El fluconazol es una antifúngico sintético de la familia de los imidazoles, que se puede administrar por vía oral e intravenosa. Su espectro de actividad es mayor que el de otros antifúngicos imidazólicos incluyendo el miconazol, el ketoconacol o el clotrimazol. Además, el fluconazol es más resistente al metabolismo hepático de primer paso, es menos lipofílico y se une menos a las proteínas del plasma, por lo que tiene una mayor biodisponibilidad.
Mecanismo de acción: como otros antifúngicos azoles, el fluconazol ejerce su efecto alterando la membrana celular del hongo.
Fluconazole inhibits ergosterol synthesis by interacting with 14-alpha demethylase, a cytochrome P-450 enzyme that is needed to convert lanosterol to ergosterol, an essential component of the membrane. In contrast, amphotericin B binds to ergosterol after it is synthesized. Inhibition of ergosterol synthesis results in increased cellular permeability causing leakage of cellular contents. Fluconazole does not appear to have the same activity on human cholesterol synthesis. Other antifungal effects of azole compounds have been proposed and include: inhibition of endogenous respiration, interaction with membrane phospholipids, and inhibition of the transformation of yeasts to mycelial forms. Other mechanisms may involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.. The following organisms are generally considered susceptible to fluconazole in vitro: Aspergillus flavus; Aspergillus fumigatus; Blastomyces dermatitidis; Candida albicans; Candida glabrata; Candida kefyr; Candida tropicalis; Coccidioides immitis; Cryptococcus neoformans; Histoplasma capsulatum.
Pharmacokinetics: Fluconazole is administered orally and intravenously. The pharmacokinetics of both IV and oral fluconazole are similar. GI absorption is rapid and almost complete. Oral bioavailability is over 90% in fasting adults, and peak serum concentrations are attained within 1—2 hours after oral administration. Food affects neither the rate nor the extent of absorption. Unlike ketoconazole, gastric pH has no effect on fluconazole bioavailability. Peak serum concentrations and AUC increase in proportion to the dose. Steady-state fluconazole plasma concentrations are achieved within 5—10 days at doses within the range of 50—400 mg/day, and within 2 days when a loading dose of twice the usual daily dosage is first given. Fluconazole is widely distributed into body tissues and fluids. Saliva, sputum, nail, blister, and vaginal secretion concentrations are approximately equal to plasma concentrations. Urine and skin concentrations are approximately 10 times that of plasma concentrations. High concentrations also can be achieved in the cornea, aqueous humor, and vitreous body following IV administration. Fluconazole distributes well into the CSF, and achieves CSF concentrations that are 50—94% of plasma concentrations, regardless of the degree of meningeal inflammation. Protein binding ranges from 11—12%. Fluconazole's distribution into human milk and across the placenta are not known. Fluconazole does not appear to undergo first-pass metabolism. Elimination is mainly renal, and about 60—80% of a dose is excreted in the urine unchanged, and 11% as metabolites. Renal dysfunction prolongs the half-life and increases plasma concentrations. Plasma elimination half-life in adults with normal renal function is approximately 30 hours (range: 20—50 hours). Mean elimination half-life in children (ages 1—15 years) without HIV infection ranges from 15.6—18.1 hours. Fluconazole half-life in premature neonates has been reported to be roughly 88 hours after the first treatment dose; after two weeks of therapy, the half-life declines to approximately 55 hours. The elimination half-life of fluconazole is inversely proportional to the patient's creatinine clearance. Elimination of the drug also can be impaired in elderly patients. Hepatic dysfunction has no effect on the half-life or elimination of fluconazole. Small amounts of fluconazole are excreted in the feces. Fluconazole is removed by both hemodialysis and peritoneal dialysis. Three hours of hemodialysis decreases plasma concentrations by approximately 50% but depends on the type of coil used and the dialysis flow rate.
INDICACIONES Y POSOLOGIA
Tratamiento de una candidemia invasiva sistémica:
Administración oral o intravenosa:
Tratamiento de una infección del tracto urinario producida por Candida sp. (p.ej. candiduria)
Administración oral o intravenosa:
Adults: The optimum dosage has not been established, however doses of 50—200 mg PO or IV once daily have been used.
•for the treatment of peritonitis caused by Candida sp.: Oral or Intravenous dosage: Adults: The optimum dosage has not been established, however doses of 50—200 mg PO or IV once daily have been used.
