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: 400   Usually at least 6 cryptococcal          mg on Day 1         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 prevent                        daily dose of 200 relapse of                                mg 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 candidiasis                           Loading dose: 800   In general, the 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: 200   7 to 21 days (until mucosal candidiasis      candidiasis           mg to 400 mg on     oropharyngeal Day 1               candidiasis is in
Subsequent dose:    remission).
100 mg to 200 mg    Longer periods once daily          may be used in patients with severely compromised immune function.


                                   - Oesophageal         Loading dose: 200   14 to 30 days candidiasis           mg to 400 mg on     (until oesophageal
Day 1               candidiasis is in
Subsequent dose:    remission).
100 mg to 200 mg    Longer periods once daily          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 atrophic    50 mg once daily    14 days 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 relapse    - Oropharyngeal       100 mg to 200 mg    An indefinite of mucosal               candidiasis           once daily or 200   period for patients candidiasis in                                 mg 3 times per      with chronic patients infected                              week.               immune with HIV who are at                                                suppression.
high risk of             - Oesophageal         100 mg to 200 mg    An indefinite experiencing relapse     candidiasis           once daily or 200   period for patients mg 3 times per      with chronic week                immune suppression.
Prophylaxis of                                 200 mg to 400 mg    Treatment should candidal infections                            once daily          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 to once daily                       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 disease cryptococcal meningitis in children with high risk of recurrence
- Prophylaxis of Candida in     Dose: 3 to 12 mg/kg once         Depending on the immunocompromised               daily                            extent and duration of patients                                                         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 for       A maximum dose of 12 (0 to 14 days)             infants, toddlers and children   mg/kg every 72 hours should should be given every 72         not be exceeded hours
Term newborn infants       The same mg/kg dose as for       A maximum dose of 12 (from 15 to 27 days)       infants, toddlers and children   mg/kg every 48 hours should should be given every 48         not be exceeded 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. The capsule formulation is not adapted for use in infants and small children. Oral liquid formulations of fluconazole are available that are more suitable in this population.

Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute.
Triflucan I.V. 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 Triflucan I.V. 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.