Posology : מינונים

4.2     Posology and method of administration
Posology

The dose should be based on the nature and severity of the fungal infection. Treatment of infections requiring multiple dosing 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.
Adults

Indications                            Posology        Duration of treatment 
Cryptococcosis            - Treatment of         Loading dose:        Usually at least 6 to 8 weeks.
cryptococcal           400 mg on Day 1      In life threatening infections meningitis             Subsequent dose:     the daily dose can be increased 200 mg to 400        to 800 mg mg once daily
- Maintenance therapy 200 mg once           Indefinitely at a daily dose of to prevent relapse of  daily                200 mg cryptococcal meningitis in patients with high risk of recurrence.
Coccidioidomycosis                               200 mg to 400        11 months up to 24 months or mg once daily        longer depending on the patient. 800 mg daily may be considered for some infections and especially for meningeal disease
Invasive candidiasis                               Loading dose:      In general, the recommended 800 mg on Day 1    duration of therapy for
Subsequent dose:   candidemia is for 2 weeks
400 mg once        after first negative blood daily              culture result and resolution of signs and symptoms attributable to candidemia.


Indications                             Posology        Duration of treatment 
Treatment of              - Oropharyngeal           Loading dose:       7 to 21 days (until mucosal candidiasis       candidiasis               200 mg to 400       oropharyngeal candidiasis is in mg on Day 1         remission).
Subsequent dose:    Longer periods may be used in
100 mg to 200       patients with severely mg once daily       compromised immune function
- Oesophageal             Loading dose:       14 to 30 days (until candidiasis               200 mg to 400       oesophageal candidiasis is in mg on Day 1         remission).
Subsequent dose:    Longer periods may be used in
100 mg to 200       patients with severely mg once daily       compromised immune function
- Candiduria              200 mg to 400       7 to 21 days. Longer periods mg once daily       may be used in patients with severely compromised immune function.
- Chronic atrophic        50 mg once daily    14 days candidiasis
- Chronic                 50 mg to 100 mg     Up to 28 days. Longer periods mucocutaneous             once daily          depending on both the severity candidiasis                                   of infection or underlying immune compromisation and infection
Prevention of             - Oropharyngeal           100 mg to 200       An indefinite period for relapse of mucosal        candidiasis               mg once daily or    patients with chronic immune candidiasis in                                      200 mg 3 times      suppression patients infected                                   per week.
with HIV who are          - Oesophageal             100 mg to 200       An indefinite period for at high risk of           candidiasis               mg once daily or    patients with chronic immune experiencing                                        200 mg 3 times      suppression relapse                                             per week

Genital candidiasis       - Acute vaginal           150 mg              Single dose candidiasis
- Candidal balanitis
- Treatment and           150 mg every        Maintenance dose: 6 months.
prophylaxis of            third day for a recurrent vaginal         total of 3 doses candidiasis (4 or more    (day 1, 4, and 7) episodes a year)          followed by
150 mg once weekly maintenance dose
Dermatomycosis            - tinea pedis,            150 mg once         2 to 4 weeks, tinea pedis may - tinea corporis,         weekly or 50 mg     require treatment for up to 6 - tinea cruris,           once daily          weeks
- candida infections
- tinea versicolor        300 mg to 400       1 to 3 weeks mg once weekly
50 mg once daily    2 to 4 weeks

Indications                             Posology         Duration of treatment 
- tinea unguium           150 mg once         Treatment should be continued (onychomycosis)           weekly              until infected nail is replaced (uninfected nail grows in).
Regrowth of fingernails and toenails normally requires 3 to
6 months and 6 to 12 months,
respectively. However, growth rates may vary widely in individuals, and by age. After successful treatment of long- term chronic infections, nails occasionally remain disfigured.
Prophylaxis of                                      200 mg to 400       Treatment should start several candidal infections                                 mg once daily       days before the anticipated in patients with                                                        onset of neutropenia and prolonged                                                               continue for 7 days after neutropenia                                                             recovery from neutropenia after the neutrophil count rises above 1000 cells per mm3.


Special populations
Elderly
Dosage should be adjusted based on the renal function (see “Renal impairment”).

