[, Johnson & Johnson News: Janssen Announces U.S. FDA Approval of First and Only Complete, Single-Pill, Two-Drug Regimen, JULUCA (Dolutegravir and Rilpivirine), for the Treatment of HIV-1 Infection [, FDA Approved Drug Products: Triumeq/Triumeq PD (abacavir, dolutegravir, and lamivudine) for oral administration [, FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [, FDA Approved Drug Products: JULUCA (dolutegravir and rilpivirine tablets), for oral use [, FDA Approved Drug Products: DOVATO (dolutegravir and lamivudine) tablets, for oral use [, Waki K, Sugawara Y: Implications of integrase inhibitors for HIV-infected transplantation recipients: raltegravir and dolutegravir (S/GSK 1349572). Pharmacol Toxicol. [, Mukkavilli R, Jadhav G, Vangala S: Evaluation of Drug Transport in MDCKII-Wild Type, MDCKII-MDR1, MDCKII-BCRP and Caco-2 Cell Lines. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Rifampin: (Moderate) Rifampin is a potent enzyme inducer and can increase the metabolism of fluconazole. In at least one case, the interaction resulted in an increased incidence of TCA-related side effects, like dizziness and syncope. Mol Med Rep. 2017 Apr;15(4):1593-1600. doi: 10.3892/mmr.2017.6214. If you believe you are experiencing an interaction, contact a healthcare provider immediately. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Coadministration may result in elevated plasma concentrations of alfuzosin, causing an increased risk for adverse events, such as QT prolongation. Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of fluconazole is necessary. 2011 Apr;20(4):537-48. doi: 10.1517/13543784.2011.562189. If fluconazole is administered concurrently with ibuprofen, monitor for NSAID-related side-effects such as fluid retention, GI irritation, or renal dysfunction and adjust the ibuprofen dose, if needed. Of the 16 NMEs approved as of the mid-point of 2022 (as of July 25, 2022), 75%, or 12 drugs, were small molecules, and 25%, or four were biologic-based drugs ( see Figure 2 ). Nat Rev Drug Discov. If signs and symptoms of hepatotoxicity develop, fluconazole therapy should be stopped. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Ribociclib; Letrozole: (Contraindicated) The concurrent use of fluconazole with drugs that are associated with QT prolongation and are CYP3A4 substrates, such as ribociclib, is contraindicated. Coadministration with fluconazole is predicted to increase selpercatinib exposure by 60% to 99%. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2-fold, respectively. Mol Pharmacol. 12 mg/kg/dose IV once daily as an alternative therapy to conventional amphotericin B in patients who have not been receiving fluconazole prophylaxis. However, in some patients there are decreases up to 47% of ethinyl estradiol concentrations. Levofloxacin: (Moderate) Concomitant use of levofloxacin and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. If fluconazole is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Eliglustat: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of fluconazole and eliglustat is not recommended. 150 mg PO once weekly for 6 months. The dose of fluconazole may need to be increased in patients also receiving rifampin to assure adequate fluconazole plasma concentrations. Hydrochlorothiazide may decrease the renal clearance of fluconazole. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor. Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with fluconazole is necessary. Paclitaxel: (Minor) Paclitaxel is metabolized by hepatic cytochrome P450 isoenzymes 2C8 and 3A4. Fluconazole is also recommended for coccidioidomycosis in hematopoietic stem cell transplant (HSCT), solid organ transplant, and patients receiving biologic response modifiers. Increased S-(+)-ibuprofen concentrations leads to increased inhibition of both COX-1 and COX-2, and impaired ibuprofen metabolism due to mutations in the CYP2C9 gene increases the risk of acute gastrointestinal bleeding. [61514] For persons living with HIV, fluconazole is recommended for 8 weeks after an initial 2-week course of amphotericin B deoxycholate or liposomal amphotericin B plus flucytosine. Expert Opin Investig Drugs. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Monitor for an increased response to amitriptyline if fluconazole is coadministered. Afatinib may decrease the excretion rate of Prazosin which could result in a higher serum level. According to the manufacturer of fluconazole, coadministration of drugs known to prolong the QT interval and which are CYP3A4 substrates, such as aripiprazole, is contraindicated in patients receiving fluconazole. Fluconazole inhibits CYP3A4, an isoenzyme partially responsible for the metabolism of iloperidone. In contrast, amphotericin B binds to ergosterol after it is synthesized. Expert Opin Drug Metab Toxicol. When used in combination, the plasma concentrations of boceprevir may be elevated. [, Ambrosi B, Bochicchio D, Ferrario R, Colombo P, Faglia G: Effects of the opiate agonist loperamide on pituitary-adrenal function in patients with suspected hypercortisolism. The clinical significance of these interactions has not been determined. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose. Fluconazole is a fungistatic antifungal agent with concentration-independent activity. Vincristine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Arzneimittelforschung. Assess the risks and benefits of TIVICAY and TIVICAY PD and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester. Discontinuation of fluconazole in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Although specific interactions have not been studied, moderate CYP3A4 inhibitors would likely increase tadalafil exposure. The cannabinoid delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A and CYP2C9 substrates and fluconazole is a moderate CYP3A and CYP2C9 inhibitor. Amlodipine is commonly used in the treatment of high blood pressure and angina. Naunyn Schmiedebergs Arch Pharmacol. J Clin Invest. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. Absorbed slowly after oral administration with a mean bioavailability of 60%. Deflazacort is a CYP3A4 substrate; fluconazole is a moderate inhibitor of CYP3A4. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. Ergonovine: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Coadministration of eliglustat with CYP3A inhibitors, such as fluconazole, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. [, Jaillon P: Clinical pharmacokinetics of prazosin. Peak plasma levels occurs 3-7 hours post-administration. For endocarditis, treat for at least 6 weeks after valve replacement. Manufacturers of aripiprazole injections recommend adjustments when a potent CYP3A4 inhibitor will be used for more than 14 days. 12 mg/kg/dose IV once daily after initial treatment with lipid amphotericin B or an echinocandin for patients who are unlikely to have a fluconazole-resistant isolate. Hydrochlorothiazide may decrease the renal clearance of fluconazole. 