Version July 2025
Dosage guidance:
Dosing: Adjust dose based on trough serum concentration to ensure efficacy and avoid toxicity. Timing and frequency of concentration monitoring is individualized (Ref).
Dosage form information: The delayed-release tablet, IR oral suspension, and delayed-release oral suspension (not recommended in adults or pediatric patients >40 kg) are not interchangeable due to dosing differences for each formulation. The delayed-release tablet is generally preferred to the IR oral suspension because it is easier to administer, better tolerated, and more reliably absorbed (Ref). The IV formulation is given at the same dose as the delayed-release tablet.
Aspergillosis:
Chronic cavitary pulmonary (alternative agent):
Note: Some experts prefer the tablet over the IR suspension (Ref).
Delayed-release tablet: Oral: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref); for patients who are frail or low body weight (eg, BMI <18.5), some experts prefer 200 mg once daily (Ref).
IR suspension (off-label use): Oral: 200 mg 3 times daily (Ref) or 400 mg twice daily (Ref).
IV: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
Duration: ≥6 to 12 months; some patients require prolonged, potentially lifelong therapy (Ref).
Invasive (including disseminated and extrapulmonary) (alternative agent for patients who are refractory to or intolerant of first-line agents):
Oral: Note: Tablet preferred to IR suspension (Ref).
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
IR suspension (off-label use): 200 mg 3 times daily (Ref) or 200 mg 4 times daily during hospitalization, then 400 mg twice daily as an outpatient (Ref).
IV: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
Duration: Minimum of 6 to 12 weeks; total duration depends on degree/duration of immunosuppression, disease site, and response to therapy (Ref); immunosuppressed patients may require more prolonged treatment (Ref).
Candidiasis: Note: Generally reserved for fluconazole-refractory disease or as an alternative initial agent for patients with HIV or solid organ transplantation (Ref).
Esophageal, fluconazole-refractory disease (alternative agent) (off-label use): Oral:
Delayed-release tablet: 300 mg once daily (Ref).
IR suspension: 400 mg twice daily (Ref).
Duration: 14 to 28 days (Ref).
Oropharyngeal: Oral:
Initial episode (alternative agent): IR suspension: 400 mg twice daily for 1 to 3 days, then 400 mg once daily for a total duration of 7 to 14 days (Ref).
Fluconazole-refractory disease: IR suspension: 400 mg twice daily or 400 mg twice daily for 3 days, then 400 mg once daily. Duration is up to 28 days (Ref).
Coccidioidomycosis, refractory to conventional therapy (alternative agent) (off-label use): Note: Initial parenteral antifungal therapy may be warranted (Ref).
Nonmeningeal infection (eg, bone and/or joint infection, pulmonary infection in select patients): Oral:
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
IR suspension: 400 mg twice daily or 200 mg 3 times daily (Ref).
Duration: Varies by site and severity of infection, as well as patient immune status (Ref).
Meningitis: Oral:
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
IR suspension: 200 mg 4 times daily or 400 mg twice daily (Ref).
Duration: Lifelong because of the high relapse rate (Ref).
Mucormycosis, salvage and step-down therapy (off-label use): Note: For use after amphotericin B. Prompt surgical debridement is often needed to achieve clinical cure (Ref).
Oral: Note: Tablet preferred to IR suspension (Ref); some experts do not use IR suspension for mucormycosis because of suboptimal bioavailability (Ref).
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
IR suspension: 200 mg 4 times daily or 400 mg twice daily (Ref).
IV: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
Duration: Varies based on clinical and radiologic response and patient immune status; several months are often warranted, with some patients requiring lifelong therapy (Ref).
Prophylaxis against invasive fungal infections:
Hematology malignancy or hematopoietic cell transplant:
Oral: Note: Tablet preferred to IR suspension (Ref).
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily.
IR suspension: 200 mg 3 times daily (Ref).
IV: 300 mg twice daily for 2 doses, then 300 mg once daily.
Duration: Varies based on degree and duration of immunosuppression (Ref).
Solid organ transplant (eg, lung transplant recipients) (alternative agent) (off-label use): Oral:
Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (Ref).
IR suspension: 200 mg every 8 hours or 400 mg every 12 hours (Ref).
Duration: Varies by patient risk factors and transplant center protocol (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Renal clearance of posaconazole is negligible; it is primarily eliminated as unchanged drug in the feces (Ref). The IV formulation contains the excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin [SBECD]), which may accumulate in kidney impairment (eGFR <50 mL/minute/1.73 m2) (Ref). Cyclodextrins have been associated with kidney injury in animal models; however, studies of cyclodextrin-containing antifungals suggest similar rates of nephrotoxicity to noncyclodextrin-containing antifungals in patients receiving short durations (eg, <10 days) of therapy (Ref). When IV therapy is indicated, the benefits may outweigh the risks (Ref). Oral posaconazole or alternative antifungals in patients with eGFR <50 mL/minute/1.73 m2 or renal replacement therapies are preferred except when the benefits of injection outweigh the risks. If injection is used, monitor serum creatinine periodically and switch to oral therapy when clinically appropriate.
Altered kidney function:
eGFR ≥50 mL/minute/1.73 m2: Oral, IV: No dosage adjustment necessary (Ref).
eGFR <50 mL/minute/1.73 m2:
Oral: No dosage adjustment necessary (Ref).
IV: No dosage adjustment necessary (Ref). The IV formulation contains the excipient cyclodextrin (SBECD), which may accumulate. See “Note” at the beginning of "Dosing: Altered Kidney Function" for additional information.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral, IV: No dosage adjustment required (Ref).
Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref):
Oral: No dosage adjustment necessary (Ref).
IV: No dosage adjustment necessary (expert opinion). Exposure to the excipient cyclodextrin (SBECD) in the IV formulation is increased compared to patients with normal kidney function despite removal by hemodialysis. See “Note” at the beginning of "Dosing: Altered Kidney Function" for additional information.
Peritoneal dialysis: Not dialyzed (highly protein bound [>98%]) (Ref):
Oral: No dosage adjustment necessary (Ref).
IV: No dosage adjustment necessary (Ref). Exposure to the excipient cyclodextrin (SBECD) in the IV formulation is increased compared to patients with normal kidney function despite potential removal by dialysis therapies. See “Note” at the beginning of "Dosing: Altered Kidney Function" for additional information.
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: No dosage adjustment necessary (Ref).
IV: No dosage adjustment necessary. The excipient cyclodextrin (SBECD) in the IV formulation is effectively removed by CRRT (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: No dosage adjustment likely necessary since posaconazole is negligibly eliminated by the kidney and not removed by dialysis (Ref).
IV: No data, but posaconazole is negligibly eliminated by the kidney and not removed by dialysis; no dosage adjustment likely to be necessary (expert opinion). Exposure to SBECD, the carrier excipient in the IV formulation, may be increased compared to patients with normal kidney function despite removal by PIRRT. See “Note” at the beginning of "Dosing: Altered Kidney Function" for additional information.
Preexisting mild-to-severe impairment (Child-Pugh class A, B, or C): No dosage adjustment necessary.
Hepatotoxicity during treatment: There are no dosage adjustments provided in the manufacturer's labeling; consider discontinuing therapy.
Refer to adult dosing.
(For additional information see "Posaconazole: Pediatric drug information")
Dosage guidance:
Dosage form information: Use caution when selecting dosage form; the immediate-release oral suspension, delayed-release oral suspension, and delayed-release tablets are not interchangeable.
Aspergillosis, invasive, prophylaxis: Note: Duration of therapy is based on recovery from neutropenia or immunosuppression.
