Red Book Antifungals

Table 4.8.
Recommended Doses of Parenteral and Oral Antifungal Drugs
Drug Route Dose (per day) Adverse Reactionsa,b

Amphotericin B IV 1.0 mg/kg per day (or 1.5 mg/kg every other day) Fever, chills, phlebitis, gastrointestinal tract
deoxycholate (max 1.5 mg/kg/day); infuse as a single dose symptoms, headache, hypotension, renal
(see Antifungal Drugs over 2–4 h. dysfunction, hypokalemia, anemia, cardiac
for Systemic Fungal arrhythmias, neurotoxicity, anaphylaxis.
Infections, p 905, for
IT 0.01–0.025 mg, slow increase to 0.5 mg, twice/ Headache, gastrointestinal tract symptoms,
detailed information)
Red_Book_2020_SECTION 4-5_863-1026.indd 913

wk. arachnoiditis/radiculitis.
Amphotericin B lipid IV 3–5 mg/kg per day, infused over 2 h. Fever, chills, other reactions associated with
complex (Abelcet)c amphotericin B deoxycholate, but less
nephrotoxicity; hepatotoxicity has been
reported with lipid complex.
Liposomal IV 3–5 mg/kg, infused over 1–2 h. Fever, chills, fewer infusion reactions and
amphotericin B IFI prophylaxisd: 1 mg/kg/dose every other day less nephrotoxicity than associated with
(AmBisome)c or 2.5 mg/kg/dose twice/wk. amphotericin B deoxycholate; hepatotoxicity
Doses up to 10 mg/kg have been used in patients has been reported.
with mucormycosis.
Anidulafunginc,e IV For adults and adolescents 12 y and older: Fever, headache, nausea, vomiting, diarrhea,
Candidemia and other forms of Candida leukopenia, hypokalemia, hepatitis, hepatic
infections: 200 mg on day 1, followed by 100- enzyme elevations, hypersensitivity, and
mg daily dose thereafter for at least 14 days phlebitis.
after the last positive culture. Because of high alcohol content of solution, the
Esophageal candidiasis: 100 mg on day 1, rate of infusion should not exceed 1.1 mg/
and Oral Antifungal Drugs
followed by 50-mg daily dose thereafter for a minute.

minimum of 14 days and for at least 7 days
following resolution of symptoms. The rate of
Recommended Doses of Parenteral
infusion should not exceed 1.1 mg/minute.

RECOMMENDED DOSES OF PARENTERAL AND ORAL ANTIFUNGAL DRUGS 913
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Table 4.8. Recommended Doses of Parenteral and Oral Antifungal Drugs, continued
914

Dosage in pediatric patients (2 years through 11 years):
Candidemia and other forms of Candida infections:
3-mg/kg loading dose on day 1, followed by 1.5 mg/
kg once daily thereafter. Maximum loading dose and
daily dose should not exceed 100 mg/day.
Esophageal candidiasis: 1.5-mg/kg loading dose on
day 1, followed by 0.75 mg/kg once daily thereafter.

Maximum loading dose and daily dose should not
exceed 50 mg.
Caspofunginc IV Dosage in adults (18 y and older): 70-mg loading dose on Adults: Diarrhea, pyrexia, hepatic enzymes elevations,
day 1, followed by 50 mg once daily for all indications and hypokalemia.
except esophageal candidiasis. Pediatric: diarrhea, rash, hepatic enzymes elevations,
Dosage in pediatric patients (3 months through 17 y of hypokalemia, infusion-related reactions.
age): For all indications, 70-mg/m2 loading dose on Isolated cases of hepatic dysfunction, hepatitis, or
day 1, followed by 50 mg/m2 once daily thereafter. hepatic failure have been reported.
Maximum dose should not exceed 70 mg, regardless
of the patient’s weight and calculated dose.
Dosage in neonates: 25 mg/m2 daily.
Clotrimazole PO 10-mg lozenge, 5 times per day (dissolved slowly Gastrointestinal tract symptoms, hepatotoxicity.
in mouth).
RECOMMENDED DOSES OF PARENTERAL AND ORAL ANTIFUNGAL DRUGS
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f
Fluconazole IV, Oropharyngeal and esophageal candidiasis: 6 mg/kg Rash, gastrointestinal tract symptoms, hepatotoxicity,
PO (adult dose: 200 mg) on the first day, followed by 3–6 Stevens-Johnson syndrome, anaphylaxis.
mg/kg (adult dose: 100 mg) once daily. Treatment
should be given for at least 2–3 wk to decrease the
likelihood of relapse, and at least 2 weeks following
resolution of symptoms.

