brand name | preparation | manufacturer | route | form | dosage^ | cost* |
Ancobon | Flucytosine (5-FC) | ICN Pharmaceuticals | oral | capsule | 250 mg | $92.21 |
oral | capsule | 500 mg | $178.43 | |||
Flucytosine (5-FC) | Generic manufacturer | oral | capsule | 250 mg | $82.07 | |
oral | capsule | 500 mg | $158.80 |
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
25 mg/kg q6h.
25 mg/kg q6h.
CrCl 20-40 mL/min: 25 mg/kg q12
CrCl 10-19 mL/min: 25 mg/kg q24h (monitor CBC and serum levels with appropriate dose adjustments).
25 mg/kg q48h (monitor CBC serum levels closely with appropriate dose adjustments).
25 mg/kg q24-48h. Dose post-dialysis on days of dialysis (monitor CBC and serum levels w/ appropriate dose adjustment).
0.5-1.0 gm q24h (monitor CBC and serum levels w/ appropriate dose adjustments).
CVVH and CVVHD: Limited data. Consider 25 mg/kg q24 for dialysis rate of 1L/hr and 25 mg/kg q12h for dialysis rate ≥1.5 L/hr (monitor CBC and serum levels with appropriate dose adjustments).
Flucytosine interferes with protein synthesis by incorporation into fungal RNA after being converted to 5-FU intracellularly.
75-90%.
Minimal metabolism; principally excreted unchanged in the urine. Unabsorbed drug excreted in feces.
2-4%.
Cmax: 60-80 mcg/mL, Cmin: 20-40 mcg/mL after 37.5 mg/kg/dose.
2.5-6 hrs (normal renal function). Half-life may be up to 250 hrs in patients with ESRD.
Widely distributed into body tissues and fluids such as liver, kidney, spleen, heart, aqueous humor and bronchial secretion. Good CNS penetration (70-85% of serum concentration attained in the CSF).
No data. Usual dose likely.
Category C. Crosses placental barrier. Teratogenicity reported in animal studies. Three case reports of second and third exposure found no defects in infants.
No data. Breast feeding during flucytosine therapy not recommended.
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.
Comment: Amphotericin B (1 mg/kg/day) plus flucytosine (100 mg/kg/day) was associated with improved survival at day 70 as compared with amphotericin B (1 mg/kg/day) alone. Combination therapy with flucytosine also resulted in more rapid yeast clearance from CSF when compared to amphotericin monotherapy or amphotericin B plus fluconazole (800 mg/kg/day). There was no survival benefit found for those treated with amphotericin B plus fluconazole.
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).
Comment: Addition of 5FC to amphotericin resulted in faster CSF sterilization but did not improve clinical outcome.
Comment: A case report of a morbidly obese patient who received 150 mg/kg/day IBW for treatment of extrameningeal cryptococcal infection. Pharmacokinetic parameters were similar as those reported in non-obese patients receiving the same dose.
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