For the treatment of mucocutaneous candidiasis:
•for oropharyngeal candidiasis (thrush): Oral or Intravenous dosage: Adults: 200 mg PO or IV on the first day, then 100 mg PO or IV once daily. Treatment should continue for two weeks after resolution of symptoms. Pregnant females: Topical antifungal therapy such as nystatin may be preferable. Children, infants and neonates > 14 days: 6 mg/kg PO or IV on the first day, followed by 3 mg/kg PO or IV once daily. Administer treatment for at least 2 weeks to decrease the chance of relapse. Neonates 0—14 days: 6 mg/kg PO or IV on the first day, followed by 3 mg/kg PO or IV every 72 hours. After the first 2 weeks of life, administer the dose once daily.
•for esophageal candidiasis: Oral or Intravenous dosage: Adults: 200 mg IV or PO on the first day, then 100 mg PO or IV daily. Depending on the severity, up to 400 mg/day PO or IV can be given. Patients should be treated for a minimum of 3 weeks and for at least 2 weeks following the resolution of symptoms. Fluconazole 100—200 mg PO once daily was superior to ketoconazole in an 8 week study of AIDS patients with candidal esophagitis. Pregnant females: Topical antifungal therapy such as nystatin may be preferable. Children, infants, and neonates > 14 days: 6 mg/kg PO or IV on the first day, followed by 3 mg/kg PO or IV once daily. Doses up to 12 mg/kg/day PO or IV can be used if clinically necessary. Dosages above 600 mg/day are not recommended. Treatment should continue for a minimum of 3 weeks and for at least 2 weeks following the resolution of symptoms. Neonates 0—14 days: 6 mg/kg PO or IV on the first day, followed by 3 mg/kg PO or IV every 72 hours. After the first 2 weeks of life, administer the dose once daily. Doses up to 12 mg/kg PO or IV can be used if clinically necessary. Treatment should continue for a minimum of 3 weeks and for at least 2 weeks following the resolution of symptoms.
•for vulvovaginal candidiasis: Oral or Intravenous dosage: Adult and adolescent females: 150 mg PO or IV as a single dose. A single oral 150 mg dose of fluconazole was compared with seven days of intravaginal clotrimazole in 358 women with moderate to severe candida vaginitis. The response to oral fluconazole and to intravaginal clotrimazole was similar. Pregnant females: Topical antifungal therapy such as nystatin may be preferable.
•for the treatment of pneumonia caused by Candida sp.: Oral or Intravenous dosage: Adults: The optimum dosage has not been established, however doses of up to 400 mg PO or IV once daily have been used. For the treatment of coccidioidomycosis†: Oral dosage: Adults: 400—600 mg PO once daily has been recommended. For the treatment of fungal meningitis:
•for meningitis due to Cryptococcus neoformans:
Oral or Intravenous dosage:
Adults: 400 mg PO or IV on the first day or once daily until clinical response occurs, followed by 200—400 mg PO or IV once daily. Fluconazole 200 mg PO once daily should be administered for a period of 10—12 weeks after the cerebrospinal fluid cultures are negative.
Children, infants, and neonates > 14 days: 12 mg/kg PO or IV on the first day, followed by 6—12 mg/kg IV or PO once daily. Dosages above 600 mg/day are not recommended. The recommended duration of therapy is 10—12 weeks after the cerebrospinal fluid cultures are negative.
Neonates 0—14 days: 2 mg/kg PO or IV on the first day, followed by 6—12 mg/kg IV or PO every 72 hours. The recommended duration of therapy is 10—12 weeks after the cerebrospinal fluid cultures are negative. After the first 2 weeks of life, administer the dose once daily.
•for empiric treatment of chronic meningitis† due to Candida albicans, Coccidioides immitis, or Histoplasma capsulatum: Oral or Intravenous dosage: Adults: Doses of 400—800 mg PO or IV once daily, for 12—18 months, depending on response, have been suggested. Fluconazole is potentially useful for empiric therapy of chronic meningitis due to Candida albicans, Coccidioides immitis, or Histoplasma capsulatum.