Doses up to 12 mg/kg/day have been used based on
clinical judgment.
Systemic Candida infections: 12 mg/kg/day.
Prophylaxis in children (when indicated)d: 6 mg/kg once

daily (max 400 mg/day)
Cryptococcal meningitis (children): Following induction
therapy with amphotericin B plus flucytosine,
fluconazole 10–12 mg/kg/day (maximum 800
mg day) in 2 divided doses for a minimum of 8
weeks after the CSF becomes culture negative; for
suppression of relapse in children with AIDS, use 6
mg/kg once daily.
Cryptococcal meningitis (adults): Following induction
therapy with amphotericin B plus flucytosine,
fluconazole 400 mg once daily. The recommended
duration of fluconazole consolidation treatment is a
minimum of 8 wk after the CSF fluid becomes culture
negative; 200 mg once daily is used for suppression of
relapse of cryptococcal meningitis in patients with AIDS.
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916

Flucytosine PO 100 mg/kg/day, divided dosing every 6 h Bone marrow suppression, hepatotoxicity, renal
(adjust dose for renal dysfunction and neonatal age); dysfunction, gastrointestinal tract symptoms, rash,
follow 2-h post peak levels closely (therapeutic range neuropathy, confusion, hallucinations.
≤100 µg/mL). Cytosine arabinoside, a cytostatic agent, has been
reported to inactivate the antifungal activity of
flucytosine by competitive inhibition; drugs that
impair glomerular filtration may prolong the

biological half-life of flucytosine.
The hematologic parameters should be monitored
frequently; liver and kidney function should be
carefully monitored during therapy.
Flucytosine should be used in combination with
amphotericin B for the treatment of cryptococcosis
because of the emergence of resistance to flucytosine.
Griseofulvin PO Ultramicrosize: 10–15 mg/kg, once daily; maximum Rash, paresthesias, leukopenia, gastrointestinal tract
dose per day, 750 mg. symptoms, proteinuria, hepatotoxicity, mental
Microsize: 20–25 mg/kg per day divided in confusion, headache.
2 doses; maximum dose per day, 1000 mg.
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Isavuconazole (prodrug IV, PO Adults: 200 mg, every 8 h for 6 doses, then 200 mg, Most frequent adverse reactions are nausea, vomiting,
is isavuconazonium once daily (corresponding to 372 mg of the sulfate diarrhea, headache, elevated aminotransferases,
sulfate)g compound every 8 h for 6 doses, then 372 mg daily), hypokalemia, constipation, dyspnea, cough, peripheral
starting 12 to 24 h after the last loading dose. edema, and back pain.
Pediatrics: No data or dosage regimen available. CYP3A4 inhibitors or inducers may alter the plasma
concentrations of isavuconazole.

Appropriate therapeutic drug monitoring and dose
adjustment of immunosuppressants (ie, tacrolimus,
sirolimus, and cyclosporine) may be necessary when
coadministered with isavuconazole. Drugs with a
narrow therapeutic window that are P-gp substrates,
such as digoxin, may require dose adjustment
coadministered concomitantly with isavuconazole.
Itraconazolec PO Children: 10 mg/kg per day divided into 2 doses; acidic Gastrointestinal tract symptoms, rash, edema,
pH for better absorption; oral solution supplies more headache, hypokalemia, hepatotoxicity, tremor,
reliable bioavailability; confirm therapeutic trough thrombocytopenia, leukopenia; strong P450 CYP3A4
level after several days of therapy to ensure adequate inhibitor, can heighten risk of QT prolongation
drug exposure (1–2 µg/mL; when measured by high- via metabolism interference with drugs having that
pressure liquid chromatography, both itraconazole adverse effect.
and its bioactive hydroxy-itraconazole metabolite are
reported, the sum of which should be considered in
assessing drug levels); IFI prophylaxisd: 2.5 mg/kg
twice a day, with minimum therapeutic level of 0.5
µg/mL.
Adults: 200–400 mg/day once or twice a day for
treatment of blastomycosis, histoplasmosis,
and aspergillosis; 100–200 mg once daily for
oropharyngeal and esophageal candidiasis.

