Fluconazole adverse effects

Treatment of candidiasis is presented in Table 38-4. Amphotericin B may be switched to fluconazole (IV or oral) for completion of therapy. Azoles and deoxycholate amphotericin B are similarly effective however, fewer adverse effects are observed with azoles. Echinocandins are at least as effective as amphotericin B or fluconazole in nonneutropenic adult patients with candidemia. 

Fluconazole is an inhibitor of the cytochrome P450 3A4 and 2C9 enzyme systems. Coadministration of fluconazole with other drugs metabolized by the same enzyme system may result in increased plasma concentrations of the drugs, which could increase or prolong therapeutic and adverse effects. Unless otherwise specified, dosage adjustment may be necessary. 

The adverse effects that most frequently result in discontinuation of rifabutin include GI intolerance, rash, and neutropenia. Rifabutin levels will be increased with concurrent administration of fluconazole and clarithromycin, resulting in anterior uveitis, polymyalgia syndrome, and a yellowish-tan discoloration of the skin (pseudojaundice). Other adverse reactions are similar to those of rifampin, such as hepatitis, red-orange discoloration of body fluids, and drug interactions due to effects on the hepatic P450 cytochrome enzyme system. 

Adverse Effects. Hepatotoxicity is the most serious adverse effect of fluconazole this drug should be used cautiously in patients with impaired liver function. Other common side effects include headache and gastrointestinal disturbances (abdominal pain, nausea, vomiting). 

Fluconazole is used for superficial mucosal candidiasis and fungal skin infections. It should be used with caution in patients with renal and hepatic dysfunction. It is reported that teratogenicity is observed in animals hence it is not recommended for use in pregnant women.66 66g Adverse effects include abdominal pain and diarrhea. Alopecia has occasionally been reported in patients during prolonged use.67... 

FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE (POSSIBLY POSACONAZOLE) VINCA ALKALOIDS -VINBLASTINE, VINCRISTINE, VINORELBINE t adverse effects of vinblastine and vincristine Inhibition of CYP3A4-mediated metabolism. Also inhibition of P-gp efflux of vinblastine Monitor FBCs and watch for early features of toxicity (pain, numbness, tingling in the fingers and toes, jaw pain, abdominal pain, constipation, ileus). Consider selecting an alternative drug... 

Among the imidazole derivatives, numerous case reports or studies have shown that ketoconazole, fluconazole, and itraconazole can inhibit ciclosporin metabolism and increase blood ciclosporin concentrations (267). Ketoconazole, which is undoubtedly the most potent inhibitor, has been used to reduce the dose, and therefore the cost or adverse effects, of ciclosporin (268-270). There was also a beneficial effect on the rate of rejection or infection. In contrast, interactions with metronidazole and miconazole have only been described in isolated case histories (SEDA-19, 351) (5). 

The effects of fluconazole and clarithromycin on the pharmacokinetics of rifabutin and 25-O-desacetylrifabu-tin have been studied in ten HIV-infected patients who were given rifabutin 300 mg qds in addition to fluconazole 200 mg qds and clarithromycin 500 mg qds (73). There was a 76% increase in the plasma AUC of rifabutin when either fluconazole or clarithromycin was given alone and a 152% increase when both drugs were given together. The authors concluded that patients should be monitored for adverse effects of rifabutin when it is co-administered with fluconazole or clarithromycin. 

In a randomized, double-blind, placebo-controlled study in Saudi Arabia of oral fluconazole (200 mg/day for 6 weeks) in the treatment of cutaneous leishmaniasis, 106 patients were assigned to fluconazole and 103 to placebo (28). Follow-up data were available for 80 and 65 patients respectively. At the 3-month follow-up, healing of lesions was complete in 63 of the 80 patients who took fluconazole and 22 of the 65 patients who took placebo (relative risk of complete healing, 2.33 95% Cl = 1.63, 3.33). Adverse effects were mild and similar in the two groups. 

Fluconazole is generally well tolerated. The most common adverse effects are nausea and vomiting. Abnormal liver function tests and slight increases in hepatic enzymes have been reported, and there have been anecdotal reports of hepatitis and hepatic failure. Early studies have shown no changes in testosterone concentrations or in the adrenal response to ACTH. Rashes and a few cases of exfoliative skin disorder have been reported (SED-12,681) and have been seen more frequently in patients with AIDS (29). Alopecia has been reported in a few cases with the use of high doses for prolonged periods of time (SEDA-18, 281). Rare instances of anaphylactoid reactions have been reported (SED-12, 681) (30). Rare instances of hypersensitivity reactions have occurred in other individuals (SEDA-16, 293) (SEDA-17,320). Tumor-inducing effects have not been reported. 

In a study using the UK General Practice Research Database to determine rates of drug-induced, rare, serious adverse effects on the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or itraconazole, three had illnesses for which a fluconazole-induced cause could not be ruled out one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole (31). The rates were 2.8/100 000 prescriptions (95% Cl = 0.8, 10) for serious, adverse blood events and 1.4/100 000 prescriptions (95% Cl = 0.25, 8.2) for serious, adverse liver events. These results suggest that fluconazole does not commonly have serious adverse effects on the liver, kidneys, skin, or blood. 

Central nervous system abnormahties constitute the major dose-limiting adverse effects of fluconazole and are observed at dosages over 1200 mg/day (35). 

The safety profile of fluconazole has been assessed in 562 children (aged 0-17 years 323 boys and 239 girls), enrolled into 12 clinical studies of prophylactic or therapeutic fluconazole in predominantly immunocompromised patients (66). Most of the children received multiple doses of fluconazole 1-12 mg/kg, given as oral suspension or intravenously. Overall, 58 children reported 80 treatment-related adverse effects. The most common adverse effects were associated with the gastrointestinal tract (7.7%), the skin (1.2%), or the liver and biliary system (0.5% or three patients). Overall, 18 patients discontinued treatment owing to adverse effects, mainly gastrointestinal. Dosage and age did not affect the incidence and pattern of adverse effects. Treatment-related... 

In a double-blind comparison in oropharyngeal candidiasis in 244 patients with AIDS, itraconazole oral solution and fluconazole capsules (each 100 mg/day for 14 days) were equally efficacious there were no significant differences in adverse effects (17). 

In a study using the UK General Practice Research Database to determine rates of rare, serious drug-induced, adverse effects on the hver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or... 

The safety and efficacy of ravuconazole have been studied in a randomized, double-blind comparison with fluconazole in 71 patients with esophageal candidiasis ravuconazole was as effective as fluconazole and there were no apparent differences in adverse effects (1,2). 

Three large randomized studies in nonneutropenic patients have demonstrated that fluconazole at 400 mg/day and deoxycholate amphotericin B at 0.5-0.6 mg/kg per day are similarly effective however, fewer adverse effects are observed with fluconazole therapy." " Similarly, caspofungin is at least as effective as amphotericin B 0.6-0.7 mg/kg per day in (mainly nonneutropenic) adult patients with candidemia with fewer drug-related adverse events. Although the use of combination therapy (high-dose fluconazole plus amphotericin B) was demonstrated recently to be superior to treatment with fluconazole alone, the routine use of combination therapy in this patient population is not yet recommended." " Neonates with disseminated... 

Adverse effects of these drugs taken orally are generally mild such as gastrointestinal upset, headache and pruritis. In some patients, particularly those with HIV and on multiple therapy, more serious exfoliative dermatitis and Stevens-Johnson syndrome has occurred with fluconazole. 

These drugs are similar in action. However, fluconazole is 100 times more specific for the fungal cytochrome P450 enzymes than the human enzymes. This leads to substantially less adverse effects. 

---