INDICATIONS

FDA

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Ancobon

Flucytosine (5-FC)

ICN Pharmaceuticals

oral

capsule

250 mg

$22.64/100 caps

oral

capsule

500 mg

$43.81/100 caps

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

25 mg/kg q6h. Therapeutic monitoring recommended with renal insufficiency; goal peak of 30-80 mcg/mL 2 hrs post-dose after 3-5 days. .

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

25 mg/kg q6h.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

25 mg/kg q12-24h (monitor CBC and serum levels with appropriate dose adjustments).

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

25 mg/kg q24-48h (monitor CBC serum levels closely with appropriate dose adjustments).

DOSING IN HEMODIALYSIS

25 mg/kg q24-48h. Dose post-dialysis on days of dialysis (monitor CBC and serum levels w/ appropriate dose adjustment).

DOSING IN PERITONEAL DIALYSIS

0.5-1.0 gm q24h (monitor CBC and serum levels w/ appropriate dose adjustments).

DOSING IN HEMOFILTRATION

CVVH and CVVHD: No data. Consider 25 mg/kg q12h for dialysis rate > or = 1.5 L/hr or 25 mg/kg q24h for dialysis rate of 1L/hr (monitor CBC and serum levels with appropriate dose adjustments).

ADVERSE DRUG REACTIONS

OCCASIONAL

  • GI intolerance: diarrhea, dyspepsia, and abdominal pain
  • Marrow suppression w/ leukopenia or thrombocytopenia (with levels >100 mcg/mL)
  • Headache
  • Taste perversion
  • Pruritis

RARE

  • Confusion
  • Rash
  • Hepatitis (hepatic necrosis has been reported)
  • Peripheral neuropathy
  • Enterocolitis
  • Photosensitivity
  • Fatal bone marrow aplasia

DRUG INTERACTIONS

  • Cytarabine: antagonism (avoid co-administration).
  • Drugs that cause bone marrow suppression (i.e. AZT, ganciclovir, and interferon): increased bone marrow suppression.

PHARMACOLOGY

MECHANISM

Flucytosine interferes with protein synthesis by incorporation into fungal RNA after being converted to 5-FU intracellularly.

PHARMACOKINETIC PARAMETERS

Absorption

75-90%.

Metabolism and Excretion

Minimal metabolism; principally excreted unchanged in the urine. Unabsorbed drug excreted in feces.

Protein Binding

2-4%.

Cmax, Cmin, and AUC

30-40 mcg/mL after 2 g PO.

T1/2

2.5-6 hrs.

Distribution

Widely distributed into body tissues and fluids such as liver, kidney, spleen, heart, aqueous humor and bronchial secretion. Good CNS penetration (60-100% of serum concentration attained in the CSF).

DOSING FOR DECREASED HEPATIC FUNCTION

No data. Usual dose likely.

PREGNANCY RISK

Category C. Crosses placental barrier Teratogenicity reported in animal studies. 3 case reports of 2nd and 3rd exposure found no defects in infants.

BREAST FEEDING COMPATIBILITY

No data. Breast feeding during flucytosine therapy not recommended.

COMMENTS

Recommended in combination with amphotericin or liposomal amphotericin for treatment of cryptococcal meningitis. Resulting in more rapid CSF sterilization, but clinical outcome similar with or without 5FC. Should be used if tolerated, but can treat with amphotericin B alone if toxicity develops. Goal: peak of 30-80 mcg/mL 2 hrs post-dose after 3-5 days. . Close monitoring of renal function and serum level critical to prevent bone marrow suppression.

Basis for recommendation

  1. Perfect JR et al: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis 50:291, 2010  [PMID:20047480]

    Comment: 5FC plus amphotericin B, liposomal amphotericin, or amphotericin lipd complex (for ≥2 wks) is recommended for treatment of cryptococcal meningitis. Without 5FC, recommended amphotericinB treatment duration is 4-6 weeks. Fluconazole 1200 mg/day plus 5FC x 6 wks is alternative in pts unable to tolerate amphotericin.

  2. Perfect JR et al: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis 50:291, 2010  [PMID:20047480]

    Comment: 5FC plus amphotericin B, liposomal amphotericin, or amphotericin lipd complex (for ≥2 wks) is recommended for treatment of cryptococcal meningitis. Without 5FC, recommended amphotericin treatment duration is 4-6 wks. Fluconazole 1200 mg/day plus 5FC x 6 wks isalternative in pts unable to tolerate amphotericin.

References

  1. van der Horst CM et al: Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med 337:15, 1997  [PMID:9203426]

    Comment: Addition of 5FC to amphotericin resulted in faster CSF sterilization but did not improve clinical outcome.

  2. Saag MS et al: A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 28:291, 1999  [PMID:10064246]

    Comment: Fluconazole superior to itraconazole for maintenance therapy of cryptococcal meningitis. Factor best associated with relapse was having not received flucytosine during the initial 2 wks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; p=0.04).

Flucytosine is a sample topic from the Johns Hopkins HIV Guide.

To view other topics, please or purchase a subscription.

Johns Hopkins Guides provide diagnosis, management, and treatment guidance for infectious diseases, diabetes, and psychiatric conditions. Learn more.

Last updated: March 18, 2011