Indications
PO, IV: Fungal infections caused by susceptible organisms,
including: Oropharyngeal or esophageal candidiasis,
Serious systemic candidal infections, Urinary
tract infections, Peritonitis, Cryptococcal meningitis.
Prevention of candidiasis in patients who have undergone
bone marrow transplantation. PO: Single-dose
oral treatment of vaginal candidiasis. Unlabeled
Use: Prevention of recurrent vaginal yeast infections.
Action
Inhibits synthesis of fungal sterols, a necessary component
of the cell membrane. Therapeutic Effects:
Fungistatic action against susceptible organisms. May
be fungicidal in higher concentrations. Spectrum:
Cryptococcus neoformans. Candida spp.
Pharmacokinetics
Absorption: Well absorbed after oral administration.
Distribution: Widely distributed, good penetration
into CSF, saliva, sputum, vaginal fluid, skin, eye, and
peritoneum. Excreted in breast milk.
Metabolism and Excretion: 80% excreted unchanged
by the kidneys; 10% metabolized by the liver.
Half-life: Premature neonates: 46–74 hr; Children:
19–25 hr (PO) and 15–17 hr (IV); Adults: 30 hr (qin
renal impairment).
TIME/ACTION PROFILE (blood levels)
ROUTE ONSET PEAK DURATION
PO unknown 2–4 hr 24 hr
IV rapid end of infusion
24 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity to fluconazole
or other azole antifungals; Concurrent use with pimozide,
erythromycin, or quinidine.
Use Cautiously in: Renal impairment (doseprequired
if CCr 50 mL/min); Underlying liver disease;
OB: Safety not established; congenital defects have occurred
with use of high-dose fluconazole (400–800
mg/day); Lactation: Usually compatible with breast
feeding; Geri:qrisk of adverse reactions (rash, vomiting,
diarrhea, seizures); consider age-relatedpin renal
function in determining dose.
Adverse Reactions/Side Effects
Incidence of adverse reactions is increased in HIV patients.
CNS: headache, dizziness, seizures. GI: HEPATOTOXICITY,
abdominal discomfort, diarrhea, nausea, vomiting.
Derm: exfoliative skin disorders including STEVENSJOHNSON
SYNDROME. Endo: hypokalemia, hypertriglyceridemia.
Misc: allergic reactions, including ANAPHYLAXIS.
Interactions
Drug-Drug: Mayqlevels of pimozide, erythromycin,
and quinidine which can prolong the QT interval
andqthe risk of torsade de pointes. Mayqlevels of and
the risk of bleeding with warfarin. Rifampin, rifabutin,
and isoniazidplevels. Fluconazole at doses 200
mg/day may inhibit the CYP3A4 enzyme system and effect
the activity of drugs metabolized by this system.q
hypoglycemic effects of tolbutamide, glyburide, or
glipizide.qlevels and risk of toxicity from cyclosporine,
carbamazepine, celecoxib, rifabutin, tacrolimus,
sirolimus, theophylline, zidovudine, alfentanil,
and phenytoin.qlevels and effects of
benzodiazepines, amlodipine, felodipine, isradipine,
nifedipine, nisoldipine, verapamil, atorvastatin,
fluvastatin, lovastatin, simvastatin, methadone,
flurbiprofen, prednisone, saquinavir,
tricyclic antidepressants, and losartan.qlevels of
tofacitinib;pdose of tofacitinib to 5 mg once daily.
Mayqrisk of bleeding with warfarin. May antagonize
effects of amphotericin B. Mayqvoriconazole levels;
avoid concurrent use.
Route/Dosage
Oropharyngeal Candidiasis
PO, IV (Adults): 200 mg initially, then 100 mg daily
for at least 2 wk.
PO, IV (Children 14 days): 6 mg/kg initially, then 3
mg/kg/day for at least 2 wk.
PO, IV (Neonates 14 days, 30–36 wk gestation):
same dose as older children except frequency is
q 48 hr; Premature neonates 29 wk gestation: 5–6
mg/kg/dose q 48–72 hr.
Esophageal Candidiasis
PO, IV (Adults): 200 mg initially, then 100 mg once
daily for at least 3 wk (up to 400 mg/day).
PO, IV (Children 14 days): 6 mg/kg initially, then
3–12 mg/kg/day for at least 3 wk.
PO, IV (Neonates 14 days, 30–36 wk gestation):
same dose as older children except frequency is
q 48 hr; Premature neonates 29 wk gestation: 5–6
mg/kg/dose q 48–72 hr.
Vaginal Candidiasis
PO (Adults): 150-mg single dose; prevention of recurrence
(unlabeled)—150 mg daily for 3 days then
weekly for 6 mo.
Systemic Candidiasis
PO, IV (Adults): 400 mg/day initially, then 200–800
mg/day for 28 days.
PO, IV (Children 14 days): 6–12 mg/kg/day for
28 days.
PO, IV (Neonates 14 days, 30–36 wk gestation):
same dose as older children except frequency is
q 48 hr; Premature neonates 29 wk gestation: 5–6
mg/kg/dose q 48–72 hr.
Cryptococcal Meningitis
PO, IV (Adults): Treatment—400 mg once daily until
favorable clinical response, then 200–800 mg once
daily for at least 10–12 wk after clearing of CSF;
change to oral therapy as soon as possible. Suppressive
therapy—200 mg once daily.
PO, IV (Children 14 days): 12 mg/kg/day initially,
then 6–12 mg/kg/day for at least 10–12 wk after
clearing of CSF; change to oral therapy as soon as possible.
Suppressive therapy—6 mg/kg/day.
PO, IV (Neonates 14 days, 30–36 wk gestation):
same dose as older children except frequency is
q 48 hr; Premature neonates 29 wk gestation: 5–6
mg/kg/dose q 48–72 hr.
Prevention of Candidiasis after Bone
Marrow Transplant
PO, IV (Adults): 400 mg once daily; begin several
days before procedure if severe neutropenia is expected,
and continue for 7 days after ANC 1000 /mm3.
PO, IV (Children 14 days): 10–12 mg/kg/day, not
to exceed 600 mg/day.
Renal Impairment
PO, IV (Adults): CCr 50 mL/min (no hemodialysis)—
Give 50% of the usual dose (not for single-dose
therapy); Hemodialysis—Give 100% of the usual dose
after each dialysis session; give reduced dose based on
CCr on non-dialysis days (not for single-dose therapy).
Availability (generic available)
Tablets: 50 mg, 100 mg, 150 mg, 200 mg. Cost: Generic—
100 mg $88.17/30, 150 mg $6.99/1. Powder
for oral suspension (orange flavor): 10 mg/mL, 40
mg/mL. Cost: Generic—10 mg/mL $36.00/35 mL, 40
mg/mL $130.76/35 mL. Premixed infusion: 2 mg/
mL.
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