Ancotil

How long you have been taking the medicine?
advertisement

Ancotil uses


WARNING

Use with extreme caution in patients with impaired renal function. Close monitoring of hematologic, renal and hepatic status of all patients is essential. These instructions should be thoroughly reviewed before administration of Ancotil.

DESCRIPTION

Ancotil (flucytosine), an antifungal agent, is available as 250 mg and 500 mg capsules for oral administration. In addition to the active ingredient of Ancotil, each capsule contains corn starch, lactose and talc. The 250 mg capsule shell contains black iron oxide, D&C Yellow No. 10, FD&C Blue No. 1, FD&C Yellow No. 6, gelatin and titanium dioxide. The 500 mg capsule shell contains black iron oxide, gelatin and titanium dioxide.

Chemically, Ancotil is 5-fluorocytosine, a fluorinated pyrimidine which is related to fluorouracil and floxuridine. It is a white to off-white crystalline powder with a molecular weight of 129.09 and the following structural formula:

Chemical Structure

CLINICAL PHARMACOLOGY

Ancotil is rapidly and virtually completely absorbed following oral administration. Ancotil is not metabolized significantly when given orally to man. Bioavailability estimated by comparing the area under the curve of serum concentrations after oral and intravenous administration showed 78% to 89% absorption of the oral dose. Peak serum concentrations of 30 to 40 mcg/mL were reached within 2 hours of administration of a 2 g oral dose to normal subjects. Other studies revealed mean serum concentrations of approximately 70 to 80 mcg/mL 1 to 2 hours after a dose in patients with normal renal function receiving a 6-week regimen of Ancotil in combination with amphotericin B. The half-life in the majority of healthy subjects ranged between 2.4 and 4.8 hours. Ancotil is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. More than 90% of the total radioactivity after oral administration was recovered in the urine as intact drug. Ancotil is deaminated (probably by gut bacteria) to 5-fluorouracil. The area under the curve (AUC) ratio of 5-fluorouracil to Ancotil is 4%. Approximately 1% of the dose is present in the urine as the α-fluoro-β-ureido-propionic acid metabolite. A small portion of the dose is excreted in the feces.

The half-life of Ancotil is prolonged in patients with renal insufficiency; the average half-life in nephrectomized or anuric patients was 85 hours (range: 29.9 to 250 hours). A linear correlation was found between the elimination rate constant of Ancotil and creatinine clearance.

In vitro studies have shown that 2.9% to 4% of Ancotil is protein-bound over the range of therapeutic concentrations found in the blood. Ancotil readily penetrates the blood-brain barrier, achieving clinically significant concentrations in cerebrospinal fluid.

Pharmacokinetics in Pediatric Patients

Limited data are available regarding the pharmacokinetics of Ancotil administered to neonatal patients being treated for systemic candidiasis. After five days of continuous therapy, median peak levels in infants were 19.6 mcg/mL, 27.7 mcg/mL, and 83.9 mcg/mL at doses of 25 mg/kg (N=3), 50 mg/kg (N=4), and 100 mg/kg (N=3), respectively. Mean time to peak serum levels was of 2.5 ± 1.3 hours, similar to that observed in adult patients. A good deal of interindividual variability was noted, which did not correlate with gestational age. Some patients had serum levels > 100 mcg/mL, suggesting a need for drug level monitoring during therapy. In another study, serum concentrations were determined during Ancotil therapy in two patients (total assays performed =10). Median serum Ancotil concentrations at steady state were calculated to be 57 ± 10 mcg/mL (doses of 50 to 125 mg/kg/day, normalized to 25 mg/kg per dose for comparison). In three infants receiving Ancotil 25 mg/kg/day (four divided doses), a median Ancotil half-life of 7.4 hours was observed, approximately double that seen in adult patients. The concentration of Ancotil in the cerebrospinal fluid of one infant was 43 mcg/mL 3 hours after a 25 mg oral dose, and ranged from 20 to 67 mg/L in another neonate receiving oral doses of 120 to 150 mg/kg/day.