Oral:
Delayed-release formulations:
Delayed-release suspension: Children ≥2 years and Adolescents weighing 10 to 40 kg:
10 to <12 kg: Oral: 90 mg twice daily for 2 doses, followed by 90 mg once daily.
12 to <17 kg: Oral: 120 mg twice daily for 2 doses, followed by 120 mg once daily.
17 to <21 kg: Oral: 150 mg twice daily for 2 doses, followed by 150 mg once daily.
21 to <26 kg: Oral: 180 mg twice daily for 2 doses, followed by 180 mg once daily.
26 to <36 kg: Oral: 210 mg twice daily for 2 doses, followed by 210 mg once daily.
36 to ≤40 kg: Oral: 240 mg twice daily for 2 doses, followed by 240 mg once daily.
Delayed-release tablets: Children ≥2 years and Adolescents, weighing >40 kg: Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily.
Immediate-release suspension: Adolescents ≥13 years: Oral: 200 mg 3 times daily.
IV:
Children ≥2 years and Adolescents <18 years: IV: 6 mg/kg/dose twice daily for 2 doses, followed by 6 mg/kg/dose once daily; maximum dose: 300 mg/dose.
Adolescents ≥18 years: IV: 300 mg twice daily for 2 doses, followed by 300 mg once daily.
Aspergillosis, invasive, treatment (salvage): Note: A loading dose is not required when switching between IV and oral delayed-release tablet formulations. Duration of therapy is highly dependent on degree/duration of immunosuppression, disease site, and evidence of disease improvement; minimum of 6 to 12 weeks of therapy is recommended (Ref).
Oral: Adolescents:
Delayed-release tablets (preferred): Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily (Ref).
Immediate-release suspension: Limited data available: Oral: 200 mg 3 times daily or 400 mg twice daily (Ref).
IV: Adolescents: 300 mg twice daily for 2 doses, followed by 300 mg once daily (Ref).
Candidiasis, oropharyngeal, treatment:
Non-HIV-infected: Adolescents:
Initial episode: Immediate-release suspension: Oral: 100 mg twice daily for 2 doses, followed by 100 mg once daily for 13 days.
Refractory infection: Immediate-release suspension: Oral: 400 mg twice daily; duration of therapy is based on underlying disease and clinical response.
HIV-infected: Adolescents:
Initial episode (alternative to fluconazole): Immediate-release suspension: Oral: 400 mg twice daily for 2 doses, followed by 400 mg once daily for 7 to 14 days (Ref).
Refractory infection: Immediate-release suspension: Oral: 400 mg twice daily for 28 days (Ref).
Candidiasis, esophageal (azole-refractory), treatment: Adolescents (HIV-infected): Oral immediate-release suspension: 400 mg twice daily for 28 days. Note: If patient has frequent or severe recurrences may continue for suppressive therapy; consider discontinuing when CD4 >200/mm3 (Ref).
Candidiasis, invasive, prophylaxis: Note: Duration of therapy is based on recovery from neutropenia or immunosuppression.
Oral:
Delayed-release formulations:
Delayed-release suspension: Children ≥2 years and Adolescents weighing 10 to 40 kg:
10 to <12 kg: Oral: 90 mg twice daily for 2 doses, followed by 90 mg once daily.
12 to <17 kg: Oral: 120 mg twice daily for 2 doses, followed by 120 mg once daily.
17 to <21 kg: Oral: 150 mg twice daily for 2 doses, followed by 150 mg once daily.
21 to <26 kg: Oral: 180 mg twice daily for 2 doses, followed by 180 mg once daily.
26 to <36 kg: Oral: 210 mg twice daily for 2 doses, followed by 210 mg once daily.
36 to ≤40 kg: Oral: 240 mg twice daily for 2 doses, followed by 240 mg once daily.
Delayed-release tablets: Children ≥2 years and Adolescents, weighing >40 kg: Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily.
Immediate-release suspension: Adolescents ≥13 years: Oral: 200 mg 3 times daily.
IV:
Children ≥2 years and Adolescents <18 years: IV: 6 mg/kg/dose twice daily for 2 doses, followed by 6 mg/kg/dose once daily; maximum dose: 300 mg/dose.
Adolescents ≥18 years: IV: 300 mg twice daily for 2 doses, followed by 300 mg once daily.
Coccidioidomycosis, refractory to conventional therapy (alternative agent): Adolescents infected with HIV: Note: Initial parenteral antifungal therapy may be warranted; duration varies by site and severity of infection and patient immune status; treatment of meningitis is lifelong (Ref).
Delayed-release tablets: Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily (Ref).
Invasive fungal infection, prophylaxis in neutropenic patients (eg, patients with malignancy or post-hematopoietic stem cell transplant [HSCT]):
Note: Optimal dose to achieve pharmacokinetic targets has not been identified; significant inter- and intra-patient pharmacokinetic variability has been observed. Monitor serum concentrations and patient response closely, adjusting dose as appropriate (Ref). Duration dependent upon indication for prophylaxis and clinical condition of patient; consult institutional protocols.
Weight-directed dosing:
Delayed-release tablets: Very limited data available: Children ≥3 years and Adolescents ≤17 years: Oral: 5 to 7 mg/kg/dose twice daily for 2 doses, followed by 5 to 7 mg/kg/dose once daily (Ref).
Immediate-release suspension: Limited data available: Infants ≥6 months, Children, and Adolescents ≤17 years: Oral: 4 to 6 mg/kg/dose 3 times daily; maximum dose 400 mg/dose (Ref).
Fixed dosing: Limited data available:
Delayed-release tablets: Adolescents: Oral: 300 mg/dose twice daily for 2 doses, followed by 300 mg/dose once daily (Ref).
Immediate-release suspension: Adolescents: Oral: 200 mg/dose 3 times daily (Ref).
Invasive fungal infection, treatment (alternative/salvage): Limited data available:
Note: Optimal dose to achieve pharmacokinetic targets has not been identified; significant inter- and intra-patient pharmacokinetic variability has been observed. Monitor serum concentrations and patient response closely, adjusting dose as appropriate (Ref).
Immediate-release suspension:
Infants ≥5 months and Children (Ref): Oral:
<34 kg: 4.5 to 6 mg/kg/dose 4 times daily; maximum dose: 800 mg/day.
≥34 kg: 200 mg/dose 4 times daily.
Adolescents: Oral: 200 mg/dose 4 times daily.
Note: Dosing from a retrospective study (n=33; median age: 11.5 years; range: 0.5 to 23.2 years) in patients receiving posaconazole for treatment of suspected or proven fungal infections; the median dose in patients with proven infection was 16.5 mg/kg/day (range: 10.2 to 32.8 mg/kg/day); 12 of the 33 patients had posaconazole concentrations less than target of 0.7 mg/L; 3 of 14 patients with proven fungal infection experienced fungal progression. Posaconazole concentrations in this study were lower in patients ≥13 years as compared to patients <13 years of age; authors postulated that this was due to capping doses (Ref); in other trials, the reported daily doses varied from 4.8 to 33.3 mg/kg/day (Ref).
IV: Children ≤11 years: Very limited data available: 6 to 10 mg/kg/dose twice daily for 2 doses, followed by 6 to 10 mg/kg/dose once daily; maximum dose 300 mg/dose. Dosing from a retrospective study and a small case-series. In the retrospective study, patients received posaconazole for suspected, possible, or proven invasive fungal infection (IFI) (n=10; ages: 1.5 to 11 years). Patients receiving doses 6 to 8 mg/kg/dose were more likely to achieve target concentration of 0.7 mg/L compared to lower doses, and higher doses did not improve target attainment (Ref). In the case-series (n=4; all cases with possible or proven IFI; age: 3 to 9 years), maintenance doses of 8.8 to 9.7 mg/kg resulted in trough concentrations >1 mg/L (Ref). Posaconazole was well-tolerated, with reports of mild liver function test elevation and 1 patient with hypokalemia (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Parenteral:
IV: Children ≥2 years and Adolescents:
eGFR ≥50 mL/minute/1.73 m2: No dosage adjustment recommended.
eGFR <50 mL/minute/1.73 m2: Avoid use unless risk/benefit assessment warrants use; the intravenous vehicle (cyclodextrin) may accumulate. Monitor serum creatinine levels; if increases occur, consider oral therapy.
