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Noxafil
Classes
Azole Antifungals
Administration
The delayed-release tablets, delayed-release oral suspension, and immediate-release oral suspension are NOT interchangeable due to differences in dosing. Ensure dosage formulation, strength, and frequency are specified on each prescription.[32723] [60493]
Swallow intact; do not divide, chew, or crush.
Administer with or without food.
For patients who cannot eat a full meal and who can swallow tablets whole, use the delayed-released tablets instead of the immediate-release oral suspension for indications other than oropharyngeal candidiasis. The delayed-release tablets generally provide higher plasma drug exposures than the immediate-release oral suspension under both fed and fasted conditions.
Immediate-release oral suspension
Shake well before each use.
Administer using a calibrated measuring device. A measured dosing spoon is provided, marked for doses of 2.5 mL and 5 mL.
Administer during or immediately after (i.e., within 20 minutes) a full meal.
For patients who cannot eat a full meal and who can swallow tablets whole, use the delayed-release tablets instead of oral suspension for indications other than oropharyngeal candidiasis.
For patients who cannot eat a full meal and for whom the delayed-release tablets or injection are not options, administer each dose of oral suspension with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale).
For patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking the delayed-release tablets or injection, consider an alternative antifungal therapy or monitor patients closely for breakthrough fungal infections if continuing to use the oral suspension.
Rinse the measuring device with water after each administration and before storage.[32723]
PowderMix for delayed-release oral suspension
To ensure delivery of the correct dose, only the provided notched tip syringes must be used for preparation and administration. The design of the notched tip syringe prevents aggregation of the suspension during preparation and administration.
Preparation
Do not open packet in the PowderMix kit until ready to prepare the medicine.
Only use the mixing liquid in the kit to prepare the PowderMix for delayed-release oral suspension.
Remove cap from the mixing liquid and push the bottle adapter into the neck of the bottle. Once in place, the bottle adapter stays in the bottle.
Remove 9 mL of mixing liquid using the provided BLUE syringe. Put the cap back on the bottle.
Using the provided mixing cup, combine 9 mL of mixing liquid and the entire contents of 1 packet in the PowderMix kit and mix. Each single-use packet in the PowderMix kit contains 300 mg of posaconazole to be suspended in 9 mL of mixing liquid giving a final concentration of approximately 30 mg/mL.
Shake the mixing cup vigorously for 45 seconds to mix the powder and mixing liquid from the PowderMix kit. Check to make sure the powder is mixed. The mixture should look cloudy and free of clumps.
The reconstituted suspension must be used within 1 hour. Discard unused portion of the prepared drug product.[32723]
Administration
Administer with food.
Administration with alcohol is not recommended.
Choose the correct syringe based on the prescribed dose:
Use 3 mL (GREEN) syringe if dose is 3 mL or less.
Use 10 mL (BLUE) syringe if dose is more than 3 mL.
Measure the prescribed dose volume with the notched tip syringe provided with the kit and administer the dose orally. Administer the dose orally within 1 hour of mixing.
Not all the PowderMix in the mixing cup will be used. There will be some left over in the mixing cup.
The maximum dose that can be accurately withdrawn from the mixing cup after reconstitution is 240 mg (8 mL).
Discard any remaining suspension. The mixing cup may be hand washed and reused. Alternatively, the mixing cup may be discarded, and a similar mixing cup with a lid may be used for subsequent doses.
The notched tip syringes may also be hand washed and reused. For additional supply, a separate box of notched tip syringes is provided with the PowderMix kit.[32723]
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The diluted solution ranges from colorless to yellow.
Dilution
Bring refrigerated vial to room temperature before dilution.
Adults: Aseptically transfer 1 vial (16.7 mL) of posaconazole injection (containing 300 mg of posaconazole) to an intravenous bag or bottle containing a compatible diluent to achieve a final concentration of 1 to 2 mg/mL.
Pediatric patients: Aseptically transfer the appropriate dose of posaconazole injection (18 mg/mL) to an intravenous bag or bottle containing a compatible diluent to achieve a final concentration of 1 to 2 mg/mL. Discard any unused portion from the vial.
Compatible diluents include 5% Dextrose Injection, 0.45% Sodium Chloride Injection, 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose Injection with 20 mEq potassium chloride. Avoid use of other diluents as this may result in particulate formation.
Administer immediately after dilution, as the solution does not contain preservatives.
Storage: Diluted solution may be stored for up to 24 hours under refrigeration at 2 to 8 degrees C (36 to 46 degrees F); discard any unused portion.[32723]
Intermittent IV Infusion
Use of a 0.22-micron polyethersulfone (PES) or polyvinylidene difluoride (PVDF) filter is required.
Administer by slow IV infusion over approximately 90 minutes through a central line. Do not administer as an IV bolus injection.
When a central line is temporarily not available, a single dose of the diluted solution may be infused through a peripheral venous catheter over approximately 30 minutes. Do not administer multiple peripheral infusions as this may result in infusion site reactions.[32723]
Adverse Reactions
hemolytic-uremic syndrome / Delayed / 0-5.0
pulmonary embolism / Delayed / 0-5.0
thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-5.0
pancreatitis / Delayed / 0-5.0
renal failure (unspecified) / Delayed / 0-5.0
torsade de pointes / Rapid / Incidence not known
hepatic failure / Delayed / Incidence not known
hypokalemia / Delayed / 14.0-30.0
thrombocytopenia / Delayed / 7.0-29.0
anemia / Delayed / 2.0-25.0
neutropenia / Delayed / 4.0-23.0
constipation / Delayed / 8.0-21.0
dyspnea / Early / 1.0-20.0
hypertension / Early / 8.0-18.0
hypomagnesemia / Delayed / 10.0-18.0
stomatitis / Delayed / 11.0-17.0
elevated hepatic enzymes / Delayed / 1.0-17.0
peripheral edema / Delayed / 11.0-16.0
hypotension / Rapid / 14.0-14.0
sinus tachycardia / Rapid / 12.0-12.0
candidiasis / Delayed / 1.0-12.0
hyperglycemia / Delayed / 11.0-11.0
dehydration / Delayed / 1.0-11.0
vaginal bleeding / Delayed / 10.0-10.0
hyperbilirubinemia / Delayed / 3.0-10.0
hypocalcemia / Delayed / 9.0-9.0
edema / Delayed / 9.0-9.0
hepatitis / Delayed / 0-5.0
jaundice / Delayed / 0-5.0
hepatomegaly / Delayed / 0-5.0
adrenocortical insufficiency / Delayed / 0-5.0
QT prolongation / Rapid / Incidence not known
cholestasis / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
fever / Early / 6.0-45.0
diarrhea / Early / 10.0-42.0
nausea / Early / 9.0-38.0
vomiting / Early / 7.0-29.0
headache / Early / 8.0-28.0
abdominal pain / Early / 5.0-27.0
rash / Early / 3.0-24.0
cough / Delayed / 3.0-24.0
chills / Rapid / 0-20.0
anorexia / Delayed / 2.0-19.0
epistaxis / Delayed / 11.0-17.0
insomnia / Early / 1.0-17.0
fatigue / Early / 3.0-17.0
pruritus / Rapid / 11.0-16.0
musculoskeletal pain / Early / 16.0-16.0
weight loss / Delayed / 1.0-14.0
asthenia / Delayed / 2.0-13.0
infection / Delayed / 1.0-12.0
pharyngitis / Delayed / 12.0-12.0
petechiae / Delayed / 8.0-11.0
dizziness / Early / 11.0-11.0
arthralgia / Delayed / 11.0-11.0
dyspepsia / Early / 10.0-10.0
hyperhidrosis / Delayed / 2.0-10.0
back pain / Delayed / 10.0-10.0
weakness / Early / 8.0-8.0
paresthesias / Delayed / 0-5.0
Common Brand Names
Noxafil
Dea Class
Rx
Description
Oral and intravenous azole antifungal agent
Used for the treatment of invasive aspergillosis and oropharyngeal candidiasis and for prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients
Oral dose formulations not interchangeable due to differences in dosing
Dosage And Indications
100 mg PO twice daily for 1 day, then 100 mg PO once daily for 13 days.[32723]
100 mg PO twice daily for 1 day, then 100 mg PO once daily for 13 days.[32723]
400 mg PO twice daily for 1 day, then 400 mg PO once daily for 7 to 14 days as an alternative to fluconazole.[34362]
400 mg PO twice daily for 1 day, then 400 mg PO once daily for 7 to 14 days as an alternative to fluconazole.[34362]
400 mg PO twice daily for 3 days, then 400 mg PO once daily for up to 28 days.[60487] The FDA-approved dosage is 400 mg PO twice daily with duration of therapy based on the severity of the underlying disease and clinical response.[32723]
400 mg PO twice daily for 3 days, then 400 mg PO once daily for up to 28 days.[60487] The FDA-approved dosage is 400 mg PO twice daily with duration of therapy based on the severity of the underlying disease and clinical response.[32723]
400 mg PO twice daily for up to 28 days.[32723]
400 mg PO twice daily for up to 28 days.[32723]
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 6 to 12 weeks. [61353] Switching between the delayed-release tablets and intravenous is acceptable; a loading dose is not required when switching between formulations. Guidelines recommend posaconazole as salvage therapy.[61353]
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 6 to 12 weeks. [61353] Switching between the delayed-release tablets and intravenous is acceptable; a loading dose is not required when switching between formulations. Guidelines recommend posaconazole as salvage therapy.[61353]
200 mg PO 3 times daily has been recommended based on a population-pharmacokinetic modeling study in children. May increase dose to 200 to 300 mg PO 4 times daily to achieve a goal posaconazole trough concentration of at least 1 mcg/mL.[64043] Guidelines recommend posaconazole for at least 6 to 12 weeks as salvage therapy.[61353]
300 mg IV every 12 hours for 1 day, then 300 mg IV once daily for at least 6 to 12 weeks. [61353] Switching between the delayed-release tablets and intravenous is acceptable; a loading dose is not required when switching between formulations. Guidelines recommend posaconazole as salvage therapy.[61353]
300 mg IV every 12 hours for 1 day, then 300 mg IV once daily for at least 6 to 12 weeks. [61353] Switching between the delayed-release tablets and intravenous is acceptable; a loading dose is not required when switching between formulations. Guidelines recommend posaconazole as salvage therapy.[61353]
7 to 12 mg/kg/dose IV every 12 hours for 1 day, then 7 to 12 mg/kg/dose IV once daily has been effectively used in pediatric patients based on limited data.[64050] [64051] [64052] In a retrospective case series in pediatric patients (n = 30), the median dose necessary to achieve target posaconazole trough concentrations more than 1 mcg/mL was 10 mg/kg/day IV (range: 8.8 to 12.5 mg/kg/day) in those weighing less than 30 kg and 300 mg IV every 12 hours (range: 300 to 400 mg) for those weighing 30 kg or more. For patients weighing less than 30 kg, 10 mg/kg/day IV achieved target concentrations 90% of the time, and for patients weighing 30 kg or more, all but 1 patient (88.8%) achieved target concentrations at 300 mg IV every 12 hours.[64052] Guidelines recommend posaconazole for at least 6 to 12 weeks as salvage therapy.[61353]
200 mg PO 3 times daily for at least 6 to 12 weeks as salvage therapy.[61353] May increase dose to 200 mg PO 4 times daily for a subtherapeutic trough.[64072]
200 mg PO 4 times daily to achieve a goal posaconazole trough concentration of at least 1 mcg/mL.[64044] [64055] Guidelines recommend posaconazole for at least 6 to 12 weeks as salvage therapy.[61353]
18 to 24 mg/kg/day (Max: 800 mg/day) PO divided 4 times daily to achieve a goal posaconazole trough concentration of at least 1 mcg/mL has been recommended based on limited data.[64044] 300 mg PO 4 times daily has also been recommended based on a population-pharmacokinetic modeling study in children.[64043] Guidelines recommend posaconazole for at least 6 to 12 weeks as salvage therapy.[61353]
18 to 24 mg/kg/day PO divided 4 times daily to achieve a goal posaconazole trough concentration of at least 1 mcg/mL has been recommended based on limited data.[64044] An initial dose of 200 mg PO 4 times daily has also been recommended based on a population-pharmacokinetic modeling study in children.[64043] Guidelines recommend posaconazole for at least 6 to 12 weeks as salvage therapy.[61353]
NOTE: Do not use the immediate-release oral suspension, delayed-release oral suspension, and delayed-release tablets interchangeably due to the differences in the dosing of each formulation.
200 mg PO 3 times daily.[32723] A dose increase to 200 mg PO 4 times daily has been recommended for a subtherapeutic trough.[64072] Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723] [49827] [56105] [61353]
200 mg PO 3 times daily.[32723] A dose increase to 200 mg PO 4 times daily has been recommended for a subtherapeutic trough.[64072] Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723] [49827] [56105] [61353]
4 mg/kg/dose (Max: 200 mg/dose) PO 3 times daily targeted to a goal posaconazole trough concentration of 0.7 mcg/mL has been recommended. Duration of therapy is based on recovery from neutropenia or immunosuppression.
NOTE: Do not use the immediate-release oral suspension, delayed-release oral suspension, and delayed-release tablets interchangeably due to the differences in the dosing of each formulation.
240 mg PO twice daily for 1 day, followed by 240 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
210 mg PO twice daily for 1 day, followed by 210 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
180 mg PO twice daily for 1 day, followed by 180 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
150 mg PO twice daily for 1 day, followed by 150 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
120 mg PO twice daily for 1 day, followed by 120 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
90 mg PO twice daily for 1 day, followed by 90 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
NOTE: Do not use the immediate-release oral suspension, delayed-release oral suspension, and delayed-release tablets interchangeably due to the differences in the dosing of each formulation.
300 mg PO twice daily for 1 day, followed by 300 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723] [49827] [56105] [61353]
300 mg PO twice daily for 1 day, followed by 300 mg PO once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723] [49827] [56105] [61353]
300 mg IV every 12 hours for 1 day, followed by 300 mg IV once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
6 mg/kg/dose (Max: 300 mg/dose) IV every 12 hours for 1 day, followed by 6 mg/kg/dose (Max: 300 mg/dose) IV once daily. Duration of therapy is based on recovery from neutropenia or immunosuppression.[32723]
400 mg PO twice daily in persons with frequent or severe recurrences. Consider discontinuation when the CD4 count is more than 200 cells/mm3 after initiation of antiretroviral therapy. Routine primary candidiasis prophylaxis is not recommended.[34362]
400 mg PO twice daily in persons with frequent or severe recurrences. Consider discontinuation when the CD4 count is more than 200 cells/mm3 after initiation of antiretroviral therapy. Routine primary candidiasis prophylaxis is not recommended.[34362]
A 22-year old male patient undergoing induction chemotherapy for acute lymphoblastic leukemia developed periorbital cellulitis due to Rhizopus sp. and was successfully treated with posaconazole 800 mg PO once daily for 5 months.
