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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Posaconazole: Drug information

Posaconazole: Drug information
(For additional information see "Posaconazole: Patient drug information" and see "Posaconazole: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Noxafil
Brand Names: Canada
  • GLN-Posaconazole;
  • JAMP-Posaconazole;
  • Posanol;
  • Sandoz Posaconazole
Pharmacologic Category
  • Antifungal Agent, Azole Derivative;
  • Antifungal Agent, Oral
Dosing: Adult

Dosage guidance:

Dosing: Adjust dose based on trough serum concentration to ensure efficacy and avoid toxicity. Timing and frequency of concentration monitoring is individualized (AST-IDCOP [Aslam 2019]; Dekkers 2016; IDSA [Patterson 2016]).

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 (AST-IDCOP [Husain 2019]; Cumpston 2015; Durani 2015; ECMM/MSG-ERC [Cornely 2019]; Jung 2014; Leclerc 2018). The IV formulation is given at the same dose as the delayed-release tablet.

Aspergillosis

Aspergillosis:

Chronic cavitary pulmonary (alternative agent):

Oral: Note: Some experts prefer the tablet over the IR suspension (Kauffman 2020).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (IDSA [Patterson 2016]).

IR suspension (off-label use): 200 mg 3 times daily (IDSA [Patterson 2016]) or 400 mg twice daily (Felton 2010).

IV: 300 mg twice daily for 2 doses, then 300 mg once daily (IDSA [Patterson 2016]). Note: Some experts reserve IV therapy for severely ill patients (Kauffman 2020).

Duration: ≥6 months; some patients require prolonged, potentially lifelong therapy (Kauffman 2020; IDSA [Patterson 2016]).

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 (AST-IDCOP [Husain 2019]; Patterson 2022).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (AST-IDCOP [Husain 2019]; IDSA [Patterson 2016]; Maertens 2021).

IR suspension (off-label use): 200 mg 3 times daily (AST-IDCOP [Husain 2019]; IDSA [Patterson 2016]) or 200 mg 4 times daily during hospitalization, then 400 mg twice daily as an outpatient (IDSA [Tunkel 2017]; Walsh 2007).

IV: 300 mg twice daily for 2 doses, then 300 mg once daily (AST-IDCOP [Husain 2019]; IDSA [Patterson 2016]; Maertens 2021).

Duration: Minimum of 6 to 12 weeks; total duration depends on degree/duration of immunosuppression, disease site, and response to therapy (IDSA [Patterson 2016]); immunosuppressed patients may require more prolonged treatment (AST-IDCOP [Husain 2019]; Patterson 2022).

Candidiasis

Candidiasis: Note: Generally reserved for fluconazole-refractory disease or as an alternative initial agent for patients with HIV or solid organ transplantation (AST-IDCOP [Aslam 2019]; HHS [OI adult] 2020; IDSA [Pappas 2016]).

Esophageal, fluconazole-refractory disease (alternative agent) (off-label use): Oral:

Delayed-release tablet: 300 mg once daily (IDSA [Pappas 2016]).

IR suspension: 400 mg twice daily (IDSA [Pappas 2016]).

Duration: 14 to 28 days (HHS [OI adult] 2020; IDSA [Pappas 2016]; Skiest 2007).

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 (AST-IDCOP [Aslam 2019]; HHS [OI adult] 2020).

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 (AST-IDCOP [Aslam 2019]; HHS [OI adult] 2020; IDSA [Pappas 2016]; Skiest 2007).

Coccidioidomycosis, refractory to conventional therapy

Coccidioidomycosis, refractory to conventional therapy (alternative agent) (off-label use): Note: Initial parenteral antifungal therapy may be warranted (HHS [OI adult] 2020; IDSA [Galgiani 2016]).

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 (HHS [OI adult] 2020).

IR suspension: 400 mg twice daily or 200 mg 3 times daily (Anstead 2005; HHS [OI adult] 2020; Stevens 2007).

Duration: Varies by site and severity of infection, as well as patient immune status (HHS [OI adult] 2020; IDSA [Galgiani 2016]).

Meningitis: Oral:

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (HHS [OI adult] 2020).

IR suspension: 200 mg 4 times daily or 400 mg twice daily (HHS [OI adult] 2020; IDSA [Galgiani 2016]; Pitisuttithum 2005).