For fungal prophylaxis:
•for primary prophylaxis of superficial and/or systemic fungal infection in bone marrow transplant (BMT) patients: Oral dosage: Adults: 400 mg PO once daily. In patients who are anticipated to experience < 500/mm3, therapy should begin several days prior to the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises back above 1000/mm3. Both superficial and systemic fungal infections occurred less frequently in bone marrow transplant patients who received fluconazole prophylaxis until the neutrophil count reached 1000 than in patients who received placebo; however, there was a tendency for patients receiving fluconazole to develop Candida krusei infections. A lower dose of 100 mg PO once daily beginning 7 days before transplantation and continuing for 180 days post-transplant or for the duration of immunosuppression has also been recommended.
•for primary prophylaxis of superficial and/or systemic fungal infection in patients with acute leukemia: Oral or Intravenous dosage: Adults: In one study, fluconazole 400 mg PO once daily or 200 mg IV every 12 hours was begun at the initiation of chemotherapy and was continued until 7 days after the neutrophil count reached 1000/mm3. The median duration of oral therapy was 16.0 days. Both superficial and invasive fungal infections were less frequent in the fluconazole recipients than in patients receiving placebo.
•for primary prophylaxis† of systemic fungal infection in HIV-infected patients with < 200 CD4+ cells/mm3: Oral dosage: Adults: Several different oral dosages have been studied. A retrospective study of the prevention of fungal infection in HIV-positive patients with < 200 CD4+ cells demonstrated a dosage of 100 mg/day PO every third week reduced the incidence of systemic mycoses significantly compared to patients who received no antifungal prophylaxis. In patients with < 50 CD4+ cells/mm3, fluconazole 200 mg PO once daily was superior to clotrimazole lozenges in preventing the development of invasive fungal infection during a median follow-up period of 35 months.
•for oral, vaginal, or esophageal candidiasis prophylaxis† in HIV-infected patients: Oral dosage: Adults: The routine primary candidiasis prophylaxis in patients with AIDS or immunodeficiency syndrome-related complex is not recommended due to the potential of developing drug-resistant candida. For patients with frequent or severe recurrences of oral, vaginal, or esophageal candidiasis, the CDC recommends a dose of 100—200 mg PO once daily. Fluconazole 200 mg PO once per week was more effective than placebo in preventing either oropharyngeal, vaginal, or esophageal candidiasis in women with 300 CD4+ cells/mm3 or less during a median follow-up period of 29 months. In a study of HIV-positive patients with previous thrush episodes, thrush occurred in 8 of 13 patients receiving placebo and in none of 12 patients receiving fluconazole 100 mg PO once daily for 12 weeks. A dose of 150 mg PO once weekly has also been successful in preventing relapse. Doses of 50 mg PO every other day or 150 mg as a single PO dose were adequate protection for the 3 months' duration in patients with less advanced HIV disease and who had just experienced their first episode of candidiasis while 50 mg PO every day was best for patients with full-blown AIDS. Pregnant females: Topical antifungal therapy such as nystatin may be preferable. Children and infants: The CDC recommends 3—6 mg/kg PO once daily. The routine preventive therapy of candidiasis in HIV patients is not recommended due to the potential of developing drug-resistant candida.
•for cryptococcosis prophylaxis† in HIV-infected patients: Oral dosage: Adults and adolescents: For primary prophylaxis in HIV-infected patients with a CD4+ count < 50, fluconazole 100—200 mg PO once daily may be given; however, use is not routinely indicated. The CDC recommends fluconazole 200 mg PO once daily for secondary prophylaxis. Fluconazole is superior to itraconazole in preventing relapse and is considered the preferred agent. Although patients receiving secondary prophylaxis (chronic maintence therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ cell count increases to > 100 cells/µL on highly active antiretroviral therapy (HAART), the number of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Pregnant females: Fluconazole is not recommended. Amphotericin B is the preferred agent, especially in the first trimester. Children and infants: The CDC recommends 3—6 mg/kg PO once daily.
