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 cryptococcal         400 mg on Day 1       weeks. In life threatening meningitis           Subsequent dose:      infections the daily dose
200 mg to 400         can be increased to 800 mg once daily         mg.

- Maintenance      200 mg once daily       Indefinitely at a daily dose therapy to prevent                         of 200 mg.
relapse of cryptococcal meningitis in patients with high risk of recurrence


Coccidioidomycosis                               200 mg to 400 mg      11 months up to 24 once daily            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 duration of Subsequent dose:    therapy for candidemia is
400 mg once daily   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 (until mucosal                  candidiasis       200 mg to 400       oropharyngeal candidiasis candidiasis                                mg on Day 1         is in remission).
Subsequent dose:    Longer periods may be
100 mg to 200       used in patients with mg once daily       severely compromised immune function.

- Oesophageal     Loading dose:       14 to 30 days (until candidiasis       200 mg to 400       oesophageal candidiasis mg on Day 1         is in remission).
Subsequent dose:    Longer periods may be
100 mg to 200       used in patients with mg once daily       severely compromised immune function.

- Candiduria      200 mg to 400       7 to 21 days. Longer mg once daily       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. Longer mucocutaneous     once daily          periods depending on candidiasis                           both the severity of infection or underlying immune compromisation and infection.

Prevention of relapse    - Oropharyngeal   100 mg to 200       An indefinite period for of mucosal               candidiasis       mg once daily or    patients with chronic candidiasis in                             200 mg 3 times      immune suppression.
patients infected with                     per week
HIV who are at high risk of experiencing relapse
- Oesophageal     100 mg to 200       An indefinite period for candidiasis       mg once daily or    patients with chronic
200 mg 3 times      immune suppression.
per week
Prophylaxis of                                   200 mg to 400 mg      Treatment should start candidal infections                              once daily            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:               used on the first
3 mg/kg once daily             day to achieve steady state levels more rapidly


- Invasive candidiasis        Dose: 6 to 12 mg/kg            Depending on - Cryptococcal meningitis     once daily                     the severity of the disease
- Maintenance therapy to      Dose: 6 mg/kg once daily       Depending on prevent relapse of                                           the severity of cryptococcal meningitis in                                   the disease children with high risk of recurrence
- Prophylaxis of Candida      Dose: 3 to 12 mg/kg            Depending on the in immunocompromised          once daily                     extent and 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.

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            The same mg/kg dose as          A maximum dose of infants (0 to 14        for infants, toddlers and       12 mg/kg every 72 hours days)                   children should be given        should not be exceeded every 72 hours
Term newborn            The same mg/kg dose as          A maximum dose of infants (from 15 to     for infants, toddlers and       12 mg/kg every 48 hours 27 days)                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 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.
      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. Fluconazole MBI 2 mg/ml 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 Fluconazole MBI 2 mg/ml 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.