FLUZORAL Capsule

INDICATIONS:

1. Treatment of oropharyngeal, esophageal, vulvovaginal candidiasis and other serious systemic candidal infection (e.g. urinary tract infections, peritonitis, candidemia, disseminated candidiasis, meningitis, pneumonia).

2. Treatment of cryptococcosis caused by Cryptococcus neoformans, including meningitis and infections of other sites.

3. Prophylaxis of serious fungal infections in patients with HIV infections, or patients receiving cytotoxic chemotherapy and/or radiation therapy.

DOSAGE:

Adults and elderly:

Oropharyngeal candidiasis: oral, 200mg as a single dose on the first day, then 100 or 200mg once daily for at least two weeks.

Esophageal candidiasis: oral, 200mg as a single dose on the first day, then 100 or 200mg once daily for a minimum of three weeks and for at least two weeks after symptoms have resolved.

Vulvovaginal candidiasis: oral, 150mg as a single dose one day only.

Systemic candidiasis: oral, 400mg as a single dose on the first day, then 200mg once daily for a minimum of four weeks and for at least two weeks after symptom have resolved.

Cryptococcal meningitis: oral, 400mg as a single dose on the first day, then 200 to 400mg once daily for 10 to 12 weeks after the CSF is sterile.

For suppressive or maintenance therapy to prevent recurrence or relapsed of cryptococcal meningitis in patients with HIV infections who have had documented adequately treated infections: oral, 200mg once daily.

For the prevention of candidiasis in patients with cancer: oral, 400mg once daily

Tinea corporis, Tinea cruris, or Tinea pedis: oral, 150mg once weekly or 50mg once daily for two to six weeks.

Children 6 months of age and older:

Use of fluconazole in children 6 months of age and older with fungal infections is supported by evidence from adequate and well controlled studies in adults, with additional data from pediatric pharmacokinetics studies and controlled clinical trials in pediatric patients.

Oropharyngeal candidiasis: oral, 6mg per kg on the first day, then 3mg per kg once daily for a minimum of two weeks.

Esophageal candidiasis: oral, 6mg per kg on the first day, then 3mg per kg once daily for a minimum of three weeks and for at least two weeks after symptoms have resolved.

* Note: the dosage may be increased up to 12mg per kg once daily if necessary, based on the condition of the patient and the respond to the drug.

Systemic candidiasis: oral, 6-12mg per kg daily

Cryptococcal meningitis: oral, 12mg per kg on the first day, then 6mg per kg daily for 10 to 12 weeks after the CSF becomes culture negative.

* The dosage may be increased to 12mg per kg daily if necessary, based on the condition of the patient and the response of the drug.

For suppressive or maintenance therapy to prevent recurrence or relapsed of cryptococcal meningitis or oropharyngeal candidiasis in children with HIV infections: oral, 3-6mg once daily

Dosage in Renal impairment:

Adults or elderly with impaired renal function should receive an initial loading dose of 50-400mg of fluconazole depending on the type of infection being treated, then the dosage must be modified based on the patient’s creatinine clearance as following:

- Creatinine Clearance: > 50mL/min (use 100% of the usual daily dose)

- Creatinine Clearance: ≤ 50mL/min (use 50% of the usual daily dose)

- Patients undergoing regular dialysis (use 100% of the usual daily dose after each dialysis period)

- Modification of the single oral dose for the treatment of vulvovaginal candidiasis is unnecessary in patients with renal impairment.

It is contraindicated in patients with known hypersensitivity to fluconazole or other azole compounds, children young than 6 months of age, during pregnancy, and in nursing women.

The most common side-effects are GI effects including mild to moderate nausea, vomiting, abdominal pain and diarrhea. Rash, serious hepatic reactions, dizziness and headache, eosinophilia, fever have been reported rarely. The overall side-effects have been reported more frequently in patients with HIV infections than in patients without HIV infections.

1. Concurrent use of fluconazole with a coumarin anticoagulant (e.g., warfarin) increases prothrombin time (PT), so PT must be monitored carefully in patients.

2. Administration of fluconazole in patients receiving tolbutamide, glyburide, glipizide, or any other oral sulfonylurea antidiabetic agent has increased the plasma concentrations and the reduce metabolism of these antidiabetic agents. Hypoglycemia has been noted. Blood glucose concentrations should be monitored, and the dose of the oral hypoglycemic agent may need to be reduced.

3. Concomitant use of fluconazole and hydrochlorothiazide results in increased peak plasma concentrations and the AUC of fluconazole. It has been suggested that the thiazide diuretic decreases renal clearance of fluconazole by about 20%. However, adjustment of fluconazole dosage does not appear to be necessary.

4. Concurrent use of fluconazole with cyclosporine may result in increased plasma cyclosporine concentrations and serum creatinine concentrations. As a result, the levels should be monitored carefully, and the dose of cyclosporine may need to be reduced.

5. Fluconazole has been found to increase serum theophylline concentrations, which may lead to toxicity. Serum theophylline concentrations should be monitored carefully.

6. Concomitant use of terfenadine and fluconazole in a daily dosage of 400mg or greater is contraindicated. If lower fluconazole dosages (i.e., less than 400mg daily) are administered, patients should be carefully monitored.

7. Phenytoin and fluconazole should be used concomitantly with caution. Concurrent use has resulted in increased phenytoin concentrations and AUC and has resulted in phenytoin toxicity. Plasma phenytoin concentrations should be monitored carefully and its dosage adjusted accordingly whenever fluconazole is initiated or discontinued.

1. Use with caution in patients with impaired hepatic function or a history of alcoholism.

2. Fluconazole therapy should be discontinued if signs and symptoms consistent with liver disease develop.

3. If abnormal liver function test results occur during fluconazole therapy, the patient should be closely monitored for the development of more severe hepatic injury.

4. A reduction in dosage, or increase in dosing interval, is recommended in patients with impaired renal function.

5. Immunocompromised patients (e.g. patients with HIV infections) who develop rash during fluconazole therapy should be monitored closely and the drug discontinued if the lesions progress.

Mechanism of action: Fluconazole is a synthetic azole antifungal agent, its antifungal activity is resulted from inhibition of fungal sterol synthesis by interfering with cytochrome P-450 enzyme activity. Decrease in ergosterol content in cellular membranes leads to the alteration of membrane functions and permeability. Fluconazole is active against many fungi including yeast and dermatophyes. It does not appear to have antibacterial activity.