•For secondary coccidioidomycosis prophylaxis† in HIV-infected patients: Oral dosage: Adults and adolescents: The CDC recommends 400 mg PO once daily. Although patients receiving secondary prophylaxis (chronic maintence therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ cell count increases to > 100 cells/µL on highly active antiretroviral therapy (HAART), the number of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Pregnant females: Fluconazole is not recommended. Amphotericin B is the preferred agent, especially in the first trimester. Children and infants: The CDC recommends 6 mg/kg PO once daily. Patients with renal impairment: CrCl > 50 ml/min: no dosage adjustment needed. CrCl 21—50 ml/min: following the usual loading dose, reduce recommended maintenance dose by 50%. CrCl 11—20 ml/min: following the usual loading dose, reduce recommended maintenance dose by 75%. Intermittent hemodialysis: The manufacturer recommends 100% of the usual daily dose after each dialysis session. Further adjustments may be needed depending upon the clinical situation. Continuous hemodialysis (CAVHD, CVVHD): Definitive dosage recommendations have not been established. Fluconzole is significantly removed by CAVHD or CVVHD. A dose roughly 3.8 times that used for anuric nondialyzed patients has been recommended, assuming a combined dialysis and ultrafiltrate flow rate of 1.5 L/hr. †non-FDA-approved indication [ Revised 2/15/01 ]
El fluconazol puede ser hepatotóxico y se debe utilizar con precaución en pacientes con enfermedades hepáticas prexistentes. Si durante un tratamiento con fluconazol se desarrollasen síntomas de hepatotoxicidad, se debe discontinuar inmediatamente el tratamiento.
Debido a que el fluconazol se excreta por vía urinaria en un 60-80%, debe considerarse una reducción de la dosis o un aumento del intervalo entre dosis en los pacientes con insuficiencia renal.
and should be used with caution in patients with preexisting hepatic disease. The related azole, ketoconazole, also has been associated with hepatotoxicity. Liver-function tests should be monitored. If signs and symptoms of hepatotoxicity develop, fluconazole therapy should be stopped. Approximately 60—80% of fluconazole is renally excreted (see Pharmacokinetics). Dose reduction or extension of the dosing interval is indicated in patients with renal impairment. Fluconazole should be used cautiously in patients with renal disease. Fluconazole is classified as a FDA category C drug for use during pregnancy. It should be used during pregnancy only when the potential benefits outweigh the risks. There have been reports of infants with severe skeletal abnormalities born to women who used fluconazole while pregnant. Fluconazole may produce a Antley-Bixler-like syndrome when used at high doses for long duration in early pregnancy. The nature of the observed birth defects suggests that the teratogenic effect may occur early in the first trimester. The revised CDC Guidelines for the Prevention of Opportunistic Infections in Patients with HIV recommend that oral azole antifungals, including fluconazole, not be started during pregnancy and that these agents should be discontinued in HIV-positive women who become pregnant. Women receiving fluconazole should take effective birth control. Fluconazole should be used with caution in patients with azole hypersensitivity. Fluconazole may have a cross sensitivity with other azole derivatives such as itraconazole, clotrimazole, ketoconazole, and miconazole.
El fluconazol inhibe de forma significativa el metabolismo del celecoxib, aumentando las concentraciones plasmáticas de este fármaco en un 200%.
Los antifúngicos imidazólicos inhiben la síntesis del ergosterol de los hongos, mientras que la amfotericina B actúa como fungicida al unirse al ergosterol, por lo que desde el punto de vista teórico, el fluconazol podría interferir con la actividad antufúngica de la amfoterina. Aunque no existe información clínica relacionada con esta interacción, en modelos en animales se ha encontrado una importante interacción entre el ketoconazol y la amfotericina B, no solo durante la administración concomitante de ambos fármacos, sino también cuando el imidazol fué administrado con anterioridad a la amfotericina. Los clinicos deben tener en cuenta que puede darse un fracaso terapeútico si se administra amfotericina B después de un tratamiento con un antifúngico imidazólico
El fluconazol en dosis bajas puede afectar ligeramente el metabolismo hepático de la warfarina pero dosis altas pueden aumentar el INR de forma significatica. Se recomienda vigilar estrechamente este parámetro en los pacientes anticoagulados que inicien un tratamiento con fluconazol. Si el tratamiento con warfarina se inicia una vez establecido el tratamiento con fluconazol, esta interacción tiene una menor importanciae
The combined use of fluconazole and cisapride is contraindicated. Cisapride is metabolized by cytochrome P-450 3A4 and fluconazole is an inhibitor of this isoenzyme. In patients receiving fluconazole 200 mg daily and cispapride 20 mg four times daily starting 7 days after beginning fluconazole, fluconazole significantly increased the AUC of cisapride following both single and multiple doses of cisapride. Fluconazole significantly increased the QTc interval; torsade de pointes has been reported.
