Fluconazole

Indications

Fluconazole is used for: Cryptococcal meningitis, Candidiasis, Tinea pedis, Tinea cruris, Tinea corporis, Vaginal candidiasis, Onychomycosis, Coccidioidomycosis, Cryptococcosis, Histoplasmosis, Mucosal candidiasis, Candidal balanitis, Dermatophytosis

Adult Dose

Oral Oropharyngeal Candidiasis 200 mg PO on Day 1, THEN 100 mg qDay Treatment should be continued for at least 2 weeks to decrease likelihood of relapse Esophageal Candidiasis 200 mg PO on Day 1, THEN 100 mg qDay; doses up to 400 mg/day may be used based on patient’s response Treat for a minimum of 3 weeks and for at least 2 weeks following resolution of symptoms Vaginal candidiasis; Candidal balanitis Uncomplicated: 150 mg PO as a single dose Complicated: 150 mg PO q72hr for 3 doses Recurrent: 150 mg PO qDay for 10-14 days followed by 150 mg once weekly for 6 months Cutaneous candidiasis; Dermatophytosis; Pityriasis versicolor Adult: 50 mg once daily for up to 6 wk. Systemic candidiasis ; Cryptococcal infections Adult: Initially, 400 mg, followed by 200-400 mg once daily. Treatment duration is based on clinical and mycological response, but is usually at least 6-8 wk in cryptococcal meningitis. To prevent relapse after a primary course of treatment for acute cryptococcal meningitis in AIDS patients: 100-200 mg daily. Prophylaxis of fungal infections in immunocompromised patients Adult: 50-400 mg daily. Prophylaxis in patients undergoing bone marrow transplantation: The recommended daily dosage is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start Fluconazole Injection, USP prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Child Dose

Child: PO 3–12 mg/kg/day, max 600 mg/day q24h Max 800–1,000 mg/day may be used for some CNS fungal infections Age Average Weight Dose/Day 1 year: 9 kg - ½ spoonful 1-2 years: 12 kg- 1 spoonful 2-3 years: 14 kg- 1½ spoonful 3-4 years: 16 kg- 2 spoonful

Renal Dose

Renal impairment: Haemodialysis patients: Usual dose given after each session. CrCl (ml/min) Dosage Recommendation <50 and not receiving dialysis 50% of the usual dose. >50 Usual dose.

Administration

May be taken with or without food Reconstitution: Powd for oral susp: Add 24 mL of distilled or purified water to the container labeled as containing 0.35 g or 1.4 g of fluconazole to provide a susp containing 50 mg or 200 mg per 5 mL, respectively. Shake vigorously to suspend the powd.

Contra Indications

Hypersensitivity.

Precautions

Renal or hepatic impairment. May prolong QT interval. Pregnancy, lactation. CDC guidelines recommend only using topical antifungal products to treat pregnant women with vulvovaginal yeast infections, including for longer periods than usual if these infections persist or recur. Lactation Enters breast milk; use caution

Pregnancy-Lactation

Pregnancy Single maternal PO dose of 150 mg for vaginal candidiasis Results of a Danish study concludes there is a possible increased risk of miscarriage; women who are pregnant or actively trying to get pregnant should ask their physician about alternative treatments Spontaneous abortion between 7 and 22 weeks' gestation occurred significantly more often in women exposed to oral fluconazole than unexposed pregnancies (4.43% vs. 4.25%; hazard ratio, 1.48); fluconazole was also compared with intravaginal azole antifungals to account for confounding by candidiasis, again, the oral drug was associated with significantly increased risk for spontaneous abortion - JAMA. 2016;315(1):58-67 CDC guidelines recommend only using topical antifungal products to treat pregnant women with vulvovaginal yeast infections, including for longer periods than usual if these infections persist or recur All other indications Use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus A 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 Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with 400-800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose Reported anomalies are similar to those seen in animal studies and consist of brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease Lactation Secreted in human milk at concentrations similar to maternal plasma concentrations; use caution (AAP Committee states "compatible with nursing")

Interactions

May increase plasma concentrations of oral hypoglycaemics (e.g. tolbutamide, glyburide, glipizide), phenytoin, theophylline, tofacitinib, rifabutin. May increase prothrombin time w/ anticoagulants. May cause significant increase in ciclosporin levels in renal transplant patients w/ or w/o renal impairment. Rifampicin reduces fluconazole levels. May increase risk of nephrotoxicity w/ tacrolimus. May increase the effect of short-acting benzodiazepines (e.g. midazolam). Potentially Fatal: Increased risk of cardiac arrhythmias or QT prolongation w/ terfenadine, cisapride, astemizole, pimozide, quinidine, halofantrine and erythromycin.

Side Effects

Side effects of Fluconazole : >10% Headache (2-13%) 1-10% Nausea (2-7%), Abdominal pain (2-6%), Diarrhea (2-3%), Rash (2%), Vomiting (2-5%) Frequency Not Defined QT prolongation, Torsades de pointes, Alopecia, Anaphylactic reactions, Angioedema, Cholestasis, Dizziness, Dyspnea, Hepatic failure, Hepatitis, Hypertriglyceridemia, Hypokalemia, Increased alkaline phosphatase, Increased ALT/AST, Jaundice, Leukopenia, Pallor, Seizures, Stevens-Johnson syndrome, Taste perversion, Thrombocytopenia, Toxic epidermal necrolysis Potentially Fatal: Hepatotoxicity; rarely anaphylaxis; Stevens-Johnson syndrome.

Mode of Action

Fluconazole decreases ergosterol synthesis by interfering w/ cytochrome P450 activity, thus inhibiting cell membrane formation of susceptible fungi including B. dermatitidis, Candida spp., C. immitis, C. neoformans, Epidermophyton spp., H. capsulatum, Micosporum spp., Trichophyton spp.