Mycozole/Mycozole IV

Mycozole: Each capsule contains: Fluconazole 50 mg or 150 mg.
Mycozole IV: Each mL contains: Fluconazole 2 mg, sodium chloride (w/v) 0.9%, water for injection q.s.

Pharmacology: Pharmacokinetics: Fluconazole is well absorbed after oral doses, bioavailability from the oral route being 90% or more of that from the intravenous route. Peak concentrations are reached within one to two hours of oral administration. Plasma concentrations are proportional to the dose over a range of 50 to 400 mg. Multiple dosing leads to increase in peak plasma concentrations; steady-state concentrations are reached in 5 to 10 days but may be attained on day 2 if a loading dose is given.
Fluconazole is widely distributed and the apparent volume of distribution is close to that of total body water. Concentrations in breast milk, joint fluid, saliva, sputum, vaginal fluids, and peritoneal fluid are similar to those achieved in plasma. Concentrations in the cerebrospinal fluid range from 50 to 90% of plasma concentrations, even in the absences of meningeal inflammation. Protein binding is only about 12%.
About 80% of a dose is excreted unchanged in the urine and about 11% as metabolites. The elimination half-life of fluconazole is about 30 hours and is increased in patients with renal impairment. Fluconazole is removed by dialysis.
Distribution: Salivary concentrations of fluconazole after oral doses should be adequate for the treatment of oropharyngeal and esophageal candidiasis even in patients with AIDS who may have decreased salivation. Treatment failures are more likely to be due to inadequate dosage or resistant organisms than to decreased salivary secretion.
Pharmacologically active concentrations of fluconazole have been detected in scalp hair and nails after oral treatment with conventional daily doses and with once-weekly administration.
Microbiology: Antimicrobial Action: Fluconazole is a triazole antifungal drug wherein sensitive fungi inhibits cytochrome P450-dependent enzymes, resulting in impairment of ergosterol synthesis in fungal cell membranes. It is active against Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Microsporum spp., and Trichophyton spp.
Resistance has developed in some Candida spp. following long-term prophylaxis with fluconazole, and cross-resistance with other azoles has been reported.
Resistance: The emergence of strains of Candida species resistant to fluconazole has become increasingly important, particularly in immunocompromised patients receiving long-term prophylaxis with fluconazole. In addition to resistance in C. albicans, infections with C. dubliniensis, C. glabrata, and C. krusei, all of which may be less sensitive to fluconazole than C. albicans, have been noted in these patients, and secondary resistance of C. glabrata has been reported during fluconazole therapy. Resistance to fluconazole has been reported to occur more frequently than resistance to either ketoconazole or itraconazole and may be related to the widespread use of this drug. Cross-resistance with other azoles and with amphotericin B has been reported.
Fluconazole resistance has also been reported in Cryptococcus neoformans and Histoplasma capsulatum. Histoplasmosis developed during treatment with fluconazole in a patient with HIV infection. Fluconazole-resistant C. neoformans has been isolated from an immunocompetent patient who had not been exposed to azole antifungals previously.

Fluconazole (Mycozole) is indicated for the treatment of candidiasis, fungal skin infections. It is also given for systemic infections including systemic candidiasis, coccidioidomycosis, and cryptococcosis, and has been tried in blastomycosis, histoplasmosis and sporotrichosis.

Mycozole: Adults: For systemic candidiasis: take 400 mg on Day 1, followed by 200 mg daily for 28 days.
For cryptococcal meningitis: take 400 mg for acute and 200 mg for relapse on Day 1, followed by 200 mg daily. Duration of therapy is 10-12 weeks after CSF culture becomes negative.
For superficial mucosal candidiasis: usual dose is 50mg daily, 100mg daily may be given if necessary. Treatment usually continues for 7 to 14 days in oropharyngeal candidiasis (except in severely immunocompromised patients), for 14 days in atrophic oral candidiasis associated with dentures, and for 14 to 30 days in other mucosal candidal infections including esophagitis.
For vaginal candidiasis: 150mg by mouth as a single dose.
For dermatophytosis, pityriasis versicolor, and Candida infections: 50mg daily for up to 6 weeks.
For immunocompromised patients at risk of fungal infections: a prophylactic dose of 50 to 400mg daily.
Children: Over 4 weeks of age: 3mg/kg daily for superficial infections (a loading dose of 6mg/kg may be used on the first day if necessary), and 6 to 12mg/kg daily for systemic infections.
For prophylaxis in immunocompromised children: 3 to 12mg/kg daily.
For infants under 2 weeks of age: all these doses should be given once every 72 hours.
Aged between 2 and 4 weeks: the doses should be given every 48 hours.
Mycozole IV: It is given as a sodium containing 2 mg/mL at a rate of 5 to 10 mL/minute (300 to 600 mL/hour). In the USA, a maximum infusion rate of 100 mL/hour is recommended.
Doses for children over 4 weeks of age is 6 to 12 mg/kg daily for systemic infections. For prophylaxis in immunocompromised children, a dose of 3 to 12 mg/kg daily may be given. For infants under 2 weeks of age, all these doses should be given once every 72 hours; for those aged between 2 and 4 weeks, the doses should be given every 48 hours. A maximum dose of 400 mg daily should not be exceeded in children, or 12 mg/kg in appropriate intervals in infants.
Dosage may need to be reduced in patients with renal impairment.

