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Posaconazole

Medically reviewed by Drugs.com. Last updated on Jul 13, 2020.

Pronunciation

(poe sa KON a zole)

Index Terms

  • SCH 56592

Dosage Forms

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

Solution, Intravenous [preservative free]:

Noxafil: 300 mg/16.7 mL (16.7 mL) [contains edetate disodium]

Suspension, Oral:

Noxafil: 40 mg/mL (105 mL) [contains polysorbate 80, sodium benzoate; cherry flavor]

Tablet Delayed Release, Oral:

Noxafil: 100 mg

Generic: 100 mg

Brand Names: U.S.

  • Noxafil

Pharmacologic Category

  • Antifungal Agent, Oral

Pharmacology

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

Absorption

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]).

Tablet (delayed-release): Predictable (preferably administered with food, but absorption is sufficient under fasting conditions).

Distribution

Vd: Oral: 287 L; Injection: ~261 L

Metabolism

Not significantly metabolized; 17% undergoes non-CYP-mediated metabolism, primarily via hepatic glucuronidation into metabolites

Excretion

Feces 71% (~66% of the total dose as unchanged drug); urine 13% (<0.2% of the total dose as unchanged drug)

Time to Peak

Plasma:

Children 2 to <7 years: Suspension: Day 1 of therapy: Median range: 3.99 to 7.95 hours (range: 2.92 to 11.6 hours) (Arietta 2019).

Children ≥7 years and Adolescents: Suspension: Day 1 of therapy: Median range: 3.12 to 5 hours (range 2.92 to 8.08 hours) (Arietta 2019).

Adults: Suspension: ~3 to 5 hours; Tablets: ~4 to 5 hours.

Half-Life Elimination

Suspension: 35 hours (range: 20 to 66 hours); Tablets: 26 to 31 hours; Injection: ~27 hours

Protein Binding

>98%; predominantly bound to albumin

Special Populations: Children

Pharmacokinetic data in pediatric patients are limited. Significant interpatient variability in serum concentrations has been observed, particularly with the use of oral suspension; it may be difficult to attain pharmacokinetic targets in children (Arietta 2019; Boonsathorn 2019; Döring 2017a; Gwee 2015; Red Book [AAP 2018]).

Use: Labeled Indications

Candidiasis, oropharyngeal: Suspension (patients ≥13 years of age): Treatment of oropharyngeal candidiasis (including patients refractory to itraconazole and/or fluconazole).

Prophylaxis against invasive fungal infections, hematology malignancy patients or hematopoietic cell transplant recipients: Suspension and delayed-release tablets (patients ≥13 years of age) and injection (patients ≥18 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.

Off Label Uses

Aspergillosis, chronic cavitary pulmonary

Data from a small, retrospective study suggest that posaconazole suspension may be beneficial for the treatment of chronic cavitary pulmonary aspergillosis [Felton 2010]

Based on the Infectious Diseases Society of America (IDSA) practice guidelines for the diagnosis and management of aspergillosis, posaconazole is an effective and recommended alternative option in the treatment of chronic cavitary pulmonary aspergillosis [IDSA [Patterson 2016]].

Aspergillosis, invasive (including disseminated and extrapulmonary)

Based on the IDSA practice guidelines for the diagnosis and management of aspergillosis, posaconazole is an effective and recommended therapeutic option for salvage therapy (alone or in combination with another antifungal) in the treatment of invasive aspergillosis [IDSA [Patterson 2016]].

Candidiasis, esophageal, fluconazole-refractory disease

Based on the IDSA clinical practice guideline for the management of candidiasis and the US Department of Health and Human Services (HHS) guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV, posaconazole may be considered as an alternative for patients with esophageal candidiasis refractory to conventional therapy [HHS [OI adult] 2020], [IDSA [Pappas 2016]].

Coccidioidomycosis, refractory to conventional therapy

Based on the IDSA clinical practice guideline for the treatment of coccidioidomycosis and the HHS guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV, posaconazole is an effective and recommended alternative agent in the treatment of coccidioidomycosis in patients who are refractory to conventional therapy [HHS [OI adult] 2020], [IDSA [Galgiani 2016]].

Mucormycosis, salvage and step-down therapy

Data from a limited number of patients studied suggest that posaconazole suspension may be beneficial as salvage therapy for mucormycosis [Greenberg 2006], [van Burik 2006].

Based on the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium global guidelines for the diagnosis and management of mucormycosis, posaconazole is effective and recommended as salvage therapy for mucormycosis, with the delayed-release tablet and IV formulations preferred to the oral suspension [ECMM/MSG-ERC [Cornely 2019]].

