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.
meningitis.              Subsequent dose:   In life threatening
200 mg to 400      infections the daily dose mg once daily      can be increased to 800 mg
- Maintenance            200 mg once        Indefinitely at a daily therapy to prevent       daily              dose of 200 mg relapse of cryptococcal meningitis in patients with high risk of recurrence.
Coccidioidomycosis                                 200 mg to 400      11 months up to 24 mg once daily      months or longer depending on the patient. 800 mg daily may be considered for some infections and especially for meningeal disease


Indications                                          Posology            Duration of treatment Invasive candidiasis                                 Loading dose:       In general, the 800 mg on Day 1     recommended duration
Subsequent dose:    of therapy for
400 mg once         candidemia is for 2 daily               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       oropharyngeal mg on Day 1         candidiasis is in
Subsequent dose:    remission).
100 mg to 200       Longer periods may be mg once daily       used in patients with 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             - Oropharyngeal            100 mg to 200       An indefinite period for relapse of mucosal        candidiasis                mg once daily or    patients with chronic candidiasis in                                       200 mg 3 times      immune suppression patients infected                                    per week with HIV who are at       - Oesophageal              100 mg to 200       An indefinite period for high risk of              candidiasis                mg once daily or    patients with chronic experiencing relapse                                 200 mg 3 times      immune suppression per week
Genital candidiasis       - Acute vaginal            150 mg              Single dose candidiasis
- Candidal balanitis
- Treatment and            150 mg every        Maintenance dose: 6 prophylaxis of             third day for a     months.
recurrent vaginal          total of 3 doses candidiasis (4 or          (day 1, 4, and 7)
Indications                                        Posology            Duration of treatment more episodes a          followed by 150 year).                   mg once weekly maintenance dose
Dermatomycosis            - tinea pedis,           150 mg once         2 to 4 weeks, tinea pedis - tinea corporis,        weekly or 50 mg     may require treatment
- tinea cruris,          once daily          for up to 6 weeks
- candida infections
- tinea versicolor       300 mg to 400       1 to 3 weeks mg once weekly
50 mg once daily    2 to 4 weeks
- tinea unguium          150 mg once         Treatment should be
(onychomycosis)          weekly              continued 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 candidal infections                                mg once daily       several days before the in patients with                                                       anticipated onset of prolonged                                                              neutropenia and neutropenia                                                            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 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 14       The same mg/kg dose as for          A maximum dose of 12 days)                               infants, toddlers and children      mg/kg every 72 hours should be given every 72 hours      should not be exceeded
Term newborn infants (from 15       The same mg/kg dose as for          A maximum dose of 12 to 27 days)                         infants, toddlers and children      mg/kg every 48 hours should be given every 48 hours      should not be 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 formulations of fluconazole are available that are more suitable in this population.

The capsules should be swallowed whole and independent of food intake.