Renal impairment
Fluconazole is predominantly excreted in the urine as unchanged active substance. No adjustments in single dose therapy are necessary. In patients (including paediatric population) with impaired renal function who will receive multiple doses of fluconazole, an initial dose of 50 mg to 400 mg should be given, based on the recommended daily dose for the indication.
After this initial loading dose, the daily dose (according to indication) should be based on the following table:

Creatinine clearance (ml/min)                      Percent of recommended dose >50                                                100%
≤50 (no haemodialysis)                             50%
Haemodialysis                                      100% after each haemodialysis 
Patients on haemodialysis should receive 100% of the recommended dose after each haemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

Hepatic impairment
Limited data are available in patients with hepatic impairment, therefore fluconazole should be administered with caution to patients with liver dysfunction (see sections 4.4 and 4.8).

Paediatric population
A maximum dose of 400 mg daily should not be exceeded in paediatric population.

As with similar infections in adults, the duration of treatment is based on the clinical and mycological response. Fluconazole is administered as a single daily dose.


For paediatric patients with impaired renal function, see dosing in “Renal impairment”. The pharmacokinetics of fluconazole has not been studied in paediatric population with renal insufficiency (for “Term newborn infants” who often exhibit primarily renal immaturity please see below).

Infants, toddlers and children (from 28 days to 11 years old):

Indication                            Posology                       Recommendations - Mucosal candidiasis               Initial dose: 6 mg/kg               Initial dose may be used on the Subsequent dose: 3 mg/kg once       first day to achieve steady state daily                               levels more rapidly
- Invasive candidiasis              Dose: 6 to 12 mg/kg once daily      Depending on the severity of - Cryptococcal meningitis                                               the disease 
- Maintenance therapy to            Dose: 6 mg/kg once daily            Depending on the severity of prevent relapse of cryptococcal                                         the disease meningitis in children with high risk of recurrence
- Prophylaxis of Candida in         Dose: 3 to 12 mg/kg once daily      Depending on the extent and immunocompromised patients                                              duration of the induced neutropenia (see Adults posology)

Adolescents (from 12 to 17 years old):
Depending on the weight and pubertal development, the prescriber would need to assess which posology (adults or children) is the most appropriate. Clinical data indicate that children have a higher fluconazole clearance than observed for adults. A dose of 100, 200 and 400 mg in adults corresponds to a 3, 6 and 12 mg/kg dose in children to obtain a comparable systemic exposure.

Safety and efficacy for genital candidiasis indication in paediatric population has not been established. Current available safety data for other paediatric indications are described in section 4.8. If treatment for genital candidiasis is imperative in adolescents (from 12 to 17 years old), the posology should be the same as adults posology.

Term newborn infants (0 to 27 days):
Neonates excrete fluconazole slowly.
There are few pharmacokinetic data to support this posology in term newborn infants (see section 5.2).

Age group                              Posology                      Recommendations Term newborn infants (0 to          The same mg/kg dose as for          A maximum dose of 12 mg/kg 14 days)                            infants, toddlers and children      every 72 hours should not be should be given every 72 hours      exceeded
Term newborn infants (from 15       The same mg/kg dose as for          A maximum dose of 12 mg/kg to 27 days)                         infants, toddlers and children      every 48 hours should not be should be given every 48 hours      exceeded


Method of administration
Fluconazole may be administered either orally (Capsules and Powder for Oral Suspension) or by intravenous infusion (Solution for Infusion), 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 dose.

The physician should prescribe the most appropriate pharmaceutical form and strength according to age, weight and dose. The capsule formulation is not adapted for use in infants and small children. Oral liquid formulation of fluconazole is available that is more suitable in this population.

Diflucan can be taken with or without food.

For instructions on reconstitution of the medicinal product before administration, see section 6.6. The reconstituted suspension will provide a white to off-white orange-flavoured suspension after reconstitution.

For dose conversion of the powder for oral suspension from mg/ml to ml/kg body weight (BW) for paediatric patients, see section 6.6.

For adult patients, please calculate the dose in ml to administer according to the posology in mg recommended and the product strength.