Drug Interactions between fluconazole and posaconazole

Food significantly increases the absorption of posaconazole from the tablet or suspension formulations. The manufacturer recommends that you take the tablet with food and the oral suspension during or immediately (within 20 minutes) after a full meal. If you cannot eat a full meal, you should take the oral suspension with a liquid nutritional supplement like Ensure or an acidic carbonated beverage like ginger ale. Do not take these medications on an empty stomach, as it may lead to inadequate blood levels and reduced effectiveness. Ask your doctor before using alcohol together with posaconazole from delayed release suspension formulations as this may cause an increase in side effects. Talk to your doctor or pharmacist if you have any questions on how to use the medication properly.

Posaconazole powder for delayed-release oral suspension is contraindicated in patients with known/suspected hereditary fructose intolerance (HFI). This formulation contains sorbitol (inactive ingredient) and may precipitate a metabolic crisis that may include (but is not limited to) life-threatening hypoglycemia, hypophosphatemia, lactic acidosis, and hepatic failure in patients with HFI. Careful history of HFI symptoms (nausea, vomiting, abdominal pain) with sorbitol/fructose/sucrose exposure should be obtained before administration of posaconazole powder for delayed-release oral suspension because a diagnosis of HFI may not yet be established in pediatric patients.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Patients with severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when using posaconazole delayed-release tablets, oral suspension, or powder for delayed-release oral suspension.

Electrolyte disturbances (especially those involving potassium, magnesium, or calcium levels) should be monitored and corrected as needed before and during posaconazole therapy.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

Posaconazole has been associated with hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis); cases of more severe hepatic reactions (including cholestasis or hepatic failure including deaths) have been reported during therapy in patients with serious underlying medical conditions (e.g., hematologic malignancy), primarily in patients receiving 800 mg/day. Liver tests should be assessed at the start of and during posaconazole therapy. No dose adjustment of posaconazole is necessary in patients with mild to severe liver dysfunction (Child-Pugh A, B, or C). However, posaconazole delayed-release tablets, powder for delayed-release oral suspension, and injection have not been specifically studied; caution is recommended.

Posaconazole has been associated with hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis); cases of more severe hepatic reactions (including cholestasis or hepatic failure including deaths) have been reported during therapy in patients with serious underlying medical conditions (e.g., hematologic malignancy), primarily in patients receiving 800 mg/day. Liver tests should be assessed at the start of and during posaconazole therapy. No dose adjustment of posaconazole is necessary in patients with mild to severe liver dysfunction (Child-Pugh A, B, or C). However, posaconazole delayed-release tablets, powder for delayed-release oral suspension, and injection have not been specifically studied; caution is recommended.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

Posaconazole injection should be avoided in patients with moderate or severe renal dysfunction (estimated glomerular filtration rate [eGFR] less than 50 mL/min) unless an assessment of the risks and benefits justifies its use. Since the IV vehicle, betadex sulfobutyl ether sodium (SBECD), is expected to accumulate in patients with moderate or severe renal dysfunction using the injection, serum creatinine levels should be closely monitored in these patients, and if increases occur, switching to oral posaconazole therapy should be considered. No dose adjustment is needed for oral dosing in patients with mild to severe renal dysfunction; however, patients with severe renal dysfunction (eGFR less than 20 mL/min/1.73 m2) should be closely monitored for breakthrough fungal infections due to variability in exposure with posaconazole delayed-release tablets, oral suspension, and powder for delayed-release oral suspension.

Patients with severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when using posaconazole delayed-release tablets, oral suspension, or powder for delayed-release oral suspension.

The recommended maximum number of medicines in the 'antifungal agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antifungal agents' category:

• fluconazole
• posaconazole

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.