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 12 months as an alternative in patients who are intolerant to itraconazole.[34362]
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 12 months as an alternative in patients who are intolerant to itraconazole.[34362]
NOTE: Mild to moderate infections may include patients with focal pneumonia or positive serology but with mild or without illness.[34362]
Oral dosage (delayed-release tablet) Adults
300 mg PO twice daily for 1 day, then 300 mg PO once daily as an alternative therapy in patients who failed to respond to itraconazole or fluconazole. May discontinue therapy in patients who have clinically responded to 3 months or more of antifungal therapy and who have a CD4 count of 250 cells/mm3 or more, virological suppression on antiretrovirals, and continued monitoring for recurrence can be performed using serial chest radiograph and coccidioidal serology.
300 mg PO twice daily for 1 day, then 300 mg PO once daily as an alternative therapy in patients who failed to respond to itraconazole or fluconazole. May discontinue therapy in patients who have clinically responded to 3 months or more of antifungal therapy and who have a CD4 count of 250 cells/mm3 or more, virological suppression on antiretrovirals, and continued monitoring for recurrence can be performed using serial chest radiograph and coccidioidal serology.
In a retrospective study of open label trials, 10 of 21 patients refractory to or intolerant of standard antifungal therapy were successfully treated with posaconazole 800 mg/day PO divided in 2 to 4 doses for up to 12 months. Most patients who had leukemia with persistent neutropenia or who underwent hematopoietic stem cell transplantation (HSCT) had a low response rate to posaconazole. However, success was noted in a majority of patients with leukemia who recovered from neutropenia and were treated for more than 3 days with posaconazole.
400 mg PO twice daily for 6 to 12 months as an alternative for mild-to-moderate pulmonary disease or 200 mg PO 4 times daily or 400 mg PO twice daily for 10 to 12 weeks as an alternative for salvage consolidation therapy for relapsed disease.
300 mg PO twice daily on day 1, followed by 300 mg PO once daily as an alternative to itraconazole in persons with asthma or cystic fibrosis.
300 mg PO twice daily on day 1, followed by 300 mg PO once daily has been used based on limited data. Guidelines recommend posaconazole as an alternative to itraconazole in persons with asthma or cystic fibrosis.
200 mg PO 3 times daily is recommended as an alternative to itraconazole in persons with asthma or cystic fibrosis.
400 mg PO twice daily has been used based on limited data. Guidelines recommend posaconazole as an alternative to itraconazole in persons with asthma or cystic fibrosis.
300 mg PO twice daily has been used based on limited data. Guidelines recommend posaconazole as an alternative to itraconazole in persons with asthma or cystic fibrosis.
18 to 24 mg/kg/day PO divided 4 times daily has been used based on limited data.[64044] [64054] Guidelines recommend posaconazole as an alternative to itraconazole in persons with asthma or cystic fibrosis.[61353]
400 mg PO twice daily for 14 to 21 days.
300 mg PO once daily for 14 to 21 days.
300 mg PO once daily as an alternative to itraconazole for patients with severe disseminated or CNS infection after completing at least 12 months of therapy and relapse despite appropriate initial therapy. Consider discontinuation if persons have received treatment for at least 1 year, have negative blood cultures, have a serum or urine Histoplasma antigen below the level of quantification, have an undetectable viral load, and have a CD4 count of more than 150 cells/mm3 on antiretroviral therapy for at least 6 months. Resume secondary prophylaxis if the CD4 count decreases below 150 cells/mm3.[34362]
300 mg PO once daily as an alternative to itraconazole for patients with severe disseminated or CNS infection after completing at least 12 months of therapy and relapse despite appropriate initial therapy. Consider discontinuation if persons have received treatment for at least 1 year, have negative blood cultures, have a serum or urine Histoplasma antigen below the level of quantification, have an undetectable viral load, and have a CD4 count of more than 150 cells/mm3 on antiretroviral therapy for at least 6 months. Resume secondary prophylaxis if the CD4 count decreases below 150 cells/mm3.[34362]
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 12 months and until resolution of abnormal CSF findings in patients who are intolerant to itraconazole.[34362]
300 mg PO twice daily for 1 day, then 300 mg PO once daily for at least 12 months and until resolution of abnormal CSF findings in patients who are intolerant to itraconazole.[34362]
300 mg PO twice daily for 1 day, then 300 mg PO once daily as an alternative to fluconazole. Continue lifelong suppressive therapy.[34362]
300 mg PO twice daily for 1 day, then 300 mg PO once daily as an alternative to fluconazole. Continue lifelong suppressive therapy.[34362]
200 mg PO 3 times daily for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
200 mg PO 4 times daily, targeted to a goal posaconazole trough concentration of at least 1 mcg/mL, has been recommended based on limited data. Treat for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
18 to 24 mg/kg/day (Max: 800 mg/day) PO divided 4 times daily, targeted to a goal posaconazole trough concentration of at least 1 mcg/mL, has been recommended based on limited data. An initial dose of 300 mg PO 4 times daily has also been recommended based on a population-pharmacokinetic modeling study in children. Treat for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
18 to 24 mg/kg/day PO divided 4 times daily, targeted to a goal posaconazole trough concentration of at least 1 mcg/mL, has been recommended based on limited data. An initial dose of 200 mg PO 4 times daily has also been recommended based on a population-pharmacokinetic modeling study in children. Treat for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
300 mg PO twice daily on the first day, followed by 300 mg PO once daily for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
300 mg PO twice daily on the first day, followed by 300 mg PO once daily, targeted to a goal posaconazole trough concentration of at least 1 mcg/mL, has been recommended based on limited data. Treat for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
200 mg PO 3 times daily, targeted to a goal posaconazole trough concentration of at least 1 mcg/mL, has been recommended based on a population-pharmacokinetic modeling study in children. May increase dose to 200 to 300 mg PO 4 times daily for a trough concentration less than 1 mcg/mL. Treat for at least 14 days after catheter removal as salvage therapy for filamentous fungi such as Aspergillus.
†Indicates off-label use
Dosing Considerations
Use with caution in patients with hepatic impairment. No dosage adjustments are recommended for mild to severe hepatic impairment (Child-Pugh Class A, B, or C).
Renal ImpairmentCrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl less than 50 mL/minute: Avoid use of the injectable formulation as accumulation of the intravenous vehicle (betadex sulfobutyl ether sodium) may occur. For the oral formulations, no dosage adjustment is recommended; however, due to a variability in exposure, monitor patients with severe renal impairment closely for breakthrough invasive fungal infections.
Intermittent hemodialysis
Posaconazole is not removed by hemodialysis.
Drug Interactions
Abemaciclib: (Major) If coadministration with posaconazole is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If posaconazole is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of posaconazole. Abemaciclib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Abrocitinib: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with abrocitinib is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and posaconazole; significantly increased acalabrutinib exposure may occur. If short-term posaconazole use is unavoidable, interrupt acalabrutinib therapy. Wait at least 24 hours after posaconazole has been discontinued before resuming acalabrutinib at the previous dosage. Acalabrutinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
Acetaminophen: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Aspirin: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Caffeine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with posaconazole may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Posaconazole is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Chlorpheniramine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Diphenhydramine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Ibuprofen: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If posaconazole 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. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Phenylephrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Acetaminophen; Pseudoephedrine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Adagrasib: (Contraindicated) Avoid concomitant use of adagrasib and posaconazole. Concomitant use may increase concentrations of both medications and result in additive risk for QT/QTc prolongation and torsade de pointes (TdP). The use of posaconazole with a CYP3A substrate that causes QT prolongation, such as adagrasib, is contraindicated per the manufacturer of posaconazole. If use is necessary, wait for adagrasib levels to reach steady state (approximately 8 days after initiation), monitor for posaconazole-related adverse effects, and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use before adagrasib steady state is achieved may increase adagrasib exposure and the risk for adagrasib-related adverse reactions. Adagrasib is a CYP3A substrate and P-gp inhibitor, posaconazole is a P-gp substrate and strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted at steady state.
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of posaconazole with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until posaconazole has cleared from the circulation (approximately 3 half-lives of posaconazole) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; posaconazole is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Afatinib: (Moderate) If the concomitant use of posaconazole and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of posaconazole. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and posaconazole is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Albuterol; Budesonide: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events.
Alfentanil: (Moderate) Posaconazole and alfentanil should be coadministered with caution due to an increased potential for alfentanil-related adverse events and prolonged effects. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of alfentanil. These drugs used in combination may result in elevated alfentanil plasma concentrations, causing an increased risk for alfentanil-related adverse events.
Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with posaconazole due to the potential for serious/life-threatening reactions, including hypotension and QT prolongation. Coadministration is expected to reduce the metabolism and increase systemic exposure to alfuzosin. Alfuzosin is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
Aliskiren: (Moderate) Posaconazole and aliskiren should be coadministered with caution due to an increased potential for aliskiren-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of aliskiren. These drugs used in combination may result in elevated aliskiren plasma concentrations, causing an increased risk for aliskiren-related adverse events.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Posaconazole and aliskiren should be coadministered with caution due to an increased potential for aliskiren-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of aliskiren. These drugs used in combination may result in elevated aliskiren plasma concentrations, causing an increased risk for aliskiren-related adverse events.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with posaconazole is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and posaconazole should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Alosetron: (Moderate) Posaconazole and alosetron should be coadministered with caution due to an increased potential for alosetron-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of alosetron. These drugs used in combination may result in elevated alosetron plasma concentrations, causing an increased risk for alosetron-related adverse events.
Alprazolam: (Contraindicated) Coadministration of posaconazole and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with posaconazole, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Amiodarone: (Contraindicated) The concurrent use of posaconazole and amiodarone is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Both posaconazole and amiodarone are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of amiodarone. Further, amiodarone is an inhibitor of the drug efflux protein, P-glycoprotein (P-gp), for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with posaconazole. Amisulpride causes dose- and concentration- dependent QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Atorvastatin: (Contraindicated) The concurrent use of posaconazole and atorvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If treatment with posaconazole is unavoidable, a brief suspension of atorvastatin therapy can be considered. Coadministration of these drugs may result in elevated atorvastatin plasma concentrations, causing an increased risk for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for atorvastatin metabolism. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) The concurrent use of posaconazole and clarithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Consider use of azithromycin in place of clarithromycin. Both posaconazole and clarithromycin are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of clarithromycin. Further, clarithromycin is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and clarithromycin and an increased risk for serious adverse events. Additionally, both drugs have been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Amphotericin B: (Moderate) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazole antifungal agents may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include posaconazole.
Apalutamide: (Major) Coadministration of apalutamide with posaconazole should generally be avoided due to the possibility of decreased posaconazole plasma concentrations, unless the benefit outweighs the risk. If concomitant use is unavoidable, closely monitor for breakthrough fungal infections and for an increase in apalutamide-related adverse reactions. Consider reducing the dose of apalutamide if necessary based on tolerability in patients experiencing grade 3 or higher adverse reactions or intolerable toxicities. Posaconazole is a P-glycoprotein (P-gp) substrate and strong CYP3A4 inhibitor. Apalutamide is a weak P-gp inducer and a CYP3A4 substrate. Inducers of P-gp may affect posaconazole plasma concentrations. Coadministration with one strong CYP3A4 inhibitor decreased the Cmax of single-dose apalutamide by 22% and the AUC remained similar. Concomitant use with another strong CYP3A4 inhibitor is predicted to increase the single-dose apalutamide AUC by 24% but have no effect on Cmax; the steady-state Cmax and AUC are predicted to increase by 38% and 51%, respectively, with this inhibitor. The predicted steady-state exposure of the active moieties (unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) is predicted to increase by 28%.
Apixaban: (Major) Reduce the apixaban dose by 50% when coadministered with drugs that are both strong inhibitors of CYP3A4 and P-gp, such as posaconazole. If patients are already receiving 2.5 mg twice daily, avoid concomitant administration of apixaban and posaconazole. Concomitant administration of posaconazole and apixaban results in increased exposure to apixaban and an increase in the risk of bleeding.
Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with posaconazole since concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of posaconazole with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant. If coadministration cannot be avoided, use caution and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Posaconazole is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions.
Aripiprazole: (Contraindicated) Avoid concomitant use of aripiprazole and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, posaconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, posaconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Arsenic Trioxide: (Major) Concurrent use of arsenic trioxide and posaconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, posaconazole should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide; TdP and complete atrioventricular block have been reported. Posaconazole has also been associated with QT prolongation and in rare cases, TdP.
Artemether; Lumefantrine: (Contraindicated) The concurrent use of posaconazole and artemether; lumefantrine is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of both artemether and lumefantrine. These drugs used in combination may result in elevated artemether; lumefantrine plasma concentrations, causing an increased risk for artemether; lumefantrine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as artemether; lumefantrine. (Contraindicated) The concurrent use of posaconazole and artemether; lumefantrine is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of both artemether and lumefantrine. These drugs used in combination may result in elevated artemether; lumefantrine plasma concentrations, causing an increased risk for artemether; lumefantrine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as artemether; lumefantrine.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with posaconazole is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Asenapine: (Contraindicated) The concurrent use of posaconazole and asenapine is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of asenapine. These drugs used in combination may result in elevated asenapine plasma concentrations, causing an increased risk for asenapine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as asenapine.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If posaconazole 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.
Atazanavir: (Major) The concurrent use of posaconazole and atazanavir should be avoided, if possible, due to the potential for atazanavir-related toxicities. If coadministered, frequently monitor for increased side effects from atazanavir. Dosage adjustment recommendations are not available. Both drugs are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of atazanavir. In one study, coadministration of posaconazole (400 mg PO twice daily) with atazanavir (300 mg PO daily) resulted in significant increases in atazanavir mean Cmax (155% increase) and mean AUC (268% increase). Further, administering posaconazole (400 mg PO twice daily) to volunteers receiving atazanavir boosted with ritonavir (300 mg/100 mg PO daily) also resulted in an increase in the mean Cmax (53% increase) and AUC (146% increase) of atazanavir.
Atazanavir; Cobicistat: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4. (Major) The concurrent use of posaconazole and atazanavir should be avoided, if possible, due to the potential for atazanavir-related toxicities. If coadministered, frequently monitor for increased side effects from atazanavir. Dosage adjustment recommendations are not available. Both drugs are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of atazanavir. In one study, coadministration of posaconazole (400 mg PO twice daily) with atazanavir (300 mg PO daily) resulted in significant increases in atazanavir mean Cmax (155% increase) and mean AUC (268% increase). Further, administering posaconazole (400 mg PO twice daily) to volunteers receiving atazanavir boosted with ritonavir (300 mg/100 mg PO daily) also resulted in an increase in the mean Cmax (53% increase) and AUC (146% increase) of atazanavir.
Atogepant: (Major) Avoid use of atogepant and posaconazole when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with posaconazole. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and posaconazole is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Atorvastatin: (Contraindicated) The concurrent use of posaconazole and atorvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If treatment with posaconazole is unavoidable, a brief suspension of atorvastatin therapy can be considered. Coadministration of these drugs may result in elevated atorvastatin plasma concentrations, causing an increased risk for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for atorvastatin metabolism.
