Composition
Each capsule contains:
Fluconazole ................................................................................................. 150 mg
Inactive ingredients:
Lactose, microcrystalline cellulose, magnesium stearate, sodium lauryl sulphate.
Therapeutic Indications
TREFLUCAN is indicated in the following fungal infections:
TREFLUCAN is indicated in Adults for the Treatment of:
Vaginal candidiasis, acute or recurrent; when local therapy is not appropriate.
Candidal balanitis when local therapy is not appropriate.
Dermatomycosis including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and dermal candida infections when systemic therapy is indicated.
Tinea unguinium (onychomycosis) when other agents are not considered appropriate.
TREFLUCAN is indicated in Adults for Prophylaxis:
To reduce the incidence of recurrent vaginal candidiasis (4 or more episodes a year).
Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Hematopoietic Stem Cell Transplantation).
Dosage and Administration
Dosage:
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:
Genital Candidiasis:
Acute Vaginal Candidiasis: 150 mg as a single dose.
Candidal balanitis: 150 mg as a single dose.
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, and Candida infections:
150 mg once weekly for 2 to 4 weeks, tinea pedis may require treatment for up to 6 weeks.
Tinea versicolor: 300-400 mg once weekly for 1 to 3 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.
Special populations:
Elderly:
Dosage should be adjusted based on the renal function (see Renal impairment).
Renal impairment:
No adjustments in single dose therapy are necessary. 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 TREFLUCAN should be administered with caution to patients with liver dysfunction.
Pediatric population:
Safety and efficacy for genital candidiasis indication in pediatric population has not been established.
Administration:
TREFLUCAN Capsules should be swallowed whole and independent of food intake.
Contraindications
TREFLUCAN should not be used in patients with known hypersensitivity to fluconazole or to related azole compounds or any other ingredient in the formulation.
Co-administration of other drugs known to prolong the QT interval and which are metabolised via the enzyme CYP3A4 such as cisapride, astemizole, pimozide and quinidine are contraindicated in patients receiving TREFLUCAN (see Warnings and Precautions and Drug Interactions).
Warnings and Precautions
Tinea capitis:
Fluconazole has been studied for treatment of tinea capitis in children. It was shown not to be superior to griseofulvin and the overall success rate was less than 20%. Therefore, TREFLUCAN should not be used for tinea capitis.
Renal system:
TREFLUCAN should be administered with caution to patients with renal dysfunction.
Hepatobiliary system:
TREFLUCAN should be administered with caution to patients with liver dysfunction.
Fluconazole has been associated with rare cases of serious hepatic toxicity including fatalities, primarily in patients with serious underlying medical conditions. In cases of fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patient has been observed. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy.
Patients who develop abnormal liver function tests during TREFLUCAN therapy must be monitored closely for the development of more serious hepatic injury.
The patient should be informed of suggestive symptoms of serious hepatic effect (important asthenia, anorexia, persistent nausea, vomiting and jaundice). Treatment of TREFLUCAN should be immediately discontinued and the patient should consult a physician.
Cardiovascular system:
Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and Torsade de Pointes in patients taking fluconazole. These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant treatment that may have been contributory.
TREFLUCAN should be administered with caution to patients with these potentially proarrhythmic conditions.
Co-administration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 are contraindicated.
Halofantrine: Halofantrine has been shown to prolong QTc interval at the recommended therapeutic dose and is a substrate of CYP3A4. The concomitant use of TREFLUCAN and halofantrine is therefore not recommended.
Dermatological reactions:
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 medicinal products.
If a rash, which is considered attributable to TREFLUCAN, develops in a patient treated for a superficial fungal infection, further therapy with this medicinal product should be discontinued. If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and TREFLUCAN discontinued if bullous lesions or erythema multiforme develop.
Hypersensitivity:
In rare cases anaphylaxis has been reported.
Cytochrome P450:
Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Fluconazole is also an inhibitor of CYP2C19.
TREFLUCAN-treated patients who are concomitantly treated with medicinal products with a narrow therapeutic window metabolised through CYP2C9, CYP2C19 and CYP3A4, should be monitored.
Terfenadine:
The co-administration of fluconazole at doses lower than 400 mg per day with terfenadine should be carefully monitored.
Excipients:
TREFLUCAN Capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Drug Interactions
Concomitant use of the following other medicinal products is contraindicated:
Cisapride: There have been reports of cardiac events including Torsade de Pointes in patients to whom fluconazole and cisapride were co-administered.
Terfenadine: Because of the occurrence of serious cardiac dysrhythmias secondary to prolongation of the QTc interval in patients receiving azole antifungals in conjunction with terfenadine, interaction studies have been performed.
