In cases of fluconazole associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patient has been observed. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy.
Patients who develop abnormal liver function tests during fluconazole therapy must be monitored closely for the development of more serious hepatic injury. The patient should be informed of suggestive symptoms of serious hepatic effect important asthenia, anorexia, persistent nausea, vomiting and jaundice. Treatment of fluconazole should be immediately discontinued and the patient should consult a physician.
Cardiovascular system Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram.
During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking Fluconazole. These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant treatment that may have been contributory.
Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions. Coadministration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P CYP 3A4 are contraindicated see sections 4. The concomitant use of fluconazole and halofantrine is therefore not recommended see section 4.
Dermatological reactions Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, during treatment with fluconazole. AIDS patients are more prone to the development of severe cutaneous reactions to many medicinal products. If a rash, which is considered attributable to fluconazole, develops in a patient treated for a superficial fungal infection, further therapy with this medicinal product should be discontinued.
Hypersensitivity In rare cases anaphylaxis has been reported see section 4. Fluconazole is also an inhibitor of CYP2C Terfenadine The coadministration of fluconazole at doses lower than mg per day with terfenadine should be carefully monitored see sections 4.
This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Adrenal insufficiency Ketoconazole is known to cause adrenal insufficiency, and this could also although rarely seen be applicable to fluconazole. Adrenal insufficiency relating to concomitant treatment with Prednisone is described in section 4.
The effect of fluconazole on other medicinal products 4. There have been reports of cardiac events including torsades de pointes in patients to whom fluconazole and cisapride were co-administered. If you notice other effects not listed above, contact your doctor or pharmacist. In the US - Call your doctor for medical advice about side effects. In Canada - Call your doctor for medical advice about side effects.
You may report side effects to Health Canada at Precautions Before taking fluconazole , tell your doctor or pharmacist if you are allergic to it; or to other azole antifungal drugs such as ketoconazole , itraconazole ; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems.
Talk to your pharmacist for more details. Before using this medication , tell your doctor or pharmacist your medical history, especially of: Fluconazole may cause a condition that affects the heart rhythm QT prolongation. Ask your doctor or pharmacist for advice.
This medicine may rarely cause liver problems. For this reason you should stop taking this medicine and consult your doctor if you develop any of the following symptoms while taking it, as they may indicate a problem with your liver: Who should not take Diflucan capsule? People with rare hereditary blood disorders called porphyrias.
An oral dose of 7. Both oral and IV fluconazole increased the pharmacodynamic effects of midazolam. Azithromycin An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single mg oral dose of fluconazole on the pharmacokinetics of a single mg oral dose of azithromycin as well as the effects of azithromycin on the pharmacokinetics of fluconazole.
There was no significant pharmacokinetic interaction between fluconazole and azithromycin. Concurrent administration of oral Voriconazole mg Q12h for 1 day, then mg Q12h for 2. Concomitant administration of voriconazole and fluconazole at any dose is not recommended. Close monitoring for adverse events related to voriconazole is recommended if voriconazole is used sequentially after fluconazole, especially within 24 h of the last dose of fluconazole. This enzyme functions to convert lanosterol to ergosterol.
Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Point mutations in the gene ERG11 encoding for the target enzyme lead to an altered target with decreased affinity for azoles.
Overexpression of ERG11 results in the production of high concentrations of the target enzyme, creating the need for higher intracellular drug concentrations to inhibit all of the enzyme molecules in the cell. The second major mechanism of drug resistance involves active efflux of fluconazole out of the cell through the activation of two types of multidrug efflux transporters; the major facilitators encoded by MDR genes and those of the ATP-binding cassette superfamily encoded by CDR genes.
Upregulation of the MDR gene leads to fluconazole resistance, whereas, upregulation of CDR genes may lead to resistance to multiple azoles.
Resistance in Candida glabrata usually includes upregulation of CDR genes resulting in resistance to multiple azoles. 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. Fluconazole increases the effect of amitriptyline and nortriptyline. 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.
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.
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. 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.
One fatal case of possible fentanyl Fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers it was shown that Fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression.
Fluconazole can increase halofantrine plasma concentration due to an inhibitory effect on CYP3A4. If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. Fluconazole inhibits the metabolism of losartan to its active metabolite E 74 which is responsible for most of the angiotensin Il-receptor antagonism which occurs during treatment with losartan.
Patients should have their blood pressure monitored continuously. Fluconazole may enhance the serum concentration of methadone. Do not use fluconazole in animals with liver disease. Use with caution in pets with kidney disease. Do not use in pregnant pets unless the benefit outweighs the risk. What other medications will affect fluconazole? Tell your veterinarian if your pet is using any of the following medications: There may be other drugs not listed that can affect fluconazole.
Tell your veterinarian about all prescription and non-prescription OTC medications, including vitamins, minerals, herbal products, and drugs prescribed by other veterinarians.
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