Atorvastatin; Ezetimibe: (Contraindicated) The concurrent use of posaconazole and atorvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If treatment with posaconazole is unavoidable, a brief suspension of atorvastatin therapy can be considered. Coadministration of these drugs may result in elevated atorvastatin plasma concentrations, causing an increased risk for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for atorvastatin metabolism.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of posaconazole is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including posaconazole, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Avapritinib: (Major) Avoid coadministration of avapritinib with posaconazole due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with posaconazole due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after posaconazole is discontinued. Axitinib is a CYP3A4/5 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Azithromycin: (Major) Concomitant use of posaconazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. 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.
Bedaquiline: (Contraindicated) The concurrent use of posaconazole and bedaquiline is considered contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Consider an alternative to posaconazole. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bedaquiline. These drugs used in combination may result in elevated bedaquiline plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as bedaquiline.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with posaconazole may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of posaconazole 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. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Posaconazole is a strong inhibitor of CYP3A4. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking posaconazole. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor for an increase in posaconazole-related adverse reactions as concurrent use may also increase posaconazole exposure. Both drugs are P-gp substrates and inhibitors. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Posaconazole is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving posaconazole. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving posaconazole. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; posaconazole inhibits P-gp.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Bortezomib: (Moderate) Posaconazole and bortezomib should be coadministered with caution due to an increased potential for bortezomib-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of bortezomib. These drugs used in combination may result in elevated bortezomib plasma concentrations, causing an increased risk for bortezomib-related adverse events.
Bosentan: (Moderate) Posaconazole and bosentan should be coadministered with caution due to an increased potential for bosentan-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of bosentan. These drugs used in combination may result in elevated bosentan plasma concentrations, causing an increased risk for bosentan-related adverse events.
Bosutinib: (Major) Avoid concomitant use of bosutinib and posaconazole; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. In a cross-over trial in 24 healthy volunteers, the Cmax and AUC values of bosutinib were increased 5.2-fold and 8.6-fold, respectively, when a single oral dose of bosutinib 100 mg PO was administered after 5 days of a strong CYP3A4 inhibitor.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as posaconazole. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level.
Brigatinib: (Major) Avoid coadministration of brigatinib with posaconazole if possible due to increased plasma exposure of brigatinib; an increase in posaconazole exposure may also occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of posaconazole, resume the brigatinib dose that was tolerated prior to initiation of posaconazole. Brigatinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively. Brigatinib is also a P-glycoprotein (P-gp) inhibitor in vitro and may have the potential to increase concentrations of P-gp substrates like posaconazole.
Bromocriptine: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia, and/or other serious effects).
Budesonide: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events.
Budesonide; Formoterol: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events.
Bupivacaine Liposomal: (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Bupivacaine: (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Bupivacaine; Epinephrine: (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Bupivacaine; Lidocaine: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events. (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Bupivacaine; Meloxicam: (Moderate) Posaconazole and bupivacaine should be coadministered with caution due to an increased potential for bupivacaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of bupivacaine. These drugs used in combination may result in elevated bupivacaine plasma concentrations, causing an increased risk for bupivacaine related adverse events.
Buprenorphine: (Contraindicated) Concurrent use of buprenorphin
Buprenorphine; Naloxone: (Contraindicated) Concurrent use of buprenorphine and posaconazole is considered contraindicated. Buprenorphine, a CYP3A4 substrate, and posaconazole, a CYP3A4 inhibitor, are both associated with a risk for QT prolongation and torsade de pointes (TdP). The combined use of two drugs that can cause QT prolongation and TdP, along with a possible increased risk for these effects due to elevated plasma concentrations of buprenorphine via CYP3A4 inhibition by posaconazole, warrants a contraindication for concurrent use.
Buspirone: (Moderate) Posaconazole and buspirone should be coadministered with caution due to an increased potential for buspirone-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
Butalbital; Acetaminophen: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Butalbital; Acetaminophen; Caffeine: (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with posaconazole if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Contraindicated) Concurrent use of posaconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ripivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for rilpivirine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and posaconazole due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with posaconazole 2 to 3 days after discontinuation of posaconazole. Cabozantinib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Cannabidiol: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with cannabidiol is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in treatment-related adverse reactions if coadministration of capmatinib with posaconazole is necessary. Capmatinib is a CYP3A substrate and P-glycoprotein (P-gp) inhibitor. Posaconazole is a strong CYP3A4 inhibitor and a P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%. Inhibitors of P-gp may increase posaconazole exposure.
Carbamazepine: (Major) Posaconazole and carbamazepine should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of carbamazepine. Further, carbamazepine is an inducer of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate. This complex interaction may cause alterations in the serum concentrations of both posaconazole and carbamazepine, ultimately resulting in an increased risk of adverse events. Monitor carbamazepine serum concentrations, and adjust the carbamazepine dose as needed.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as posaconazole, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in a patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
Carvedilol: (Moderate) Altered concentrations of posaconazole and/or carvedilol may occur during coadministration. Carvedilol and posaconazole are both substrates and inhibitors of P-glycoprotein (P-gp). Use caution if concomitant use is necessary and monitor for increased side effects.
Celecoxib; Tramadol: (Major) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with posaconazole is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of posaconazole, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Ceritinib: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as ceritinib, is contraindicated. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation. If concomitant use is unavoidable, the manufacturer of ceritinib recommends decreasing the dose of ceritinib by approximately one-third when administered in combination with strong CYP3A4 inhibitors, rounding to the nearest multiple of 150 mg and monitoring for ceritinib-related adverse reactions. After posaconazole is discontinued, resume the dose of ceritinib taken prior to initiating posaconazole. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Chlordiazepoxide: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including chlordiazepoxide.
Chlordiazepoxide; Amitriptyline: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including chlordiazepoxide.
Chlordiazepoxide; Clidinium: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including chlordiazepoxide.
Chloroquine: (Major) Avoid coadministration of chloroquine with posaconazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Posaconazole has been associated with QT prolongation and TdP.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with posaconazole may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Posaconazole is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpromazine: (Major) Concurrent use of chlorpromazine and posaconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Posaconazole has been associated with QT prolongation and in rare cases, TdP. Phenothiazines have also been associated with a QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
Cilostazol: (Moderate) Posaconazole and cilostazol should be coadministered with caution due to an increased potential for cilostazol-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of cilostazol. These drugs used in combination may result in elevated cilostazol plasma concentrations, causing an increased risk for cilostazol-related adverse events.
Cimetidine: (Major) The concurrent use of posaconazole immediate-release oral suspension and cimetidine should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If this combination is required, closely monitor for breakthrough fungal infections. When posaconazole oral suspension (200 mg PO daily) was administered with cimetidine (400 mg PO twice daily), the mean reductions in both posaconazole Cmax and AUC were 39%. The administration of posaconazole oral suspension with antacids and H2-blockers other than cimetidine has not resulted in clinically significant adverse events; no dosage adjustments of posaconazole are required when administered concomitantly with antacids or H2-blockers other than cimetidine. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by antacids or H2-blockers.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of posaconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Cisapride: (Contraindicated) The concurrent use of posaconazole and cisapride is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of cisapride. These drugs used in combination may result in elevated cisapride plasma concentrations, causing an increased risk for cisapride-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as cisapride.
Citalopram: (Contraindicated) The concurrent use of posaconazole and citalopram is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of citalopram. Using these drugs in combination may result in elevated citalopram plasma concentrations, causing an increased risk for adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as citalopram.
Clarithromycin: (Contraindicated) The concurrent use of posaconazole and clarithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Consider use of azithromycin in place of clarithromycin. Both posaconazole and clarithromycin are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of clarithromycin. Further, clarithromycin is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and clarithromycin and an increased risk for serious adverse events. Additionally, both drugs have been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of posaconazole as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; posaconazole is a strong inhibitor of CYP3A4.
Clofazimine: (Moderate) Concomitant use of clofazimine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Clonazepam: (Moderate) Use posaconazole cautiously and carefully monitor patients receiving concurrent clonazepam due to impaired metabolism of clonazepam leading to exaggerated concentrations and adverse effects, such as CNS and/or respiratory depression. Clonazepam is a CYP3A4 substrate. Posaconazole is a strong CYP3A4 inhibitor.
Clorazepate: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including clorazepate.
Clozapine: (Contraindicated) Concurrent use of posaconazole and clozapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of clozapine. These drugs used in combination may result in elevated clozapine plasma concentrations, causing an increased risk for clozapine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as clozapine.
Cobicistat: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with posaconazole due to the risk of cobimetinib toxicity. Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; posaconazole is a P-gp inhibitor as well as a strong CYP3A inhibitor. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), another strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4. (Moderate) Concomitant use of promethazine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with posaconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of posaconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If posaconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Posaconazole is a strong inhibitor of CYP3A4. (Moderate) Concomitant use of promethazine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and posaconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Posaconazole can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor/P-gp inhibitor like posaconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. The recommended dose of colchicine oral solution when co-administered with posaconazole is 0.24 mg.
Conivaptan: (Contraindicated) Coadministration of conivaptan and posaconazole is contraindicated due to the potential for increased conivaptan exposure. Concomitant use may also increase posaconazole exposure and risk for posaconazole-related adverse effects. Conivaptan is a CYP3A substrate and P-gp inhibitor; posaconazole is a P-gp substrate and strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens; Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with posaconazole, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and posaconazole if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor.
Crizotinib: (Contraindicated) The concurrent use of posaconazole and crizotinib is contraindicated due to the risk of QT prolongation and torsade de pointes (TdP); increased plasma concentrations of crizotinib may also occur, which may increase the incidence and severity of adverse reactions. If an alternative is not available and concomitant use is unavoidable for adults with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), reduce the dose of crizotinib to 250 mg PO once daily. If concomitant use is necessary for young adult or pediatric patients with anaplastic large cell lymphoma or pediatric patients with IMT, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Resume the original crizotinib dose after discontinuation of posaconazole. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Crizotinib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
Cyclosporine: (Major) The interactions between cyclosporine and systemic azole antifungals can be significant. Posaconazole may inhibit cyclosporine CYP3A4-mediated metabolism, which may result in increased cyclosporine blood concentrations. Cyclosporine concentrations may increase within 1 to 3 days after starting azole antifungal therapy, and may persist for > 1 week after discontinuing antifungal treatment. Posaconazole appears to inhibit cyclosporine metabolism in a dose-dependent fashion; higher doses result in greater inhibition of cyclosporine metabolism than do lower doses. Increased cyclosporine serum concentrations occurred when posaconazole was given to patients stabilized on cyclosporine. Reduce cyclosporine doses to three-fourths the original dose when initiating therapy with posaconazole. In all cases, renal function in these patients should be carefully monitored. Close monitoring of cyclosporine concentrations is required when given in combination with systemic azole antifungals; a 50% reduction in cyclosporine dosage may be required.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with posaconazole, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like posaconazole in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with posaconazole, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Dabrafenib: (Major) Avoid the concomitant use of dabrafenib, a CYP3A4 substrate, and posaconazole, a strong CYP3A4 inhibitor, as dabrafenib levels may increase. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as posaconazole. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects. In addition, the therapeutic effects of posaconazole, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor.
Dapagliflozin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and posaconazole are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as posaconazole.
Dapsone: (Moderate) Posaconazole and dapsone should be coadministered with caution due to an increased potential for dapsone-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of dapsone. These drugs used in combination may result in elevated dapsone plasma concentrations, causing an increased risk for dapsone-related adverse events.
Daridorexant: (Major) Avoid concomitant use of daridorexant and posaconazole. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with posaconazole due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor.
Darolutamide: (Moderate) Monitor patients more frequently for darolutamide-related adverse reactions if coadministration with posaconazole is necessary due to the risk of increased darolutamide exposure; decrease the dose of darolutamide for grade 3 or 4 adverse reactions or for otherwise intolerable adverse reactions. Posaconazole is a P-glycoprotein (P-gp) inhibitor and a strong CYP3A4 inhibitor; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp inhibitor and strong CYP3A4 inhibitor increased the mean AUC and Cmax of darolutamide by 1.7-fold and 1.4-fold, respectively.
Darunavir: (Moderate) Posaconazole and darunavir should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and darunavir are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of darunavir. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and darunavir, ultimately resulting in an increased risk of adverse events.
Darunavir; Cobicistat: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4. (Moderate) Posaconazole and darunavir should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and darunavir are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of darunavir. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and darunavir, ultimately resulting in an increased risk of adverse events.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4. (Moderate) Posaconazole and darunavir should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and darunavir are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of darunavir. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and darunavir, ultimately resulting in an increased risk of adverse events.
Dasatinib: (Contraindicated) Concurrent use of posaconazole and dasatinib is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Increased dasatinib exposure may also occur. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and TdP. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with posaconazole. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; posaconazole is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Delavirdine: (Moderate) Posaconazole and delavirdine should be coadministered with caution due to an increased potential for delavirdine-related adverse events. Both posaconazole and delavirdine are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of delavirdine. These drugs used in combination may result in elevated delavirdine plasma concentrations, causing an increased risk for delavirdine-related adverse events.
Desogestrel; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Deutetrabenazine: (Moderate) Use posaconazole with caution in combination with deutetrabenazine. Posaconazole has been associated with QT prolongation as well as rare cases of torsade de pointes (TdP). Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions if coadministration of posaconazole with dexamethasone is necessary, due to increased dexamethasone exposure; Cushing's syndrome and adrenal suppression could potentially occur with long-term use. Consider the use of corticosteroids such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A inhibitors, especially for long-term use. Dexamethasone is primarily metabolized by CYP3A and posaconazole is a strong CYP3A inhibitor. Another strong CYP3A inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Dextromethorphan; Quinidine: (Contraindicated) The concurrent use of posaconazole and quinidine (or products containing quinidine such as dextromethorphan; quinidine) is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinidine. Further, both posaconazole and quinidine are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of either drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinidine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinidine.
Diazepam: (Moderate) Diazepam is a substrate of CYP2C19 and CYP3A4, and inhibition of metabolism by posaconazole could lead to elevated diazepam blood levels.
Dichlorphenamide: (Moderate) Use dichlorphenamide and antifungals together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) Posaconazole and diclofenac should be coadministered with caution due to an increased potential for diclofenac-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of diclofenac. These drugs used in combination may result in elevated diclofenac plasma concentrations, causing an increased risk for diclofenac-related adverse events.
Diclofenac; Misoprostol: (Moderate) Posaconazole and diclofenac should be coadministered with caution due to an increased potential for diclofenac-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of diclofenac. These drugs used in combination may result in elevated diclofenac plasma concentrations, causing an increased risk for diclofenac-related adverse events.
Dienogest; Estradiol valerate: (Minor) Estradiol valerate and dienogest are both substrates of CYP3A4. Certain azole antifungals, including fluconazole, itraconazole, ketonconazole, miconazole (systemic formulation only), posaconazole, and voriconazole, are CYP3A4 inhibitors and therefore may inhibit the metabolism of dienogest; estradiol valerate, possibly leading to increased serum concentrations. In a pharmacokinetic study evaluating the effect of ketoconazole on dienogest and estradiol, co-administration with ketoconazole increased the AUC at steady-state for dienogest and estradiol by 2.86 and 1.57-fold, respectively. There was also a 1.94 and 1.65-fold increase of Cmax at steady-state for dienogest and estradiol when co-administered with ketoconazole. (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Digoxin: (Moderate) Posaconazole and digoxin should be used together with caution due to the potential for digoxin-related adverse events. If used in combination, carefully monitor digoxin plasma concentrations during and at discontinuation of posaconazole therapy. Both posaconazole and digoxin are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. Increased plasma concentrations of digoxin have been reported during coadministration with posaconazole.
