Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom
Diflucan is indicated in the following fungal infections (see section 5.1).
Diflucan is indicated in adults for the treatment of:
Diflucan is indicated in adults for the prophylaxis of:
*Relapse of crytopcoccal meningitis in patients with high risk of recurrence.
Diflucan is indicated in term newborn infants, infants, toddlers, children and adolescents aged from 0 to 17 years old:
Diflucan is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients. Diflucan can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence (see section 4.4).
Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.
Consideration should be given to official guidance on the appropriate use of antifungals.
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.
| Indications | Posology | Duration of treatment | |
|---|---|---|---|
| Cryptococcosis | Treatment of cryptococcal meningitis. | Loading dose: 400 mg on Day 1. Subsequent dose: 200 mg to 400 mg once daily | Usually at least 6 to 8 weeks. In life threatening infections the daily dose can be increased to 800 mg. |
| Maintenance therapy to prevent relapse of cryptococcal meningitis in patients with high risk of recurrence. | 200 mg once daily | Indefinitely at a daily dose of 200 mg. | |
| Coccidioidomycosis | 200 mg to 400 mg once daily | 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: 800 mg on Day 1. Subsequent dose: 400 mg once daily. | In general, the recommended duration of therapy for candidemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidemia. | |
| Treatment of mucosal candidiasis | Oropharyngeal candidiasis | Loading dose: 200 mg to 400 mg on Day 1. Subsequent dose: 100 mg to 200 mg once daily. | 7 to 21 days (until oropharyngeal candidiasis is in remission). Longer periods may be used in patients with severely compromised immune function. |
| Oesophageal candidiasis | Loading dose: 200 mg to 400 mg on Day 1. Subsequent dose: 100 mg to 200 mg once daily | 14 to 30 days (until oesophageal candidiasis is in remission). Longer periods may be used in patients with severely compromised immune function. | |
| Candiduria | 200 mg to 400 mg once daily | 7 to 21 days. Longer periods may be used in patients with severely compromised immune function. | |
| Chronic atrophic candidiasis | 50 mg once daily | 14 days | |
| Chronic mucocutaneous candidiasis | 50 mg to 100 mg once daily | Up to 28 days. Longer periods depending on both the severity of infection or underlying immune compromisation and infection | |
| Prevention of relapse of mucosal candidiasis in patients infected with HIV who are at high risk of experiencing relapse | Oropharyngeal candidiasis | 100 mg to 200 mg once daily or 200 mg 3 times per week | An indefinite period for patients with chronic immune suppression. |
| Oesophageal candidiasis | 100 mg to 200 mg once daily or 200 mg 3 times per week | An indefinite period for patients with chronic immune suppression. | |
| Genital candidiasis | Acute vaginal candidiasis. | 150 mg | Single dose |
| Candidal balanitis | |||
| Treatment and prophylaxis of recurrent vaginal candidiasis (4 or more episodes a year). | 150 mg every third day for a total of 3 doses (day 1, 4, and 7) followed by 150 mg once weekly maintenance dose. | Maintenance dose: 6 months. | |
| Dermatomycosis | Tinea pedis, tinea corporis, tinea cruris, candida infections | 150 mg once weekly or 50 mg once daily | 2 to 4 weeks, tinea pedis may require treatment for up to 6 weeks |
| tinea versicolor | 300 mg to 400 mg once weekly – 50 mg once daily | 1 to 3 weeks – 2 to 4 weeks | |
| tinea unguium (onychomycosis) | 150 mg once weekly | Treatment should be 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 candidal infections in patients with prolonged neutropenia | 200 mg to 400 mg once daily | Treatment 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. | |
Dosage should be adjusted based on the renal function (see “Renal impairment”).
Diflucan 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.
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).
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. Diflucan 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).
| Indication | Posology | Recommendations |
|---|---|---|
| Mucosal candidiasis | Initial dose: 6 mg/kg | Initial dose may be used on the first day to achieve steady state levels more rapidly |
| Subsequent dose: 3 mg/kg once daily | ||
| Invasive candidiasis, Cryptococcal meningitis | Dose: 6 to 12 mg/kg once daily | Depending on the severity of the disease |
| Maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of recurrence | Dose: 6 mg/kg once daily | Depending on the severity of the disease |
| Prophylaxis of Candida in immunocompromised patients | Dose: 3 to 12 mg/kg once daily | Depending on the extent and duration of the induced neutropenia (see Adults posology) |
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.
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 days) | The same mg/kg dose as for infants, toddlers and children should be given every 72 hours | A maximum dose of 12 mg/kg every 72 hours should not be exceeded |
| Term newborn infants (from 15 to 27 days) | The same mg/kg dose as for infants, toddlers and children should be given every 48 hours | A maximum dose of 12 mg/kg every 48 hours should not be exceeded |
Diflucan 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.
Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute. Diflucan 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 Diflucan 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.
There have been reports of overdose with Diflucan. Hallucination and paranoid behaviour have been concomitantly reported.
In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if necessary) may be adequate.
Fluconazole is largely excreted in the urine; forced volume diuresis would probably increase the elimination rate. A three-hour haemodialysis session decreases plasma levels by approximately 50%.
Glass vials: 5 years.
Plasticised PVC bags: 12 months.
Once opened the product should be used immediately. Any unused infusion should be discarded.
From a microbiological point of view, the dilutions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Glass vials: Do not freeze.
Plasticised PVC bags: Store below 30°C. Do not freeze.
For storage conditions after dilution of the medicinal product, see section 6.3.
Clear Type I glass infusion vial sealed closed with rubber stoppers and aluminium caps.
Plasticised PVC bag.
Pack sizes:
1 vial containing 25 ml solution for infusion
1, 48 vial(s) containing 50 ml solution for infusion
1, 40 vial(s) containing 100 ml solution for infusion
1 vial containing 200 ml solution for infusion
1, 5, 10, 20 plasticised PVC bag(s) containing 100 ml solution for infusion
1, 5, 10, 20 plasticised PVC bag(s) containing 200 ml solution for infusion
Not all pack sizes may be marketed.
Fluconazole intravenous infusion is compatible with the following administration fluids:
Fluconazole may be infused through an existing line with one of the above listed fluids. Although no specific incompatibilities have been noted, mixing with any other medicinal products prior to infusion is not recommended.
The solution for infusion is for single use only.
The dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discoloration prior to administration. The solution should only be used if the solution is clear and free from particles.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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