Duration: Lifelong because of the high relapse rate (HHS [OI adult] 2020; IDSA [Galgiani 2016]).

Mucormycosis, salvage and step-down therapy

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 (ECMM/MSG-ERC [Cornely 2019]).

Oral: Note: Tablet preferred to IR suspension (ECMM/MSG-ERC [Cornely 2019]); some experts do not use IR suspension for mucormycosis because of suboptimal bioavailability (Cox 2021).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (ECMM/MSG-ERC [Cornely 2019]).

IR suspension: 200 mg 4 times daily or 400 mg twice daily (ECMM/MSG-ERC [Cornely 2019]; Greenberg 2006; van Burik 2006).

IV: 300 mg twice daily for 2 doses, then 300 mg once daily (ECMM/MSG-ERC [Cornely 2019]).

Duration: Varies based on clinical and radiologic response and patient immune status; several months are often warranted, with some patients requiring lifelong therapy (ECMM/MSG-ERC [Cornely 2019]).

Prophylaxis against invasive fungal infections

Prophylaxis against invasive fungal infections:

Hematology malignancy or hematopoietic cell transplant:

Oral: Note: Tablet preferred to IR suspension (Wingard 2022a; Wingard 2021).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily.

IR suspension: 200 mg 3 times daily (Cornely 2007; Ullmann 2007).

IV: 300 mg twice daily for 2 doses, then 300 mg once daily.

Duration: Varies based on degree and duration of immunosuppression (ASBMT [Tomblyn 2009]; Cornely 2007; IDSA [Patterson 2016]; IDSA [Taplitz 2018]; Ullmann 2007).

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 (AST-IDCOP [Husain 2019]; Jeong 2018; Launay 2018).

IR suspension: 200 mg every 8 hours or 400 mg every 12 hours (Jeong 2018; Stelzer 2018).

Duration: Varies by patient risk factors and transplant center protocol (AST-IDCOP [Husain 2019]; Fishman 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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 (Krieter 2004; manufacturer's labeling). 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) (Hoover 2018). 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 (Kim 2016; Lilly 2013; Neofytos 2012; Oude Lashof 2012). When IV therapy is indicated, the benefits may outweigh the risks (Chen 2020). 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 (Courtney 2005; manufacturer's labeling).

eGFR <50 mL/minute/1.73 m2:

Oral: No dosage adjustment necessary (Courtney 2005; Hachem 2008; manufacturer's labeling).

IV: No dosage adjustment necessary (Courtney 2005; Hachem 2008). 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 (Bilbao-Meseguer 2018; Udy 2010).

Oral, IV: No dosage adjustment required (Sime 2018; expert opinion).

Hemodialysis, intermittent (thrice weekly): Not dialyzable (Courtney 2005; manufacturer's labeling):

Oral: No dosage adjustment necessary (Courtney 2005; Sedlacek 2008; manufacturer's labeling).

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%]) (expert opinion):

Oral: No dosage adjustment necessary (expert opinion).

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 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 (expert opinion).

IV: No dosage adjustment necessary. The excipient cyclodextrin (SBECD) in the IV formulation is effectively removed by CRRT (Morris 2015; expert opinion).

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 (expert opinion).

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.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(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

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

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 (IDSA [Patterson 2016]).

Oral: Adolescents:

Delayed-release tablets (preferred): Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily (manufacturer's labeling).

Immediate-release suspension: Limited data available: Oral: 200 mg 3 times daily or 400 mg twice daily (AST-IDCOP [Husain 2019]).

IV: Adolescents: 300 mg twice daily for 2 doses, followed by 300 mg once daily (manufacturer's labeling).

Candidiasis, oropharyngeal; treatment

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 (HHS [OI adult 2021]).

Refractory infection: Immediate-release suspension: Oral: 400 mg twice daily for 28 days (HHS [OI adult 2021]).

Candidiasis, esophageal, treatment

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 (HHS [OI adult 2021]).

Candidiasis, invasive; prophylaxis

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

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 (HHS [OI adult 2021]).

Delayed-release tablets: Oral: 300 mg twice daily for 2 doses, followed by 300 mg once daily (HHS [OI adult 2021]).