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918

h
Micafungin IV Adults: 100 mg daily for treatment of candidemia, acute Fever, headache, nausea, vomiting, diarrhea, rash,
disseminated candidiasis, Candida peritonitis and thrombocytopenia, hepatic enzyme elevations,
abscesses; 150 mg daily for esophageal candidiasis; histamine-mediated symptoms including rash,
and 50 mg daily for prophylaxis of candida infections pruritus, facial swelling, and vasodilatation can occur
in HSCT recipients. during infusion.
Pediatric: 2 mg/kg/day (maximum 100 mg daily) for
candidemia and acute disseminated candidiasis,

Candida peritonitis and abscesses; 1 mg/kg/day
(maximum 50 mg daily) for prophylaxis of Candida
infections; for treatment of esophageal candidiasis,
3 mg/kg/day is used for children ≤30 kg and 2.5
mg/kg/day with a maximum 150 mg daily is used
for children ≥30 kg; neonatal dosing is 10 mg/kg/
day. Doses up to 7 mg/kg/day have been used for
disseminated candidiasis.
Nystatin PO Infants: 200 000 U, 4 times a day, after meals. Gastrointestinal tract symptoms, rash.
Children and adults: 400 000–600 000 U,
3 times a day, after meals.
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c i j
Posaconazole PO, IV Adults and adolescents : for prophylaxis of invasive Diarrhea, nausea, fever, vomiting, headache,
Aspergillus and Candida infectionsd: IV formulation is coughing, hypokalemia, rash, edema, headache,
approved only for use in patients 18 y or older. 300 anemia, neutropenia, thrombocytopenia, fatigue,
mg, IV, twice a day on first day, followed by 300 mg, thrombophlebitis, arthralgia, myalgia, fever;
IV, once daily starting on second day. interactions with P450 CYP3A4 substrate drugs
Oral suspension and delayed-release tablets can be used and can potentiate QT prolongation; posaconazole

in the age group 13 y and older; 300 mg delayed- injection should be avoided in patients with moderate
release tablets twice a day on the first day followed or severe renal impairment (creatinine clearance <50
by 300 mg once daily, starting on second day; or 200 mL/min), higher rate of adverse effects when trough
mg (5-mL) oral solution 3 times a day; duration of levels exceed 1 µg/mL.
therapy for both IV and oral is based on recovery
from neutropenia or immunosuppression; tablet
and liquid forms are not interchangeable given
bioavailability and dosing differences.
For oropharyngeal candidiasis: oral suspension 100 mg
(2.5 mL) twice a day on first day followed by 100 mg
once daily for 13 days.
For oropharyngeal candidiasis refractory to itraconazole
and/or fluconazole: oral suspension 400 mg (10
mL) twice a day; duration of therapy is based on the
severity of the patient’s underlying disease and clinical
response.
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920

Children: Non–FDA-approved dosing used by St.
Jude’s Children’s Research Hospital suggested
treatment dose range in those weighing <34 kg is
18–24 mg/kg/day and in those weighing ≥34 kg
is 800 mg/day, all divided into 4 doses; minimum
target trough concentrations for efficacy of 0.7 µg/
mL, progressing to ≥1.25 µg/mL if poor response;

