Mycozole

Description

FORMULATION

Each capsule contains:

Fluconazole ………………………………… 50 mg

Fluconazole ………………………………… 150 mg

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., Coccidiodes immitis, Crytococcus 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.

PHARMACOKINETIC PROPERTIES

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 increases in peak plasma concentrations; steady-state concentrations are reached in 5 to 10 days but may be attained on day 1 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 absence 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 orophayrngeal and esophageal candidiasis even in patients with AIDS who may have decreased salivation. Treatment failures are more likely 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.

INDICATIONS

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.

DOSAGE AND ADMINISTRATION

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 50 mg daily, 100 mg daily may be given if necessary. Treatment usually continues 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 candida infections including esophagitis.

For vaginal candidiasis: 150 mg by mouth as a single dose.

For dermatophytosis, pityriasis versicolor, and Candida infections: 50 mg daily for up to 6 weeks.

For immunocompromised patients at risk of fungal infections: a prophylactic dose of 50 to 400 mg daily.

CHILDREN

Over 4 weeks of age: 3 mg/kg daily for superficial infections (a loading dose of 6 mg/kg may be used on the first day if necessary), and 6 to 12 mg/kg daily for systemic infections.

For prophylaxis in immunocompromised children: 3 to 12 mg/kg daily

For infants under 2 weeks of age: all doses should be given once every 72 hours.

Aged between 2 and 4 weeks: doses should be given every 48 hours.

DRUG INTERACTIONS

ADVERSE EFFECTS

• Abdominal pain
• Diarrhea
• Flatulence
• Nausea and vomiting
• Taste disturbance
• Headache
• Dizziness
• Leucopenia
• Thrombocytopenia
• Hyperlipidaemia
• Increased liver enzyme
• Exfoliative cutaneous reactions such as toxic epidermal necrolysis and
• Stevens-Johnson syndrome (more commonly in patients with AIDS)
• Rashes
• Dyspepsia
• Hepatic disorders
• Angioedema
• Anaphylaxis
• Seizures
• Alopecia
• Pruritis
• Hypokalemia

PRECAUTIONS

Fluconazole should be used with caution in patients with impaired hepatic or renal function. Abnormalities in haematological, hepatic and renal function tests have been reported 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.

PREGNANCY AND LACTATION

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 breastfeeding is not recommended in nursing mothers.

DRUG INTERACTIONS

• 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 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 hypoglycemics 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 concentration may be increased in patients given with fluconazole and the efficacy of oral contraceptives may be affected.

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 have 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.

STORAGE

Store at temperatures not exceeding 30°C.

AVAILABILITY

Fluconazole (MYCOZOLE) 50 mg Capsule: Blister Pack x10’s (Box of 20’s).

Fluconazole (MYCOZOLE) 150 mg Capsule: Blister Pack x10’s (Box of 20’s).