Invasive fungal infection, prophylaxis in neutropenic patients

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 (Arrieta 2019; Vicenzi 2018). 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 (Döring 2017b).

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 (Arrieta 2019; Döring 2012; Döring 2015; Döring 2017a; Döring 2017b; Vicenzi 2018).

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 (Döring 2017b).

Immediate-release suspension: Adolescents: Oral: 200 mg/dose 3 times daily (Science 2014).

Invasive fungal infection, treatment

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 (Arrieta 2019; Vicenzi 2018).

Immediate-release suspension:

Infants ≥5 months and Children (Bernardo 2013): 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 (Bernardo 2013); in other trials, the reported daily doses varied from 4.8 to 33.3 mg/kg/day (Lehrnbecher 2010; McMahon 2017; Vicenzi 2018).

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 (Nickless 2019). 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 (Strommen 2018). Posaconazole was well-tolerated, with reports of mild liver function test elevation and 1 patient with hypokalemia (Nickless 2019; Strommen 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypertension (8% to 20%), hypotension (oral: 14%), lower extremity edema (oral: 15%), peripheral edema (11% to 16%), tachycardia (oral: 12%), thrombophlebitis (IV via peripheral venous catheter: 60%)

Dermatologic: Pruritus (11% to 22%), skin rash (3% to 24%)

Endocrine & metabolic: Dehydration (oral: 1% to 11%), hyperglycemia (oral: 11%), hypokalemia (14% to 30%), hypomagnesemia (10% to 18%), weight loss (oral: 1% to 14%)

Gastrointestinal: Abdominal pain (5% to 27%), anorexia (oral: 2% to 19%), constipation (8% to 21%), decreased appetite (10% to 15%), diarrhea (10% to 42%), nausea (9% to 38%), oral candidiasis (oral: 1% to 12%), stomatitis (11% to 20%), upper abdominal pain (6% to 11%), vomiting (7% to 29%)

Hematologic & oncologic: Anemia (2% to 25%), febrile neutropenia (15% to 31%), neutropenia (oral: 4% to 23%; severe neutropenia: 10%), petechia (8% to 11%), thrombocytopenia (7% to 29%)

Hepatic: Increased serum alanine aminotransferase (3% to 17%), increased serum alkaline phosphatase (1% to 13%), increased serum aspartate aminotransferase (3% to 17%)

Infection: Herpes simplex infection (oral: 3% to 11%)

Nervous system: Chills (10% to 16%), dizziness (oral: 11%), fatigue (3% to 17%), headache (8% to 28%), insomnia (oral: 1% to 17%), pain (oral: 1% to 11%), rigors (oral: ≤20%)

Neuromuscular & skeletal: Arthralgia (oral: 11%), asthenia (oral: 2% to 13%), musculoskeletal pain (oral: 16%)

Respiratory: Cough (3% to 25%), dyspnea (1% to 20%), epistaxis (11% to 17%), pharyngitis (oral: 12%), pneumonia (3% to 13%)

Miscellaneous: Fever (6% to 45%), inflammation (mucosal: 14% to 28%)

1% to 10%:

Cardiovascular: Edema (oral: 9%), pulmonary embolism (<5%), torsades de pointes (<5%)

Dermatologic: Diaphoresis (oral: 2%)

Endocrine & metabolic: Adrenocortical insufficiency (<5%), hypocalcemia (oral: 9%)

Gastrointestinal: Dyspepsia (oral: 10%), pancreatitis (<5%)

Genitourinary: Vaginal hemorrhage (oral: 10%)

Hematologic & oncologic: Hemolytic-uremic syndrome (<5%), thrombotic thrombocytopenic purpura (<5%)

Hepatic: Hepatic insufficiency (<5%), hepatitis (<5%), hepatomegaly (<5%), increased liver enzymes (<5%), increased serum bilirubin (3% to 10%), jaundice (<5%)

Hypersensitivity: Hypersensitivity reaction (<5%)

Nervous system: Paresthesia (<5%)

Neuromuscular & skeletal: Back pain (oral: 10%)

Renal: Acute kidney injury (<5%)

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG, septic shock

Respiratory: Pulmonary aspergillosis, respiratory failure, respiratory insufficiency

Postmarketing:

Endocrine & metabolic: Pseudoaldosteronism

Gastrointestinal: Cholestasis, hepatic failure

Contraindications

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.

