Fluco-Avenir

/ BioAvenir

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
The drug is intended for intravenous Infusion only, may be administered by intravenous Infusion at a rate of approximately 5-10 ml/min, the route being dependent on the clinical state of the patient, should be administered at a maximum rate of approximately 200 mg/hour, given as a continuous infusion.
On transferring from the intravenous to the oral route or vice versa, there is no need to change the daily dose.
This formulation is formulated in 0.9% sodium chloride solution, each 200 mg (100 ml bottle) containing 15 mmol each of Na+ and Cl-. Because this solution is available as a dilute saline solution, in patients requiring sodium or fluid restriction, consideration should be given to the rate of fluid administration.
The daily should be based on the nature and severity of the fungal infection.
Therapy for those types of infections requiring multiple dose treatment 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. Patients with AIDS and cryptococcal meningitis usually require maintenance therapy to prevent relapse.
Adults:
Cryptococcal meningitis and cryptococcal infections at other sites: The usual dose is 400 mg on the first day followed by 200 mg-400 mg once daily. Duration of treatment for cryptococcal infections will depend on the clinical and mycological response, but is usually at least 6-8 weeks for cryptococcal meningitis. For the prevention of relapse of cryptococcal meningitis in patients with AIDS, after the patient receives a full course of primary therapy, this solution may be administered indefinitely at a daily dose of 200 mg.
Candidaemia, disseminated candidiasis and other invasive candidal infections: The usual dose is 400 mg on the first day followed by 200 mg daily. Depending on the clinical response, the dose may be increased to 400 mg daily. Duration of treatment is based upon the clinical response.
Mucosal Candidiasis: Oropharyngeal candidiasis: The usual dose is 50 mg once daily for 7-14 days. Treatment can be continued for longer periods in patients with severely compromised immune function. For atrophic oral candidiasis associated with dentures, the usual dose is 50mg once daily for 14 days administered concurrently with local antiseptic measures to the denture.
Other candidal infections of mucosa (except vaginal candidiasis, e.g. esophagitis, non-invasive bronchopulmonary infections, candiduria, mucocutaneous candidiasis etc.:  The usual effective dose is 50mg-100mg daily, given for 14-30 days.
Children: A maximum dosage of 400 mg daily should not be exceeded in children. As with similar infections in adults, the duration of treatment is based on the clinical and mycological response. This formulation is administered as a single daily dose.
Children over four weeks of age: The recommended dose of this formulation  solution for mucosal candidiasis is 3 mg/kg daily. A loading dose of 6 mg/kg may be used on the first day, to achieve steady state levels more rapidly. For the treatment of systemic candidiasis and cryptococcal infection, the recommended dosage is 6-12 mg/kg daily, depending on the severity of the disease. Despite extensive data supporting the use of fluconazole in children, there are limited data available on the use of fluconazole for genital candidiasis in children below 16 years. Use at present is not recommended unless antifungal treatment is imperative and no suitable alternative agent exists.
Children four weeks of age and younger: Neonates excrete fluconazole slowly. In the first two weeks of life, the same mg/kg dosing used in older children should be adopted but administered every 72 hours. During weeks 2-4 of life, the same dose should be given every 48 hours. A maximum dosage of 12 mg/ kg every 72 hours should not be exceeded in children in the first two weeks of life. For children between three and four weeks of life, 12 mg/kg every 48 hours should not be exceeded. For children with impaired renal function, the daily dose should be reduced in accordance with the guidelines given for adults.
Elderly: The normal adult dose should be used if there is no evidence of renal impairment. In patients with renal impairment (creatinine clearance less than 50 ml/min), the dosage schedule should be adjusted as described below.
Patients with renal impairment (Adults): Fluconazole is excreted predominantly in the urine as unchanged drug. No adjustments in single dose therapy are required for those with renal impairment. In patients with impaired renal function who will receive multiple doses of fluconazole, for the normal recommended doses (according to indication).
Patients receiving regular dialysis: One dose after every dialysis session; 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 prescribing information for full details.

Systemic candidiasis. Mucosal candidiasis. Cryptococcosis.

Patients with known hypersensitivity to fluconazole or to related azole compounds or any of the excipients.
Concomitant use with cisapride, zidovudine, rifabutine, tacrolimus.
The use of fluconazole in patients concurrently taking astemizole or other drugs metabolized by the cytochrome P450 system, may be associated with elevations in serum levels of these drugs.
In the absence of definitive information, caution should be used when co administering fluconazole. Patients should be carefully monitored.

