INDICATIONS
Fluconazole is indicated for the treatment of:- 1. Vaginal Candidiasis (vaginal yeast
infections due to Candida).
- 2. Oropharyngeal and esophageal
candidiasis. In open
noncomparative studies of relatively small numbers of patients,
fluconazole was also effective for the treatment
of Candida urinary tract
infections, peritonitis, and systemic Candida
infections including candidemia, disseminated
candidiasis, and pneumonia.
- 3. Cryptococcal meningitis. Before prescribing fluconazole
for AIDS patients with cryptococcal meningitis, please
see CLINICAL STUDIES. Studies comparing fluconazole
to amphotericin B in non-HIV infected patients have
not been conducted.
Prophylaxis: Fluconazole is also
indicated to decrease the incidence of candidiasis in patients
undergoing bone wmarrow transplantation who receive cytotoxic
chemotherapy and/or radiation therapy.
Specimens for fungal culture and other relevant laboratory
studies (serology, histopathology) should be obtained
prior to therapy to isolate and identify causative organisms.
Therapy may be instituted before the results of the cultures
and other laboratory studies are known; however, once
these results become available, anti-infective therapy
should be adjusted accordingly.
DOSAGE AND ADMINISTRATION
Dosage and Administration in Adults
Single Dose: Vaginal candidiasis:
The recommended dosage of fluconazole for vaginal candidiasis
is 150 mg as a single oral dose.
Multiple Dose: SINCE ORAL ABSORPTION
IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE
IS THE SAME FOR ORAL (TABLETS AND SUSPENSION) AND INTRAVENOUS
ADMINISTRATION. In general, a leading dose of twice the
daily dose is recommended on the first day of therapy
to result in plasma concentrations close to steady-state
by the second day of therapy.
The daily dose of fluconazole for the treatment of infections
other than vaginal candidiasis should be based on the
infecting organism and the patient's response to therapy.
Treatment should be continued until clinical parameters
or laboratory tests indicate that active fungal infection
has subsided. An inadequate period of treatment may lead
to recurrence of active infection. Patients with AIDS
and cryptococcal meningitis or recurrent oropharyngeal
candidiasis usually require maintenance therapy to prevent
relapse.
Oropharyngeal Candidiasis:
The recommended dosage of fluconazole for oropharyngeal
candidiasis is 200 mg on the first day, followed by 100
mg once daily. Clinical evidence of oropharyngeal candidiasis
generally resolves within several days, but treatment
should be continued for at least 2 weeks to decrease the
likelihood of relapse.
Esophageal Candidiasis: The
recommended dosage of fluconazole for esophageal candidiasis
is 200 mg on the first day, followed by 100 mg once daily.
Doses up to 400 mg/day may be used, based on medical judgment
of the patient's response to therapy. Patients with esophageal
candidiasis should be treated for a minimum of three weeks
and for at least two weeks following resolution of symptoms.
Systemic Candida Infections:
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.
Urinary Tract Infection and Peritonitis:
For the treatment of Candida urinary tract infections
and peritonitis, daily doses of 50-200 mg have been used
in open, noncomparative studies of small numbers of patients.
Cryptococcal Meningitis: The
recommended dosage for treatment of acute cryptococcal
meningitis is 400 mg on the first day, followed by 200
mg once daily. A dosage of 400 mg once daily may be used,
based on medical judgment of the patient's response to
therapy. The recommended duration of treatment for initial
therapy of cryptococcal meningitis is 10-12 weeks after
the cerebrospinal fluid becomes culture negative. The
recommended dosage of fluconazole for suppression of relapse
of cryptococcal meningitis in patients with AIDS is 200
mg once daily.
Prophylaxis in Patients Undergoing Bone Marrow
Transplantation: The recommended fluconazole
daily dosage for the prevention of candidiasis of patients
undergoing bone wmarrow transplantation is 400 mg once
daily. Patients who are anticipated to have severe granulocytopenia
(less than 500 neutrophils per cu mm) should start fluconazole
prophylaxis several days before the anticipated onset
of neutropenia, and continue for 7 days after the neutrophil
count rises above 1000 cells per cu mm.
Dosage and Administration in Children
The following dose equivalency scheme should generally provide
equivalent exposure in pediatric and adult patients (see
TABLE 7).
| TABLE 7 |
| Pediatric Patients |
Adults |
| 3 mg/kg |
100 mg |
| 6 mg/kg |
200 mg |
| 12* mg/kg |
400 mg |
| * Some older
children may have clearances similar to that of adults.