2006 Dec;5(12):993-6. Androgen deprivation therapy may prolong the QT/QTc interval. Mobocertinib: (Major) Avoid concomitant use of mobocertinib and fluconazole; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Epub 2013 Jul 18. In addition, some experts recommend a loading dose of approximately twice the prescribed daily dose be used to achieve therapeutic concentrations faster (e.g., 25 mg/kg loading dose on day 1, then 12 mg/kg/day). This drug is indicated for the treatment of hypertension (high blood pressure). Hydrocodone is a substrate for CYP3A4. Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use fluconazole with caution in combination with relugolix. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. Fluconazole has been associated with QT prolongation and rare cases of TdP. Amlodipine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. Fluconazole is not likely to cause QT prolongation or torsade de pointes when administered at usual therapeutic dosages. PLoS One. Transplantation. The available data indicate that the decreases in some individual ethinyl estradiol AUC values with fluconazole treatment are likely due to random variation. Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Meperidine; Promethazine: (Moderate) Concomitant use of promethazine and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Ruxolitinib: (Major) Avoid concomitant use of ruxolitinib with fluconazole doses greater than 200 mg/day; increased exposure and toxicity may occur. [, Roge J, Baumer P, Berard H, Schwartz JC, Lecomte JM: The enkephalinase inhibitor, acetorphan, in acute diarrhoea. [53038] [60487] However, for premature neonates younger than 30 weeks gestation, some recommend extending the interval to 48 hours during the first week of life. [61514] For persons living with HIV, fluconazole is recommended for 8 weeks after an initial 2-week course of amphotericin B deoxycholate or liposomal amphotericin B plus flucytosine. Apixaban is indicated for reducing the risk of stroke and systemic embolism in patients who have nonvalvular atrial fibrillation, prophylaxis of deep vein thrombosis(DVT) leading to pulmonary embolism(PE) in patients after a hip or knee replacement surgery, and treatment of DVT and PE to reduce the risk of recurrenceLabel,1,2. Fluconazole significantly inhibits the metabolism of celecoxib via CYP2C9. Doxorubicin Liposomal: (Major) Avoid coadministration of fluconazole with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. In some cases, dosage adjustment of the sulfonylurea may be necessary. Increased adverse effects of flurbiprofen may occur, especially if the two drugs are used concurrently over several days. Guanfacine: (Major) Fluconazole may significantly increase guanfacine plasma concentrations. Interrupt tolvaptan in ADPKD patients if the recommended reduced doses are not available in patients requiring short-term therapy of fluconazole. Restart suppressive therapy if CD4 count is less than 100 cells/mm3. Abemaciclib may decrease the excretion rate of Prazosin which could result in a higher serum level. from the respiratory tract typically reflects colonization and rarely requires antifungal therapy. Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of fluconazole. Toremifene: (Contraindicated) The concurrent use of fluconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as toremifene, is contraindicated. Ouabain: The risk or severity of adverse effects can be increased when Amphotericin B is combined with Ouabain. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. Ophthalmological examination is recommended for all patients. Budesonide: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Taking these drugs together may increase the risk for terbinafine related adverse effects. Pentobarbital: (Minor) Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of fluconazole. Fluconazole may rarely cause dizziness or seizures. Known inhibitors of CYP3A4, such as fluconazole, may result in increased systemic levels of bupivacaine when given concurrently, with potential for toxicity. Patients with this genotype have increased risk of adverse cardiovascular outcomes with diuretics. Epub 2016 Apr 25. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with fluconazole. 2009;17(11-12):527-33. If fluconazole is administered concurrently with ibuprofen, monitor for NSAID-related side-effects such as fluid retention, GI irritation, or renal dysfunction and adjust the ibuprofen dose, if needed. In patients with graft-versus-host disease (GVHD), reduce the initial ruxolitinib dosage to 5 mg PO once daily in patients with acute GVHD and 5 mg twice daily in patients with chronic GVHD. 800 mg PO once daily for at least 12 months for patients who are intolerant to itraconazole. Coadministration of fluconazole 100 mg PO and hydrochlorothiazide 50 mg PO for 10 days in normal volunteers (n = 13) resulted in a significant increase in fluconazole AUC and Cmax compared to fluconazole given alone. Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of fluconazole is necessary. Fluconazole has been associated with QT prolongation and rare cases of TdP. (Moderate) The dose of celecoxib may need to be reduced in patients receiving fluconazole. Fluconazole has been associated with QT prolongation and rare cases of TdP. 6 mg/kg/dose (Max: 400 mg/dose) PO once, then 3 to 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days. Fluconazole tablets, administered concomitantly with oral contraceptives containing ethinyl estradiol have resulted in an overall mean increase in ethinyl estradiol compared to placebo. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. 12 mg/kg/dose PO once daily for fluconazole-susceptible isolates. Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. VIVJOA (oteseconazole) capsules, for oral use . Nevirapine is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Drug Metab Dispos. Monitor sirolimus serum concentrations as appropriate and watch for sirolimus-related adverse reactions with coadministration of fluconazole. Fluconazole significantly inhibits the metabolism of celecoxib via CYP2C9. Vardenafil: (Contraindicated) Avoid concomitant use of vardenafil and fluconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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