Astemizole: Concomitant administration of fluconazole with astemizole may decrease the clearance of astemizole. Resulting increased plasma concentrations of astemizole can lead to QT prolongation and rare occurrences of Torsade de Pointes. Co-administration of TREFLUCAN and astemizole is contraindicated.
Pimozide: Although not studied in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of Torsade de Pointes. Co-administration of TREFLUCAN and pimozide is contraindicated.
Quinidine: Although not studied in vitro or in vivo, concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of Torsade de Pointes. Co-administration of TREFLUCAN and quinidine is contraindicated.
Erythromycin: Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, Torsades de Pointes) and consequently sudden heart death. Co-administration of TREFLUCAN and erythromycin is contraindicated.
Concomitant use of the following other medicinal products cannot be recommended:
Halofantrine: Fluconazole can increase halofantrine plasma concentration due to an inhibitory effect on CYP3A4. Concomitant use of TREFLUCAN and halofantrine has the potential to increase the risk of cardiotoxicity (prolonged QT interval, Torsade de Pointes) and consequently sudden heart death. This combination should be avoided.
Co-administeration of fluconazole with food, cimetidine, antacids or following total body irradiation for bone marrow transplantation, no clinically significant impairment of fluconazole absorption occurs.
Concomitant use of the following other medicinal products lead to precautions and dose adjustments:
The effect of other medicinal products on fluconazole:
Rifampicin: Concomitant administration of fluconazole and rifampicin resulted in a 25% decrease in the AUC and 20% shorter half-life of fluconazole. In patients receiving concomitant rifampicin, an increase in the TREFLUCAN dose should be considered.
The effect of fluconazole on other medicinal products:
Fluconazole is a potent inhibitor of cytochrome P450 (CYP) isoenzyme 2C9 and a moderate inhibitor of CYP3A4. In addition to the observed/documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolized by CYP2C9 and CYP3A4 co-administered with fluconazole. Therefore caution should be exercised when using these combinations and the patients should be carefully monitored. The enzyme inhibiting effect of fluconazole persists 4-5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole.
Alfentanil: Concomitant treatment with fluconazole reduced clearance and distribution volume as well as prolongation of T½ of alfentanil. A possible mechanism of action is fluconazole's inhibition of CYP3A4. Dosage adjustment of alfentanil may be necessary.
Amphotericine B: Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, no interaction in intracranial infection with Cryptococcus neoformans, and antagonism of the two drugs in systemic infection with A. fumigatus.
Anticoagulants: Concurrent administration with fluconazole increased the prothrombin time. Prothrombin time in patients receiving coumarin-type anticoagulants should be carefully monitored.
Azithromycin: An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single 1200 mg oral dose of azithromycin on the pharmacokinetics of a single 800 mg oral dose of fluconazole as well as the effects of fluconazole on the pharmacokinetics of azithromycin. There was no significant pharmacokinetic interaction between fluconazole and azithromycin.
Benzodiazepines (Short-acting i.e. midazolam, triazolam): Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. If concomitant benzodiazepine therapy is necessary in patients being treated with TREFLUCAN, consideration should be given to decreasing the benzodiazepine dosage and the patients should be appropriately monitored.
Fluconazole increases the AUC of triazolam (single dose) by approximately 50%, Cmax with 20-32% and increases t½ by 25-50% due to the inhibition of metabolism of triazolam. Dosage adjustments of triazolam may be necessary.
Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed. There is a risk of developing carbamazepine toxicity. Dosage adjustment of carbamazepine may be necessary depending on concentration measurements/effect.
Calcium Channel Blockers: Certain dihydropyridine calcium channel antagonists (nifedipine, isradipine, amlodipine and felodipine) are metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended.
Celecoxib: During concomitant treatment with fluconazole (200 mg daily) and celecoxib (200 mg) the celecoxib Cmax and AUC increased by 68% and 134%, respectively. Half of the celecoxib dose may be necessary when combined with fluconazole.
Cyclophosphamide: Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine.
Fentanyl: One fatal case of possible fentanyl fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Patients should be monitored closely for the potential risk of respiratory depression. Dosage adjustment of fentanyl may be necessary.
HMG-CoA reductase inhibitors: The risk of myopathy and rhabdomyolysis increases when fluconazole is co-administered with HMG-CoA reductase inhibitors metabolised through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected.
Immunosuppresors (i.e. ciclosporin, everolimus, sirolimus and tacrolimus):
Ciclosporin: Fluconazole significantly increases the concentration and AUC of ciclosporin. During concomitant treatment with fluconazole 200 mg daily and ciclosporin (2.7 mg/kg/day) there was a 1.8-fold increase in ciclosporin AUC. This combination may be used by reducing the dose of ciclosporin depending on ciclosporin concentration.