MICROBIOLOGY

Mechanism of Action

Ancotil is taken up by fungal organisms via the enzyme cytosine permease. Inside the fungal cell, Ancotil is rapidly converted to fluorouracil by the enzyme cytosine deaminase. Fluorouracil exerts its antifungal activity through the subsequent conversion into several active metabolites, which inhibit protein synthesis by being falsely incorporated into fungal RNA or interfere with the biosynthesis of fungal DNA through the inhibition of the enzyme thymidylate synthetase.

Activity In Vitro

Ancotil has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.

Candida albicans

Cryptococcus neoformans

The following in vitro data are available, but their clinical significance is unknown.

Ancotil exhibits in vitro minimum inhibitory concentrations of 4 mcg/mL, or less against most (≥90%) strains of the following microorganisms, however, the safety and effectiveness of Ancotil in treating clinical infections due to these microorganisms have not been established in adequate and well control trials.

Candida dubliniensis

Candida glabrata

Candida guilliermondii

Candida lusitaniae

Candida parapsilosis

Candida tropicalis

Candida krusei should be considered to be resistant to Ancotil.

In vitro activity of Ancotil is affected by the test conditions. It is essential to follow the approved standard method guidelines.1

Susceptibility Testing Methods

Cryptococcus neoformans:

No interpretive criteria have been established for Cryptococcus neoformans.

Candida species:

Broth Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of Candida spp. to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth)1 with standardized inoculum concentrations and standardized concentrations of Ancotil powder. The MIC values should be interpreted according to the criteria in Table 1.


Broth Dilution at 48 hours

(MIC in mcg/mL)


Antifungal Agent


Susceptible (S)


Intermediate (I)


Resistant (R)


Ancotil


≤4.0


8.0-16


>32


A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected. Because of other significant host factors, in vitro susceptibility may not correlate with clinical outcomes.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard Ancotil powder should provide the range of MIC values noted in Table 2. NOTE: Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within fungi; the specific strains used for microbiological control are not clinically significant.

QC Strain Macrodilution

(MIC in mcg/mL)

at 48 hours

Microdilution

(MIC in mcg/mL)

at 48 hours


Candida parapsilosis ATCC 22019


0.12-0.5


0.12-0.5


Candida krusei ATCC 6258


4.0-16


8.0-32

Drug Resistance

Ancotil resistance may arise from a mutation of an enzyme necessary for the cellular uptake or metabolism of Ancotil or from an increased synthesis of pyrimidines, which compete with the active metabolites of Ancotil (fluorinated antimetabolites). Resistance to Ancotil has been shown to develop during monotherapy after prolonged exposure to the drug.

Candida krusei should be considered to be resistant to Ancotil.

Drug Combination

Antifungal synergism between Ancotil and polyene antibiotics, particularly amphotericin B has been reported in vitro. Ancotil is usually administered in combination with amphotericin B due to lack of cross-resistance and reported synergistic activity of both drugs.

advertisement

INDICATIONS AND USAGE

Ancotil is indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus.

Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with Ancotil. Limited trials in pulmonary infections justify the use of Ancotil

Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported.

Ancotil should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Ancotil (see MICROBIOLOGY ).

CONTRAINDICATIONS

Ancotil should not be used in patients with a known hypersensitivity to the drug.

WARNINGS

Ancotil must be given with extreme caution to patients with impaired renal function. Since Ancotil is excreted primarily by the kidneys, renal impairment may lead to accumulation of the drug. Ancotil serum concentrations should be monitored to determine the adequacy of renal excretion in such patients. Dosage adjustments should be made in patients with renal insufficiency to prevent progressive accumulation of active drug.

Ancotil must be given with extreme caution to patients with bone marrow depression. Patients may be more prone to depression of bone marrow function if they: 1) have a hematologic disease, 2) are being treated with radiation or drugs which depress bone marrow, or 3) have a history of treatment with such drugs or radiation. Bone marrow toxicity can be irreversible and may lead to death in immunosuppressed patients. Frequent monitoring of hepatic function and of the hematopoietic system is indicated during therapy.

advertisement

PRECAUTIONS

General

Before therapy with Ancotil is instituted, electrolytes and the hematologic and renal status of the patient should be determined (see WARNINGS ). Close monitoring of the patient during therapy is essential.