Oral:
Delayed-release tablets, Delayed-release suspension: Children ≥2 years and Adolescents weighing >40 kg:
eGFR ≥20 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <20 mL/minute/1.73 m2: No dosage adjustment necessary; however, monitor for breakthrough fungal infections due to variability in posaconazole exposure.
Immediate-release suspension: Adolescents ≥13 years:
eGFR ≥20 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <20 mL/minute/1.73 m2: No dosage adjustment necessary; however, monitor for breakthrough fungal infections due to variability in posaconazole exposure.
Hemodialysis: Not removed by dialysis.
Children ≥2 years and Adolescents:
Hepatotoxicity prior to initiating therapy (mild to severe): No dosage adjustment necessary.
Hepatotoxicity during treatment: There are no dosage adjustments provided in the manufacturer's labeling; consider discontinuing therapy if signs and symptoms consistent with liver disease that may be attributable to posaconazole develop.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (8% to 20%), hypotension (14%), peripheral edema (11% to 16%; including lower extremity edema), tachycardia (12%), thrombophlebitis (IV via peripheral venous catheter: 60%)
Dermatologic: Pruritus (11% to 22%), skin rash (14% to 24%)
Endocrine & metabolic: Hyperglycemia (11%), hypokalemia (14% to 30%), hypomagnesemia (10% to 18%)
Gastrointestinal: Abdominal pain (10% to 27%), anorexia (15%), constipation (8% to 21%), decreased appetite (10% to 15%), diarrhea (18% to 42%), nausea (16% to 38%), stomatitis (11% to 20%), upper abdominal pain (6% to 11%), vomiting (12% to 29%)
Hematologic & oncologic: Anemia (7% to 25%), febrile neutropenia (15% to 31%), neutropenia (23%), petechia (8% to 11%), thrombocytopenia (7% to 29%)
Hepatic: Increased serum alanine aminotransferase (6% to 17%), increased serum aspartate aminotransferase (3% to 13%)
Nervous system: Chills (10% to 16%), dizziness (11%), fatigue (8% to 17%), headache (12% to 28%), insomnia (17%), rigors (20%)
Neuromuscular & skeletal: Arthralgia (11%), musculoskeletal pain (16%)
Respiratory: Cough (9% to 24%), dyspnea (7% to 20%), epistaxis (11% to 17%), pharyngitis (12%), pneumonia (13%)
Miscellaneous: Fever (21% to 45%), inflammation (mucosal; 14% to 28%)
1% to 10%:
Cardiovascular: Edema (9%), pulmonary embolism (<5%), torsades de pointes (<5%)
Endocrine & metabolic: Adrenocortical insufficiency (<5%), hypocalcemia (9%)
Gastrointestinal: Dyspepsia (10%), pancreatitis (<5%)
Genitourinary: Vaginal hemorrhage (10%)
Hematologic & oncologic: Hemolytic-uremic syndrome (<5%), thrombotic thrombocytopenic purpura (<5%)
Hepatic: Abnormal liver function (<5%), hepatitis (<5%), hepatomegaly (<5%), increased liver enzymes (<5%), increased serum alkaline phosphatase (1% to 7%), increased serum bilirubin (7% to 10%), jaundice (<5%)
Hypersensitivity: Hypersensitivity reaction (<5%)
Nervous system: Asthenia (8% to 10%), paresthesia (<5%)
Neuromuscular & skeletal: Back pain (10%)
Renal: Acute kidney injury (<5%)
Frequency not defined: Cardiovascular: Prolonged QT interval on ECG
Postmarketing:
Endocrine & metabolic: Pseudoaldosteronism
Gastrointestinal: Cholestasis
Hepatic: Hepatic failure
Coadministration with sirolimus, ergot alkaloids (eg, ergotamine, dihydroergotamine), HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (eg, atorvastatin, lovastatin, simvastatin), CYP3A4 substrates that prolong the QT interval (eg, pimozide, quinidine), or venetoclax (during initiation or ramp up phase in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma); hypersensitivity to posaconazole, other azole antifungal agents, or any component of the formulation; known or suspected hereditary fructose intolerance (delayed-release oral suspension only).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Hepatic effects: Hepatic dysfunction has occurred, ranging from mild/moderate increases of ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis to severe reactions (cholestasis, hepatic failure including death). Elevations in LFTs have been generally reversible after posaconazole has been discontinued; some cases resolved without drug interruption. More severe reactions have been observed in patients with underlying serious medical conditions (eg, hematologic malignancy) and primarily with IR oral suspension total daily doses of 800 mg. Monitor LFTs at baseline and periodically during therapy. If increases occur, monitor for severe hepatic injury development. Consider discontinuation of therapy in patients who develop clinical evidence of liver disease that may be secondary to posaconazole.
• Pseudoaldosteronism: Reports of pseudoaldosteronism, manifested by the onset or exacerbation of hypertension and abnormal laboratory tests (eg, decreased aldosterone, increased 11-deoxycortisol, hypokalemia, decreased serum renin) have occurred. Discontinuation of therapy, switching to another antifungal, or use of an aldosterone receptor antagonist may be necessary.
Disease-related concerns:
• Arrhythmias: Use caution in patients with an increased risk of arrhythmia (long QT syndrome, concurrent QTc-prolonging drugs metabolized through CYP3A4, hypokalemia). Development of QTc prolongation, including torsades de pointes, has been reported.
• Electrolyte abnormalities: Correct electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia) prior to initiating and during therapy.
• Renal impairment: Do not use injection in patients with eGFR <50 mL/minute/1.73 m2, unless risk/benefit has been assessed. See "Dosage Forms Specific Issues: Injection Formulation." Evaluate renal function (particularly serum creatinine) at baseline and periodically during therapy. If increases occur, consider oral therapy. Monitor closely for breakthrough fungal infections in patients with severe renal impairment taking delayed-release oral suspension, delayed-release tablets, or IR oral suspension due to variability in posaconazole exposure.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Injection formulation: Do not give as an IV bolus injection. Avoid/limit use of IV formulation in patients with eGFR <50 mL/minute/1.73 m2; injection contains excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin [SBECD]), which may accumulate although the clinical significance of this finding is uncertain (Luke 2010); consider using oral posaconazole in these patients unless benefit of injection outweighs the risk. If injection is used in patients with eGFR <50 mL/minute, monitor serum creatinine closely; if increases occur, consider changing therapy to oral posaconazole. In critically ill patients undergoing concurrent continuous venovenous hemofiltration (CVVH), the use of standard doses of IV posaconazole has been used without SBECD accumulation (Morris 2015).
• Oral formulations: The delayed-release tablet, delayed-release oral suspension, and IR oral suspension are not to be used interchangeably due to dosing differences for each formulation. Monitor patients taking oral formulations who experience severe diarrhea or vomiting for breakthrough fungal infections.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Sorbitol: Some dosage forms may contain sorbitol.
Special populations:
• Obesity: Patients weighing >120 kg may have lower plasma drug exposure; monitor closely for breakthrough fungal infections.