Dihydroergotamine: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Diltiazem: (Moderate) Monitor blood pressure and heart rate if coadministration of diltiazem with posaconazole is necessary. Concurrent use may result in elevated diltiazem concentrations. Diltiazem is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Disopyramide: (Contraindicated) The concurrent use of posaconazole and disopyramide is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of disopyramide. These drugs used in combination may result in elevated disopyramide plasma concentrations, causing an increased risk for disopyramide-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as disopyramide.
Disulfiram: (Moderate) Posaconazole and disulfiram should be coadministered with caution due to an increased potential for disulfiram-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of disulfiram. These drugs used in combination may result in elevated disulfiram plasma concentrations, causing an increased risk for disulfiram-related adverse events.
Docetaxel: (Major) Avoid coadministration of docetaxel with posaconazole if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dofetilide: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as dofetilide, is contraindicated. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Posaconazole has also been associated with QT prolongation and TdP.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with posaconazole. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Contraindicated) Concurrent use of posaconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ripivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for rilpivirine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
Donepezil: (Moderate) Use donepezil with caution in combination with posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Doravirine: (Minor) Coadministration of doravirine and posaconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; posaconazole is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Minor) Coadministration of doravirine and posaconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; posaconazole is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with posaconazole. Posaconazole is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
Doxorubicin Liposomal: (Major) Avoid coadministration of posaconazole with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Posaconazole is a strong CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYPsA4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of posaconazole with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Posaconazole is a strong CYP3A4 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4 and P-gp. Concurrent use of CYPsA4 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Major) Use caution if coadministration of dronabinol with posaconazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; posaconazole is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Contraindicated) The concurrent use of posaconazole and dronedarone is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Both posaconazole and dronedarone are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of dronedarone. Further, dronedarone is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and dronedarone and an increased risk for serious adverse events. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Contraindicated) The concurrent use of posaconazole and droperidol is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of droperidol, Further, both posaconazole and droperidol are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and droperidol and an increased risk for serious adverse events. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as droperidol.
Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Posaconazole is a strong CYP3A4 inhibitor and may increase drospirenone concentrations. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Estetrol: (Moderate) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Posaconazole is a strong CYP3A4 inhibitor and may increase drospirenone concentrations. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Posaconazole is a strong CYP3A4 inhibitor and may increase drospirenone concentrations. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Drospirenone; Ethinyl Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Posaconazole is a strong CYP3A4 inhibitor and may increase drospirenone concentrations. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Posaconazole is a strong CYP3A4 inhibitor and may increase drospirenone concentrations. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Dutasteride: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like posaconazole are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Dutasteride; Tamsulosin: (Major) Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Plasma concentrations of tamsulosin are increased with concomitant use of ketoconazole, a strong inhibitor of CYP3A4. Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as ketoconazole, itraconazole, posaconazole, or voriconazole should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like posaconazole are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studie d. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with posaconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as posaconazole.
Edoxaban: (Moderate) Coadministration of edoxaban and posaconazole may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and posaconazole may inhibit P-gp. Increased concentrations of edoxaban may occur during concomitant use of posaconazole; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
Efavirenz: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as efavirenz, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. In addition, concomitant use may increase the risk for breakthrough fungal infection. Efavirenz is believed to interact with posaconazole by inducing UDP glucuronidation. When posaconazole was administered with efavirenz, the mean reductions in Cmax were 45% and the mean reductions in AUC were 50% for posaconazole.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as efavirenz, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. In addition, concomitant use may increase the risk for breakthrough fungal infection. Efavirenz is believed to interact with posaconazole by inducing UDP glucuronidation. When posaconazole was administered with efavirenz, the mean reductions in Cmax were 45% and the mean reductions in AUC were 50% for posaconazole. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as efavirenz, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. In addition, concomitant use may increase the risk for breakthrough fungal infection. Efavirenz is believed to interact with posaconazole by inducing UDP glucuronidation. When posaconazole was administered with efavirenz, the mean reductions in Cmax were 45% and the mean reductions in AUC were 50% for posaconazole. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Elacestrant: (Major) Avoid concomitant use of elacestrant and posaconazole due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. The exposure of posaconazole may also be increased. Elacestrant is a CYP3A substrate and P-gp inhibitor and posaconazole is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and posaconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and posaconazole to 6 months. Elagolix is a CYP3A substrate; posaconazole is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and posaconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and posaconazole to 6 months. Elagolix is a CYP3A substrate; posaconazole is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with posaconazole should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Posaconazole is a strong inhibitor of the hepatic enzyme CYP3A, while elbasvir is metabolized by CYP3A. (Major) Concurrent administration of grazoprevir with posaconazole should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of grazoprevir and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Posaconazole is a strong inhibitor of the hepatic enzyme CYP3A, while grazoprevir is metabolized by CYP3A.
Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of posaconazole due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
Elexacaftor; tezacaftor; ivacaftor: (Major) If posaconazole and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Additionally, monitor for an increase in posaconazole-related adverse reactions. Ivacaftor is a CYP3A substrate and a P-gp inhibitor, and posaconazole is a strong CYP3A inhibitor and a P-gp substrate. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with posaconazole; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; posaconazole is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with posaconazole; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); posaconazole is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Contraindicated) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of posaconazole and eliglustat is contraindicated; recommendations for extensive CYP2D6 metabolizers (EMs) is less clear. Both eliglustat and posaconazole can independently prolong the QT interval. Posaconazole is a strong CYP3A inhibitor and P-glycoprotein (P-gp) substrate; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Both drugs have the potential to increase each other's blood concentrations, and therefore, further increase the risk of QT prolongation. Posaconazole's product labeling contraindicates coadministration of a number of other drugs that prolong the QT interval and are metabolized by CYP3A4. The product labeling of ketoconazole (another systemic azole and strong CYP3A inhibitor) carries the same contraindication, but pharmacokinetic data examining the interaction between ketoconazole and eliglustat support a dose reduction of eliglustat to 84 mg PO once daily in EMs rather than contraindication. However, extrapolation of this data to posaconazole must be undertaken with extreme caution because posaconazole is a P-gp substrate (ketoconazole is not), and eliglustat is a P-gp inhibitor. The additional risk that increased posaconazole exposure could pose is not known. The coadministration of eliglustat with both posaconazole and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution is warranted when cobicistat is administered with posaconazole as there is a potential for elevated posaconazole and cobicistat concentrations. Posaconazole is a CYP3A4 inhibitor and a P-glycoprotein (P-gp) substrate. Cobicistat is an inhibitor of P-gp and a substrate of CYP3A4. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Concurrent use of posaconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ripivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for rilpivirine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of posaconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ripivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for rilpivirine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Enasidenib: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with enasidenib is necessary. Posaconazole is a P-glycoprotein (P-gp) substrate; enasidenib is a P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and posaconazole due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of posaconazole. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If posaconazole is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of posaconazole. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Coadministration of posaconazole with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
Enfortumab vedotin: (Moderate) Closely monitor for signs of enfortumab vedotin-related adverse reactions if concurrent use with posaconazole is necessary. Concomitant use may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the incidence or severity of enfortumab-vedotin toxicities. MMAE, the microtubule-disrupting component of enfortumab vedotin, is a CYP3A4 and P-gp substrate; posaconazole is a dual P-gp/strong CYP3A4 inhibitor. Based on physiologically-based pharmacokinetic (PBPK) modeling predictions, concomitant use of enfortumab vedotin with another dual P-gp/strong CYP3A4 inhibitor is predicted to increase the exposure of unconjugated MMAE by 38%.
Entrectinib: (Major) Avoid coadministration of entrectinib with posaconazole due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If posaconazole is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of posaconazole. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Eplerenone: (Contraindicated) Coadministration of posaconazole and eplerenone is contraindicated. Posaconazole potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and posaconazole due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If posaconazole is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
Ergoloid Mesylates: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Ergot alkaloids: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Ergotamine: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Ergotamine; Caffeine: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include posaconazole.
Erlotinib: (Major) Avoid coadministration of erlotinib with posaconazole if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
Erythromycin: (Major) Caution is advised when administering posaconazole with drugs that are known to prolong that QT interval, such as erythromycin. Both erythromycin and posaconazole are associated with QT prolongation and torsade de pointes (TdP); coadministration may increase this risk. Both posaconazole and erythromycin are inhibitors and substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and erythromycin and an increased risk for serious adverse events.
Escitalopram: (Moderate) Concomitant use of escitalopram and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Estazolam: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including estazolam.
Estradiol: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol; Levonorgestrel: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol; Norethindrone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol; Norgestimate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol; Progesterone: (Moderate) Use caution if coadministration of posaconazole with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Posaconazole is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin). (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with posaconazole. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold.
Ethanol: (Major) Advise patients that administration of the posaconazole delayed-release oral suspension with alcohol is not recommended. Posaconazole was found to release faster from the delayed-release oral suspension in the presence of alcohol in vitro, which may interfere with its delayed release characteristics.
Ethinyl Estradiol; Norelgestromin: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Ethinyl Estradiol; Norgestrel: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Ethosuximide: (Moderate) Posaconazole and ethosuximide should be coadministered with caution due to an increased potential for ethosuximide-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of ethosuximide. These drugs used in combination may result in elevated ethosuximide plasma concentrations, causing an increased risk for ethosuximide-related adverse events.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Etonogestrel: (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as posaconazole may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events. (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as posaconazole may increase the serum concentration of etonogestrel.
Etravirine: (Moderate) Posaconazole and etravirine should be coadministered with caution due to an increased potential for etravirine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of etravirine. Further, etravirine is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and etravirine, ultimately resulting in an increased risk of adverse events.
Everolimus: (Major) Coadministration of everolimus with everolimus requires a dose reduction for some indications and close monitoring for others. For patients with oncology indications and tuberous sclerosis complex (TSC)-associated renal angiomyolipoma, reduce the initial dose of everolimus to 2.5 mg PO once daily; the dose may be increased to 5 mg PO once daily if the 2.5 mg dose is tolerated. For patients with TSC-associated subependymal giant cell astrocytoma (SEGA) and TSC-associated partial-onset seizures, reduce the daily dose of everolimus by 50%, changing to every-other-day dosing if the reduced dose is lower than the lowest available strength; assess the everolimus whole blood trough concentration 2 weeks after initiation of everolimus and adjust the dose as necessary to remain in the recommended therapeutic range. Also monitor everolimus whole blood trough concentrations for patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Everolimus is a moderate CYP3A4 and P-gp inhibitor. Coadministration with other moderate CYP3A4/P-gp inhibitors increased the AUC of everolimus by 3.5 to 4.4-fold.
Ezetimibe; Simvastatin: (Contraindicated) The concurrent use of posaconazole and simvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If therapy with posaconazole is unavoidable, simvastatin therapy must be suspended during the course of posaconazole treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Fedratinib: (Major) Avoid coadministration of fedratinib with posaconazole as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If posaconazole is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Felodipine: (Moderate) Concurrent use of felodipine and posaconazole should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If posaconazole is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with posaconazole. Avoid use of fesoterodine and posaconazole in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Fexofenadine: (Moderate) Posaconazole and fexofenadine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both fexofenadine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and fexofenadine, ultimately resulting in an increased risk of adverse events.
Fexofenadine; Pseudoephedrine: (Moderate) Posaconazole and fexofenadine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both fexofenadine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and fexofenadine, ultimately resulting in an increased risk of adverse events.
Finasteride; Tadalafil: (Major) Posaconazole and tadalafil should be coadministered with caution due to an increased potential for tadalafil-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of tadalafil. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. The manufacturer of tadalafil recommends that in patients receiving concomitant potent CYP3A4 inhibitors, the 'as needed' dose should not exceed 10 mg within a 72 hour time period and the 'once-daily' dose should not exceed 2.5 mg.
Finerenone: (Contraindicated) Concomitant use of finerenone and posaconazole is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with posaconazole as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Flecainide: (Major) Concomitant use of posaconazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. 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.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as posaconazole, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Major) Concomitant use of posaconazole and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. 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.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Fluphenazine: (Minor) Use posaconazole with caution in combination with fluphenazine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Flurazepam: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including flurazepam.
Flutamide: (Moderate) Posaconazole and flutamide should be coadministered with caution due to an increased potential for flutamide-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of flutamide. These drugs used in combination may result in elevated flutamide plasma concentrations, causing an increased risk for flutamide-related adverse events.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with posaconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluvoxamine: (Moderate) Use posaconazole with caution in combination with fluvoxamine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). QT prolongation and TdP have been reported during fluvoxamine post-marketing use.
Food: (Major) Advise patients to avoid cannabis use during posaconazole treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and posaconazole is a strong CYP3A inhibitor. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively.
Formoterol; Mometasone: (Moderate) Concomitant administration of posaconazole and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with posaconazole long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Fosamprenavir: (Moderate) Monitor for breakthrough fungal infections and increased fosamprenavir toxicity if concomitant use of posaconazole and fosamprenavir is necessary. Concomitant use may decrease the plasma concentrations of posaconazole and increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with fosamprenavir decreased the AUC of posaconazole by 23%.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as posaconazole. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Posaconazole has also been associated with prolongation of the QT interval as well as rare cases of TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Major) The concurrent use of posaconazole and phenytoin or fosphenytoin should be avoided, if possible, due to the potential for decreased posaconazole efficacy and increased phenytoin plasma concentrations. If used in combination, closely monitor for breakthrough fungal infections as well as phenytoin plasma concentrations, with consideration for phenytoin dosage reductions. Phenytoin induces UDP-glucuronidase resulting in decreased posaconazole plasma concentrations. When posaconazole was administered with phenytoin (both 200 mg PO daily), the mean reductions in Cmax were 41% and the mean reductions in AUC were 50% for posaconazole. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of phenytoin. Coadministration of posaconazole (200 mg PO daily) with phenytoin (200 mg PO daily) increased both the mean phenytoin Cmax and AUC by 16%. The concomitant use of phenytoin with posaconazole should be avoided unless the benefits outweigh the risks; dosage adjustment recommendations are not available.
Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Fostemsavir: (Contraindicated) Avoid concomitant use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A substrates, such as fostemsavir. Closely monitor electrolytes and ECG if concomitant use is necessary. Posaconazole has been associated with QT prolongation and torsade de pointes and is a strong CYP 3A inhibitor. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Futibatinib: (Major) Avoid concurrent use of futibatinib and posaconazole. Concomitant use may increase futibatinib exposure and the risk of adverse effects (e.g., ocular toxicity, hyperphosphatemia). Concomitant use may also increase posaconazole exposure. Futibatinib is a substrate of CYP3A and P-gp and a P-gp inhibitor; posaconazole is a P-gp substrate and dual P-gp and strong CYP3A inhibitor. Coadministration with another dual P-gp and strong CYP3A inhibitor increased futibatinib exposure by 41%.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with posaconazole is necessary. Gefitinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gemifloxacin: (Moderate) Use posaconazole with caution in combination with gemifloxacin as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use posaconazole with caution in combination with gemtuzumab as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Consider an alternative to posaconazole during treatment with gilteritinib due to a risk of increased exposure of both medications and the potential for additive QT prolongation. If coadministration is required, frequently monitor for gilteritinib or posaconazole-related adverse effects. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate and P-gp inhibitor; posaconazole is a strong CYP3A4 inhibitor and a P-gp substrate. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study. Both drugs have been associated with QT prolongation. Monitor for an increase in posaconazole-related adverse reactions if coadministration with gilteritinib is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; gilteritinib is a P-gp inhibitor.
