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Fluconazole is a synthetic antimycotic drug of the triazole class of compunds. The drug is sold under the brand name Diflucan´┐Ż. It is used orally and intravenously to treat yeast and other fungal infections.
Mode of action
Fluconazole inhibits, much like the imidazole-antimycotics, the fungal P450-enzyme. The consequences are that Lanosterol can no longer be converted to Ergosterol. Ergosterol is an essential part of the fungal membrane and its deficit alters the permeability of the membrane and this eventually disrupts fungal growth. It acts fungistatic or fungizide depending on the susceptibility of the strain and the dose regime used. Fluconazole is theoretically capable of inhibiting demethylases in the human body, but this effect is not seen with therapeutic doses.

Diflucan Drug

Susceptible fungi
Animal models (infection studies) showed that fluconazole is active against infections with strains of Candida, Cryptococcus, Aspergillus, Blastomyces, Coccidioides and Histoplasma. In vitro test systems are still inreliable.

Pharmacokinetic data
Following oral dosing, fluconazole is almost completely absorbed within two hours. The high bioavailability of over 90% is not significantly reduced by concomitant intake of meals and co-medication with H2-antagonists (e.g. cimetidine, ranitidine). Concentrations measured in urine, saliva, sputum and vaginal secrete are approximately equal to the plasma concentration measured following a wide dose range from 100 to 400 mg oral as a single dose. The half-life of fluconazole is approximately 30 hours and is increased in patients with impaired renal function.


Elimination and excretion
Fluconazole is renally eliminated and primarily (80%) excreted in the urine as unchanged drug.

Male rats treated with 5 mg and 10 mg/kg weight respectively showed a higher incidence of hepatocelluar adenomas than expected. No data exists on human carcinogenity.

Infections with Candida in mouth and esophagus.
Recurrent vaginal infections, if local therapy is not sufficient.
Prophylaxis of infections with Candida in tumor patients receiving chemo- or radiotherapy.
Treatment of deep or recurrent fungal infection of the skin (dermatomycosis), if local treatment was not successful. The efficacy of fluconazole in the treatment of onchomycosis (fungal infection of the nails) has not been demonstrated.
Sepsis due to emergence of Candida in the blood (candidaemia).
Meningitis and prophylaxis of meningitis caused by cryptococcus in AIDS-Patients. In a subgroup of patients Fluconazole acts more slowly than amphotericin B alone or in combination with flucytosine. Nonetheless, response and curation rates were not significantly different.
Treatment of blastomycosis, histoplasmosis, coccidioidomycosis, sporotrichosis, and aspergillosis. Sometimes amphotericin B is the preferred agent.

Off-label uses
Infections with cryptococcus on other locations of the body (e.g. on the skin or pulmonary).
Prophylaxis of fungal infections in patients with AIDS, posttransplant-patients, or otherwise immunecompromised patients.

Contraindications and cautions
Known hypersensitivity to fluconazole is an absolute contraindication.
Fluconazole may infrequently cause severe or lethal hepatotoxicity. Liver function studies should be obtained regularly. Patients showing clinical signs of liver damage should be immediately withdrawn from the drug. Patients with preexisting liver disease should be treated with particular care.
Some patients develop severe skin reactions (Steven-Johnson-Syndrome or toxic epidermal necrolysis) under treatment. Patients with HIV-infections are particularly prone. All patients should be carefully watched for development of any skin reaction and should be advised to discontinue the drug immediately if rash or other forms of skin reactions are observed.
Fluconazole may cause rare cases of prolongation of the QT interval, leading to serious arrhythmias. Risk factors are preexisting prolonged QT interval, electrolyte imbalances including hypokalemia, low serum level of magnesium and hypocalemia. These patients should be treated with caution and the electrolyte imbalances should be corrected before therapy is initiated.

Pediatric use
The use in newborns, children and adolescents is possible. Newborns up to 4 weeks excrete fluconazole very slowly, while the half-life in older children and adolescents is reduced to 20 hours.

Pregnancy and lactation
In animal studies fluconazole proved to be an experimental fetotoxic agent. Women with childbearing potential should avoid to become pregnant during therapy and 7 days after. The drug may be given to patients already pregnant, if the severity of the disease outweighs the potential harm to the fetus.

High concentrations in the milk of breastfeeding mothers have been measured. Mothers should not breastfeed during treatment.

GI tract: Nausea, dyspepsia, abnormal taste, abdominal pain, vomiting, diarrhea, and flatulence were reported in 5.3% of patients. In female patients receiving a high single dose treatment for vaginal infections, the incidence of these side-effects may be higher.
Skin : Skin rash, diffuse reaction with eosinophilia, and pruritus were encountered in up to 5%. Also alopecia and exfoliative skin reactions (including Stevens-Johnson-Syndrome and Lyell's-Syndrome) were seen. The latter had been fatal in some patients.
Liver, kidney, hematology : Some patients, particular those with AIDS or malignancies, developed increased liver enzymes, bilirubin, AP, BUN, serum creatinine, eosinophilia, anemia, and leukopenia including agranulocytosis as well as thrombopenia. Symptomatic hepatotoxicity (hepatitis, hepatic necrosis, jaundice, cholostatic hepatosis, and fulminant liver failure) including fatalities had been infrequent.
Central nervous system : Frequently headache, less frequently vertigo and convulsions. Some of these side-effects might have been due to the underlying disease (cryptococcal meningitis). An acute psychotic (paranoid) reaction had been noted in one case of overdose.
Heart : QT interval prolongation and torsade de pointes (a serious arrhythmia) may occur.


Different Side-Effects : Anaphylactic reaction (including facial edema, angioedema, and pruritus). Hypokalema, increased triglycerides, and increased cholesterol had also been encountered.
Sometimes patients who respond to therapy experience a recurrence of their disease after the drug treatment is terminated. Most often female patients with complicated vaginal infection due to Candida are concerned.

Numerous pharmacodynamic and pharmacokinetic interactions exist.

According to individual scheme depending on disease, weight of the patient and renal function. Therapy is either orally or per i.v.-infusion. Duration of treatment or prophylactic treatment is also strictly individual. Special guidelines for the treatment of pediatric patients are existing.

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