IFI prophylaxisd: 4 mg/kg/dose (max 200 mg) 3 times
daily with target trough ≥0.7 µg/mL (patients with
GVHD may achieve lower levels); large variability in
resultant trough levels particularly in children <12 y
of age.
Terbinafine PO Children: once daily dosing. Common adverse events include headache, diarrhea,
Onychomycosis: 10–20 kg: 62.5 mg/day; 21–40 kg: 125 rash, dyspepsia, liver enzyme abnormalities, pruritus,
mg/day; >40 kg: 250 mg/day; treatment course of 12 taste disturbance, nausea, abdominal pain, and
wk for toenails, 6 wk for fingernails. flatulence; liver failure, sometimes leading to liver
Tinea capitis: <25 kg: 125 mg/day, 25–35 kg: 187.5 transplant or death, has been reported with the use of
mg/day; >35 kg: 250 mg once daily; treatment course oral terbinafine.
of 6 wk. Terbinafine is an inhibitor of CYP450 2D6 isozyme and
Adults: 250 mg, once daily. has an effect on metabolism of desipramine.
Drug interactions with cimetidine, fluconazole,
cyclosporine, rifampin, and caffeine have also been
reported.
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c d
Voriconazole IV Treatment or IFI prophylaxis in children: if 2–<12 y Concentration- or dose-related toxicities: hepatic
of age or 12–14 y of age and weight <50 kg: 9 mg/ toxicity, arrhythmias/QT prolongation, dermatologic
kg, IV, twice daily on day 1 of treatment; thereafter 8 reactions, visual disturbance, hallucinations, increased
mg/kg, IV, twice daily or 9 mg/kg, PO, twice daily; if liver enzymes and bilirubin, encephalopathy;
≥15 y of age or 12–14 y of age and weight ≥50 kg: 6 phototoxicity, rash; CNS related toxicities are more
mg/kg, IV, on day 1 of treatment; thereafter 4 mg/kg, associated with trough levels above 6 μg/mL; there

IV, twice daily or 200 mg, PO, twice daily; therapeutic have been postmarketing reports of pancreatitis
drug monitoring is needed to ensure trough levels 2–6 in pediatric patients; drug interactions or genetic
µg/mL. polymorphisms involving P450 CYP2C19 can
A simpler proposed oral regimen for IFI prophylaxisd: alter voriconazole pharmacokinetics markedly
200 mg, PO, twice daily if weight is ≥40 kg and 100 and enhance toxicity risk; has now been identified
mg, PO, twice daily if weight is <40 kg; if IV needed, as an independent risk factor for development of
then 4 mg/kg every 12 h is administered. cutaneous malignancies in lung transplant patients;
pharmacogenetic testing may lead to optimized
dosing earlier in the treatment course.
Voriconazole is not approved for a prophylaxis indication.

CYP indicates cytochrome P; GVDH, graft versus host disease; IFI, Invasive fungal infection; IT, intrathecal; IV, intravenous; PO, oral.
a
See package insert or listing in current edition of the Physicians’ Desk Reference or www.pdr.net (for registered users only).
b
Interactions with other drugs are common. Consult www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions and the Physicians’ Desk Reference (a drug
interaction reference or database) or a pharmacist before prescribing these medications.
c
Efficacy and safety have not been established for pediatric patients. Limited or no information about use in newborn infants is available.
d
Invasive fungal infection prophylaxis in at-risk pediatric patients with immunosuppression attributable to cancer or hematopoietic stem cell transplant.
e
Safety and effectiveness of anidulafungin in patients ≤16 years of age has not been established.
f
Experience with fluconazole in neonates is limited to pharmacokinetic studies in preterm newborn infants. Based on the prolonged half-life seen in preterm newborn infants (gestational age 26 to 29
weeks), these children, in the first 2 weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first 2 weeks, these children should be dosed
once daily.
g
Safety and effectiveness of isavuconazole in patients younger than 18 years have not been established.
h
Efficacy and safety in pediatric patients younger than 4 months of age have not been established.
i
IV formulation of posaconazole is recommended only for 18 years or older. For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage
and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.
j
Safety and effectiveness of posaconazole have been established in the age groups 13 years and older.
24/03/21 2:28 PM

Red Book Antifungals

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Table 4.8.

Recommended Doses of Parenteral and Oral Antifungal Drugs

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 913

followed by 50-mg daily dose thereafter for a minute.

infusion should not exceed 1.1 mg/minute.

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 914

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 915

Prophylaxis in children (when indicated)d: 6 mg/kg once

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 916

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 917

oropharyngeal and esophageal candidiasis.

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 918

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 919

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 920

Drug Route Dose (per day) Adverse Reactionsa,b

Red_Book_2020_SECTION 4-5_863-1026.indd 921

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