Fluconazole should be used with caution in patients with impaired hepatic or renal function. Abnormalities in haematological, hepatic, and renal-function tests have been observed in patients with serious underlying diseases such as AIDS or malignancy. Cases of torsade de pointes and QT prolongation have been reported rarely and caution is advised when giving fluconazole to patients with proarrhythmic conditions.
Mycozole IV: Teratogenicity has occurred in animals given in high doses of fluconazole and its use is not recommended in pregnancy.

Mycozole: High toxic doses of fluconazole have been reported to be teratogenic in animals and its use is not recommended in pregnancy.
Fluconazole is distributed into breast milk, achieving concentrations similar to those found in maternal plasma, and its use in women who are breast feeding is not recommended in nursing mothers.
Mycozole IV: Teratogenicity has occurred in animals given in high doses of fluconazole and its use is not recommended in pregnancy.

Adverse effects reported with fluconazole most commonly affect the gastrointestinal tract and include abdominal pain, diarrhea, flatulence, nausea and vomiting, and taste disturbance. Other adverse effects include headache, dizziness, leucopenia, thrombocytopenia, hyperlipidemias, and raised liver enzyme values. Serious hepatoxicity has been reported in patients with severe underlying disease such as AIDS or malignancy. Anaphylaxis and angioedema have been reported rarely.
Skin reactions are rare but exfoliative cutaneous reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have occurred, more commonly in patients with AIDS.

Mycozole: Rifampicin: decreased plasma concentrations of fluconazole.
Hydrochlorothiazide: increased plasma concentrations of fluconazole.
Fluconazole may interfere with the metabolism of some drugs if given concomitantly, mainly through inhibition of the cytochrome P450 enzymes CYP3A4 and CYP2C9. This may account for the reported increases in plasma concentrations of bosentan, ciclosporin, midazolam, nevirapine, amitriptyline, phenytoin, rifabutin, sulfonylurea hypoglycaemics and nateglinide.
Selective cyclo-oxygenase-2-inhibitors such as celecoxib and parecoxib, tacrolimus, triazolam, warfarin, and zidovudine: fluconazole may inhibit the formation of a toxic metabolite of sulfamethoxazole.
Terfenadine, astemizole and cisapride: increased concentrations following high doses of fluconazole have been associated with ECG abnormalities and toxicity. Therefore, the use of these drugs with fluconazole should be avoided because of the risk of cardiac arrhythmias.
Amitriptyline: syncope attributed to increased amitriptyline concentrations has occurred when amitriptyline was given with fluconazole.
Theophylline: may reduce its clearance when given with fluconazole.
Contraceptive steroids: its concentrations may be increased in patients given with fluconazole and the efficacy of oral contraceptives may be affected.
Mycozole IV: In general, fewer interactions are considered to occur with fluconazole than with either itraconazole or ketoconazole. Use of rifampicin with fluconazole results in reduced plasma concentrations of fluconazole. Use of hydrochlorothiazide and fluconazole has resulted in clinically insignificant increases in plasma fluconazole concentrations. Fluconazole may interfere with the metabolism of some other drugs mainly through inhibition of the cytochrome P450 isoenzymes CYP3A4 and CYP2C9. This may account for the reported increases in plasma concentrations of bosentan, ciclosporin, midazolam, nevirapine, amitriptyline, nortriptylinr, phenytoin, rifabutin, sulfonylurea hypoglycaemics and nateglinide, selective cyclo-oxygenase-2-inhibitors such as celecoxib and parecoxib, tacrolimus, triazolam, warfarin, and zidovudine; amitfluconazole may inhibit the formation of a toxic metabolite of sulfamethoxazole.
Increase in terfenadine concentrations following high doses of fluconazole have been associated with ECG abnormalities. A similar effect may be anticipated with astemizole. Use of fluconazole with cisapride could result in increased cisapride concentrations and associated toxicity. The use of fluconazole with astemizole, cisapride, or terfenadine should therefore be avoided because of the risk of cardiac arrhythmias. Syncope attributed to increased amitriptyline concentrations has occurred when amitriptyline was given with fluconazole. Fluconazole may also reduce the clearance of theophylline. The concentration of contraceptive steroids has been reported to be both increased and decreased in patients receiving fluconazole and the efficacy of oral contraceptives may be affected.

Mycozole: Store at temperatures not exceeding 30°C.
Mycozole IV: Store at temperatures not exceeding 30°C. Protect from light. Do not freeze.

Antifungals

J02AC01 - fluconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.

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