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 cryptococcal          400 mg on Day 1     6 to 8 weeks. In meningitis            Subsequent dose:    life threatening
200 mg to 400 mg    infections the once daily          daily dose can be increased to
800 mg
- Maintenance         200 mg once daily   Indefinitely at a therapy to                                daily dose of prevent relapse                           200 mg of cryptococcal meningitis in patients with high risk of recurrence

Coccidioidomycosis                        200 mg to 400 mg    11 months up to once daily          24 months or longer depending on the patient.
800 mg daily may be considered for some infections and especially for meningeal disease
Invasive                                  Loading dose:       In general, the candidiasis                               800 mg on Day 1     recommended Subsequent dose:    duration of
400 mg once daily   therapy for candidemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidemia
Treatment of         - Oropharyngeal      Loading dose:       7 to 21 days mucosal              candidiasis          200 mg to 400 mg    (until candidiasis                               on Day 1            oropharyngeal Subsequent dose:    candidiasis is in
100 mg to 200 mg    remission).
once daily          Longer periods may be used in patients with severely compromised immune function
- Oesophageal        Loading dose:       14 to 30 days candidiasis          200 mg to 400 mg    (until on Day 1            oesophageal
Subsequent dose:    candidiasis is in
100 mg to 200 mg    remission).
once daily          Longer periods may be used in patients with severely compromised immune function


- Candiduria         200 mg to 400 mg    7 to 21 days.
once daily          Longer periods may be used in patients with severely compromised immune function
- Chronic            50 mg once daily    14 days atrophic candidiasis
- Chronic            50 mg to 100 mg     Up to 28 days.
mucocutaneous        once daily          Longer periods candidiasis                              depending on both the severity of infection or underlying immune compromisation and infection
Prevention of         - Oropharyngeal      100 mg to 200 mg    An indefinite relapse of mucosal    candidiasis          once daily or 200   period for candidiasis in                             mg 3 times per      patients with patients infected                          week.               chronic immune with HIV who are                                               suppression at high risk of       - Oesophageal        100 mg to 200 mg    An indefinite experiencing          candidiasis          once daily or 200   period for relapse                                    mg 3 times per      patients with week                chronic immune suppression
Prophylaxis of                             200 mg to 400 mg    Treatment candidal infections                        once daily          should start several days before the anticipated onset of neutropenia and continue for
7 days after 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 Subsequent dose: 3 mg/kg used on the first day once daily                    to achieve steady state levels more rapidly
- Invasive candidiasis       Dose: 6 to 12 mg/kg once      Depending on the - Cryptococcal meningitis daily                            severity of the disease
- Maintenance therapy to     Dose: 6 mg/kg once daily      Depending on the prevent relapse of                                         severity of the cryptococcal meningitis in                                 disease children with high risk of recurrence
- Prophylaxis of Candida Dose: 3 to 12 mg/kg once          Depending on the in immunocompromised         daily                         extent and duration patients                                                   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.

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

Method of administration
Fluconazole may be administered either orally 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.

Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute. Stabilanol is formulated in sodium chloride 9 mg/ml (0.9%) solution for infusion, each 200 mg (100 ml bottle) containing 15 mmol each of Na+ and C1-. Because Stabilanol is available as a dilute sodium chloride solution, in patients requiring sodium or fluid restriction, consideration should be given to the rate of fluid administration.

For instruction on dilution of the medicinal product before administration, see section 6.6.