Other warnings/precautions:
• Appropriate use: For patients prescribed posaconazole IR oral suspension who are unable to eat, take with a high-fat meal, or tolerate nutritional supplements or acidic carbonated beverages (eg, ginger ale) and do not have the option of taking the delayed-release tablet, delayed-release suspension, or injection, consider alternative antifungal therapy or closely monitor for breakthrough fungal infections. Delayed-release suspension is not recommended in adults or pediatric patients >40 kg; recommended dosage cannot be achieved.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral, (for Delayed Release Suspension):
Noxafil: 300 mg (1 ea, 8 ea) [contains carrageenan, methylparaben, propylparaben, saccharin sodium; berry flavor]
Solution, Intravenous:
Generic: 300 mg/16.7 mL (16.7 mL)
Solution, Intravenous [preservative free]:
Noxafil: 300 mg/16.7 mL (16.7 mL) [contains edetate (edta) disodium]
Generic: 300 mg/16.7 mL (16.7 mL)
Suspension, Oral, (Immediate Release Suspension):
Noxafil: 40 mg/mL (105 mL) [contains polysorbate 80, sodium benzoate; cherry flavor]
Generic: 40 mg/mL (105 mL)
Tablet Delayed Release, Oral:
Noxafil: 100 mg
Generic: 100 mg
May be product dependent
Pack (Noxafil Oral)
300 mg (per each): $246.71
Solution (Noxafil Intravenous)
300 mg/16.7 mL (per mL): $38.12
Solution (Posaconazole Intravenous)
300 mg/16.7 mL (per mL): $19.40 - $38.12
Suspension (Noxafil Oral)
40 mg/mL (per mL): $16.45
Suspension (Posaconazole Oral)
40 mg/mL (per mL): $14.81 - $15.63
Tablet, EC (Noxafil Oral)
100 mg (per each): $82.24
Tablet, EC (Posaconazole Oral)
100 mg (per each): $7.40 - $78.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Posanol: 300 mg/16.7 mL (16.7 mL) [contains edetate (edta) disodium]
Suspension, Oral, (Immediate Release Suspension):
Posanol: 40 mg/mL (105 mL) [contains polysorbate 80, sodium benzoate]
Generic: 40 mg/mL (105 mL)
Tablet Delayed Release, Oral:
Posanol: 100 mg
Generic: 100 mg
Oral:
IR suspension: Shake well before use. Administer with provided measured dosing spoon during or within 20 minutes following a full meal; patients who are unable to eat a full meal may take each dose with an oral liquid nutritional supplement or acidic carbonated beverage (eg, ginger ale). Consider an alternative antifungal in patients unable to eat a full meal or tolerate a liquid nutritional supplement or acidic carbonated beverage and who do not have the option of taking the delayed-release tablet or injection.
Delayed-release tablets: Administer with food when possible, but may be given with or without food. The manufacturer recommends to swallow tablets whole; do not divide, crush, dissolve, or chew.
Bariatric surgery: Some institutions may have specific protocols that conflict with manufacturer's recommendations; refer to institutional protocols as appropriate. Oral IR suspension and injectable formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.
Closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Posaconazole administration via enteral feeding tube (EFT) is not well-established; when selecting a formulation for EFT administration, take into consideration risks versus benefits and patient-specific factors (eg, indication, availability of timely serum concentration monitoring, previous therapy). Instructions are provided below if acceptable alternative is not available; monitor serum concentrations closely to ensure adequate absorption and make dosage adjustments as necessary; if therapeutic level is unable to be achieved, consider an alternative route or medication (Ref).
Oral packet for suspension, delayed release:
EFT administration of the oral packet for delayed-release suspension has not been studied; there is a risk of aggregation of the oral suspension and the inactive ingredients in this product suggest a high osmolality and viscosity, all of which may contribute to decreased tolerance and absorption (Ref). If used, consider risks versus benefits and ensure adequate volumes of purified water are utilized during administration.
Oral suspension, immediate release (commercially available):
Note: Nasogastric administration of posaconazole IR suspension results in decreased absorption. Monitor serum concentrations closely and adjust dose as necessary to achieve therapeutic targets (Ref).
Gastric (eg, NG, G-tube ) tube (≥8 French): Schedule administration in close proximity to enteral nutrition (EN) to maximize bioavailability. Shake suspension well prior to drawing up dose for dilution. Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity. Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: One undiluted formulation has been reported to have an osmolality of ~2,050 mOsm/kg (Ref); oral suspensions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold EN during posaconazole administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 20 mL) and restart EN immediately following administration (Ref).
Oral tablet, delayed release:
Note: While successful administration of crushed delayed-release tablets via EFT has been reported in some patient populations, higher and/or more frequent dosing may be necessary to achieve target concentrations due to potential decreased absorption (Ref). If used, monitor serum concentrations closely and adjust dose as necessary to achieve therapeutic targets (Ref).
Gastric (eg, NG, G-tube) tube: Schedule administration in close proximity to EN to maximize bioavailability (Ref). Crush tablet(s) into a fine powder and disperse in 30 mL purified water immediately prior to administration. Draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated posaconazole tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold EN during posaconazole administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart EN immediately following administration (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
IV: Infuse over 90 minutes via a central venous line. Do not administer IV push or bolus. Must be infused through an in-line filter (0.22 micron polyethersulfone [PES] or polyvinylidene difluoride [PVDF]). Infusion through a peripheral line should only be used as a one-time infusion over 30 minutes in a patient who will be receiving a central venous line for subsequent doses, or to bridge a period during which a central venous line is to be replaced or is in use for another infusion. May be an irritant. Note: In clinical trials, multiple peripheral infusions given through the same vein resulted in infusion-site reactions.
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: Note: The delayed-release oral suspension packets, immediate-release oral suspension, and delayed-release tablets are not interchangeable.
Delayed-release suspension packet (commercially available): Prepare solution just prior to administration. To reconstitute suspension, open 1 Posaconazole PowderMix kit packet (300 mg) and place it in the provided mixing cup. Shake the provided mixing liquid well, then use the provided blue syringe to withdraw 9 mL of the mixing liquid and add to the PowderMix kit packet in the mixing cup. Close the lid of mixing cup, shake vigorously for 45 seconds, and ensure the powder is mixed; the mixture should be cloudy and free of clumps. The resulting concentration is 30 mg/mL; however, only ≤8 mL (240 mg) can be accurately withdrawn from the reconstituted suspension. Administer reconstituted suspension with food within 1 hour of preparation using the appropriate manufacturer-provided syringe. Do not administer with alcohol, which may interfere with the delayed-release mechanism. Appropriate syringe depends on dose volume:
Dose ≤3 mL: Use provided green 3-mL notch-tipped syringe.
Dose >3 mL: Use provided blue 10-mL notch-tipped syringe.
After administering dose, discard any suspension remaining in the mixing cup. Hand wash mixing cup, syringes, and plungers with warm water and dish soap; rinse and air dry. Do not use other dosing syringes other than the ones provided; use of provided notched tip syringes prevents aggregation of the suspension and using other syringes may result in inaccurate dose.
Administration via feeding tube: Enteral feeding tube administration of delayed-release posaconazole oral suspension has not been studied. There is a risk of aggregation of the oral suspension, and the inactive ingredients in this product suggest a high osmolality and viscosity. These factors may contribute to decreased tolerance and absorption and a risk of clogging the tube (Ref). If used, consider risks vs benefits and patient-specific factors (eg, indication, availability of timely serum concentration monitoring, exposure target, previous therapy). Ensure adequate volumes of purified water are utilized during administration; monitor serum concentrations closely and adjust dose as necessary to achieve therapeutic targets (Ref).