Laboratory Tests

Since renal impairment can cause progressive accumulation of the drug, blood concentrations and kidney function should be monitored during therapy. Hematologic status (leucocyte and thrombocyte count) and liver function (alkaline phosphatase, SGOT and SGPT) should be determined at frequent intervals during treatment as indicated.

Drug Interactions

Cytosine arabinoside, a cytostatic agent, has been reported to inactivate the antifungal activity of Ancotil by competitive inhibition. Drugs which impair glomerular filtration may prolong the biological half-life of Ancotil.

Drug/Laboratory Test Interactions

Measurement of serum creatinine levels should be determined by the Jaffé reaction, since Ancotil does not interfere with the determination of creatinine values by this method. Most automated equipment for measurement of creatinine makes use of the Jaffé reaction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Ancotil has not undergone adequate animal testing to evaluate carcinogenic potential. The mutagenic potential of Ancotil was evaluated in Ames-type studies with five different mutants of S. typhimurium and no mutagenicity was detected in the presence or absence of activating enzymes. Ancotil was nonmutagenic in three different repair assay systems.

There have been no adequate trials in animals on the effects of Ancotil on fertility or reproductive performance. The fertility and reproductive performance of the offspring (F1 generation) of mice treated with 100 mg/kg/day (345 mg/M2/day or 0.059 times the human dose), 200 mg/kg/day (690 mg/M2/day or 0.118 times the human dose) or 400 mg/kg/day (1380 mg/M2/day or 0.236 times the human dose) of Ancotil on days 7 to 13 of gestation was studied; the in utero treatment had no adverse effect on the fertility or reproductive performance of the offspring.

Pregnancy

Teratogenic Effects

Ancotil was shown to be teratogenic (vertebral fusions) in the rat at doses of 40 mg/kg/day (298 mg/M2/day or 0.051 times the human dose) administered on days 7 to 13 of gestation. At higher doses (700 mg/kg/day; 5208 mg/M2/day or 0.89 times the human dose administered on days 9 to 12 of gestation), cleft lip and palate and micrognathia were reported. Ancotil was not teratogenic in rabbits up to a dose of 100 mg/kg/day (1423 mg/M2/day or 0.243 times the human dose) administered on days 6 to 18 of gestation. In mice, 400 mg/kg/day of Ancotil (1380 mg/M2/day or 0.236 times the human dose) administered on days 7 to 13 of gestation was associated with a low incidence of cleft palate that was not statistically significant. Studies in pregnant rats have shown that Ancotil injected intraperitoneally crosses the placental barrier. There are no adequate and well-controlled studies in pregnant women. Ancotil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Ancotil, 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.

Pediatric Use

The efficacy and safety of Ancotil have not been systematically studied in pediatric patients. A small number of neonates have been treated with 25 to 200 mg/kg/day of Ancotil, with and without the addition of amphotericin B, for systemic candidiasis. No unexpected adverse reactions were reported in these patients. It should be noted, however, that hypokalemia and acidemia were reported in one patient who received Ancotil in combination with amphotericin B, and anemia was observed in a second patient who received Ancotil alone. Transient thrombocytopenia was noted in two additional patients, one of whom also received amphotericin B.

advertisement

ADVERSE REACTIONS

The adverse reactions which have occurred during treatment with Ancotil are grouped according to organ system affected.

Cardiovascular: Cardiac arrest, myocardial toxicity, ventricular dysfunction.

Respiratory: Respiratory arrest, chest pain, dyspnea.

Dermatologic: Rash, pruritus, urticaria, photosensitivity.

Gastrointestinal: Nausea, emesis, abdominal pain, diarrhea, anorexia, dry mouth, duodenal ulcer, gastrointestinal hemorrhage, acute hepatic injury including hepatic necrosis with possible fatal outcome in debilitated patients, hepatic dysfunction, jaundice, ulcerative colitis, enterocolitis, bilirubin elevation, increased hepatic enzymes.