The potential exists for a similar drug interaction between fluconazole and terfenadine, although high doses of fluconazole (e.g., 400—800 mg/day) appear to be necessary for the interaction to be clinically significant. Nevertheless, coadministration of terfenadine is contraindicated in patients receiving fluconazole 400 mg/day or higher. Finally, similar caution should be observed during concomitant administration of fluconazole with astemizole.
Fluconazole may inhibit the metabolism of cyclosporine, sirolimus, and tacrolimus and lead to increased concentrations. Plasma cyclosporine concentrations should be monitored closely if fluconazole is added. There have been reports of nephrotoxicity in patients to whom fluconazole and tacrolimus have been coadministered. Renal function in these patients should be carefully monitored.
Se ha observado un aumento del 75% en las concentraciones plasmáticas de fenitoína en algunos pacientes tratados con este anticonvulsivo y fluconazol. Este efecto se debe a que el fluconazol puede inihibir el metabolismo de la fenitoína, recomendándose la monitorización de los niveles plasmáticos de esta. También se ha descrito una elevación de los niveles plasmáticos de carbamazepina en un paciente tratado con ambos fármacos,
Uveitis has been reported with concomitant use of fluconazole and rifabutin. Since fluconazole has been shown to significantly increase rifabutin AUC, it is likely that the development of uveitis is directly associated with rifabutin plasma concentrations. Because HIV-infected patients are likely to be receiving rifabutin and fluconazole concomitantly, these patients should be monitored for this adverse reaction. Limited data suggest that the risk of MAC bacteremia is lowered when fluconazole is added to rifabutin.
Rifampin is a potent enzyme inducer and can increase the metabolism of fluconazole. The dose of fluconazole may need to be increased in patients also receiving rifampin to assure adequate fluconazole plasma concentrations. Although available data are inconclusive, rifabutin may be less likely than rifampin to interact with fluconazole in this manner. Fluconazole can inhibit the clearance of some benzodiazepines. Although data are limited, it appears that fluconazole can increase midazolam serum concentrations. Until more data are available, clinicians should be alert to the possibility of an exaggerated or a prolonged response to midazolam in patients receiving fluconazole. In a study of fluconazole with triazolam, fluconazole increased triazolam Cpmax, area-under-the-curve, and half-life and potentiated the pharmacodynamic effects of triazolam. The metabolism of estazolam may also be inhibited by fluconazole. Limited data suggest that testosterone concentrations increase during fluconazole administration. It appears that fluconazole doses of 200 mg/day or greater are more likely to produce this effect than doses of 25—50 mg/day. The clinical significance of this interaction is unclear at this time. Fluconazole can increase tolbutamide plasma concentrations, presumably by inhibiting tolbutamide metabolism. Although the increase in tolbutamide concentrations was statistically significant, hypoglycemia has not been observed. Nevertheless, blood glucose concentrations should be monitored because the dose of the oral hypoglycemic may need to be reduced. Thiazide diuretics can decrease renal clearance of fluconazole by up to 20%, but dosage adjustment does not appear to be necessary during combined therapy with fluconazole and thiazides.
Cilostazol is extensively metabolized by the CYP3A4 and CYP2C19 hepatic isoenzyme and appears to have pharmacokinetic interactions with many medications that are potent inhibitors of these isoenzymes. Fluconazole has been shown to increase both cilostazol AUC and Cmax when administered concurrently. In some studies, co-administration of these agents with cilostazol resulted in increased incidences of adverse effects, such as headache. When significant CYP3A4 and/or CYP2C19 inhibitors are administered concomitantly with cilostazol, the cilostazol dosage should be reduced by 50%.
Modafinil is significantly metabolized by the CYP3A4 hepatic microsomal enzyme system. Azole antifungals are significant inhibitors of this isoenzyme and may reduce the clearance of modafinil.
Fluconazole may decrease the systemic clearance of alfentanil, fentanyl, or methadone. Prolonged duration of opiate action, increased sedation, respiratory depression or other opiate side effects may occur. Close monitoring of patients is warranted.
Drugs that inhibit the cytochrome CYP 2C9 isoenzyme in vitro should be used cautiously in patients receiving irbesartan until further data are available regarding the clinical significance of theoretical drug interactions. Irbesartan is a substrate of the CYP 2C9 isoenzyme.
Inhibitors of the CYP 2C9 isoenzyme based on in vitro studies and known inhibitory interactions with phenytoin (CYP 2C9 substrate) include drugs such as fluconazole.
