinue or reduce dose if WBC falls below 3000/mm³ or platelets below 75,000/mm³.
Renal Function (Serum Creatinine, BUN)
Frequency: Weekly, or more frequently in patients with impaired renal function or those receiving nephrotoxic drugs.
Target: Maintain within acceptable limits for patient's baseline.
Action Threshold: Dose adjustment required if CrCl decreases; consider discontinuation if renal function significantly deteriorates.
Liver Function Tests (AST, ALT, ALP, Bilirubin)
Frequency: Weekly, or more frequently if abnormalities develop.
Target: Maintain within acceptable limits.
Action Threshold: Consider dose reduction or discontinuation if significant elevation (e.g., >3x ULN) occurs.
Serum Flucytosine Levels
Frequency: Recommended, especially in patients with renal impairment, severe illness, or when used with amphotericin B. Obtain peak (2 hours post-dose) and trough (just before next dose) levels.
Target: Peak: 25-100 mcg/mL; Trough: <25 mcg/mL.
Action Threshold: Adjust dose to maintain levels within therapeutic range. Levels >100-125 mcg/mL are associated with increased toxicity.
Symptom Monitoring
- Signs of bone marrow depression (e.g., fever, sore throat, unusual bleeding or bruising, fatigue)
- Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, abdominal pain)
- Signs of hepatotoxicity (e.g., jaundice, dark urine, pale stools, right upper quadrant pain)
- Skin rash or itching
Special Patient Groups
Pregnancy
Category C. Flucytosine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown teratogenic effects.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenic effects observed in animal studies. Avoid if possible.
Second Trimester:
Use with caution; monitor fetal development.
Third Trimester:
Use with caution; monitor fetal development.
Lactation
Excreted into breast milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Risk of bone marrow depression, gastrointestinal disturbances, and other adverse effects in the infant. L3 (Moderate risk).
Pediatric Use
Dosing is similar to adults on a mg/kg basis, but careful monitoring of hematologic, renal, and hepatic parameters, as well as serum drug levels, is crucial due to potential for severe toxicity and variability in pharmacokinetics in younger patients. Safety and efficacy in neonates and very young infants are not well established.
Geriatric Use
Elderly patients are more likely to have decreased renal function, which necessitates careful dose adjustment and close monitoring of renal function and serum flucytosine levels to prevent accumulation and toxicity. Increased susceptibility to bone marrow depression may also be a concern.
Clinical Information
Clinical Pearls
- Flucytosine should almost always be used in combination with amphotericin B for serious systemic fungal infections, especially cryptococcal meningitis, to achieve synergistic antifungal activity and prevent the development of resistance.
- Therapeutic drug monitoring (TDM) of serum flucytosine levels is highly recommended, particularly in patients with renal impairment, severe illness, or when used concomitantly with amphotericin B, to optimize efficacy and minimize toxicity.
- Bone marrow suppression is the most significant dose-limiting toxicity; frequent monitoring of CBC is essential.
- Administering flucytosine with food can help mitigate common gastrointestinal side effects like nausea and vomiting.
Alternative Therapies
- Amphotericin B (various formulations)
- Fluconazole
- Itraconazole
- Voriconazole
- Posaconazole
- Isavuconazole
- Echinocandins (e.g., Caspofungin, Micafungin, Anidulafungin)
Cost & Coverage
Average Cost:
Not available (highly variable) per 30 capsules
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty/Non-preferred Brand) for brand; Tier 1 or 2 for generic, depending on plan.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.