Genitourinary: Azotemia, creatinine and BUN elevation, crystalluria, renal failure.

Hematologic: Anemia, agranulocytosis, aplastic anemia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, and fatal cases of bone marrow aplasia.

Neurologic: Ataxia, hearing loss, headache, paresthesia, parkinsonism, peripheral neuropathy, pyrexia, vertigo, sedation, convulsions.

Psychiatric: Confusion, hallucinations, psychosis.

Miscellaneous: Fatigue, hypoglycemia, hypokalemia, weakness, allergic reactions, Lyell’s syndrome.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda,.gov/medwatch.

OVERDOSAGE

There is no experience with intentional overdosage. It is reasonable to expect that overdosage may produce pronounced manifestations of the known clinical adverse reactions. Prolonged serum concentrations in excess of 100 mcg/mL may be associated with an increased incidence of toxicity, especially gastrointestinal (diarrhea, nausea, vomiting), hematologic (leukopenia, thrombocytopenia) and hepatic (hepatitis).

In the management of overdosage, prompt gastric lavage or the use of an emetic is recommended. Adequate fluid intake should be maintained, by the intravenous route if necessary, since Ancotil is excreted unchanged via the renal tract. The hematologic parameters should be monitored frequently; liver and kidney function should be carefully monitored. Should any abnormalities appear in any of these parameters, appropriate therapeutic measures should be instituted.

Since hemodialysis has been shown to rapidly reduce serum concentrations in anuric patients, this method may be considered in the management of overdosage.

advertisement

DOSAGE AND ADMINISTRATION

The usual dosage of Ancotil is 50 to 150 mg/kg/day administered in divided doses at 6-hour intervals. Nausea or vomiting may be reduced or avoided if the capsules are given a few at a time over a 15-minute period. If the BUN or the serum creatinine is elevated, or if there are other signs of renal impairment, the initial dose should be at the lower level (see WARNINGS ).

Ancotil should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Ancotil (see MICROBIOLOGY ).

HOW SUPPLIED

ANCOBON® Capsules are supplied as capsules containing 250 mg and 500 mg Ancotil.


Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F).

KEEP OUT OF REACH OF CHILDREN

REFERENCES


Manufactured for:

Valeant Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA

Manufactured by:

Valeant Pharmaceuticals International, Inc.

Steinbach, MB R5G 1Z7, Canada

Ancotil is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.

©Valeant Pharmaceuticals North America LLC


Rev. 04/2017

LB0096-00

Rev. 02/13

NDC 0187-3554-10

Rx only

Ancotil ®

(flucytosine)

250 mg

Each capsule

contains 250

mg Ancotil

100 Capsules

VALEANT

NDC 0187-3555-10

Rx only

Ancotil ®

(flucytosine)

500 mg

Each capsule

contains 500

mg Ancotil

100 Capsules

VALEANT

Ancotil pharmaceutical active ingredients containing related brand and generic drugs:


Ancotil available forms, composition, doses:


Ancotil destination | category:


Ancotil Anatomical Therapeutic Chemical codes:


Ancotil pharmaceutical companies:


advertisement

References

  1. Dailymed."ANCOBON (FLUCYTOSINE) CAPSULE [VALEANT PHARMACEUTICALS NORTH AMERICA LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Ancotil?

Depending on the reaction of the Ancotil after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ancotil not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Ancotil addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Ancotil, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Ancotil consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

One visitor reported doses

What is the dose of Ancotil drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 201-500mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
201-500mg1
100.0%

Two visitors reported time for results

What is the time duration Ancotil drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed > 3 month to notice the result from using Ancotil drug. The time needed to show improvement in health condition after using the medicine Ancotil need not be same for all the users. It varies based on other factors.
Visitors%
> 3 month1
50.0%
3 days1
50.0%

Visitor reported administration

No survey data has been collected yet

One visitor reported age

Visitors%
> 601
100.0%

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 16 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2024 "sdrugs.com". All Rights Reserved