Absolute doses exceeding 600 mg/day are not recommended. |
Experience with fluconazole in neonates is limited to pharmacokinetic
studies in premature newborns. (See CLINICAL PHARMACOLOGY.)
Based on the prolonged half-life seen in premature newborns
(gestational age 26 to 29 weeks), these children, in the
first two weeks of life, should receive the same dosage
(mg/kg) as in older children, but administered every 72
hours. After the first two weeks, these children should
be dosed once daily. No information regarding fluconazole
pharmacokinetics in full-term newborns is available.
Oropharyngeal Candidiasis:
The recommended dosage of fluconazole for oropharyngeal
candidiasis in children is 6 mg/kg on the first day, followed
by 3 mg/kg once daily. Treatment should be administered
for at least 2 weeks to decrease the likelihood of relapse.
Esophageal Candidiasis: For
the treatment of esophageal candidiasis, the recommended
dosage of fluconazole in children is 6 mg/kg on the first
day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day
may be used based on medical judgment of the patient's
response to therapy. Patients with esophageal candidiasis
should be treated for a minimum of three weeks for at
least 2 weeks following the resolution of symptoms.
Systemic Candida Infections: For
the treatment of candidemia and disseminated Candida infections,
daily doses of 6-12 mg/kg/day have been used in an open,
noncomparative study of a small number of children.
Cryptococcal Meningitis: For
the treatment of acute cryptococcal meningitis, the recommended
dosage is 12 mg/kg on the first day, followed by 6 mg/kg
once daily. A dosage of 12 mg/kg once daily may be used,
based on medical judgment of the patient's response to
therapy. The recommended duration of treatment for initial
therapy of cryptococcal meningitis is 10-12 weeks after
the cerebrospinal fluid becomes culture negative. For
suppression of relapse of cryptococcal meningitis in children
with AIDS, the recommended dose of fluconazole is 6 mg/kg
once daily.
Dosage in Patients with Impaired Renal Function
Fluconazole is cleared primarily by renal excretion as unchanged
drug. There is no need to adjust single dose therapy for
vaginal candidiasis because of impaired renal function.
In patients with impaired renal function who will receive
multiple doses of fluconazole, an initial loading dose of
50 to 400 mg should be given. After the loading dose, the
daily dose (according to indication) should be based on
TABLE 8
| TABLE 8 |
| Creatinine Clearance (ml/min) |
Percent of Recommended
Dose |
| >50 |
100% |
| 11-50 |
50% |
| Patients receiving regular
hemodialysis |
One recommended dose after
each dialysis |
These are suggested dose adjustments based on pharmacokinetics
following administration of multiple doses. Further adjustment
may be needed depending upon clinical condition.
When serum creatinine is the only measure of renal function
available, the formula below (based on sex, weight, and
age of the patient) should be used to estimate the creatinine
clearance
Males: [Weight (kg) ´
(140-Age)] ¸
[72 ´ Serum Creatnine
(mg/100ml]
Females: 0.85 ´ the
above value
Although the pharmacokinetics of fluconazole has not been
studied in children with renal insufficiency, dosage reduction
in children with renal insufficiency should parallel that
recommended for adults. The formula below may be used to
estimate creatinine clearance in children:
[K ´
Linear Length or Height (cm)] ¸
[Serum Creatnine (mg/100 ml)]
K=0.55 for children older than 1 year and 0.45 for
infants.
Administration
Fluconazole may be administered either orally or by intravenous
infusion. Diflucan injection has been used safely for
up to fourteen days of intravenous therapy. The intravenous
infusion of fluconazole should be administered at a maximum
rate of approximately 200 mg/hour, given as a continuous
infusion.
Fluconazole injections in glass and Viaflex Plus plastic
containers are intended only for intravenous administration
using sterile equipment.
Parenteral drug products should be inspected visually
for particulate matter and discoloration prior to administration
whenever solution and container permit.
Do not use if the solution is cloudy or precipitated or
if the seal is not intact.
Directions for Mixing the Oral Suspension
Prepare a suspension at time of dispensing as follows: tap
bottle until all the powder flows freely. To reconstitute,
add 24 ml of distilled water or Purified Water (USP) to
fluconazole bottle and shake vigorously to suspend powder.
