Funcid

Composition

Each 100 ml contains: fluconazole USP – 200 mg

Excipients q.s.

Indications for use

Funcid is indicated in the following fungal infections. Funcid is indicated in adults for the treatment of:

• Cryptococcal meningitis
• Coccidioidomycosis. Invasive candidiasis
• Mucosal candidiasis including oropharyngeal, oesophageal candidiasis, candiduria and chronic mucocutaneous candidiasis
• Chronic oral atrophic candidiasis (denture sore mouth) if dental hygiene topical treatment are insufficient.

Funcid is indicated in adults for the prophylaxis of:

• Relapse of crytopcoccal meningitis in patients with high risk of recurrence.
• Relapse of oropharyngeal or oesophageal candidiasis in patients infected with HIV who are at high risk of experiencing relapse
• Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Hematopoietic Stem Cell Transplantation).

Funcid is indicated in term newborn infants, infants, toddlers, children and adolescents aged from 0 to 17 years old:

• Funcid is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients. Funcid can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence.

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.

Mode 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: Cryptococcosis:

• Treatment of cryptococcal meningitis – Loading dose: 400 mg on Day 1. Subsequent dose: 200 mg to 400 mg daily. Duration of treatment – 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 daily. Duration of treatment – Indefinitely at a daily dose of 200 mg. Coccidioidomycosis – 200 mg to 400 mg. Duration of treatment – 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 daily. Duration of treatment – 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 daily. Duration of treatment – 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 daily. Duration of treatment – 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 daily. Duration of treatment – 7 to 21 days. Longer periods may be used in patients with severely compromised immune function.
• Chronic atrophic candidiasis – 50 mg daily. Duration of treatment – 14 days.
• Chronic mucocutaneous candidiasis – 50 mg to 100 mg daily. Duration of treatment – 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 daily or 200 mg 3 times per week. Duration of treatment – An indefinite period for patients with chronic immune suppression.
• Oesophageal candidiasis – 100 mg to 200 mg daily or 200 mg 3 times per week. Duration of treatment – An indefinite period for patients with chronic immune suppression. Prophylaxis of candidal infections – 200 mg to 400 mg. Duration of treatment – 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.

Special populations: Elderly: Dosage should be adjusted based on the renal function.

Renal impairment: Funcid 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) >50 – Percent of recommended dose – 100%

Creatinine clearance (ml/min) ≤50 (no dialysis) – Percent of recommended dose – 50%

Creatinine clearance (ml/min) Regular dialysis  – Percent of recommended dose – 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.

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. Funcid 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): Mucosal candidiasis – Initial dose: 6 mg/kg. Subsequent dose: 3 mg/kg daily. Initial dose may be used on the first day to achieve steady state levels more rapidly.

Invasive candidiasis, Cryptococcal meningitis – Dose: 6 to 12 mg/kg 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 daily. Depending on the severity of the disease.

Prophylaxis of Candida in immunocompromised patients – Dose: 3 to 12 mg/kg daily. Depending on the extent and 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. 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.

Method of administration: Funcid 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. Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute. Funcid 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 Funcid 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.