Warnings/Precautions

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.

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral:

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:

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

Generic Equivalent Available: US

May be product dependent

Pricing: US

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): $74.01 - $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.

Dosage Forms: Canada

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:

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

Administration: Adult

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. However, several case series have reported successful administration of crushed delayed-release tablets via enteral feeding tubes. If tablets are crushed, monitor serum concentrations to ensure absorption; dosage adjustments may be required (Dieringer 2022; Manesh 2022; Mason 2019; Stevens 2023). One study used the following method for preparation: crush tablet into a fine powder, dilute with 30 mL purified water, administer immediately, and flush tube with an additional 10 mL purified water. Administer separately from feeding formula (Manesh 2022).

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.

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.

Administration: Pediatric

Oral: Note: The immediate-release oral suspension, delayed-release oral suspension, and delayed-release tablets are not interchangeable.

Delayed-release suspension: 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 syringe.

Dose >3 mL: Use provided blue 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.

Immediate-release suspension: 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. 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. Note: Nasogastric administration results in decreased absorption; monitor patient closely if this route is used (McMahon 2017; manufacturer's labeling).

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; do not divide, crush, or chew. However, several case series in pediatric and adult patients have reported successful administration of crushed delayed-release tablets via enteral feeding tubes. If tablets are crushed, monitor serum concentrations to ensure absorption; dosage adjustments may be required (Bio 2024; Dieringer 2022; Manesh 2022; Mason 2019; Stevens 2023).

Administration via feeding tube: Intragastric (eg, nasogastric tube) or post-pyloric placement (eg, nasoduodenal tube): Crush tablet into a fine powder and dilute in water. 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 (Bio 2024). In an adult case series, crushed tablets were diluted with 30 mL purified water and administered immediately, and the tube was flushed with an additional 10 mL purified water (Manesh 2022). Flush feeding tube with an appropriate volume of water before and after administration (Boullata 2019; Pickering 2015); hold enteral nutrition during drug administration; restart enteral nutrition following flush (Boullata 2019; Manesh 2022; Pickering 2015).

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.

Use: Labeled Indications

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).

Use: Off-Label: Adult

Aspergillosis, chronic cavitary pulmonary; Aspergillosis, invasive (including disseminated and extrapulmonary); Candidiasis, esophageal, fluconazole-refractory disease; Coccidioidomycosis, refractory to conventional therapy; Mucormycosis, salvage and step-down therapy; Prophylaxis against invasive fungal infections, solid organ transplant recipients

Medication Safety Issues
Sound-alike/look-alike issues:

Noxafil may be confused with minoxidil

Posaconazole may be confused with itraconazole

International issues:

Noxafil [US and multiple international markets] may be confused with Noxidil brand name for minoxidil [Thailand]

Preparation issues:

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.

Metabolism/Transport Effects

Substrate of UGT1A4; Inhibits CYP3A4 (strong), P-glycoprotein/ABCB1

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Acalabrutinib. Risk X: Avoid combination

Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the 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 the serum concentration of Posaconazole. Risk X: Avoid combination

ALfentanil: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Alfuzosin. Risk X: Avoid combination

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Alosetron. Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Risk X: Avoid combination

AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy

Apalutamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apalutamide. Risk C: Monitor therapy

Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the 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 the serum concentration of Aprepitant. Risk X: Avoid combination

ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the 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

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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

Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Asciminib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asciminib. Risk C: Monitor therapy

Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Risk X: Avoid combination

Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination

Atazanavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy

Atogepant: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Atorvastatin. Risk X: Avoid combination

Avacopan: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Avanafil. Risk X: Avoid combination

Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. Risk X: Avoid combination

Axitinib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Barnidipine. Risk X: Avoid combination

Beclomethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Beclomethasone (Systemic). Risk C: Monitor therapy

Benidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benidipine. Risk C: Monitor therapy

Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Risk C: Monitor therapy

Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Nasal). Risk C: Monitor therapy

Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor therapy

Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy

Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Topical). Risk C: Monitor therapy

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination

Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Risk X: Avoid combination

Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy

Bosentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Risk C: Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Risk X: Avoid combination

Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy

Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the 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 the serum concentration of Bromperidol. Risk C: Monitor therapy

Brotizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brotizolam. Risk C: Monitor therapy

Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Budesonide (Topical). Risk X: Avoid combination

Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy

BusPIRone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Butorphanol. Risk C: Monitor therapy

Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Calcifediol. Risk C: Monitor therapy

Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy

Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy

Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

Capivasertib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Capmatinib. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of CarBAMazepine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Cariprazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Decrease cariprazine dose 50% (4.5 mg to 1.5 mg or 3 mg; 1.5 mg to 1.5 mg every other day) if starting a strong CYP3A4 inhibitor. If on a strong CYP3A4 inhibitor, start cariprazine at 1.5 mg day 1, 0 mg day 2, then 1.5 mg daily. May increase to 3 mg daily Risk D: Consider therapy modification

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy

ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy

Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Risk C: Monitor therapy

Cilnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilnidipine. Risk C: Monitor therapy

Cilostazol: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Cinacalcet. Risk C: Monitor therapy

Cisapride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cisapride. Risk X: Avoid combination

Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy

ClonazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ClonazePAM. Risk C: Monitor therapy

CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Cobicistat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobicistat. Risk C: Monitor therapy

Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Risk X: Avoid combination

Codeine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy

Colchicine: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Conivaptan. Risk X: Avoid combination

Copanlisib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Cortisone. Risk C: Monitor therapy

CycloSPORINE (Systemic): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of CycloSPORINE (Systemic). Fluconazole and isavuconazonium considerations are addressed in separate monographs. 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 the serum concentration of Cyproterone. Risk C: Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Dapoxetine. Risk X: Avoid combination

Daridorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daridorexant. Risk X: Avoid combination

Darifenacin: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Darolutamide. Risk C: Monitor therapy

Darunavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Darunavir. Risk C: Monitor therapy

Deflazacort: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy

DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy

DiazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Dichlorphenamide: Antifungal Agents (Azole Derivatives, Systemic) may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. Risk C: Monitor therapy

Digoxin: Posaconazole may increase the serum concentration of Digoxin. Risk C: Monitor therapy

DilTIAZem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy

DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Domperidone. Risk X: Avoid combination

Doxazosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Doxazosin. Risk C: Monitor therapy

Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

DroNABinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DroNABinol. Risk C: Monitor therapy

Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination

Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy

Duvelisib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Dydrogesterone. Risk C: Monitor therapy

Ebastine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ebastine. Risk C: Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy

Efavirenz: May decrease the serum concentration of Posaconazole. Risk X: Avoid combination

Efonidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Efonidipine. Risk C: Monitor therapy

Elacestrant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elacestrant. Risk X: Avoid combination

Elagolix: CYP3A4 Inhibitors (Strong) may increase the 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

Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease the serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid combination

Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Eletriptan. Risk X: Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy

Enzalutamide: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy

Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination

Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Erlotinib: CYP3A4 Inhibitors (Strong) may increase the 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

Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Etizolam. Risk C: Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

Etravirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etravirine. Risk C: Monitor therapy

Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Everolimus. Risk X: Avoid combination

Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Risk C: Monitor therapy

Fedratinib: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the 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 serum concentrations of the active metabolite(s) 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 serum concentrations of the active metabolite(s) 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 the serum concentration of Finerenone. Risk X: Avoid combination

Flibanserin: CYP3A4 Inhibitors (Strong) may increase the 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 combination

Flucloxacillin: May decrease the serum concentration of Posaconazole. Risk C: Monitor therapy

Flunitrazepam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flunitrazepam. Risk C: Monitor therapy

Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk X: Avoid combination

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Fluticasone (Topical). Risk C: Monitor therapy

Fosamprenavir: Posaconazole may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Posaconazole. Risk C: Monitor therapy

Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination

Fosphenytoin-Phenytoin: May decrease the 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 serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy

Futibatinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Futibatinib. Risk X: Avoid combination

Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy

Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy

Gepirone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gepirone. Risk X: Avoid combination

Glasdegib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

GlipiZIDE: Posaconazole may enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Halofantrine. Risk X: Avoid combination

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Posaconazole. Risk C: Monitor therapy

Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy

Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the 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 decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Risk C: Monitor therapy

Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Risk C: Monitor therapy

Indinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Indinavir. Risk C: Monitor therapy

Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the 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 serum concentrations of the active metabolite(s) 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 serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid combination

Isradipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Isradipine. Risk C: Monitor therapy

Istradefylline: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Itraconazole. Risk C: Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Risk X: Avoid combination

Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the 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

Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Ketamine. Risk C: Monitor therapy

Ketoconazole (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy

Lacidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacidipine. Risk C: Monitor therapy

Lapatinib: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid combination

Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. Risk X: Avoid combination

Leniolisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leniolisib. Risk X: Avoid combination

Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Risk X: Avoid combination

Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy

Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy

Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy

Levoketoconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levoketoconazole. Risk X: Avoid combination

Levomethadone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomethadone. Risk C: Monitor therapy

Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Risk X: Avoid combination

Lonafarnib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination

Lopinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lopinavir. Risk C: Monitor therapy

Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the 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 serum concentrations of the active metabolite(s) of Lovastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of Posaconazole. Management: Concurrent use of lumacaftor/ivacaftor and posaconazole is not recommended. Consider an alternative antifungal such as fluconazole if appropriate. If this combination cannot be avoided, monitor patients for decreased posaconazole efficacy. Risk D: Consider therapy modification

Lumateperone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Lurasidone. Risk X: Avoid combination

Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Macitentan. Risk X: Avoid combination

Manidipine: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Mavacamten. Risk X: Avoid combination

Mefloquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mefloquine. Risk C: Monitor therapy

Meperidine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. Risk C: Monitor therapy

MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy

Metoclopramide: May decrease the serum concentration of Posaconazole. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the 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 the serum concentration of Mirtazapine. Risk C: Monitor therapy

Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor therapy

Mitapivat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mitapivat. Risk X: Avoid combination

Mizolastine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Mizolastine. Risk X: Avoid combination

Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Nasal). Risk C: Monitor therapy

Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy

Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Topical). Risk C: Monitor therapy

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy

Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy

Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Risk X: Avoid combination

Nelfinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nelfinavir. Risk C: Monitor therapy

Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Risk X: Avoid combination

NiCARdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiCARdipine. Risk C: Monitor therapy

NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Nilvadipine. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Risk X: Avoid combination

Nintedanib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Nintedanib. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor therapy

Nirogacestat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nirogacestat. Risk X: Avoid combination

Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination

Nitrendipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy

Olaparib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

Omaveloxolone: CYP3A4 Inhibitors (Strong) may increase the 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

Orelabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination

Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Ospemifene. Risk C: Monitor therapy

OxyBUTYnin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyBUTYnin. Risk C: Monitor therapy

OxyCODONE: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy

PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

Pacritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pacritinib. Risk X: Avoid combination

Palbociclib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Palovarotene. Risk X: Avoid combination

Panobinostat: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor therapy

Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pemigatinib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced. For the 125 mg capsules: 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 the 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 the metabolism of Pimecrolimus. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Piperaquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy

Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Risk C: Monitor therapy

PONATinib: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Prazepam. Risk C: Monitor therapy

Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy

PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy

PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Risk C: Monitor therapy

QT-prolonging CYP3A4 Substrates: Posaconazole may increase the 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 combination

QuiNIDine: Posaconazole may increase the serum concentration of QuiNIDine. Risk X: Avoid combination

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy

Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Risk X: Avoid combination

Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy

Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination

Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Risk C: Monitor therapy

Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk X: Avoid combination

Regorafenib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the 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

Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the 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 therapy

Rifabutin: May decrease the serum concentration of Posaconazole. Posaconazole may increase the 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 the serum concentration of Posaconazole. Risk C: Monitor therapy

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy

Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Risk C: Monitor therapy

Rimegepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rimegepant. Risk X: Avoid combination

Riociguat: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the 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 concentrations of the active metabolite(s) of Ripretinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib. Risk C: Monitor therapy

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

Ritonavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ritonavir. Risk C: Monitor therapy

Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination

Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy

RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. Risk X: Avoid combination

Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Ruxolitinib (Topical). Risk X: Avoid combination

Saccharomyces boulardii: Antifungal Agents (Systemic and Oral [Non-Absorbable]) may diminish the therapeutic effect of Saccharomyces boulardii. Risk X: Avoid combination

Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination

SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the 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 the serum concentration of Sertindole. Risk X: Avoid combination

Sibutramine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. Risk C: Monitor therapy

Sildenafil: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Silodosin. Risk X: Avoid combination

Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Risk X: Avoid combination

Simvastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination

Sirolimus (Conventional): Posaconazole may increase the serum concentration of Sirolimus (Conventional). Risk X: Avoid combination

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Topical). Risk C: Monitor therapy

Solifenacin: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Sonidegib. Risk X: Avoid combination

Sparsentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sparsentan. Risk X: Avoid combination

SUFentanil: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Suvorexant. Risk X: Avoid combination

Tacrolimus (Systemic): Posaconazole may increase the 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 the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy

Tadalafil: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Talazoparib. Risk C: Monitor therapy

Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination

Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy

Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. Risk X: Avoid combination

Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy

Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) 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 the serum concentration of Teniposide. Risk C: Monitor therapy

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Risk X: Avoid combination

Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the 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 serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the 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 serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination

Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy

Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Tolvaptan. Risk X: Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Risk X: Avoid combination

TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of TraMADol. CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

TraZODone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Tretinoin (Systemic). Risk C: Monitor therapy

Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Nasal). Risk C: Monitor therapy

Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor therapy

Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of Triamcinolone (Topical). Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Risk X: Avoid combination

Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. Risk X: Avoid combination

Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Risk X: Avoid combination

Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy

Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are 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 concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Strong) may increase the serum concentration 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 the 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

Vardenafil: CYP3A4 Inhibitors (Strong) may increase the 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 the 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 the serum concentration of Verapamil. Risk C: Monitor therapy

Vilanterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilanterol. Risk C: Monitor therapy

Vilazodone: CYP3A4 Inhibitors (Strong) may increase the 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 the serum concentration of VinBLAStine. Risk C: Monitor therapy

VinCRIStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Risk C: Monitor therapy

Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Risk X: Avoid combination

Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Posaconazole may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy

Voclosporin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voclosporin. Risk X: Avoid combination

Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Risk X: Avoid combination

Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification

Ziprasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ziprasidone. Risk C: Monitor therapy

Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Zopiclone: CYP3A4 Inhibitors (Strong) may increase the 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 the 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

Food Interactions

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.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Breastfeeding Considerations

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.

Dietary Considerations

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.

Monitoring Parameters

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; 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]).

Reference Range

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).

Mechanism of Action

Interferes with fungal cytochrome P450 (lanosterol-14α-demethylase) activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting fungal cell membrane formation.

Pharmacokinetics (Adult Data Unless Noted)

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).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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; Red Book [AAP 2021]).

