Monitoring for adverse events and toxicity related to voriconazole is recommended; especially, if voriconazole is started within 24 h after the last dose of Fluconazole. Drug Interaction Studies Tacrolimus Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines.

No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity.

Dosage of orally administered tacrolimus should be decreased depending on tacrolimus concentration. Drug Interaction Studies Short-acting Benzodiazepines Following oral administration of midazolam, Fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects.

This effect on midazolam appears to be more pronounced following oral administration of Fluconazole than with Fluconazole administered intravenously. If short-acting benzodiazepines, which are metabolized by the cytochrome P system, are concomitantly administered with Fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored.

Reduce the dose of tofacitinib when given concomitantly with Fluconazole i. Dosage adjustments of triazolam may be necessary. Oral contraceptives Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple-doses of Fluconazole.

Thus, multiple dose use of Fluconazole at these doses is unlikely to have an effect on the efficacy of the combined oral contraceptive. Pimozide Although not studied in vitro or in vivo, concomitant administration of Fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of Fluconazole and pimozide is contraindicated.

Quinidine Although not studied in vitro or in vivo, concomitant administration of Fluconazole with quinidine may result in inhibition of quinidine metabolism.

Use of quinidine has been associated with QT prolongation and rare occurrences of torsade de pointes. Coadministration of Fluconazole and quinidine is contraindicated. An effect of this magnitude should not necessitate a change in the Fluconazole dose regimen in subjects receiving concomitant diuretics. Dosage adjustment of alfentanil may be necessary. Amiodarone Concomitant administration of Fluconazole with amiodarone may increase QT prolongation.

Caution must be exercised if the concomitant use of Fluconazole and amiodarone is necessary, notably with high dose Fluconazole mg. Amitriptyline, nortriptyline Fluconazole increases the effect of amitriptyline and nortriptyline. Amphotericin B Concurrent administration of Fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: The clinical significance of results obtained in these studies is unknown.

Azithromycin An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single mg oral dose of azithromycin on the pharmacokinetics of a single mg oral dose of Fluconazole as well as the effects of Fluconazole on the pharmacokinetics of azithromycin.

There was no significant pharmacokinetic interaction between Fluconazole and azithromycin. There is a risk of developing carbamazepine toxicity. Calcium channel blockers Certain calcium channel antagonists nifedipine, isradipine, amlodipine, verapamil, and felodipine are metabolized by CYP3A4.

Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended. Half of the celecoxib dose may be necessary when combined with Fluconazole.

Cyclophosphamide Combination therapy with cyclophosphamide and Fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation.

Before using fluconazole, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. Talk to your doctor about using fluconazole safely.

Although uncommon, this drug may make you dizzy. An year-old male with neurofibromatosis-1 presented to the hospital in septic shock secondary to a perforated gastric volvulus. After initial stabilization, the patient underwent total gastrectomy and multiple peritoneal lavages. Culture of peritoneal fluid showed infection with Candida albicans. Therapy was started with fluconazole mg IV every 12 hours. After starting this drug, the patient developed QT prolongation and complex ventricular arrhythmia.

The drug was discontinued. Over the subsequent hours, the patient remained in sinus rhythm except for one brief run of ventricular bigeminy.

An ECG recorded 5 months after admission and about 4 months after cessation of all QT-prolonging medications showed sinus rhythm with normal heart rate and corrected QT interval. QT prolongation and torsade de pointes have also been reported during postmarketing experience. QT prolongation, torsade de pointes Frequency not reported: Prolongation of the QT interval on the ECG, palpitations , complex ventricular arrhythmia [ Ref ] Hematologic Anemia, eosinophilia , leukopenia, neutropenia , and thrombocytopenia have been reported, often in patients with severe deep fungal infections or underlying disease.

Spontaneous reports of anemia were more frequent in patients 65 years of age or older than in those between 12 and 65 years of age; however, there is a natural increase in the incidence of anemia in the elderly. A causal relationship to drug exposure could not be determined. Anemia, leukopenia, neutropenia, agranulocytosis , and thrombocytopenia have also been reported during postmarketing experience.

Anemia Rare less than 0. Leukopenia, neutropenia, agranulocytosis, thrombocytopenia Frequency not reported: Eosinophilia[ Ref ] Other Uncommon 0. Thirst, fatigue, malaise, pain, rigors, asthenia, fever, flushing, hot flushes Rare less than 0.

Face edema Frequency not reported: Infection due to resistant microorganisms[ Ref ] Fever, asthenia, fatigue, and malaise have also been reported during postmarketing experience. Back pain , myalgia Frequency not reported: Cisapride There have been reports of cardiac events, including torsade de pointes, in patients to whom fluconazole and cisapride were coadministered. A controlled study found that concomitant fluconazole mg once daily and cisapride 20 mg four times a day yielded a significant increase in cisapride plasma levels and prolongation of QTc interval.

The combined use of fluconazole with cisapride is contraindicated. Astemizole Concomitant administration of fluconazole with astemizole may decrease the clearance of astemizole.

Resulting increased plasma concentrations of astemizole can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and astemizole is contraindicated. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered.

Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored. Voriconazole Avoid concomitant administration of voriconazole and fluconazole. Monitoring for adverse events and toxicity related to voriconazole is recommended; especially, if voriconazole is started within 24 h after the last dose of fluconazole.

Tacrolimus Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines. No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity. Dosage of orally administered tacrolimus should be decreased depending on tacrolimus concentration. Short-Acting Benzodiazepines Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects.

This effect on midazolam appears to be more pronounced following oral administration of fluconazole than with fluconazole administered intravenously. If short-acting benzodiazepines, which are metabolized by the cytochrome P system, are concomitantly administered with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored. Reduce the dose of tofacitinib when given concomitantly with fluconazole i.

Dosage adjustments of triazolam may be necessary. Oral Contraceptives Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple doses of fluconazole. Thus, multiple dose use of fluconazole at these doses is unlikely to have an effect on the efficacy of the combined oral contraceptive. Pimozide Although not studied in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism.

Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and pimozide is contraindicated. Quinidine Although not studied in vitro or in vivo, concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism.

Use of quinidine has been associated with QT prolongation and rare occurrences of torsades de pointes. Coadministration of fluconazole and quinidine is contraindicated. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics.

A possible mechanism of action is fluconazole's inhibition of CYP3A4. Dosage adjustment of alfentanil may be necessary. Amiodarone Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Caution must be exercised if the concomitant use of fluconazole and amiodarone is necessary, notably with high-dose fluconazole mg.

Amitriptyline, Nortriptyline Fluconazole increases the effect of amitriptyline and nortriptyline.

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