Immediate-release suspension (commercially available): Shake well before use. Administer during or within 20 minutes following a full meal; patients who are unable to eat a full meal should take the dose with a liquid nutritional supplement or an acidic carbonated beverage (eg, ginger ale). Administer with an accurate measuring device. Consider an alternative antifungal in patients unable to eat a full meal or tolerate a liquid nutritional supplement or acidic carbonated beverage and who do not have the option of taking the delayed-release tablet or injection.
Administration via feeding tube: Note: Nasogastric administration of posaconazole immediate-release suspension results in decreased absorption. If used, consider risks vs benefits and patient-specific factors (eg, indication, availability of timely serum concentration monitoring, exposure target, previous therapy), ensure adequate volumes of purified water are utilized during administration, and monitor serum concentrations closely and adjust dose as necessary to achieve therapeutic targets (Ref).
Gastric (eg, NG, G-tube) tube (≥8 French): Shake suspension well prior to drawing up dose for dilution. Dilute dose with at least an equivalent volume of purified water immediately prior to administration to reduce osmolality and viscosity. Draw up diluted suspension into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: One undiluted formulation has been reported to have an osmolality of ~2,050 mOsm/kg (Ref); oral suspensions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during posaconazole administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref). Note: To maximize bioavailability, administer posaconazole immediate-release oral suspension just prior to a scheduled intermittent enteral feed, or restart continuous feeds immediately after final flush (Ref).
Missed doses: If a dose is missed, take as soon as remembered. If it is almost time for the next dose, skip the missed dose and return to the regular schedule. Do not double doses or take more than the prescribed dose.
Delayed-release tablets: Administer with food (high-fat meal) when possible, but may be given with or without food. The manufacturer recommends to swallow tablets whole and not to divide, crush, or chew; however, several case series have reported administration of crushed delayed-release tablets via enteral feeding tubes with appropriate monitoring (Ref).
Administration via feeding tube: Note: While successful administration of crushed delayed-release tablets via enteral feeding tubes has been reported in some patient populations, higher and/or more frequent dosing may be necessary to achieve target concentrations due to potential decreased absorption (Ref). If used, monitor serum concentrations closely and adjust dose as necessary to achieve therapeutic targets (Ref).
Gastric (eg, NG, G-tube) tube : Crush tablet into a fine powder and disperse in 30 mL purified water immediately prior to administration. Draw up mixture into enteral dosing syringe and administer via feeding tube (Ref). Alternatively, using a mortar and pestle, crush tablets into a fine powder and add 1 to 2 mL of OraBlend per tablet to form a paste, then suspend in a total of 8 mL of OraBlend per tablet; rinse mortar and pestle with 2 mL of OraBlend per tablet to provide a final concentration of 10 mg/mL. All doses should be administered within 1 hour of preparation (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated posaconazole tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed prior to administration (Ref).
General guidance: Hold enteral nutrition during posaconazole administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition immediately following administration (Ref). Note: To maximize bioavailability, administer posaconazole immediate-release oral suspension just prior to a scheduled intermittent enteral feed, or restart continuous feeds immediately after final flush (Ref).
Missed dose: If a dose is missed, take as soon as remembered. If it is <12 hours until the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
IV: Infuse over 90 minutes via a central venous line. Do not administer IV push or bolus. Must be infused through an in-line filter (0.22-micron polyethersulfone [PES] or polyvinylidene difluoride [PVDF]). If central line unavailable, may infuse through peripheral line as a one-time infusion over 30 minutes prior to patient receiving central line, or to bridge a period during which a central venous line is to be replaced or is in use for another infusion. May be an irritant. Note: In clinical trials, multiple peripheral infusions given through the same vein resulted in infusion-site reactions.
Aspergillosis, invasive: Delayed-release tablets and injection (patients ≥13 years of age): Treatment of invasive aspergillosis.
Candidiasis, oropharyngeal: IR oral suspension (patients ≥13 years of age): Treatment of oropharyngeal candidiasis (including patients refractory to itraconazole and/or fluconazole).
Prophylaxis against invasive fungal infections, severely immunocompromised patients: Delayed-release tablets (patients ≥2 years of age and >40 kg), injection (patients ≥2 years of age), delayed-release oral suspension (patients ≥2 to <18 years of age and ≤40kg), and IR oral suspension (patients ≥13 years of age): Prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised (eg, hematopoietic stem cell transplant with graft-versus-host disease, hematologic malignancy with prolonged neutropenia due to chemotherapy).
Aspergillosis, chronic cavitary pulmonary; Aspergillosis, invasive (including disseminated and extrapulmonary); Candidiasis, esophageal, fluconazole-refractory disease; Coccidioidomycosis, refractory to conventional therapy; Cryptococcal meningitis; Mucormycosis, salvage and step-down therapy; Prophylaxis against invasive fungal infections, solid organ transplant recipients
Noxafil may be confused with minoxidil
Posaconazole may be confused with itraconazole
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Noxafil [US and multiple international markets] may be confused with Noxidil brand name for minoxidil [Thailand]
The delayed release oral suspension is supplied as a kit with a 473 mL bottle of mixing liquid but each of the eight packets in the kit only require 9 mL for mixing; the excess mixing liquid may lead to confusion or mixing errors. Ensure directions for mixing are followed closely.
Substrate of UGT1A4; Inhibits CYP3A4 (Strong), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider Therapy Modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acalabrutinib. Risk X: Avoid
Acrivastine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acrivastine. Risk C: Monitor
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider Therapy Modification
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Alcohol (Ethyl): May increase serum concentration of Posaconazole. Risk X: Avoid
ALfentanil: CYP3A4 Inhibitors (Strong) may increase serum concentration of ALfentanil. Management: If use of alfentanil and strong CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider Therapy Modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Alfuzosin. Risk X: Avoid
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25 mg and maximum dose to 12.5 mg in any 24-period when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider Therapy Modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase serum concentration of Alosetron. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of ALPRAZolam. Risk X: Avoid
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase serum concentration of AmLODIPine. Risk C: Monitor
Apalutamide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Apalutamide. Risk C: Monitor
Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Risk D: Consider Therapy Modification
Aprepitant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Artemether and Lumefantrine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. Risk C: Monitor
Asciminib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Asciminib. Risk C: Monitor
Atazanavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Atazanavir. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended atogepant dose is 10 mg once daily with a concurrent strong CYP3A4 inhibitor. If used for treatment of chronic migraine, concurrent use of atogepant with strong CYP3A4 inhibitors should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: Posaconazole may increase serum concentration of Atorvastatin. Risk X: Avoid
Avacopan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk D: Consider Therapy Modification
Barnidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Barnidipine. Risk X: Avoid
Beclomethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Beclomethasone (Systemic). Risk C: Monitor
Benidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benidipine. Risk C: Monitor
Benperidol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benperidol. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Nasal). Risk C: Monitor
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor
Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Systemic). Risk C: Monitor
Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Topical). Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Blonanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Blonanserin. Risk X: Avoid
Bortezomib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosentan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bosentan. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bosutinib. Risk X: Avoid
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider Therapy Modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider Therapy Modification
Bromperidol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bromperidol. Risk C: Monitor
Brotizolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brotizolam. Risk C: Monitor
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Nasal). Risk C: Monitor
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Strong) may increase serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider Therapy Modification
Butorphanol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Butorphanol. Risk C: Monitor
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Risk D: Consider Therapy Modification
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cannabidiol. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Capivasertib. Management: Avoid concomitant use of capivasertib with strong CYP3A4 inhibitors when possible. If combined, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification
Capmatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Capmatinib. Risk C: Monitor
CarBAMazepine: CYP3A4 Inhibitors (Strong) may increase serum concentration of CarBAMazepine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of CarBAMazepine. Risk C: Monitor
Cariprazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a strong CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase serum concentration of ChlordiazePOXIDE. Risk C: Monitor
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ciclesonide (Oral Inhalation). Risk C: Monitor
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cilnidipine. Risk C: Monitor
Cilostazol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Cimetidine: May decrease serum concentration of Posaconazole. Management: Avoid concurrent cimetidine unless potential benefits outweigh the risks of possible inadequate response. If concomitant use cannot be avoided, monitor steady state posaconazole trough levels and monitor for evidence of decreased antifungal effects. Risk D: Consider Therapy Modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cinacalcet. Risk C: Monitor
Cisapride: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cisapride. Risk X: Avoid
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase serum concentration of ClonazePAM. Risk C: Monitor
CloZAPine: CYP3A4 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobicistat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cobicistat. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Colchicine. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of P-gp inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Conivaptan. Risk X: Avoid
Copanlisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider Therapy Modification
Cortisone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cortisone. Risk C: Monitor
CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may increase serum concentration of CycloSPORINE (Systemic). Management: Consider reducing cyclosporine doses by 50% to 80% during coadministration with ketoconazole, 50% with voriconazole or itraconazole, and 25% with posaconazole. Cyclosporine dose reductions may be required with other azoles. Risk D: Consider Therapy Modification
Cyproterone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cyproterone. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider Therapy Modification
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk X: Avoid
Daridorexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Daridorexant. Risk X: Avoid
Darifenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are combined. Risk D: Consider Therapy Modification
Darolutamide: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Darolutamide. Risk C: Monitor
Darunavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Darunavir. Risk C: Monitor
Deflazacort: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
DiazePAM: CYP3A4 Inhibitors (Strong) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dienogest. Risk C: Monitor
Digitoxin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Digitoxin. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase serum concentration of DilTIAZem. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Risk D: Consider Therapy Modification
Domperidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Domperidone. Risk X: Avoid
Doxazosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Doxazosin. Risk C: Monitor
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
DroNABinol: CYP3A4 Inhibitors (Strong) may increase serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dronedarone. Risk X: Avoid
Dutasteride: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dutasteride. Risk C: Monitor
Duvelisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider Therapy Modification
Dydrogesterone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dydrogesterone. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ebastine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ebastine. Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Efavirenz: May decrease serum concentration of Posaconazole. Risk X: Avoid
Efonidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Efonidipine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elacestrant. Risk X: Avoid
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid
Elagolix: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider Therapy Modification
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider Therapy Modification
Eletriptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Administer elexacaftor/tezacaftor/ivacaftor in the morning, twice a week, 3 to 4 days apart, with no evening doses of ivacaftor alone. Specific dosing varies by age and weight. See full monograph for details. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Enfortumab Vedotin: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor
Ensartinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ensartinib. Risk X: Avoid
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Enzalutamide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Enzalutamide. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Enzalutamide. Risk C: Monitor
Eplerenone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eplerenone. Risk X: Avoid
Erdafitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid
Erlotinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider Therapy Modification
Esketamine (Injection): CYP3A4 Inhibitors (Strong) may increase serum concentration of Esketamine (Injection). Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider Therapy Modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Etizolam. Risk C: Monitor
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Etravirine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Etravirine. Risk C: Monitor
Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Everolimus. Risk X: Avoid
Evogliptin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Evogliptin. Risk C: Monitor
Fedratinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider Therapy Modification
Felodipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider Therapy Modification
FentaNYL: CYP3A4 Inhibitors (Strong) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a strong CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider Therapy Modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in patients who are also receiving strong CYP3A4 inhibitors. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider Therapy Modification
Fexinidazole: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Fexinidazole. Management: Avoid use of fexinidazole and strong CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider Therapy Modification
Finerenone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Flibanserin. Management: Use of flibanserin with strong CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid
Flucloxacillin: May decrease serum concentration of Posaconazole. Risk C: Monitor
Flunitrazepam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Flunitrazepam. Risk C: Monitor
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Fluticasone (Nasal). Risk X: Avoid
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider Therapy Modification
Fluticasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Fluticasone (Topical). Risk C: Monitor
Fosamprenavir: May decrease serum concentration of Posaconazole. Posaconazole may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Posaconazole. Management: Concomitant use of posaconazole and fosphenytoin/phenytoin should be avoided unless the benefit to the patient outweighs the risk. If concomitant administration is required, close monitoring for breakthrough fungal infections is recommended. Risk D: Consider Therapy Modification
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Fostamatinib. Risk C: Monitor
Futibatinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Futibatinib. Risk X: Avoid
Gefitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gepirone. Risk X: Avoid
Gepotidacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gepotidacin. Management: Avoid coadministration of gepotidacin and strong CYP3A4 inhibitors if possible. If coadministration cannot be avoided, conduct a baseline ECG, monitor closely for altered electrolytes, and correct electrolyte abnormalities as needed. Risk D: Consider Therapy Modification
Glasdegib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
GlipiZIDE: Posaconazole may increase hypoglycemic effects of GlipiZIDE. Posaconazole may increase serum concentration of GlipiZIDE. Risk C: Monitor
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification
Halofantrine: Posaconazole may increase serum concentration of Halofantrine. Risk X: Avoid
Histamine H2 Receptor Antagonists: May decrease serum concentration of Posaconazole. Risk C: Monitor
Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase serum concentration of Hormonal Contraceptives. Risk C: Monitor
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Ibrutinib: Posaconazole may increase serum concentration of Ibrutinib. Management: Ibrutinib dose reductions are required when combined with posaconazole. Dose recommendations depend on the indication for ibrutinib, age of the patient, and the posaconazole dose. See full Lexi Interact monograph for details. Risk D: Consider Therapy Modification
Idelalisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider Therapy Modification
Ifosfamide: CYP3A4 Inhibitors (Strong) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Imatinib. Risk C: Monitor
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Imidafenacin. Risk C: Monitor
Indinavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Indinavir. Risk C: Monitor
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease serum concentration of Posaconazole. Management: Avoid coadministration of PPIs or PCABs and posaconazole oral suspension. Posaconazole delayed-release tablets do not appear to be sensitive to this interaction and do not required dose adjustment if coadministered with PPIs or PCABs. Risk D: Consider Therapy Modification
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid
Isradipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider Therapy Modification
Itraconazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of Itraconazole. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider Therapy Modification
Ivosidenib: Posaconazole may increase serum concentration of Ivosidenib. Ivosidenib may decrease serum concentration of Posaconazole. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Ketamine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ketamine. Risk C: Monitor
Ketoconazole (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ketoconazole (Systemic). Risk C: Monitor
Lacidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lacidipine. Risk C: Monitor
Lapatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Larotrectinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider Therapy Modification
Lefamulin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid
Lemborexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lercanidipine. Risk X: Avoid
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levobupivacaine. Risk C: Monitor
Levoketoconazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Lidocaine (Systemic). Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lomitapide. Risk X: Avoid
Lonafarnib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lonafarnib. Risk X: Avoid
Lopinavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lopinavir. Risk C: Monitor
Lorlatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider Therapy Modification
Lovastatin: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Lovastatin. CYP3A4 Inhibitors (Strong) may increase serum concentration of Lovastatin. Risk X: Avoid
Lumacaftor and Ivacaftor: May decrease serum concentration of Posaconazole. Posaconazole may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives to this combination. If combined, monitor for reduced posaconazole serum concentrations and efficacy. If lumacaftor/ivacaftor is initiated in patients taking posaconazole, lumacaftor/ivacaftor dose reductions are needed. Risk D: Consider Therapy Modification
Lumateperone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Lurasidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lurasidone. Risk X: Avoid
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and strong CYP3A4 inhibitors. If coadministration with a strong CYP3A4 inhibitor cannot be avoided, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider Therapy Modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider Therapy Modification
Mavacamten: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mavacamten. Management: For patients on stable therapy with a strong CYP3A4 inhibitor initiate mavacamten at 2.5 mg daily. For patients initiating a strong CYP3A4 inhibitor during mavacamten therapy, dose reductions are recommended. See full mono for details. Risk D: Consider Therapy Modification
Mavorixafor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mavorixafor. Management: Decrease the mavorixafor dose to 200 mg daily if combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Mefloquine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mefloquine. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Meperidine. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Metoclopramide: May decrease serum concentration of Posaconazole. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Midazolam. Management: Avoid use of nasal midazolam and strong CYP3A4 inhibitors whenever possible, and consider alternatives to use with other routes of midazolam (oral, IV, IM). If combined, consider lower midazolam doses and monitor for increased midazolam toxicities. Risk D: Consider Therapy Modification
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider Therapy Modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider Therapy Modification
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirtazapine. Risk C: Monitor
Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mitapivat. Risk X: Avoid
Mizolastine: Antifungal Agents (Azole Derivatives, Systemic) may increase serum concentration of Mizolastine. Risk X: Avoid
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Nasal). Risk C: Monitor