Glasdegib: (Contraindicated) Coadministration of glasdegib and posaconazole is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP); glasdegib exposure may be increased further increasing the risk of QT prolongation. Glasdegib is a CYP3A4 substrate that may cause QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and posaconazole as coadministration may increase serum concentrations of posaconazole and increase the risk of adverse effects. Posaconazole is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and posaconazole as coadministration may increase serum concentrations of posaconazole and increase the risk of adverse effects. Posaconazole is a substrate of P-glycoprotein (P-gp); pibrentasvir is a P-gp inhibitor.
Glipizide: (Moderate) No clinically relevant interactions were reported when posaconazole was administered with glipizide during clinical trials; adjustments in posaconazole doses are not required. However, some healthy volunteers given the combination had decreased glucose concentrations. Therefore, glucose concentrations should be monitored in patients with diabetes when posaconazole is coadministered with glipizide.
Glipizide; Metformin: (Moderate) No clinically relevant interactions were reported when posaconazole was administered with glipizide during clinical trials; adjustments in posaconazole doses are not required. However, some healthy volunteers given the combination had decreased glucose concentrations. Therefore, glucose concentrations should be monitored in patients with diabetes when posaconazole is coadministered with glipizide.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Granisetron: (Moderate) Use posaconazole with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Granisetron has been associated with QT prolongation.
Grapefruit juice: (Major) Posaconazole and grapefruit juice should be coadministered with caution due to a potential for altered posaconazole plasma concentrations. Both posaconazole and grapefruit juice are inhibitors of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate. This interaction may cause alterations in the plasma concentrations of posaconazole, ultimately resulting in an increased risk of adverse events.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Posaconazole may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon posaconazole discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and posaconazole is a strong CYP3A4 inhibitor.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with posaconazole. Halogenated anesthetics can prolong the QT interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Haloperidol: (Contraindicated) FDA-approved labeling for posaconazole contraindicates coadministration with CYP3A4 substrates that also cause QT prolongation such as haloperidol. If alternative therapy is not available and concurrent use cannot be avoided, closely monitor for evidence of QT prolongation; a haloperidol dose reduction may be necessary. Posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like posaconazole can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If posaconazole is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxychloroquine: (Major) Concomitant use of posaconazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. 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.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with posaconazole. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Reduce the initial ibrutinib dosage to 140 mg/day PO in patients receiving ibrutinib for a B-cell malignancy or 280 mg/day PO in patients aged 12 years or older receiving ibrutinib for chronic graft-versus-host disease (cGVHD) if coadministered with posaconazole oral suspension 100 mg/day to 400 mg/day. Reduce the initial ibrutinib dosage to 70 mg/day PO in patients with a B-cell malignancy or 140 mg/day PO in patients aged 12 years and older with cGVHD if coadministered with posaconazole oral suspension 600 mg/day to 800 mg/day or posaconazole 300 mg (delayed-release tablets or IV) once daily. In patients aged 1 to 11 years receiving ibrutinib for cGVHD, reduce the initial ibrutinib dose to 80 mg/m2 per day PO if coadministered with any dosage of posaconazole. Resume ibrutinib at the previous dose if posaconazole is discontinued. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); interrupt or modify ibrutinib therapy as recommended if toxicity occurs. Ibrutinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Simulations under fed conditions suggest that coadministration with posaconazole may increase ibrutinib exposure by 3- to 10-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If posaconazole 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.
Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as posaconazole. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with posaconazole is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Posaconazole is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Contraindicated) The concurrent use of posaconazole and iloperidone is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of iloperidone. These drugs used in combination may result in elevated iloperidone plasma concentrations, causing an increased risk for iloperidone-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as iloperidone.
Imatinib: (Moderate) Posaconazole and imatinib, STI-571 should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and imatinib are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of imatinib. Further, both imatinib and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and imatinib, ultimately resulting in an increased risk of adverse events.
Indinavir: (Moderate) No clinically significant interactions were observed when posaconazole (200 mg PO daily) was administered with indinavir; thus, indinavir dosage adjustments are not required. However, use caution when administering posaconazole concurrently with indinavir. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of indinavir. Further, both posaconazole and indinavir are substrates for the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction could ultimately result in altered plasma concentrations of both posaconazole and indinavir.
Infigratinib: (Major) Avoid concomitant use of infigratinib and posaconazole. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with posaconazole in due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Posaconazole has also been associated with QT interval prolongation as well as rare cases of TdP.
Irinotecan Liposomal: (Major) Avoid administration of posaconazole during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Posaconazole is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38.
Irinotecan: (Major) Avoid administration of posaconazole during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Posaconazole is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with posaconazole is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; posaconazole is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor. Elevated posaconazole concentrations may also be seen with coadministration, as posaconazole is a substrate and isavuconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp).
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Do not administer rifampin with posaconazole when treating an invasive fungal infection. If treating non-invasive fungal infection, these drugs may be administered together with monitoring of posaconazole concentration and appropriate dose modifications. Taking these drugs together is expected to significantly reduce posaconazole plasma concentrations. Rifampin is an inducer and substrate of the drug efflux protein, P-glycoprotein, for which posaconazole is an inhibitor and also a substrate.
Isoniazid, INH; Rifampin: (Major) Do not administer rifampin with posaconazole when treating an invasive fungal infection. If treating non-invasive fungal infection, these drugs may be administered together with monitoring of posaconazole concentration and appropriate dose modifications. Taking these drugs together is expected to significantly reduce posaconazole plasma concentrations. Rifampin is an inducer and substrate of the drug efflux protein, P-glycoprotein, for which posaconazole is an inhibitor and also a substrate.
Isradipine: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with posaconazole is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with posaconazole as istradefylline exposure and adverse effects may increase. Posaconazole is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Itraconazole: (Major) Typically posaconazole and itraconazole would not be used in combination due to similar mechanisms of action and indications for use (duplicate therapies). Posaconazole may inhibit the CYP3A4 metabolism of itraconazole, resulting in increased itraconazole serum concentrations. Furthermore, all systemic azole antifungal agents have been associated with prolongation of the QT interval. Coadministration would increase the risk of QT prolongation.
Ivabradine: (Contraindicated) Coadministration of ivabradine and posaconazole is contraindicated. Ivabradine is primarily metabolized by CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If posaconazole and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Additionally, monitor for an increase in posaconazole-related adverse reactions. Ivacaftor is a CYP3A substrate and a P-gp inhibitor, and posaconazole is a strong CYP3A inhibitor and a P-gp substrate. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivermectin: (Moderate) Posaconazole and ivermectin should be coadministered with caution due to an increased potential for ivermectin-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ivermectin. These drugs used in combination may result in elevated ivermectin plasma concentrations, causing an increased risk for ivermectin-related adverse events.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with posaconazole due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If posaconazole is discontinued, wait at least 5 half-lives of posaconazole before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Posaconazole is a strong CYP3A4 inhibitor associated with QT prolongation, as well as rare cases of torsade de pointes. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax. Additive QT prolongation may also occur.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and posaconazole due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of posaconazole and clarithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Consider use of azithromycin in place of clarithromycin. Both posaconazole and clarithromycin are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of clarithromycin. Further, clarithromycin is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and clarithromycin and an increased risk for serious adverse events. Additionally, both drugs have been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Lapatinib: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as lapatinib, is contraindicated according to the manufacturer of posaconazole. The manufacturer of lapatinib recommends avoidance of concurrent use if possible, but if unavoidable, decrease the dose of lapatinib to 500 mg PO once daily while monitoring ECGs and electrolytes. Correct any electrolyte abnormalities prior to treatment. If posaconazole is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Lapatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with posaconazole due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If posaconazole is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of posaconazole. Larotrectinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
Lasmiditan: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of posaconazole and ledipasvir; sofosbuvir. Both ledipasvir and posaconazole are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lefamulin: (Major) Avoid coadministration of lefamulin with posaconazole as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Posaconazole is a P-gp and strong CYP3A4 that has been associated with prolongation of the QT interval. Coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and posaconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lenacapavir: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with lenacapavir is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; lenacapavir is a P-gp inhibitor.
Leniolisib: (Major) Avoid concomitant use of leniolisib and posaconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with posaconazole due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Levomilnacipran: (Major) The adult dose of levomilnacipran should not exceed 80 mg/day during concurrent use of strong CYP3A4 inhibitors. Posaconazole is considered a strong inhibitor of CYP3A4. Levomilnacipran is partially metabolized by CYP3A4, and decreased metabolism of the drug can lead to an increased risk of adverse effects such as urinary retention.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Lidocaine: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events.
Lidocaine; Epinephrine: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events.
Lidocaine; Prilocaine: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events.
Lithium: (Moderate) Concomitant use of lithium and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with posaconazole due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Lomitapide: (Contraindicated) Concomitant use of posaconazole and lomitapide is contraindicated. If treatment with posaconazole is unavoidable, lomitapide should be stopped during the course of treatment. Posaconazole is a strong CYP3A4 inhibitor. The exposure to lomitapide was increased 27-fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and posaconazole is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and P-gp inhibitor. Posaconazole strong CYP3A4 inhibitor and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
Loperamide: (Contraindicated) Avoid concomitant use of loperamide and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a CYP3A4 and P-gp substrate and posaconazole is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Contraindicated) Avoid concomitant use of loperamide and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a CYP3A4 and P-gp substrate and posaconazole is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with posaconazole due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). (Moderate) Perform frequent monitoring of adverse effects and toxicity of ritonavir during coadministration with posaconazole. These drugs used in combination may result in elevated ritonavir plasma concentrations, causing an increased risk for ritonavir-related adverse events. Data from one study found the Cmax and AUC of ritonavir increased by 49% and 80%, respectively, when administered with posaconazole.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with posaconazole due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions; posaconazole exposure may also decrease. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If posaconazole is discontinued, resume the original dose of lorlatinib after 3 half-lives of posaconazole. Lorlatinib is a CYP3A substrate and P-glycoprotein (P-gp) inducer. Posaconazole is a strong CYP3A inhibitor and a P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%.
Lovastatin: (Contraindicated) Concurrent use of lovastatin and posaconazole is contraindicated. The risk of developing myopathy, rhabdomyolysis, and acute renal failure is substantially increased if lovastatin is administered concomitantly with strong CYP3A4 inhibitors including posaconazole. If no alternative to a short course of treatment with posaconazole is available, a brief suspension of lovastatin therapy during such treatment can be considered as there are no known adverse consequences to brief interruptions of long-term cholesterol-lowering therapy.
Lumacaftor; Ivacaftor: (Major) If posaconazole and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Additionally, monitor for an increase in posaconazole-related adverse reactions. Ivacaftor is a CYP3A substrate and a P-gp inhibitor, and posaconazole is a strong CYP3A inhibitor and a P-gp substrate. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of posaconazole; concomitant use is not recommended. Consider alternative antifungals such as fluconazole. If concomitant use of posaconazole is necessary, carefully monitor for antifungal efficacy. Lumacaftor; ivacaftor dosage adjustment is not required when posaconazole is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking posaconazole, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking posaconazole. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Posaconazole is a strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Although posaconazole is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold. Posaconazole is a substrate for P-glycoprotein (P-gp) efflux, and lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect on P-gp substrates is not clear, but their exposure may be affected.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use of posaconazole is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as posaconazole, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with inhibitors of CYP3A4.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and posaconazole due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as posaconazole. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Maprotiline: (Moderate) Use posaconazole with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A/P-gp substrate, with posaconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with posaconazole (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended.
Maribavir: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with maribavir is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; maribavir is a P-gp inhibitor.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with posaconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with posaconazole, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Mefloquine: (Contraindicated) The concurrent use of posaconazole and mefloquine is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of mefloquine, Further, both posaconazole and mefloquine are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and mefloquine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as mefloquine.
Metformin; Repaglinide: (Moderate) Coadministration of repaglinide and posaconazole may increase plasma concentrations of repaglinide; if coadministration is necessary, repaglinide dosage adjustment may be required and an increased frequency of glucose monitoring is recommended. Repaglinide is a CYP3A4 substrate and posaconazole is an inhibitor of CYP3A4.
Metformin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and posaconazole are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as posaconazole.
Methadone: (Contraindicated) The concurrent use of posaconazole and methadone is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of methadone, Further, both posaconazole and methadone are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and methadone and an increased risk for serious adverse events. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as methadone.
Methylergonovine: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Methylprednisolone: (Moderate) Monitor for corticosteroid-related adverse events if methylprednisolone is used with posaconazole. Concurrent use may increase the exposure of methylprednisolone. Methylprednisolone is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Other strong CYP3A inhibitors have been reported to decrease the metabolism of certain corticosteroids by up to 60%.
Metoclopramide: (Major) Avoid coadministration of metoclopramide with posaconazole immediate-release oral suspension unless the benefits outweigh the risks of decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by metoclopramide. Metoclopramide increases gastric motility resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with metoclopramide (10 mg PO three times daily for 2 days), the mean reductions in Cmax were 21% and the mean reductions in AUC were 19% for posaconazole.
Metronidazole: (Moderate) Concomitant use of metronidazole and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Midazolam: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including midazolam.
Midostaurin: (Contraindicated) Avoid concomitant use of midostaurin and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase midostaurin exposure and the risk for other midostaurin-related adverse effects; midostaurin is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Mifepristone: (Contraindicated) Coadministration of posaconazole and mifepristone is contraindicated due to the risk of additive QT prolongation and life threatening arrhythmias such as torsades de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving posaconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg daily if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with posaconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg/day. Both mifepristone and posaconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Mirtazapine: (Contraindicated) The concurrent use of posaconazole, a potent CYP3A4 inhibitor, with drugs that are associated with QT prolongation and are CYP3A4 substrates, such as mirtazapine, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes (TdP). Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of posaconazole is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with posaconazole due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations and may increase posaconazole exposure. Mitapivat is a CYP3A substrate and P-gp inhibitor and posaconazole is a strong CYP3A inhibitor and P-gp substrate. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and posaconazole. Concomitant use increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase mobocertinib exposure and the risk for mobocertinib-related adverse reactions. Mobocertinib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
Modafinil: (Moderate) Posaconazole and modafinil should be coadministered with caution due to an increased potential for modafinil-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of modafinil. These drugs used in combination may result in elevated modafinil plasma concentrations, causing an increased risk for modafinil-related adverse events.
Mometasone: (Moderate) Concomitant administration of posaconazole and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with posaconazole long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Morphine: (Moderate) Posaconazole and morphine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both morphine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and morphine, ultimately resulting in an increased risk of adverse events.