Everolimus: Although not studied in vivo or in vitro, fluconazole may increase serum concentrations of everolimus through inhibition of CYP3A4.
Sirolimus: Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. This combination may be used with a dose adjustment of sirolimus depending on the effect/concentration measurements.
Tacrolimus: Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines. No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity. Dose of orally administered tacrolimus should be decreased depending on tacrolimus concentration.
Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74) which is responsible for most of the angiotensin Il receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously.
Methadone: Fluconazole may enhance the serum concentration of methadone. Dosage adjustment of methadone may be necessary.
Non-steroidal anti-inflammatory drugs: The Cmax and AUC of flurbiprofen was increased by 23% and 81%, respectively, when co-administered with fluconazole compared to administration of flurbiprofen alone. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] was increased by 15% and 82%, respectively, when fluconazole was co-administered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone. Although not specifically studied, fluconazole has the potential to increase the systemic exposure of other NSAIDs that are metabolized by CYP2C9 (e.g. naproxen, lornoxicam, meloxicam, diclofenac). Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dosage of NSAIDs maybe needed.
Phenytoin: Fluconazole inhibits the hepatic metabolism of phenytoin. Concomitant repeated administration of 200 mg fluconazole and 250 mg phenytoin intravenously, caused an increase of the phenytoin AUC24 by 75% and Cmin by 128%. With co-administration, serum phenytoin concentration levels should be monitored in order to avoid phenytoin toxicity.
Prednisone: There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a three month therapy with fluconazole was discontinued. The discontinuation of fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone. Patients on long-term treatment with TREFLUCAN and prednisone should be carefully monitored for adrenal cortex insufficiency when TREFLUCAN is discontinued.
Rifabutin: There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin. There have been reports of uveitis in patients to whom fluconazole and rifabutin were co-administered. Patients receiving rifabutin and TREFLUCAN concomitantly should be carefully monitored.
Saquinavir: Fluconazole increases the AUC of saquinavir with approximately 50%, Cmax with approximately 55% and decreases clearance of saquinavir with approximately 50% due to inhibition of saquinavir's hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein. Dosage adjustment of saquinavir may be necessary.
Sulphonylureas: Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulphonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) in healthy volunteers. Frequent monitoring of blood glucose and appropriate reduction of sulfonylurea dose is recommended during co-administration.
Theophylline: Patients who are receiving high doses of theophylline or who are otherwise at increased risk for theophylline toxicity should be observed for signs of theophylline toxicity while receiving TREFLUCAN , and the therapy modified appropriately if signs of toxicity develop.
Vinca Alkaloids: Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids (e.g. vincristine and vinblastine) and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4.
Vitamin A: Based on a case-report in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, CNS-related undesirable effects have developed in the form of pseudotumour cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS-related undesirable effects should be borne in mind.
Because of the potential seriousness of such an interaction, co-administration of cisapride is contraindicated in patients receiving TREFLUCAN (see Contraindications). Zidovudine: Concomitant administration of zidovudine with fluconazole increases Cmax and AUC of zidovudine by 84% and 74%, respectively, due to an approximate 45% decrease in oral zidovudine clearance. The half-life of zidovudine was likewise prolonged by approximately 128% following combination therapy with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.
Azithromycin: No significant interaction between fluconazole and azithromycin.
Oral contraceptives: Unlikely to have an effect on the efficacy of the combined oral contraceptive.
Pregnancy and Lactation
Pregnancy:
Data from several hundred pregnant women treated with standard doses (< 200 mg/day) of fluconazole, administered as a single or repeated dosage in the first trimester, show no undesired effects in the fetus. There have been reports of multiple congenital abnormalities in infants whose mothers were treated for at least three or more months with high doses (400-800 mg daily) of fluconazole for coccidioidomycosis. The relationship between fluconazole and these events is unclear.
TREFLUCAN in standard doses and short-term treatments should not be used in pregnancy unless clearly necessary.
TREFLUCAN in high dose and/or in prolonged regimens should not be used during pregnancy except for potentially life-threatening infections.
Lactation:
Fluconazole passes into breast milk to reach concentrations lower than those in plasma. Breastfeeding may be maintained after a single use of a standard dose 200 mg fluconazole or less. Breastfeeding is not recommended after repeated use or after high dose TREFLUCAN.
Effects on ability to drive and to use machines
Patients should be warned about the potential for dizziness or seizures while taking TREFLUCAN and should be advised not to drive or operate machines if any of these symptoms occur.
Undesirable Effects
The most frequently (<1/10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood alkaline phosphatase and rash. The following adverse reactions have been observed and reported during treatment with fluconazole with the following frequencies: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
Blood and the Lymphatic system disorders:
Uncommon: Anaemia.
