1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
DIFLUCAN contains as its active ingredient fluconazole 50 mg, 100 mg and 150
mg as capsules, and as 2 mg/ml in a saline solution for intravenous
Fluconazole is a bis-triazole, having the following chemical name : 2-(2,
4-difluorophenyl)-1, 3-bis (1 H, 2, 4-triazol-1-yl)2-propanol. It has a
molecular weight of 306.3.
3. PHARMACEUTICAL FORM
Capsule and solution for intravenous infusion.
4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
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.
1. Cryptococcosis, including cryptococcal meningitis and infections of other
sites (e.g., pulmonary, cutaneous). Normal hosts and patients with AIDS,
organ transplants or other causes of immunosuppression may be treated.
Fluconazole can be used as maintenance therapy to prevent relapse of
cryptococcal disease in patients with AIDS.
2. Systemic candidiasis, including candidemia, disseminated candidiasis and
other forms of invasive candidal infection. These include infections of the
peritoneum, endocardium, eye, and pulmonary and urinary tracts. Patients
with malignancy, in intensive care units, receiving cytotoxic or
immunosuppressive therapy, or with other factors predisposing to candidal
infection may be treated.
3. Mucosal candidiasis. These include oropharyngeal, esophageal,
non-invasive bronchopulmonary infections, candiduria, mucocutaneous and
chronic oral atrophic candidiasis (denture sore mouth). Normal hosts and
patients with compromised immune function may be treated. Prevention of
relapse of oropharyngeal candidiasis in patients with AIDS.
4. Genital candidiasis. Vaginal candidiasis, acute or recurrent; and
prophylaxis to reduce the incidence of recurrent vaginal candidiasis (3 or
more episodes a year). Candidal balanitis.
5. Prevention of fungal
infections in patients with malignancy who are predisposed to such
infections as a result of cytotoxic chemotherapy or radiotherapy.
6. Dermatomycosis including tinea pedis, tinea corporis, tinea cruris, tinea
versicolor, and dermal candida infections.
4.2 Posology and Method of
The daily dose of fluconazole should be based on the nature and severity of
the fungal infection. Most cases of vaginal candidiasis respond to single
dose therapy. Therapy for those types of infections requiring multiple dose
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.
Use In Adults
1. For cryptococcal meningitis and cryptococcal infections at other sites,
the usual dose is 400 mg on the first day followed by 200 to 400 mg once
daily. Duration of treatment for cryptococcal infections will depend on the
clinical and mycological response, but is usually at least 6-8 weeks for
For the prevention of relapse of cryptococcal meningitis in patients with
AIDS, after the patient receives a full course of primary therapy,
fluconazole may be administered indefinitely at a daily dose of 200 mg.
2. For candidemia, disseminated candidiasis and other invasive candidal
infections, the usual dose is 400 mg on the first day followed by 200 mg
daily. Depending on the clinical response, the dose may be increased to 400
mg daily. Duration of treatment is based upon the clinical response.
3. For oropharyngeal candidiasis, the usual dose is 50 to 100 mg once daily
for 7-14 days. If necessary, treatment can be continued for longer periods
in patients with severely compromised immune function. For atrophic oral
candidiasis associated with dentures, the usual dose is 50 mg once daily for
14 days administered concurrently with local antiseptic measures to the
For other candidal infections of mucosa except genital candidiasis [see
below] (e.g., esophagitis, non-invasive bronchopulmonary infections,
candiduria, mucocutaneous candidiasis, etc.) the usual effective dose is 50
to 100 mg daily, given for 14-30 days.
For the prevention of relapse of oropharyngeal candidiasis in patients with
AIDS, after the patient receives a full course of primary therapy,
fluconazole may be administered at a 150 mg once weekly dose.
4. For the treatment of vaginal candidiasis, fluconazole 150 mg should be
administered as a single oral dose.
To reduce the incidence of recurrent vaginal candidiasis, a 150 mg once
monthly dose may be used. The duration of therapy should be individualized,
but ranges from 4-12 months. Some patients may require more frequent dosing.
For Candida balanitis, fluconazole 150 mg should be administered as a single
5. The recommended fluconazole dosage for the prevention of candidiasis is
50 to 400 mg once daily, based on the patient's risk for developing fungal
infection. For patients at high risk of systemic infection, e.g., patients
who are anticipated to have profound or prolonged neutropenia, the
recommended daily dose is 400 mg once daily. Fluconazole administration
should start several days before the anticipated onset of neutropenia and
continue for 7 days after the neutrophil count rises above 1000 cells per mm3.
6. For dermal infections
including tinea pedis, corporis, cruris and candida infections the
recommended dosage is 150 mg once weekly or 50 mg once daily. Duration of
treatment is normally 2 to 4 weeks but tinea pedis may require treatment for
up to 6 weeks.
For tinea versicolor, the recommended dose is 300 mg once weekly for 2
weeks; a third weekly dose of 300 mg may be needed in some patients,
whereas, in some patients, a single dose of 300 to 400 mg may be sufficient.
An alternate dosing regimen is 50 mg once daily for 2 to 4 weeks.
Use In Children
As with similar infections in adults, the duration of treatment is based on
the clinical and mycological response. The maximum adult daily dosage should
not be exceeded in children. Fluconazole is administered as a single dose
The recommended dosage fluconazole for mucosal candidiasis is 3 mg/kg daily.
A loading dose of 6 mg/kg maybe
used on the first day to achieve steady state levels more rapidly.
For the treatment of systemic candidiasis and cryptococcal infections, the
recommended dosage is 6 to 12 mg/kg daily, depending on the severity of the
For the prevention of fungal infections in immunocompromised patients
considered at risk as a consequence of neutropenia following cytotoxic
chemotherapy or radiotherapy, the dose should be 3 to 12 mg/kg daily,
depending on the extent and duration of the induced neutropenia (see Use In
Adults). (For children with impaired renal functions, see Use In Renal
Use In Children below 4 weeks of age and younger
Neonates excrete fluconazole slowly. In the first two weeks of life, the
same mg/kg dosing as in older children should be used but administered every
72 hours. During weeks 2-4 of life, the same dose should be given every 48
Use In Elderly
Where there is no evidence of renal impairment, normal dosage
recommendations should be adopted. For patients with renal impairment (creatinine
clearance <50 ml/min) the dosage schedule should be adjusted as described
Use In Renal Impairment
Fluconazole is predominantly excreted in the urine as unchanged drug. No
adjustments in single-dose therapy are necessary. In patients (including
children) 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 the following table:
|Creatinine Clearance (ml/min)
||Dosage Intervals/ Daily Dose
||100% or 24 hours
|<50 (no dialysis)
||50% or 48 hours
||100% after each dialysis
These are suggested dose
adjustments based on pharmacokinetics following administration of single
doses. Further adjustment may be needed depending on clinical condition.
Fluconazole maybe administered either orally or by intravenous infusion at a
rate not exceeding 10 ml/minute, the route being dependent on the clinical
state of the patient. On transferring from the intravenous to the oral
route, or vice versa, there is no need to change the daily dosage.
Fluconazole is formulated in 0.9% sodium chloride solution, each 200 mg (100
ml bottle) containing 15 mmol each of Na+ and C1-. Because fluconazole is
available as a dilute saline solution, in patients requiring sodium or fluid
restriction, consideration should be given to the rate of fluid