Posology : מינונים

4.2.   Posology and method of administration

Posology
The dose should be based on the nature and severity of the fungal infection. The treatment of infections requiring multiple dosing should be continued until clinical parameters or laboratory results show that the active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of the active infection.

Adults:

Indications                                         Posology                   Duration of treatment Cryptococcosis         Treatment of                 Loading dose:              Usually at least 6 to 8 cryptococcal meningitis      400 mg on Day 1            weeks. In life threatening Subsequent dose:           infections the daily dose
200 mg to 400 mg daily     can be increased to 800 mg
Maintenance therapy to       200 mg daily               Indefinitely at a daily prevent relapse of                                      dose of 200 mg cryptococcal meningitis in patients with high risk of recurrence
Coccidioidomycosis                                  200 mg to 400 mg           11 months up to 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:              In general, the 800 mg on Day 1            recommended duration of
Subsequent dose:           therapy for candidemia is
400 mg 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   candidiasis               200 mg to 400 mg on      oropharyngeal candidiasis Day 1                    is in remission).
Subsequent dose:         Longer periods may be
100 mg to 200 mg daily   used in patients with severely compromised immune function
Oesophageal candidiasis   Loading dose:            14 to 30 days (until 200 mg to 400 mg on      oesophageal candidiasis is
Day 1                    in remission).
Subsequent dose:         Longer periods may be
100 mg to 200 mg daily   used in patients with severely compromised immune function
Candiduria                200 mg to 400 mg daily   7 to 21 days. Longer periods may be used in patients with severely compromised immune function.
Chronic atrophic          50 mg daily              14 days candidiasis
Chronic mucocutaneous     50 mg to 100 mg daily    Up to 28 days. Longer candidiasis                                        periods depending on both the severity of infection or underlying immune compromisation and infection
Prevention of         Oropharyngeal             100 mg to 200 mg daily   An indefinite period for relapse of mucosal    candidiasis               or 200 mg daily or 200   patients with chronic candidiasis in                                  mg 3 times per week      immune suppression patients infected     Oesophageal candidiasis   100 mg to 200 mg daily   An indefinite period for with HIV who are                                or 200 mg 3 times per    patients with chronic at high risk of                                 week                     immune suppression experiencing relapse
Prophylaxis of                                  200 mg to 400 mg         Treatment should start candidal infections                                                      several days before the in patients                                                              anticipated onset of neutropenia and continue for 7 days after recovery from neutropenia after the neutrophil count rises above 1 000 cells per mm3.


Special populations

Older people
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
Percentage of recommended dose
(ml/min)
> 50                            100%
≤ 50 (no dialysis)              50%
Regular dialysis                100% after each dialysis

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; 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 first Subsequent dose: 3 mg/kg      day to achieve steady state levels daily                         more rapidly
Invasive candidiasis                Dose: 6 to 12 mg/kg daily     Depending on the severity of the Cryptococcal meningitis                                           disease Maintenance therapy to prevent      Dose: 6 mg/kg daily           Depending on the severity of the relapse of cryptococcal                                           disease meningitis in children with high risk of recurrence
Prophylaxis of Candida in           Dose: 3 to 12 mg/kg 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.

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

Method of administration
Intravenous use
Fluconazole may be administered either orally or by intravenous 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 administered at a rate not exceeding 10 ml/minute.
Fluconazole 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 Cl-. Because Fluconazole 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 instructions on the handling of the medicinal product before administration, see section 6.6.