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Topical). Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Naldemedine. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Naloxegol. Risk X: Avoid
Nelfinavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nelfinavir. Risk C: Monitor
Neratinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Neratinib. Risk X: Avoid
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NiCARdipine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of NIFEdipine (Topical). Risk X: Avoid
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider Therapy Modification
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NiMODipine. Risk X: Avoid
Nintedanib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Nintedanib. Risk C: Monitor
Nirmatrelvir and Ritonavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nitrendipine. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Risk D: Consider Therapy Modification
Oliceridine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 50 mg daily and monitor closely for adverse reactions. Discontinue coadministration if adverse reactions occur. Risk D: Consider Therapy Modification
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Ospemifene: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ospemifene. Risk C: Monitor
OxyBUTYnin: CYP3A4 Inhibitors (Strong) may increase serum concentration of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CYP3A4 Inhibitors (Strong) may increase adverse/toxic effects of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pacritinib. Risk X: Avoid
Palbociclib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider Therapy Modification
Palovarotene: CYP3A4 Inhibitors (Strong) may increase serum concentration of Palovarotene. Risk X: Avoid
Panobinostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider Therapy Modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Paricalcitol. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider Therapy Modification
Pexidartinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease metabolism of Pimecrolimus. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pirtobrutinib. Management: Avoid concomitant use when possible. If combined, reduce the pirtobrutinib dose by 50 mg. If current dose is 50 mg, interrupt pirtobrutinib treatment during strong CYP3A4 inhibitor use. Risk D: Consider Therapy Modification
Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Risk C: Monitor
PONATinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Pralsetinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider Therapy Modification
Prazepam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Strong) may increase serum concentration of Praziquantel. Risk C: Monitor
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inhibitors (Strong) may increase serum concentration of PredniSONE. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging CYP3A4 Substrates: Posaconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
QuiNIDine: Posaconazole may increase serum concentration of QuiNIDine. Risk X: Avoid
Radotinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Radotinib. Risk X: Avoid
Ramelteon: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ramelteon. Risk C: Monitor
Ranolazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ranolazine. Risk X: Avoid
Reboxetine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Reboxetine. Risk C: Monitor
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk X: Avoid
Regorafenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Regorafenib. Risk X: Avoid
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repaglinide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Repotrectinib. Risk X: Avoid
Retapamulin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor
Revumenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Revumenib. Management: If combined use is required, decrease revumenib dose for patients weighing 40 kg or more to 160 mg orally twice/day; for patients weighing less than 40 kg to 95 mg/m2 twice daily. Risk D: Consider Therapy Modification
Rifabutin: May decrease serum concentration of Posaconazole. Posaconazole may increase serum concentration of Rifabutin. Management: Avoid coadministration of posaconazole and rifabutin if possible. If coadministration cannot be avoided, monitor patients for rifabutin adverse effects (eg, neutropenia, uveitis) and lack of posaconazole efficacy. Risk D: Consider Therapy Modification
RifAMPin: May decrease serum concentration of Posaconazole. Risk C: Monitor
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rilpivirine. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rimegepant. Risk X: Avoid
Riociguat: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Riociguat. Management: Consider a riociguat starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving strong CYP3A4 and P-gp inhibitors. Monitor for hypotension when these agents are combined and reduce the riociguat dose as needed. Risk D: Consider Therapy Modification
Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ripretinib. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ripretinib. Risk C: Monitor
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
Ritonavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ritonavir. Risk C: Monitor
Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Rivaroxaban. Risk X: Avoid
Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase serum concentration of RomiDEPsin. Risk C: Monitor
Rupatadine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rupatadine. Risk X: Avoid
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ruxolitinib (Topical). Risk X: Avoid
Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may decrease therapeutic effects of Saccharomyces boulardii. Risk X: Avoid
Salmeterol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Salmeterol. Risk X: Avoid
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Selpercatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 40 mg twice/day, or from 160 mg twice/day to 80 mg twice/day. Risk D: Consider Therapy Modification
Selumetinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider Therapy Modification
Sertindole: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider Therapy Modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Silodosin. Risk X: Avoid
Simeprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Simvastatin. CYP3A4 Inhibitors (Strong) may increase serum concentration of Simvastatin. Risk X: Avoid
Sirolimus (Conventional): Posaconazole may increase serum concentration of Sirolimus (Conventional). Risk X: Avoid
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Sirolimus (Topical). Risk C: Monitor
Solifenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit doses in pediatric patients to the recommended weight-based starting dose (and do not increase the dose) when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sonidegib. Risk X: Avoid
Sparsentan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sparsentan. Risk X: Avoid
SUFentanil: CYP3A4 Inhibitors (Strong) may increase serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Risk D: Consider Therapy Modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Suvorexant. Risk X: Avoid
Suzetrigine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): Posaconazole may increase serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to approximately one-third of original dose when starting posaconazole. Tacrolimus blood concentrations should be monitored closely beginning within 1 to 3 days of coadministration. Risk D: Consider Therapy Modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Tadalafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D: Consider Therapy Modification
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk X: Avoid
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tasimelteon. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tazemetostat. Risk X: Avoid
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph for details. Risk D: Consider Therapy Modification
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Thiotepa. CYP3A4 Inhibitors (Strong) may increase serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider Therapy Modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ticagrelor. Risk X: Avoid
Tilidine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Tilidine. Risk C: Monitor
Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider Therapy Modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tolvaptan. Risk X: Avoid
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Trabectedin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Trabectedin. Risk X: Avoid
TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Strong) may increase serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Tretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inhibitors when possible. If combined, monitor for increased tretinoin concentrations and toxicities (eg, pseudotumor cerebri, hypercalcemia). Risk D: Consider Therapy Modification
Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Nasal). Risk C: Monitor
Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Triamcinolone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Topical). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Triazolam. Risk X: Avoid
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ubrogepant. Risk X: Avoid
Udenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Udenafil. Risk X: Avoid
Ulipristal: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ulipristal. Risk C: Monitor
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are often needed when combined with strong CYP3A4 inhibitors. Specific adjustments vary based on upadacitinib indication. See full interact monograph for details. Risk D: Consider Therapy Modification
Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vamorolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vamorolone. Management: Reduce the vamorolone dose to 4 mg/kg daily, with a maximum dose of 200 mg daily for patients weighing over 50 kg, when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification
Venetoclax: Posaconazole may increase serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider Therapy Modification
Verapamil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Verapamil. Risk C: Monitor
Vilanterol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vilanterol. Risk C: Monitor
Vilazodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vilazodone. Management: Limit the maximum vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
VinBLAStine: CYP3A4 Inhibitors (Strong) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: CYP3A4 Inhibitors (Strong) may increase serum concentration of VinCRIStine. Risk X: Avoid
Vindesine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Vinflunine. Risk X: Avoid
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vinorelbine. Risk C: Monitor
Vitamin K Antagonists: Posaconazole may increase serum concentration of Vitamin K Antagonists. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Voclosporin. Risk X: Avoid
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vorapaxar. Risk X: Avoid
Zanubrutinib: Posaconazole may increase serum concentration of Zanubrutinib. Management: Reduce the dose of zanubrutinib to 80 mg twice daily during coadministration with posaconazole suspension 100 mg once daily. Reduce the dose of zanubrutinib to 80 mg once daily with higher doses of posaconazole (eg, 300 mg daily). Risk D: Consider Therapy Modification
Ziprasidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ziprasidone. Risk C: Monitor
Zolpidem: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zolpidem. Risk C: Monitor
Zopiclone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider Therapy Modification
Zuranolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zuranolone. Management: Reduce the zuranolone dose to 30 mg once daily when used concomitantly with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
IR oral suspension: Bioavailability increased ~3 times when posaconazole IR oral suspension was administered with a nonfat meal or an oral liquid nutritional supplement; increased ~4 times when administered with a high-fat meal. Management: IR oral suspension must be administered with or within 20 minutes of a full meal, an oral liquid nutritional supplement, or an acidic carbonated beverage (eg, ginger ale). Consider alternative antifungal therapy in patients with inadequate oral intake or severe diarrhea/vomiting.