Rare: Agranulocytosis, leukopenia, thrombocytopenia, neutropenia.
Immune system disorders:
Rare: Anaphylaxis.
Metabolism and Nutrition disorders:
Uncommon: Decreased appetite.
Rare: Hypercholesterolaemia, hypertriglyceridaemia, hypokalemia.
Psychiatric disorders:
Uncommon: Somnolence, insomnia.
Nervous System Disorders:
Common: Headache.
Uncommon: Seizures, paraesthesia, dizziness, taste perversion.
Rare: Tremor.
Ear and Labyrinth disorders:
Uncommon: Vertigo.
Cardiac disorders:
Rare: Torsade de Pointes, QT prolongation.
Gastrointestinal disorders:
Common: Abdominal pain, vomiting, diarrhoea, nausea.
Uncommon: Constipation dyspepsia, flatulence, dry mouth.
Hepatobiliary disorders:
Common: Increased alanine aminotransferase, increased aspartate aminotransferase, increased blood alkaline phosphatase.
Uncommon: Cholestasis, jaundice, increased bilirubin.
Rare: Hepatic failure, hepatocellular necrosis, hepatitis, hepatocellular damage.
Skin and Subcutaneous tissue disorders:
Common: Rash.
Uncommon: Drug eruption, urticaria, pruritus, increased sweating.
Rare: Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalised exanthematous pustulosis, exfoliative dermatitis , angioedema, face oedema, alopecia.
Musculoskeletal and Connective tissue disorders:
Uncommon: Myalgia.
General disorders and Administration site conditions:
Uncommon: Fatigue, malaise, asthenia, fever.
Overdose
There have been reports of overdose with fluconazole and 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%.
Pharmacological Properties
Pharmacodynamic properties:
Pharmacotherapeutic group: Antimycotics for systemic use, triazole derivatives.
TREFLUCAN is a triazole antifungal agent. Its primary mode of action is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane and may be responsible for the antifungal activity of fluconazole. Fluconazole has been shown to be more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems.
Pharmacokinetic properties:
Absorption: After oral administration, fluconazole is well absorbed. Oral absorption is not affected by concomitant food intake. Peak plasma concentrations in the fasting state occur between 0.5 and 1.5 hours post-dose. Plasma concentrations are proportional to dose. Ninety percent steady state levels are reached by day 4-5 with multiple once daily dosing. Administration of a loading dose (on day 1) of twice the usual daily dose enables plasma levels to approximate to 90% steady-state levels by day 2.
Distribution: The apparent volume of distribution approximates to total body water. Plasma protein binding is low (11-12%).
Fluconazole achieves good penetration in all body fluids studied. The levels of fluconazole in saliva and sputum are similar to plasma levels. In patients with fungal meningitis, fluconazole levels in the CSF are approximately 80% the corresponding plasma levels.
High skin concentration of fluconazole, above serum concentrations, are achieved in the stratum corneum, epidermis-dermis and eccrine sweat. Fluconazole accumulates in the stratum corneum. At the 150 mg once-a-week dose, the concentration of fluconazole in stratum corneum on day 7 was 23.4 µg/g and 7 days after the second dose was still 7.1 µg/g.
Concentration of fluconazole in nails after 4 months of 150 mg once-a-week dosing was 4.05 µg/g in healthy and 1.8 µg/g in diseased nails; and, fluconazole was still measurable in nail samples 6 months after the end of therapy.
Biotransformation: Fluconazole is metabolised only to a minor extent. Of a radioactive dose, only 11% is excreted in a changed form in the urine. Fluconazole is a selective inhibitor of the isozymes CYP2C9 and CYP3A4. Fluconazole is also an inhibitor of the isozyme CYP2C19.
Excretion: Plasma elimination half-life for fluconazole is approximately 30 hours. The major route of excretion is renal, with approximately 80% of the administered dose appearing in the urine as unchanged medicinal product. Fluconazole clearance is proportional to creatinine clearance. There is no evidence of circulating metabolites.
The long plasma elimination half-life provides the basis for single dose therapy for vaginal candidiasis, once daily and once weekly dosing for other indications.
Pharmacokinetics in renal impairment: In patients with severe renal insufficiency, (GFR < 20 ml/min) half-life increased from 30-98 hours. Consequently, reduction of the dose is needed. Fluconazole is removed by haemodialysis and to a lesser extent by peritoneal dialysis. After three hours of haemodialysis session, around 50% of fluconazole is eliminated from blood.
Storage
Store in a dry place at a temperature not exceeding 30°C.
Packaging
TREFLUCAN Capsules: Box containing 1 strip of 1 capsule.