Morphine; Naltrexone: (Moderate) Posaconazole and morphine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both morphine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and morphine, ultimately resulting in an increased risk of adverse events.
Moxifloxacin: (Major) Concurrent use of posaconazole and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Posaconazole is associated with a possible risk for QT prolongation and TdP. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with posaconazole. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a substrate of CYP3A4 and P-gp; posaconazole is a moderate P-gp inhibitor and a strong CYP3A4 inhibitor.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with posaconazole is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as posaconazole, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with posaconazole is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Contraindicated) Coadministration of posaconazole and sirolimus is contraindicated. Concomitant use has been observed to increase overall sirolimus exposure by approximately 9-fold which may increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Nefazodone: (Moderate) Posaconazole and nefazodone should be coadministered with caution due to an increased potential for nefazodone-related adverse events. Both posaconazole and nefazodone are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of nefazodone. These drugs used in combination may result in elevated nefazodone plasma concentrations, causing an increased risk for nefazodone-related adverse events.
Nelfinavir: (Major) Posaconazole and nelfinavir should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and nelfinavir are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of nelfinavir. Further, both nelfinavir and posaconazole are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and nelfinavir, ultimately resulting in an increased risk of adverse events.
Neratinib: (Major) Avoid concomitant use of posaconazole with neratinib due to an increased risk of neratinib-related toxicity; posaconazole exposure may also increase. Neratinib is a CYP3A4 substrate and a P-glycoprotein (P-gp) inhibitor. Posaconazole is a strong CYP3A4 inhibitor and a P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) The concurrent use of posaconazole and netupitant should be approached with caution. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme involved in the metabolism of netupitant. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor (e.g., posaconazole) can significantly increase the systemic exposure to netupitant. No dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
Nevirapine: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with posaconazole is necessary. Nevirapine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Niacin; Simvastatin: (Contraindicated) The concurrent use of posaconazole and simvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If therapy with posaconazole is unavoidable, simvastatin therapy must be suspended during the course of posaconazole treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Nicardipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nicardipine with posaconazole is necessary. Concurrent use may result in elevated nicardipine concentrations. Nicardipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Nifedipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with posaconazole is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Nilotinib: (Contraindicated) The concurrent use of posaconazole and nilotinib is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of nilotinib. These drugs used in combination may result in elevated nilotinib plasma concentrations, causing an increased risk for nilotinib-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Nimodipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nimodipine with posaconazole is necessary. Concurrent use may result in elevated nimodipine concentrations. Nimodipine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Perform frequent monitoring of adverse effects and toxicity of ritonavir during coadministration with posaconazole. These drugs used in combination may result in elevated ritonavir plasma concentrations, causing an increased risk for ritonavir-related adverse events. Data from one study found the Cmax and AUC of ritonavir increased by 49% and 80%, respectively, when administered with posaconazole.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with posaconazole due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and posaconazole is a CYP3A4 inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Norethindrone; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Norgestimate; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Olanzapine: (Moderate) Use posaconazole with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of fluoxetine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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. (Moderate) Use posaconazole with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Use posaconazole with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olaparib: (Major) Avoid coadministration of olaparib with posaconazole due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after posaconazole is discontinued. Olaparib is a CYP3A substrate and posaconazole is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and posaconazole is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and posaconazole may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If posaconazole is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Olopatadine; Mometasone: (Moderate) Concomitant administration of posaconazole and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events. Exercise caution when administering mometasone with posaconazole long-term and monitor closely for hypercorticism and adrenal suppression. Mometasone is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and posaconazole. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) The concurrent use of posaconazole and rifabutin should be avoided, if possible, due to the potential for decreased posaconazole efficacy as well as increased risk of rifabutin related adverse events. If used in combination, closely monitor for breakthrough fungal infections and rifabutin adverse events, such as uveitis and leukopenia. Rifabutin induces UDP-glucuronidase resulting in decreased posaconazole plasma concentrations. When posaconazole (200 mg PO daily) was administered with rifabutin (300 mg PO daily), the mean reductions in Cmax were 43% and the mean reductions in AUC were 49% for posaconazole. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rifabutin. Coadministration of posaconazole (200 mg PO daily) with rifabutin (300 mg PO daily) increased the mean rifabutin Cmax (by 31%) and AUC (by 72%). The concomitant use of rifabutin with posaconazole should be avoided unless the benefits outweigh the risks; dosage adjustment recommendations are not available.
Ondansetron: (Contraindicated) Concomitant administration of posaconazole and drugs that both prolong the QT interval and are CYP3A4 substrates is contraindicated according to the FDA-approved product labeling. The exact risk for QT prolongation when posaconazole and ondansetron are administered together has not been clearly defined. If ondansetron and posaconazole are administered together, extreme caution and careful monitoring is advised, especially if higher doses are used or if other drugs that may affect CYP1A2 or CYP2D6 are also given. Posaconazole is a strong CYP3A4 inhibitor. Ondansetron is metabolized by CYP3A, CYP1A2, and CYP2D6. In vivo microsomal inhibition data has suggested that no single isoenzyme dominates ondansetron's metabolism thereby making clinically significant interactions due to inhibition of a single isoenzyme unlikely; however, since the publication of this data, ondansetron has been found to produce concentration-dependent QT prolongation. It is not clear what degree of enzyme inhibition or increased concentration is required to increase the risk of QT prolongation.
Osilodrostat: (Major) Reduce the dose of osilodrostat by one-half and consider more frequent ECG monitoring during coadministration of posaconazole; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions, including QT prolongation. Osilodrostat is a CYP3A4 substrate that is associated with dose-dependent QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Osimertinib: (Major) Avoid coadministration of posaconazole with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in posaconazole-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Posaconazole is a P-glycoprotein (P-gp) substrate that has been associated with prolongation of the QT interval as well as rare cases of TdP. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, which is also a P-gp inhibitor.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of posaconazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
Oxybutynin: (Moderate) Posaconazole and oxybutynin should be coadministered with caution due to an increased potential for oxybutynin-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of oxybutynin. These drugs used in combination may result in elevated oxybutynin plasma concentrations, causing an increased risk for oxybutynin-related adverse events.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory dep ression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If posaconazole 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.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking posaconazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Paclitaxel: (Moderate) Posaconazole and paclitaxel should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of paclitaxel. Further, both paclitaxel and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and paclitaxel, ultimately resulting in an increased risk of adverse events.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with posacaonzole is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and posacaonzole is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of posaconazole with palbociclib; significantly increased palbociclib exposure may occur. If concomitant use cannot be avoided, reduce the dose of palbociclib to 75 mg PO once daily and monitor for increased adverse reactions. If posaconazole is discontinued, increase the palbociclib dose (after 3 to 5 half-lives of posaconazole) to the dose used before initiation of posaconazole. Palbociclib is primarily metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor. In a drug interaction trial, coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of palbociclib by 87% and 34%, respectively.
Paliperidone: (Contraindicated) The concurrent use of posaconazole and paliperidone is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, paliperidone should be avoided in combination with other drugs having an association with QT prolongation.
Palovarotene: (Major) Avoid concomitant use of palovarotene and posaconazole due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Panobinostat: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes, avoid the concomitant use of ketoconazole, itraconazole, posaconazole, or voriconazole with panobinostat. These agents are strong CYP3A4 inhibitors and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in 14 patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking ketoconazole 200 mg PO twice daily for 14 days.
Paricalcitol: (Moderate) Posaconazole and paricalcitol should be coadministered with caution due to an increased potential for paricalcitol-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of paricalcitol. These drugs used in combination may result in elevated paricalcitol plasma concentrations, causing an increased risk for paricalcitol-related adverse events.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with posaconazole as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Pazopanib: (Contraindicated) Concurrent use of pazopanib and posaconazole is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Pazopanib is a substrate for CYP3A4 and P-glycoprotein (P-gp). Posaconazole is an inhibitor of CYP3A4 and P-gp. Concurrent administration of posaconazole and pazopanib may result in increased pazopanib concentrations, causing an increased risk for adverse events, such as QT prolongation.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and posaconazole due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. 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. If posaconazole is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of posaconazole. Pemigatinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
Pentamidine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with pentamidine. Both posaconazole and pentamidine have been associated with QT prolongation, while posaconazole has also been associated with rare cases of TdP.
Perampanel: (Moderate) Ketoconazole, a potent CYP3A4 inhibitor, can prolong the half-life of perampanel and decrease perampanel metabolism. Administration of a single dose of perampanel 1 mg with ketoconazole 400 mg once daily for 8 days in healthy subjects increased perampanel half-life from 58.4 to 67.8 hours, and increased perampanel AUC by 20%. Patients taking ketoconazole and perampanel should be closely monitored for adverse effects; a perampanel dose adjustment may be necessary. Caution should also be used during concomitant use of perampanel with posaconazole as this drug inhibits CYP3A4.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Perphenazine: (Minor) Use posaconazole with caution in combination with perphenazine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use posaconazole with caution in combination with perphenazine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and posaconazole due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If posaconazole is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of posaconazole. Pexidartinib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenytoin: (Major) The concurrent use of posaconazole and phenytoin should be avoided, if possible, due to the potential for decreased posaconazole efficacy and increased phenytoin plasma concentrations. If used in combination, closely monitor for breakthrough fungal infections as well as phenytoin plasma concentrations, with consideration for phenytoin dosage reductions. Phenytoin induces UDP-glucuronidase resulting in decreased posaconazole plasma concentrations. When posaconazole was administered with phenytoin (both 200 mg PO daily), the mean reductions in Cmax were 41% and the mean reductions in AUC were 50% for posaconazole. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of phenytoin. Coadministration of posaconazole (200 mg PO daily) with phenytoin (200 mg PO daily) increased both the mean phenytoin Cmax and AUC by 16%. The concomitant use of phenytoin with posaconazole should be avoided unless the benefits outweigh the risks; dosage adjustment recommendations are not available.
Pimavanserin: (Contraindicated) Coadministration of posaconazole and pimavanserin is contraindicated. The manufacturer of posaconazole contraindicates concurrent use with drugs that are CYP3A4 substrates and prolong the QT interval. Pimavanserin is primarily metabolized by CYP3A4/3A5 and has been associated with QT prolongation.
Pimozide: (Contraindicated) Posaconazole is an inhibitor of CYP3A4. Coadministration of posaconazole with drugs metabolized by 3A4, such as pimozide, may result in increased plasma concentrations of these drugs due to decreased metabolism. Increased plasma concentrations of these agents may result in QT prolongation and rare occurrences of torsade de pointes. Concomitant therapy of pimozide and posaconazole is contraindicated.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and posaconazole due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. The exposure of posaconazole may also be increased. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of posaconazole use. Resume the previous dose of pirtobrutinib after posaconazole is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and P-gp inhibitor and posaconazole is a P-gp substrate and strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Pitolisant: (Major) Avoid coadministration of pitolisant with posaconazole as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of posaconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ponatinib: (Major) Avoid coadministration of ponatinib and posaconazole due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of posaconazole and consider alternative therapy. After posaconazole has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting posaconazole. Ponatinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking posaconazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Pralsetinib: (Major) Avoid concomitant use of posaconazole and pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of pralsetinib to 200 mg once daily for patients taking a daily dose of 400 mg or 300 mg, and to 100 mg once daily for patients taking a daily dose of 200 mg. Pralsetinib is a CYP3A and P-gp substrate and posaconazole is a combined strong CYP3A and P-gp inhibitor. Coadministration with a combined strong CYP3A and P-gp inhibitor is predicted to increase the overall exposure of pralsetinib by 251%.
Prednisolone: (Moderate) Posaconazole and prednisolone should be coadministered with caution due to an increased potential for prednisolone-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of prednisolone. These drugs used in combination may result in elevated prednisolone plasma concentrations, causing an increased risk for prednisolone-related adverse events.
Prednisone: (Moderate) Posaconazole and prednisone should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of prednisone. Further, both prednisone and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and prednisone, ultimately resulting in an increased risk of adverse events.
Pretomanid: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with pretomanid is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; pretomanid is a P-gp inhibitor.
Primaquine: (Moderate) Use posaconazole with caution in combination with primaquine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Primaquine also has the potential to prolong the QT interval.
Probenecid; Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and posaconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Posaconazole can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor/P-gp inhibitor like posaconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. The recommended dose of colchicine oral solution when co-administered with posaconazole is 0.24 mg.
Procainamide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with procainamide. Procainamide is associated with a well-established risk of QT prolongation and TdP. Posaconazole also has been associated with QT prolongation and in rare cases, TdP.
Prochlorperazine: (Minor) Use posaconazole with caution in combination with prochlorperazine as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Progesterone: (Moderate) Use caution if coadministration of posaconazole with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Posaconazole is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Promethazine: (Moderate) Concomitant use of promethazine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Propafenone: (Contraindicated) Concurrent use of posaconazole and propafenone is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of propafenone. Further, propafenone is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and propafenone. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as propafenone.
Proton pump inhibitors: (Major) The concurrent use of posaconazole immediate-release oral suspension and proton pump inhibitors (PPIs) should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor for breakthrough fungal infections. PPIs increase gastric pH, resulting in decreased posaconazole absorption and lower posaconazole plasma concentrations. When a single 400 mg dose of posaconazole oral suspension was administered with esomeprazole (40 mg PO daily), the mean reductions in Cmax were 46% and the mean reductions in AUC were 32% for posaconazole. The pharmacokinetics of posaconazole delayed-release tablets and oral suspension are not significantly affected by PPIs. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of many PPIs (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole). Coadministration may result in increased plasma concentration of the PPIs.
Quazepam: (Moderate) Posaconazole inhibits CYP3A4 and may increase serum concentrations of benzodiazepines metabolized by this enzyme, including quazepam.
Quetiapine: (Contraindicated) Concurrent use of posaconazole and quetiapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quetiapine. These drugs used in combination may result in elevated quetiapine plasma concentrations, causing an increased risk for quetiapine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quetiapine.
Quinidine: (Contraindicated) The concurrent use of posaconazole and quinidine (or products containing quinidine such as dextromethorphan; quinidine) is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinidine. Further, both posaconazole and quinidine are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of either drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinidine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinidine.
Quinine: (Contraindicated) Concurrent use of posaconazole and quinine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinine. Further, quinine is an inhibitor of the drug efflux protein, P-glycoprotein (P-gp), for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinine.
Quizartinib: (Contraindicated) Concomitant use of posaconazole and quizartinib is contraindicated due to the risk for increase quizartinib exposure and QT/QTc prolongation and torsade de pointes (TdP) per the manufacturer of posaconazole. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of posaconazole use for patients already taking a daily dose of 17.7 mg. Quizartinib is a CYP3A substrate, posaconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Ramelteon: (Moderate) Posaconazole and ramelteon should be coadministered with caution due to an increased potential for ramelteon-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ramelteon. These drugs used in combination may result in elevated ramelteon plasma concentrations, causing an increased risk for ramelteon-related adverse events.