Each bottle will deliver 35 ml of suspension. The concentrations
of the reconstituted suspensions are as found in TABLE 9.
| TABLE
9 |
| Fluconazole Content
per Bottle |
Concentration of
Reconstituted Suspension |
| 350 mg |
10 mg/ml |
| 1400 mg |
40 mg/ml |
Note: Shake oral suspension well before
using. Store reconstituted suspension between 86°F (30°C)
and 41°F (5°C) and discard unused portion after
2 weeks. Protect from freezing.
Directions for IV Use of Fluconazole in Viaflex
Plus Plastic Containers
Do not remove unit from overwrap until ready for use.
The overwrap is a moisture barrier. The inner bag maintains
the sterility of the product.
CAUTION: Do not use plastic
containers in series connections. Such use could result
in air embolism due to residual air being drawn from the
primary container before administration of the fluid from
the secondary container is completed.
To Open: Tear overwrap down
side at slit and remove solution container. Some opacity
of the plastic due to moisture absorption during the sterilization
process may be observed. This is normal and does not affect
the solution quality or safety. The opacity will diminish
gradually. After removing overwrap, check for minute leaks
by squeezing inner bag firmly. If leaks are found, discard
solution as sterility may be impaired.
DO NOT ADD SUPPLEMENTARY MEDICATION.
Preparation for Administration
- 1. Suspend container
from eyelet support.
- 2. Remove plastic
protector from outlet
port at bottom of container.
- 3. Attach administration
set. Refer to complete directions accompanying set.
HOW SUPPLIED
Diflucan Tablets: Pink trapezoidal tablets containing
50, 100 or 200 mg of fluconazole are packaged in bottles
or unit dose blisters. The 150 mg fluconazole tablets
are pink and oval shaped, packaged in a single dose unit
blister.
Storage: Store tablets below
86°F (30°C).
Diflucan for Oral Suspension: Diflucan for oral suspension
is supplied as an orange-flavored powder to provide 35
ml per bottle.
Storage: Store dry powder below
86°F (30°C). Store reconstituted suspension between
86°F (30°C) and 41°F (5°C) and discard
unused portion after 2 weeks. Protect from freezing.
Diflucan Injections: Diflucan
injections for intravenous infusion administration are
formulated as sterile iso-osmotic solutions containing
2 mg/ml of fluconazole. They are supplied in glass bottles
or in Viaflex Plus plastic containers containing volumes
of 100 ml or 200 ml affording doses of 200 mg and 400
mg of fluconazole, respectively.
Storage: Store between 86°F
(30°C) and 41°F (5°C). Protect from freezing.Diflucan
injections in Viaflex Plus plastic containers are available
in both sodium chloride and dextrose diluents. Storage:
Store between 77°F (25°C) and 41°F (5°C).
Brief exposure up to 104°F (40°C) does not adversely
affect the product. Protect from freezing.
PRODUCT LISTING
| Powder
For Reconstitution - Oral - 10 mg/ml |
| 60 ml |
Diflucan,
Roerig |
00049-3440-19 |
| Powder
For Reconstitution - Oral - 40 mg/ml |
| 60 ml |
Diflucan,
Roerig |
00049-3450-19 |
| Solution
- Intravenous - 200 mg/100 ml |
| 100 ml
x 6 |
Diflucan,
Roerig |
00049-3371-26 |
| 100 ml
x 6 |
Diflucan,
Roerig |
00049-3435-26 |
| 100 ml
x 6 |
Diflucan,
Roerig |
00049-3437-26 |
| Solution
- Intravenous - 400 mg/200 ml |
| 200 ml
x 6 |
Diflucan,
Roerig |
00049-3372-26 |
| 200 ml
x 6 |
Diflucan,
Roerig |
00049-3436-26 |
| 200 ml
x 6 |
Diflucan,
Roerig |
00049-3438-26 |
| Tablet
- Oral - 50 mg |
| 30's |
Diflucan,
Roerig |
00049-3410-30 |
| Tablet
- Oral - 100 mg |
| 30's |
Diflucan,
Roerig |
00049-3420-30 |
| Tablet
- Oral - 150 mg |
| 12's |
Diflucan, Roerig |
00049-3500-79 |
| Tablet
- Oral - 200 mg |
| 30's |
Diflucan, Roerig |
00049-3430-30 |
|
|