In some patients, particularly those with serious underlying diseases such as AIDS and cancer, abnormalities in haematological, hepatic, renal and other biochemical function test results have been observed during treatment with fluconazole. However, the clinical significance and relationship to treatment is uncertain.
Very rarely, patients who died with severe underlying disease and who had received multiple doses of fluconazole, had post-mortem findings which included hepatic necrosis. These patients were receiving multiple concomitant medications, some known to be potentially hepatotoxic and/or had underlying diseases which could have caused the hepatic necrosis.
In cases of hepatotoxicity, no obvious relationship to the total daily dose of fluconazole, the duration of therapy or the sex or age of the patient has been observed. The abnormalities have usually been reversible on discontinuation of fluconazole therapy.
As a causal relationship with fluconazole cannot be excluded, patients who developed abnormal liver function tests during fluconazole therapy should be monitored for the development of more serious hepatic injury.
Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis, during treatment with fluconazole. AIDS patients are more prone to the development of severe cutaneous reactions to many drugs. I
f a rash develops in a patient treated for a superficial infection, which is considered attributable to fluconazole, further therapy with this agent should be discontinued. If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and this drug should be  discontinued if bullous lesions or erythema multiforme develop.
This drug  formulated in a 0.9% sodium chloride solution, with each 100 mg (50 ml vial) containing 7.7 mmol of NaCl, each 200mg (100 ml vial) containing 15.4 mmol of NaCl and each 400 mg (200 ml vial) containing 30.8 mmol NaCl. This should be considered in patients on a sodium or fluid restricted diet.
In rare cases, as with other azoles, anaphylaxis has been reported.
See prescribing information for full details.

Headache, abdominal pain, diarrhoea, flatulence, nausea hepatic toxicity – including rare cases of fatality, elevated alkaline phosphatase, elevated bilirubin, elevated sgot, elevated SGPT, Rash leukopenia (including neutropenia and agranulocytosis), thrombocytopenia.
See prescribing information for full details.

The following drug interactions relate to the use of multiple-dose fluconazole; their relevance to single-dose has not yet been established. Anticoagulants: In an interaction study, fluconazole increased the prothrombin time (12%) after warfarin administration in healthy males. In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria and melaena) have been reported in association with increases in prothrombin time, in patients receiving fluconazole concurrently with warfarin. Prothrombin time in patients receiving coumarin-type anticoagulants should be carefully monitored.
Benzodiazepines (short acting): Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. This effect on midazolam appears to be more pronounced following oral administration of fluconazole, than with fluconazole administered intravenously. If concomitant benzodiazepine therapy is necessary in patients being treated with fluconazole, consideration should be given to decreasing the benzodiazepine dosage and the patients should be appropriately monitored.
Sulphonylureas: Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulphonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) in healthy volunteers. Fluconazole and oral sulphonylureas may be given jointly to diabetic patients, although the possibility of hypoglycaemic episode must be considered. Blood glucose levels must therefore be monitored and the dose of sulphonylurea adjusted accordingly.
Hydrochlorothiazide: In a pharmacokinetic interaction study, the co-administration of multiple doses of hydrochlorothiazide in healthy volunteers receiving fluconazole, increased the plasma concentrations of fluconazole by 40%.
Phenytoin: the concomitant administration of fluconazole and phenytoin may increase levels of phenytoin to a clinically significant degree. If both drugs need to be given concomitantly, levels of phenytoin must be monitored and the dose of phenytoin adjusted to maintain therapeutic levels.
Rifampicin: The concomitant administration of fluconazole and rifampicin gave rise to a 25% reduction in the AUC and a 20% shorter half-life of fluconazole. Thus, an increase in the dose of fluconazole should be considered for patients receiving concomitant rifampicin.
Cyclosporin: A pharmacokinetic study conducted on kidney transplant patients, showed that a daily dose of 200 mg fluconazole slowly increased the concentrations of cyclosporin.
Theophylline: Patients receiving high doses of theophylline or patients with high risk of theophylline toxicity, should be carefully monitored for signs of theophylline toxicity when receiving fluconazole. Treatment should be appropriately modified if signs of toxicity develop.
Terfenadine: Due to the occurrence of serious dysrrhythmias (secondary to prolongation of the QTc interval), in patients receiving other azole antifungals in conjugation with terfenadine, interaction studies have been performed.
See prescribing information for full details.

Pregnancy: There are no adequate and well-controlled studies of fluconazole in pregnant women. Few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in-utero to high dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies.
Lactation: This drug is secreted in human milk at concentrations similar to maternal plasma concentrations. Caution should be exercised when fluconazole is administered to a nursing woman.                      

In the event of overdose, supportive measures and symptomatic treatment, with gastric lavage if necessary, may be adequate. As 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%.

Compatibility: The administration of this drugs with other drugs is not recommended.
Storage: The drug should be stored at room temperature (below 25°C), do not freeze.