Flucytosine

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Drugs>Antimicrobial Agents>

Flucytosine

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
02-09-2010

Zambia Specific Information

Currently not available in Zambia
In combination with amphotericin for the treatment of severe cryptococcal meningitis
Dose: 25 mg/kg q6h x 2 weeks in combination with amphotericin

REFERENCES

Zambia Information Author: Paul A. Pham, Pharm. D.

INDICATIONS

FDA

Cryptococcal and Candida endocarditis (in addition to amphotericin B).
Cryptococcal meningitis (in addition to amphotericin B or liposomal amphotericin).
Cryptococcal and Candida pneumonia (in addition to amphotericin B).
Cryptococcal and Candida septicemia (in addition to amphotericin B).
Cryptococcal and Candida urinary tract infections (in addition to amphotericin B).

FORMS

brand name	generic	Mfg	brand forms	cost*
Ancobon	Flucytosine (5-FC)	ICN Pharmaceuticals	oral capsule 250 mg	$5.29
			oral capsule 500 mg	$10.52

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^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
Peripheral neuropathy
Enterocolitis
Photosensitivity

DRUG INTERACTIONS

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

SPECTRUM

Cryptococcus neoformans and Candida spp.

PHARMACOLOGY

Pharmacology

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 Recommendations

Perfect JR. Dismukes WE, Dromer F et al. ; Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America ; Clin Infect Dis ; 2010 ; Vol. 50 ; pp. 291-322. ;
PUBMED: 20047480
Rating: Basis for recommendation
Comments: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.
Perfect JR, Dismukes WE, Dromer F, et al.; Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.; Clin Infect Dis; 2010; Vol. 50; pp. 291-322;
ISSN: 1537-6591;
PUBMED: 20047480
Rating: Basis for recommendation
Comments: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.

REFERENCES

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