Delayed-release tablet: Following administration of posaconazole delayed-release tablets, the AUC increased 51% when given with a high-fat meal compared with a fasted state. Management: Take tablet with food when possible but may be taken with or without food. Consider alternative antifungal therapy in patients with severe diarrhea/vomiting.
Adverse events have been observed in animal reproduction studies.
It is not known if posaconazole is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Delayed-release tablets: Take with food when possible but may be taken with or without food.
Delayed-release oral suspension: Take with food.
IR oral suspension: Give during or within 20 minutes following a full meal, liquid nutritional supplement, or an acidic carbonated beverage (eg, ginger ale).
Consider alternative antifungal therapy in patients with inadequate oral intake or severe diarrhea/vomiting; if alternative therapy is not an option, closely monitoring for breakthrough fungal infections.
Adequate posaconazole absorption from GI tract and subsequent plasma concentrations are dependent on food for efficacy. Lower average plasma concentrations have been associated with an increased risk of treatment failure.
Hepatic function (eg, AST/ALT, alkaline phosphatase and bilirubin) prior to initiation and during treatment; renal function, especially in patients on IV therapy if eGFR <50 mL/minute/1.73 m2; serum electrolytes (eg, calcium, magnesium, potassium) prior to initiation and during therapy; CBC; blood pressure; breakthrough fungal infections; adequate oral intake.
Evidence to support therapeutic drug monitoring for posaconazole is limited; however, due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions with posaconazole, therapeutic drug monitoring is advised, especially for patients receiving posaconazole IR oral suspension (BSMM [Ashbee 2014]; Dekkers 2016; IDSA [Patterson 2016]; McCreary 2023; MSG-ERC [Johnson 2020]).
Adult:
Timing of concentrations: Obtain trough after steady state has been reached (typically ≥5 to 7 days after therapy initiation [5 days with a loading dose and 7 days without a loading dose] or dosage change); the need for continued or repeat monitoring is a patient specific decision influenced by many factors (eg, infection severity, cost, assay availability) (BSMM [Ashbee 2014]; Dekkers 2016; Dolton 2012; IDSA [Patterson 2016], McCreary 2023).
Target trough concentrations: Target trough may need to be adjusted to achieve goal AUC24/minimum inhibitory concentration (MIC) depending on MIC of pathogen (Dekkers 2016):
Efficacy:
Prophylaxis: ≥0.5 to 0.7 mg/L (BSMM [Ashbee 2014]; Cattaneo 2015; Dekkers 2016; Dolton 2012; Lebeaux 2009; McCreary 2023; Shields 2011).
Treatment: ≥1 to 1.5 mg/L (AST-IDCOP [Husain 2019]; BSMM [Ashbee]; Dolton 2012; McCreary 2023; Walsh 2007).
Toxicity: >3 to 3.75 mg/L (McCreary 2023).
Interferes with fungal cytochrome P450 (lanosterol-14α-demethylase) activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting fungal cell membrane formation.
Absorption:
IR oral suspension: Unpredictable and variable (optimal absorption with a high-fat meal in 4 divided doses; absorption may be sufficient if taken with a nutritional supplement or acidic beverage [eg, ginger ale]).
Delayed-release tablet: AUC increased 51% when given with a high-fat meal compared with a fasted state.
Distribution: Vd: Oral: 287 L; Injection: ~261 L.
Protein binding: >98%; predominantly bound to albumin.
Metabolism: Not significantly metabolized; 17% undergoes non-CYP-mediated metabolism, primarily via hepatic glucuronidation into metabolites.
Bioavailability: Oral: Delayed-release tablet, delayed-release suspension, and IR suspension are not bioequivalent.
Delayed-release suspension: ~70% to 80%.
IR suspension: Dependent upon gastric pH environment (decreased with higher pH or increased motility) and fed-conditions (increased in high-fat environment).
Delayed-release tablet: Dependent upon fed condition: Fasted conditions: 54%; higher under high-fat fed conditions (51% increase in AUC).
Half-life elimination: IR oral suspension: 35 hours (range: 20 to 66 hours); Tablet: 26 to 31 hours; Injection: ~27 hours.
Time to peak, plasma:
Pediatric patients:
Immediate-release oral suspension: Day 1 of therapy:
Children 2 to <7 years: Median range: 3.99 to 7.95 hours (range: 2.92 to 11.6 hours) (Arrieta 2019).
Children ≥7 years and Adolescents: Median range: 3.12 to 5 hours (range: 2.92 to 8.08 hours) (Arrieta 2019).
Delayed-release oral suspension: Neutropenic patients: Steady state:
Children 2 to <7 years: Median: 4 hours (range: 2.17 to 7.92 hours).
Children ≥7 years and Adolescents <18 years: Median: 2.78 hours (range: 0 to 4 hours).
IV: Neutropenic patients: Steady state:
Children 2 to <7 years: Median: 1.75 hours (range: 1.57 to 1.83 hours).
Children ≥7 years and Adolescents <18 years: Median: 1.77 hours (range: 1.33 to 6 hours).
Adults: IR oral suspension: ~3 to 5 hours; Tablet: ~4 to 5 hours.
Excretion: Feces 71% (~66% of the total dose as unchanged drug); urine 13% (<0.2% of the total dose as unchanged drug).
Pediatric: Significant interpatient variability in serum concentrations has been observed, particularly with the use of immediate-release oral suspension; it may be difficult to attain pharmacokinetic targets in children (Arrieta 2019; Döring 2017a; Gwee 2015).
Patients with obesity: Exposure is decreased (~30% to 40%) in patients with obesity, likely due to increased volume of distribution and increased clearance (Chen 2020; Greenblatt 2018; Miceli 2015; Wasmann 2020).