Ranolazine: (Contraindicated) The concurrent use of posaconazole and ranolazine is contraindicated due to the risk of life-threatening arrhythmias such as torsades de pointes (TdP) and increased ranolazine exposure; posaconazole exposure may also be increased. Ranolazine is a CYP3A4 and P-gp substrate, and a P-gp inhibitor that is associated with dose- and plasma concentration-related increases in the QTc interval. Posaconazole is a strong CYP3A4 inhibitor and an inhibitor and substrate of P-gp that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Plasma levels of ranolazine were increased by 220% when administered with a strong CYP3A4 inhibitor.
Red Yeast Rice: (Contraindicated) Posaconzole inhibits the CYP3A4 metabolism of certain HMG-CoA reductase inhibitors, including lovastatin, increasing the potential for developing myopathy, rhabdomyolysis, and acute renal failure. Since compounds in red yeast rice claim to have HMG-CoA reductase inhibitor activity and have a similar structure and activity as lovastatin, coadministration of red yeast rice and posaconazole should be avoided.
Regorafenib: (Major) Avoid coadministration of regorafenib with posaconazole due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
Relugolix: (Major) Avoid concomitant use of relugolix and oral posaconazole. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer posaconazole at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of posaconazole is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Posaconazole is a P-gp inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP).
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral posaconazole. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer posaconazole at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of posaconazole is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Posaconazole is a P-gp inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as systemic azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, and voriconazole) may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Repaglinide: (Moderate) Coadministration of repaglinide and posaconazole may increase plasma concentrations of repaglinide; if coadministration is necessary, repaglinide dosage adjustment may be required and an increased frequency of glucose monitoring is recommended. Repaglinide is a CYP3A4 substrate and posaconazole is an inhibitor of CYP3A4.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as posaconazole, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are CYP3A4 substrates, such as ribociclib, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. Additionally, ribociclib is extensively metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are CYP3A4 substrates, such as ribociclib, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. Additionally, ribociclib is extensively metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor.
Rifabutin: (Major) The concurrent use of posaconazole and rifabutin should be avoided, if possible, due to the potential for decreased posaconazole efficacy as well as increased risk of rifabutin related adverse events. If used in combination, closely monitor for breakthrough fungal infections and rifabutin adverse events, such as uveitis and leukopenia. Rifabutin induces UDP-glucuronidase resulting in decreased posaconazole plasma concentrations. When posaconazole (200 mg PO daily) was administered with rifabutin (300 mg PO daily), the mean reductions in Cmax were 43% and the mean reductions in AUC were 49% for posaconazole. Additionally, posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of rifabutin. Coadministration of posaconazole (200 mg PO daily) with rifabutin (300 mg PO daily) increased the mean rifabutin Cmax (by 31%) and AUC (by 72%). The concomitant use of rifabutin with posaconazole should be avoided unless the benefits outweigh the risks; dosage adjustment recommendations are not available.
Rifampin: (Major) Do not administer rifampin with posaconazole when treating an invasive fungal infection. If treating non-invasive fungal infection, these drugs may be administered together with monitoring of posaconazole concentration and appropriate dose modifications. Taking these drugs together is expected to significantly reduce posaconazole plasma concentrations. Rifampin is an inducer and substrate of the drug efflux protein, P-glycoprotein, for which posaconazole is an inhibitor and also a substrate.
Rifapentine: (Major) The concurrent use of posaconazole and rifapentine should be avoided, if possible, due to the potential for decreased posaconazole efficacy. If used in combination, closely monitor posaconazole drug concentrations and adjust dose as needed. Breakthrough fungal infections may occur if these drugs are used together.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with posaconazole is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and posaconazole is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Contraindicated) Concurrent use of posaconazole and rilpivirine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of ripivirine. These drugs used in combination may result in elevated rilpivirine plasma concentrations, causing an increased risk for rilpivirine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as rilpivirine.
Rimegepant: (Major) Avoid coadministration of rimegepant with posaconazole; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate; posaconazole is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with posaconazole. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Risperidone: (Moderate) Use risperidone and posaconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Posaconazole has also been associated with QT prolongation and rare cases of TdP.
Ritonavir: (Moderate) Perform frequent monitoring of adverse effects and toxicity of ritonavir during coadministration with posaconazole. These drugs used in combination may result in elevated ritonavir plasma concentrations, causing an increased risk for ritonavir-related adverse events. Data from one study found the Cmax and AUC of ritonavir increased by 49% and 80%, respectively, when administered with posaconazole.
Rivaroxaban: (Major) Avoid concomitant administration of rivaroxaban and posaconazole; significant increases in rivaroxaban exposure may increase bleeding risk. Rivaroxaban is a substrate of CYP3A4/5 and the P-glycoprotein (P-gp) transporter. Posaconazole is a combined P-gp inhibitor and strong CYP3A4 inhibitor. Concurrent use of rivaroxaban and ketoconazole, a combined P-gp and strong CYP3A4 inhibitor, led to an increase in the steady-state rivaroxaban AUC by 160% and Cmax by 70%. Similar increases in pharmacodynamic effects such as factor Xa inhibition and PT prolongation were also observed.
Romidepsin: (Contraindicated) The concurrent use of romidepsin and posaconazole is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Romidepsin is a substrate for CYP3A4 and P-glycoprotein (P-gp). Posaconazole is an inhibitor of CYP3A4 and P-gp. Concurrent administration may cause an increase in systemic romidepsin concentrations, causing an increased risk for romidepsin-related adverse events, such as QT prolongation.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with posaconazole in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of posaconazole in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily; alternatively, ruxolitinib therapy may be interrupted for the duration of posaconazole use. Ruxolitinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
Salmeterol: (Major) Avoid concomitant use of salmeterol with posaconazole. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Contraindicated) Concurrent use of posaconazole and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Both saquinavir boosted with ritonavir and posaconazole are potent inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of saquinavir. Further, both posaconazole and saquinavir are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and saquinavir. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as posaconazole.
Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and posaconazole are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as posaconazole.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Posaconazole and ethinyl estradiol should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and ethinyl estradiol are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of ethinyl estradiol. Further, both ethinyl estradiol and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and ethinyl estradiol, ultimately resulting in an increased risk of adverse events. (Minor) Coadministration of segesterone, a CYP3A4 substrate and posaconazole, a moderate CYP3A4 inhibitor may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and posaconazole due to the risk of additive QT prolongation and increased medication exposure resulting in increased treatment-related adverse effects. If coadministration is unavoidable, reduce the dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If posaconazole is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of posaconazole. Selpercatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Coadministration with another strong CYP3A4 inhibitor increased selpercatinib exposure by 133%. Additionally, posaconazole is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Selumetinib: (Major) Avoid coadministration of selumetinib and posaconazole due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If posaconazole is discontinued, resume the original selumetinib dose after 3 elimination half-lives of posaconazole. Selumetinib is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sertraline: (Moderate) Concomitant use of sertraline and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sildenafil: (Major) Coadministration of posaconazole is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving posaconazole. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Posaconazole is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Major) Posaconazole and silodosin should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of silodosin. Further, both silodosin and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and silodosin, ultimately resulting in an increased risk of adverse events.
Simvastatin: (Contraindicated) The concurrent use of posaconazole and simvastatin is contraindicated due to the risk of myopathy, rhabdomyolysis, and acute renal failure. If therapy with posaconazole is unavoidable, simvastatin therapy must be suspended during the course of posaconazole treatment. There are no known adverse effects with short-term discontinuation of simvastatin.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving posaconazole due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Posaconazole has also been associated with prolongation of the QT interval. Additionally, concomitant use of siponimod and posaconazole may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Contraindicated) Coadministration of posaconazole and sirolimus is contraindicated. Concomitant use has been observed to increase overall sirolimus exposure by approximately 9-fold which may increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with taurursodiol is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; taurursodiol is a P-gp inhibitor.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with posaconazole. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, posaconazole is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of posaconazole, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with posaconazole. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp). In addition, posaconazole is a potent inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Solifenacin: (Contraindicated) The concurrent use of posaconazole and solifenacin is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of solifenacin. These drugs used in combination may result in elevated solifenacin plasma concentrations, causing an increased risk for solifenacin-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such solifenacin.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and posaconazole; sonidegib exposure may be significantly increased resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Sonidegib is a CYP3A substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
Sorafenib: (Major) Avoid coadministration of sorafenib with posaconazole due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Sorafenib is associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and posaconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. 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.
Sotorasib: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with sotorasib is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; sotorasib is a P-gp inhibitor.
Sparsentan: (Major) Avoid concomitant use of sparsentan and posaconazole. Concomitant use may increase the exposure of both drugs and the risk for adverse effects. Sparsentan is a CYP3A substrate and P-gp inhibitor and posaconazole is a P-gp substrate and strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
St. John's Wort, Hypericum perforatum: (Major) Posaconazole and St. John's Wort, Hypericum perforatum should be coadministered with caution due to a potential for altered posaconazole plasma concentrations. St. John's Wort is an inducer of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate. This interaction may cause alterations in the plasma concentrations of posaconazole, ultimately resulting in a risk of decreased efficacy and breakthrough fungal infections.
Sucralfate: (Major) The manufacturer suggests drugs that increase gastric pH, such as sucralfate, may decrease the absorption of posaconazole. The manufacturer recommends monitoring patients for breakthrough fungal infections.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if posaconazole must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of posaconazole is necessary. If posaconazole is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like posaconazole can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If posaconazole is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Posaconazole and sulfamethoxazole should be coadministered with caution due to an increased potential for sulfamethoxazole-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of sulfamethoxazole. These drugs used in combination may result in elevated sulfamethoxazole plasma concentrations, causing an increased risk for sulfamethoxazole-related adverse events.
Sunitinib: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as sunitinib, is contraindicated. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Sunitinib is a CYP3A4 substrate that can also prolong the QT interval.
Suvorexant: (Major) Coadministration of suvorexant and posaconazole is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Major) A reduction in tacrolimus dose, frequent monitoring of tacrolimus whole blood concentrations, and monitoring of QT prolongation is recommended if coadministered with posaconazole as concurrent use may result in an increase tacrolimus exposure and additive QT prolongation. When initiating therapy with posaconazole in patients already receiving tacrolimus, reduce the tacrolimus dose by two-thirds (i.e., administer one-third of the pre-posaconazole dose) and make subsequent tacrolimus dose adjustments based on the tacrolimus whole blood concentrations. In a pharmacokinetic study in healthy subjects, the administration of a single 0.05 mg/kg dose of immediate-release tacrolimus after 7 days of posaconazole 400 mg PO every 12 hours increased tacrolimus AUC and Cmax values by 4.5-fold and 2-fold, respectively, compared with tacrolimus alone. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range that may prolong the QT interval and cause torsade de pointes (TdP). Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and TdP.
Tadalafil: (Major) Posaconazole and tadalafil should be coadministered with caution due to an increased potential for tadalafil-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of tadalafil. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. The manufacturer of tadalafil recommends that in patients receiving concomitant potent CYP3A4 inhibitors, the 'as needed' dose should not exceed 10 mg within a 72 hour time period and the 'once-daily' dose should not exceed 2.5 mg.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with posaconazole is necessary. Talazoparib is a P-gp substrate and posaconazole is a P-gp inhibitor.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Tamsulosin: (Major) Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Plasma concentrations of tamsulosin are increased with concomitant use of ketoconazole, a strong inhibitor of CYP3A4. Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as ketoconazole, itraconazole, posaconazole, or voriconazole should be avoided.
Tasimelteon: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as posaconazole, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with posaconazole as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telavancin: (Moderate) Use posaconazole with caution in combination with telavancin as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Telavancin has also been associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with posaconazole is necessary; adjust the dose of amlodipine as clinically appropriate. Posaconazole is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Temsirolimus: (Major) Avoid coadministration of posaconazole with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus); exposure to posaconazole may also increase. If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of posaconazole before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and a P-glycoprotein (P-gp) inhibitor. Posaconazole is a strong CYP3A4 inhibitor and a P-gp substrate. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively. Concomitant use may lead to increased concentrations of posaconazole.
Teniposide: (Major) Posaconazole and teniposide should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of teniposide. Further, both teniposide and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and teniposide, ultimately resulting in an increased risk of adverse events.
Tenofovir Alafenamide: (Moderate) Close clinical monitoring adverse events are advised when administering tenofovir alafenamide with posaconazole. Use of these drugs together may result in elevated tenofovir alafenamide plasma concentrations. Posaconazole is an inhibitor of the drug transporter P-glycoprotein (P-gp). Tenofovir alafenamide is a substrate for P-gp. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as posaconazole. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Tepotinib: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with tepotinib is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; tepotinib is a P-gp inhibitor.
Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering posaconazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; posaconazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Tetrabenazine: (Major) Posaconazole has been associated with QT prolongation and in rare cases, torsade de pointes. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc inlcuding posaconazole.
Tezacaftor; Ivacaftor: (Major) If posaconazole and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Additionally, monitor for an increase in posaconazole-related adverse reactions. Ivacaftor is a CYP3A substrate and a P-gp inhibitor, and posaconazole is a strong CYP3A inhibitor and a P-gp substrate. Coadministration with another s trong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with posaconazole; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); posaconazole is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Theophylline, Aminophylline: (Major) Posaconazole and theophylline, aminophylline should be coadministered with caution due to an increased potential for theophylline-, aminophylline-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of theophylline, aminophylline. These drugs used in combination may result in elevated theophylline, aminophylline plasma concentrations, causing an increased risk for theophylline-, aminophylline-related adverse events.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with posaconazole which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and posaconazole if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; posaconazole is a strong CYP3A4 inhibitor.
Tiagabine: (Major) Posaconazole and tiagabine should be coadministered with caution due to an increased potential for tiagabine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of tiagabine. These drugs used in combination may result in elevated tiagabine plasma concentrations, causing an increased risk for tiagabine-related adverse events.
Ticagrelor: (Moderate) Coadministration of ticagrelor and posaconazole may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and posaconazole is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Tinidazole: (Major) Posaconazole and tinidazole should be coadministered with caution due to an increased potential for tinidazole-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of tinidazole. These drugs used in combination may result in elevated tinidazole plasma concentrations, causing an increased risk for tinidazole-related adverse events.
Tipranavir: (Major) Posaconazole and tipranavir should be coadministered with caution due to an increased potential for adverse events. Both posaconazole and tipranavir are inhibitors of CYP3A4, an isoenzyme partially responsible for the metabolism of tipranavir. Further, tipranavir is an inducer and substrates of the drug efflux protein, P-glycoprotein, for which posaconazole is an inhibitor and also a substrate. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and tipranavir, ultimately resulting in an increased risk of adverse events.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with posaconazole is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with posaconazole. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with posaconazole. Posaconazole is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily and monitor for evidence of QT prolongation if coadministered with posaconazole. Concurrent use may increase tolterodine exposure. Posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and posaconazole is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; posaconazole is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Topotecan: (Major) Avoid coadministration of posaconazole with oral topotecan due to increased topotecan exposure; posaconazole may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and posaconazole is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as toremifene, is contraindicated. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Toremifene is a CYP3A4 substrate that has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with posaconazole due to the risk of increased trabectedin exposure. If short-term posaconazole (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Tramadol: (Major) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with posaconazole is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of posaconazole, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Major) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with posaconazole is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of posaconazole, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist. (Moderate) Posaconazole and acetaminophen should be coadministered with caution due to an increased potential for acetaminophen-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of acetaminophen. These drugs used in combination may result in elevated acetaminophen plasma concentrations, causing an increased risk for acetaminophen-related adverse events.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with posaconazole is necessary. Concurrent use may result in elevated verapamil concentrations. Verapamil is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Trazodone: (Contraindicated) The concurrent use of posaconazole and trazodone is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of trazodone. These drugs used in combination may result in elevated trazodone plasma concentrations, causing an increased risk for trazodone-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as trazodone.