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).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Noxafil;
  • (AR) Argentina: Noxafil;
  • (AT) Austria: Noxafil | Posaconazol accord | Posaconazol ahcl | Posaconazol ratiopharm | Posaconazole stada;
  • (AU) Australia: Noxafil | Posaconazole ARX | Posaconazole juno | Posaconazole Sandoz;
  • (BE) Belgium: Noxafil | Posaconazol accord | Posaconazol sandoz | Posaconazole teva;
  • (BG) Bulgaria: Noxafil;
  • (BR) Brazil: Noxafil;
  • (CH) Switzerland: Noxafil | Posaconazol accord | Posaconazol mylan | Posaconazol sandoz | Posaconazol zentiva;
  • (CL) Chile: Noxafil;
  • (CN) China: Noxafil;
  • (CO) Colombia: Noxafil | Posiole;
  • (CZ) Czech Republic: Gudivin | Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole Sandoz | Posaconazole teva pharma | Posaconazole zentiva;
  • (DE) Germany: Noxafil | Posaconazol accord | Posaconazol al | Posaconazol beta | Posaconazol heumann | Posaconazol hexal | Posaconazol ratiopharm | Posaconazol stada | Posaconazol zentiva;
  • (DO) Dominican Republic: Noxafil;
  • (EE) Estonia: Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole stada;
  • (EG) Egypt: Noxafil;
  • (ES) Spain: Noxafil | Posaconazol Abdi | Posaconazol accord | Posaconazol ahcl | Posaconazol Fresenius Kabi | Posaconazol glenmark | Posaconazol stada;
  • (FI) Finland: Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole stada;
  • (FR) France: Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole eg | Posaconazole fresenius kabi | Posaconazole mylan | Posaconazole ohre pharma | Posaconazole zentiva;
  • (GB) United Kingdom: Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole mylan | Posaconazole Sandoz | Posaconazole stada | Posaconazole teva | Posaconazole thornton & Ross | Posaconazole zentiva;
  • (GR) Greece: Noxafil;
  • (HK) Hong Kong: Noxafil;
  • (HR) Croatia: Noxafil;
  • (HU) Hungary: Noxafil | Posaconazol teva | Posaconazole accord | Posaconazole ahcl;
  • (IE) Ireland: Noxafil | Posaconazole accord | Posaconazole clonmel | Posaconazole mylan | Posaconazole teva;
  • (IN) India: Candipoz | Candipoz gr | Critposa | Noxafil | Picasa | Picasa gr | Pocaaz | Posaforce | Posafung | Posafung gr | Posahit | Posanat | Posaone | Posarul | Posatral | Poshope | Poshope dr | Posocon | Posoxil | Posoxil gr | Xacyl;
  • (IT) Italy: Noxafil | Posaconazolo accord | Posaconazolo eg | Posaconazolo fresenius kabi | Posaconazolo mylan | Posaconazolo mylan pharma | Posaconazolo sandoz | Posaconazolo teva | Posaconazolo tillomed | Posaconazolo zentiva;
  • (KE) Kenya: Noxafil;
  • (KR) Korea, Republic of: Noxafil;
  • (KW) Kuwait: Noxafil;
  • (LB) Lebanon: Noxafil;
  • (LT) Lithuania: Noxafil | Posaconazol al | Posaconazol glenmark | Posaconazol hexal | Posaconazol zentiva | Posaconazole stada;
  • (LU) Luxembourg: Posaconazol accord;
  • (LV) Latvia: Noxafil | Posaconazole accord | Posaconazole ahcl;
  • (MX) Mexico: Spriafil;
  • (MY) Malaysia: Noxafil;
  • (NL) Netherlands: Noxafil | Posaconazol biocon | Posaconazol cf | Posaconazol fresenius | Posaconazol glenmark | Posaconazol mylan | Posaconazol sandoz | Posaconazol tillomed | Posaconazole accord | Posaconazole ahcl | Posaconazole teva;
  • (NO) Norway: Noxafil | Posaconazole accord | Posaconazole ahcl | Posaconazole mylan;
  • (NZ) New Zealand: Noxafil | Posaconazole juno;
  • (PE) Peru: Noxafil;
  • (PH) Philippines: Noxafil;
  • (PL) Poland: Noxafil | Posaconazole ahcl | Posaconazole glenmark | Posaconazole mylan | Posaconazole Sandoz | Posaconazole stada | Posaconazole teva;
  • (PR) Puerto Rico: Noxafil | Posaconazole delayed release;
  • (PT) Portugal: Noxafil | Posaconazol accord | Posaconazol mylan | Posaconazol sandoz | Posaconazol teva | Posaconazole ahcl;
  • (QA) Qatar: Noxafil;
  • (RO) Romania: Gudivin | Noxafil | Posaconazol mylan | Posaconazol stada | Posaconazol zentiva | Posaconazole accord | Posaconazole ahcl;
  • (RU) Russian Federation: Noxafil;
  • (SA) Saudi Arabia: Noxafil;
  • (SE) Sweden: Noxafil | Posaconazole abacus medicine | Posaconazole accord | Posaconazole mylan | Posaconazole Sandoz | Posaconazole stada | Posaconazole teva;
  • (SG) Singapore: Noxafil | Posaconazole Sandoz;
  • (SI) Slovenia: Noxafil | Posakonazol accord | Posakonazol stada | Posakonazol teva;
  • (SK) Slovakia: Noxafil | Posaconazole accord | Posaconazole Sandoz | Posaconazole stada | Posaconazole zentiva | Posakonazol stada | Posakonazol teva;
  • (TH) Thailand: Noxafil;
  • (TR) Turkey: Fugafyl | Noxafil | Posagil;
  • (TW) Taiwan: Posanol;
  • (UA) Ukraine: Noxafil;
  • (UY) Uruguay: Noxafil;
  • (ZA) South Africa: Noxafil
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