Clinically significant interactions between irbesartan and inhibitors of CYP 2C9 metabolism have not been reported to date.
Fluconazole inhibits the hepatic cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro; the manufacturers of pimozide consider the concomitant use of inhibitors of CYP3A4 to be contraindicated. There are rare reports of QT prolongation, ventricular arryhthmia and sudden death when a CYP3A4 inhibitor was added to the drug regimen in patients on pimozide.
Fluconazole may inhibit the metabolism of levobupivacaine. Concurrent administration of fluconazole and levobupivacaine may result in increased systemic levels of levobupivacaine resulting in toxicity.
Fluconazole may decrease the clearance of calcium-channel blockers (e.g., diltiazem, felodipine, and verapamil) via inhibition of CYP3A4 metabolism.
Bexarotene is extensively metabolized by the CYP3A4 hepatic isoenzyme. When significant CYP3A4 inhibitors like fluconazole are administered concomitantly with bexarotene, the health care professional may need to observe the patient for increased toxicity from bexarotene.
Azole antifungals such as fluconazole and itraconazole should be used with caution since they may theoretically increase dofetilide plasma concentrations via inhibition of CYP3A4 metabolism. The concomitant use of ketoconazole and dofetilide is specifically contraindicated; this interaction significantly increases dofetilide plasma concentrations with the potential risk of associated arrhythmias.
Cevimeline is metabolized by cytochrome P450 (CYP) 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as fluconazole, may lead to increased cevimeline plasma concentrations.
Alosetron is partially metabolized by cytochrome P450 3A4 (CYP3A4). Concurrent administration of inhibitors of these enzymes, such as azole antifungals (ketoconazole, fluconazole, itraconazole, systemic miconazole), may lead to increased alosetron plasma concentrations.
Zonisamide is metabolized by cytochrome P450 3A4 (CYP3A4). Concurrent administration of inhibitors of these enzymes, such as azole antifungals (ketoconazole, fluconazole, itraconazole, systemic miconazole), may lead to increased zonisamide plasma concentrations.
Hepatic CYP3A4 is partially responsible for the metabolism of galantamine. The bioavailability of galantamine may be increased when co-administered with the systemic azole antifungals, which are CYP3A4 inhibitors.
Exfoliative skin disorders, such as Stevens-Johnson syndrome, have been reported rarely in patients taking fluconazole who have concurrent malignancy or AIDS. This exfoliative skin disorder was exhibited by erythema, blisters, exfoliative dermatitis, and exfoliation mucous membranes. Since patients were often receiving multiple medications, a definite causal relationship has yet to be determined. Patients should be monitored for development of rash while receiving fluconazole. Alopecia has been reported in 33 patients during fluconazole administration. In most cases, the hair loss involved the scalp but in others substantial loss of facial, leg, axillary, pubic, or chest hair occurred. In 3 patients, scalp hair loss required the use of a wig. In almost all patients, the alopecia resolved after discontinuation or reduction in the dose of fluconazole. Mild elevations in SGOT, SGPT, alkaline phosphatase, and bilirubin have been reported in 5—7% of patients taking fluconazole. These abnormalities usually returned to pretreatment levels after completion of therapy. Rarely, hepatotoxicity has been reported in patients receiving fluconazole, which is manifested by hepatitis, dark urine, abdominal pain, anorexia, and elevated hepatic enzymes. Diarrhea, nausea/vomiting, and abdominal pain have been reported in about 10% of patients receiving fluconazole. These effects rarely required discontinuation of the drug. Headache has been reported in up to 13% of patients receiving fluconazole. Dizziness has been seen in about 2% of fluconazole patients. Fluconazole has been associated with teratogenesis when used early in a pregnancy at high doses. Fluconazole produces a chacarteristic pattern of fetal abnormalities including craniofacial, skeletal and cardiac anomolies, similar to Antley-Bixler syndrome when used during the first trimester. These effects may be dose-dependent. The nature of the observed birth defects suggests that the teratogenic effects may occur before the woman is aware she is pregnant. The exact mechanism is not known. Hypokalemia requiring either potassium supplementation or discontinuation of therapy has been seen occasionally in some patients receiving fluconazole. Thrombocytopenia and eosinophilia have been reported rarely in patients taking fluconazole.
|Monografía actualizada el 17 de Mayo de 2011. Equipo de Redacción de IQB|