Triamcinolone: (Moderate) Posaconazole may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as posaconazole, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects. Benzodiazepines not metabolized by CYP3A4 (e.g., lorazepam, oxazepam) are unlikely to be affected by azole antifungals.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. 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.
Tricyclic antidepressants: (Minor) Posaconazole is associated with QT prolongation. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, posaconazole inhibits CYP3A4, CYP2C19, and CYP3A4 may be partially involved in the metabolism of TCAs. Fluconazole has been reported to increase the effects of amitriptyline, perhaps through inhibition of the hepatic microsomal CYP2C19 or CYP3A4 isoenzymes. In at least one case, the interaction resulted in an increased incidence of TCA-related side effects, such as dizziness and syncope. In another case, QT-prolongation and torsades de pointes occurred. Monitor for an increased response to amitriptyline if fluconazole, posaconazole, or voriconazole are coadministered.
Trifluoperazine: (Minor) Use posaconazole with caution in combination with trifluoperazine. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and posaconazole is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Concomitant use of ulipristal and posaconazole may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
Upadacitinib: (Major) During concomitant use of upadacitinib and posaconazole reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valbenazine: (Major) The dose of valbenazine should be reduced to 40 mg once daily during co-administration with a strong CYP3A4 inhibitor, such as posaconazole. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant. The prescribing information for posaconazole states that posaconazole should not be administered with drugs that are known to prolong the QT interval and are metabolized by CYP3A4.
Vandetanib: (Major) Avoid coadministration of vandetanib with posaconazole due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Vardenafil: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as vardenafil, is contraindicated. Posaconazole is associated with QT prolongation, and vardenafil may cause QT prolongation at both therapeutic and supratherapeutic doses. Also, posaconazole may inhibit the metabolism of vardenafil. Posaconazole is a potent CYP3A4 inhibitor. Elevated plasma concentrations of vardenafil may also increase the risk for other vardenafil-related adverse events, such as prolonged erection or potential for syncope.
Vemurafenib: (Contraindicated) Concurrent use of posaconazole and vemurafenib is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Posaconazole has been associated with QT prolongation and torsade de pointes. Additionally, coadministration may result in increased vemurafenib exposure and an increased risk of adverse events, including QT prolongation. Vemurafenib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Coadministration of posaconazole with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of posaconazole. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 70 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 70 mg/day starting on day 4. Coadministration of posaconazole, a strong CYP3A4 and P-gp inhibitor, increased the venetoclax AUC by 90% to 144% in a drug interaction study.
Venlafaxine: (Contraindicated) Concurrent use of posaconazole and venlafaxine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of venlafaxine. These drugs used in combination may result in elevated venlafaxine plasma concentrations, causing an increased risk for venlafaxine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as venlafaxine.
Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with posaconazole is necessary. Concurrent use may result in elevated verapamil concentrations. Verapamil is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Vilazodone: (Major) Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer of vilazodone recommends that the daily dose not exceed 20 mg/day during concurrent use of a strong CYP3A4 inhibitor, such as posaconazole. The original vilazodone dose can be resumed when the CYP3A4 inhibitor is discontinued.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with posaconazole is necessary. Vinblastine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Vincristine Liposomal: (Major) Avoid coadministration of posaconazole with vincristine due to increased plasma concentrations of vincristine. Vincristine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals, including posaconazole, with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Vincristine: (Major) Avoid coadministration of posaconazole with vincristine due to increased plasma concentrations of vincristine. Vincristine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals, including posaconazole, with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Vinorelbine: (Major) Avoid coadministration of posaconazole with vinorelbine if possible due to increased plasma concentrations of vinorelbine. If concomitant use is unavoidable and alternative antifungal options are not available, frequently monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy. Vinorelbine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals, including posaconazole, with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and posaconazole is contraindicated as use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also increase the risk for posaconazole-related adverse effects and result in additive QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and P-gp inhibitor and posaconazole is a strong CYP3A4 inhibitor and P-gp substrate that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) The concurrent use of posaconazole and clarithromycin is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Consider use of azithromycin in place of clarithromycin. Both posaconazole and clarithromycin are inhibitors of CYP3A4, an isoenzyme responsible for the metabolism of clarithromycin. Further, clarithromycin is an inhibitor of the drug efflux protein, P-glycoprotein, for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and clarithromycin and an increased risk for serious adverse events. Additionally, both drugs have been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
Vorapaxar: (Major) Avoid coadministration of vorapaxar and posaconazole. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with posaconazole, a strong CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Contraindicated) Concomitant use of voriconazole with posaconazole is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole causes dose-dependent QT and PR prolongation. Voriconazole has also been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. In addition, both drugs are inhibitors and substrates of the hepatic isoenzyme CYP3A4. This complex interaction may ultimately result in altered plasma concentrations of voriconazole and posaconazole. Furthermore, both drugs are azole antifungals and concurrent use would represent duplicate therapy.
Vorinostat: (Moderate) Use posaconazole with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Vorinostat therapy is also associated with a risk of QT prolongation.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with posaconazole is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Posaconazole is a strong CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as posaconazole, may decrease the clearance of zaleplon. Routine dosage adjustments of zaleplon are not required. Dosage adjustments should be made on an individual basis according to efficacy and tolerability.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with posaconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of posaconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ziprasidone: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as ziprasidone, is considered contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes (TdP) and is a strong CYP3A4 inhibitor. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with posaconazole is necessary. Zolpidem is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors increased the AUC of zolpidem by 34% to 70%.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and posaconazole is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.
How Supplied
Noxafil Oral Pwd F/Recon: 300mg
Noxafil/Posaconazole Intravenous Inj Sol: 1mL, 18mg
Noxafil/Posaconazole Oral Susp: 1mL, 40mg
Noxafil/Posaconazole Oral Tab DR: 100mg
Maximum Dosage
delayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; immediate-release oral suspension, 800 mg/day PO; intravenous, loading dose of 600 mg/day and maintenance dose of 300 mg/day IV. Safety and efficacy of the delayed-release oral suspension have not been established.
Geriatricdelayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; immediate-release oral suspension, 800 mg/day PO; intravenous, loading dose of 600 mg/day and maintenance dose of 300 mg/day IV. Safety and efficacy of the delayed-release oral suspension have not been established.
Adolescentsweighing more than 40 kg: delayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; immediate-release oral suspension, 800 mg/day PO; intravenous, loading dose of 12 mg/kg/day (Max: 600 mg/day) and maintenance dose of 6 mg/kg/day (Max: 300 mg/day) IV. Safety and efficacy of delayed-release oral suspension have not been established.
weighing 36 to 40 kg: delayed-release oral suspension, loading dose of 480 mg/day and maintenance dose of 240 mg/day PO; immediate-release oral suspension, 800 mg/day PO; delayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; intravenous, loading dose of 12 mg/kg/day and maintenance dose of 6 mg/kg/day IV.
weighing 26 to 35 kg: delayed-release oral suspension, loading dose of 420 mg/day and maintenance dose of 210 mg/day PO; immediate-release oral suspension, 800 mg/day PO; delayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; intravenous, loading dose of 12 mg/kg/day and maintenance dose of 6 mg/kg/day IV.
2 to 12 years weighing more than 40 kg: delayed-release tablet, loading dose of 600 mg/day and maintenance dose of 300 mg/day PO; intravenous, loading dose of 12 mg/kg/day (Max: 600 mg/day) and maintenance dose of 6 mg/kg/day (Max: 300 mg/day) IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day or 1,200 mg/day PO have been used off-label. Safety and efficacy of delayed-release oral suspension have not been established.
2 to 12 years weighing 36 to 40 kg: delayed-release oral suspension, loading dose of 480 mg/day and maintenance dose of 240 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established; however, doses up to 1,200 mg/day PO have been used off-label in children 7 to 12 years who can swallow tablets.
2 to 12 years weighing 26 to 35 kg: delayed-release oral suspension, loading dose of 420 mg/day and maintenance dose of 210 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established; however, doses up to 1,200 mg/day PO have been used off-label in children 7 to 12 years who can swallow tablets.
2 to 12 years weighing 21 to 25 kg: delayed-release oral suspension, loading dose of 360 mg/day and maintenance dose of 180 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established; however, doses up to 1,200 mg/day PO have been used off-label in children 7 to 12 years who can swallow tablets.
2 to 12 years weighing 17 to 20 kg: delayed-release oral suspension, loading dose of 300 mg/day and maintenance dose of 150 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established; however, doses up to 1,200 mg/day PO have been used off-label in children 7 to 12 years who can swallow tablets.
2 to 12 years weighing 12 to 16 kg: delayed-release oral suspension, loading dose of 240 mg/day and maintenance dose of 120 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established.
2 to 12 years weighing 10 to 11 kg: delayed-release oral suspension, loading dose of 180 mg/day and maintenance dose of 90 mg/day PO; intravenous, loading dose of 12 mg/kg/day IV and maintenance dose of 6 mg/kg/day IV. Safety and efficacy of immediate-release suspension have not been established; however, doses up to 24 mg/kg/day PO have been used off-label. Safety and efficacy of delayed-release tablets have not been established.
1 year: Safety and efficacy have not been established; however, doses up to 24 mg/kg/day PO (immediate-release oral suspension) and IV have been used off-label.
Safety and efficacy have not been established; however, doses up to 24 mg/kg/day PO (immediate-release oral suspension) and IV have been used off-label.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Posaconazole exerts its effect by altering the fungal cell membrane. Azole antifungals alter the fungal cell membrane by inhibiting ergosterol synthesis through an interaction with 14-alpha demethylase, a cytochrome P-450 enzyme needed to convert lanosterol to ergosterol, an essential component of the membrane. Inhibition of ergosterol synthesis results in increased cellular permeability causing leakage of cellular contents. In contrast, amphotericin B binds to ergosterol after it is synthesized. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole. Azole compounds have a broad spectrum of antifungal activity against common fungal pathogens.
Cross-resistance of posaconazole with other azole antifungals may be possible due to common modes of action. Clinical isolates of Candida albicans and Candida glabrata with decreased posaconazole susceptibility were observed in oral swish samples taken during prophylaxis studies with posaconazole and fluconazole. This suggests a potential for development of resistance. These isolates also had reduced susceptibility to other azoles. Due to the potential for cross-resistance, specific organism susceptibility data should be reviewed before selecting an antifungal for the treatment of infections.
Pharmacokinetics
Posaconazole is administered orally and intravenously. Posaconazole has significant penetration into the body tissues, with the mean volume of distribution being 261 L (range: 226 to 295 L). Protein binding is more than 98%, predominantly to albumin. In plasma, posaconazole mainly circulates as the parent compound. The major circulating metabolites are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). There are no major circulating CYP450 (oxidative) metabolites; however, posaconazole is reported to inhibit CYP3A4 enzymes. Based on radiolabeled studies, it is mainly eliminated in the feces (71% of the radiolabeled dose up to 120 hours) primarily as parent drug (66% of radiolabeled dose). Urinary and fecal excretion account for approximately 17% of the excreted metabolites. Renal elimination is a minor pathway, with 13% of the radiolabeled dose excreted in urine up to 120 hours (less than 0.2% of the radiolabeled dose is parent drug). The mean elimination half-lives for the different formulations are as follows: 35 hours (range: 20 to 66 hours) for the immediate-release oral suspension, 26 to 31 hours for the delayed-release tablet, and 27 hours for the injection for infusion; the elimination half-life for the delayed-release suspension has not been determined.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
Posaconazole is metabolized via UDP glucuronidation and is a substrate for and may inhibit P-glycoprotein (P-gp). It is a potent inhibitor of CYP3A4.
Delayed-release tablets: After oral administration in healthy adult volunteers, posaconazole delayed-release tablets are absorbed with a median Tmax of 4 to 5 hours. The absolute bioavailability is approximately 54%. When administered with a high fat meal, the Cmax and AUC are increased by 16% and 51%, respectively, compared to the fasted state. Steady-state plasma concentrations are reached within 6 days. Dose proportional pharmacokinetics occur after single and multiple dosing up to 300 mg.
Delayed-release oral suspension: The absolute bioavailability of the delayed-release oral suspension is approximately 70% to 80%. The effect of food on the pharmacokinetics of the delayed-release oral suspension has not been determined.
Immediate-release oral suspension: After oral administration, posaconazole immediate-release oral suspension is absorbed with a median Tmax of about 3 to 5 hours. Dose proportional increases in AUC occur after single oral doses from 50 to 800 mg and after multiple dose administration of 50 to 400 mg twice daily. No further increases in AUC were observed when the dose was increased from 400 to 600 mg twice daily in febrile neutropenic patients or those with refractory invasive fungal infections. Steady-state plasma concentrations are reached within 7 to 10 days. Food significantly increases the oral absorption of posaconazole from the suspension. In pharmacokinetic studies and relative to the fasting state, the mean AUC and Cmax after a 200 mg single dose are about 3-fold higher when administered with a nonfat meal and about 4-fold higher when given with a high fat meal (approximately 50 g fat). After a single 400 mg dose, the mean AUC and Cmax are approximately 3-fold higher when administered with a liquid nutritional supplement (14 g fat) relative to the fasted state. Gastric acid conditions may affect the absorption of posaconazole. In a single-dose, cross-over, pharmacokinetic study in 12 healthy adults, volunteers received posaconazole oral solution alone, with ginger ale (an acidic beverage), with esomeprazole, or with both ginger ale and esomeprazole in a fasted state. Coadministration with ginger ale increased the mean Cmax by 92% and the AUC by 70% compared to posaconazole alone. Coadministration with esomeprazole decreased the mean Cmax by 46% and the AUC by 32% compared to posaconazole alone. Coadministration with ginger ale and esomeprazole decreased the Cmax by 33% and the AUC by 21% as compared to posaconazole alone.
When administered to healthy volunteers, intravenously infused posaconazole exhibited dose proportional pharmacokinetics after single doses between 200 mg and 300 mg.
Pregnancy And Lactation
Available data for posaconazole use in pregnancy are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women; advise pregnant women of the potential risk to a fetus. Skeletal malformations (cranial malformations and missing ribs) were observed in the offspring of pregnant rats exposed to posaconazole during organogenesis at doses 1.4 times or more the recommended oral human dose (RHD). In pregnant rabbits, no malformations were observed at doses up to 5 times the RHD; however, increased resorptions and reduced litter size were observed at posaconazole doses of 3- or 5 times the RHD.[32723]
There are no data on the presence of posaconazole in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for posaconazole and any potential adverse effects on the breast-fed infant from posaconazole or the underlying maternal condition. Fluconazole and ketoconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent.[27500] [32723] [47037]