Prophylaxis against invasive fungal infections, solid organ transplant recipients

Data from a limited number of patients studied suggest posaconazole may be beneficial as prophylaxis against invasive fungal infections in solid organ transplant recipients [Stelzer 2018].

Based on the American Society of Transplantation Infectious Disease Community of Practice guidelines for invasive aspergillosis in solid-organ transplant recipients, posaconazole delayed-release tablet is an effective and recommended alternative agent for prophylaxis of invasive fungal infections in lung transplant recipients [AST-IDCOP [Husain 2019]].

Contraindications

Coadministration with sirolimus, ergot alkaloids (eg, ergotamine, dihydroergotamine), HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (eg, atorvastatin, lovastatin, simvastatin), or CYP3A4 substrates that prolong the QT interval (eg, pimozide, quinidine); hypersensitivity to posaconazole, other azole antifungal agents, or any component of the formulation.

Dosing: Adult

Note: Formulations: The delayed-release tablet and oral suspension are not interchangeable due to dosing differences for each formulation. The delayed-release tablet is generally preferred to the 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. Therapeutic drug monitoring: 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]).

Aspergillosis:

Chronic cavitary pulmonary (alternative agent) (off-label use):

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

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

Suspension: 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 (Denning 2020).

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

Invasive (including disseminated and extrapulmonary) (alternative agent for patients who are refractory to or intolerant of first-line agents) (off-label use):

Oral: Note: Tablet preferred to suspension (AST-IDCOP [Husain 2019]; Patterson 2020).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (AST-IDCOP [Husain 2019]; IDSA [Patterson 2016]; Patterson 2020).

Suspension: 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]).

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 2020).

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]).

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): 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: 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 (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).

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).

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 (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 suspension (ECMM/MSG-ERC [Cornely 2019]); some experts do not use suspension for mucormycosis because of suboptimal bioavailability (Cox 2020).

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

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:

Hematology malignancy or hematopoietic cell transplant:

Oral: Note: Tablet preferred to suspension (Wingard 2020a; Wingard 2020b).

Delayed-release tablet: 300 mg twice daily for 2 doses, then 300 mg once daily (manufacturer's labeling).

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).

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: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Use caution when selecting dosage form; the delayed-release tablet and oral suspension are not interchangeable.

Aspergillosis, invasive; prophylaxis:

Oral: Adolescents:

Oral delayed-release tablets (preferred): 300 mg twice daily for 1 day, followed by 300 mg once daily; duration is based on recovery from neutropenia or immunosuppression.

Oral suspension: 200 mg 3 times daily; duration of therapy is based on recovery from neutropenia or immunosuppression.

IV: Adolescents ≥18 years: 300 mg twice daily for 1 day, followed by 300 mg once daily starting on day 2. Duration is based on recovery from neutropenia or immunosuppression.

Aspergillosis, invasive; treatment (salvage): Limited data available (AST [Husain 2019]; IDSA [Patterson 2016]): Note: 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:

Oral delayed-release tablets (preferred): 300 mg twice daily for 1 day, followed by 300 mg once daily.

Oral suspension: 200 mg 3 times daily or 400 mg 2 times daily.

IV: Adolescents ≥18 years: 300 mg twice daily for 1 day, followed by 300 mg once daily starting on day 2.

Candidiasis, oropharyngeal; treatment:

Non-HIV-exposed/-infected: Adolescents:

Initial episode: Oral suspension: 100 mg twice daily on day 1, followed by 100 mg once daily for 13 days.

Refractory infection: Oral suspension: 400 mg twice daily; duration of therapy is based on underlying disease and clinical response.

HIV-exposed/-infected: Adolescents:

Initial episode (alternative to fluconazole): Oral suspension: 400 mg twice daily on day 1, followed by 400 mg once daily for 7 to 14 days (HHS [OI adult 2019]).

Refractory infection: Oral suspension: 400 mg twice daily for 28 days (HHS [OI adult 2019]).

Candidiasis, esophageal (azole-refractory); treatment: Adolescents (HIV-infected): Oral 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 2019]).

Candidiasis, invasive; prophylaxis:

Oral: Adolescents:

Oral delayed-release tablets (preferred): 300 mg twice daily for 1 day, followed by 300 mg once daily. Duration is based on recovery from neutropenia or immunosuppression.

Oral suspension: 200 mg 3 times daily; duration of therapy is based on recovery from neutropenia or immunosuppression.

IV: Adolescents ≥18 years: 300 mg twice daily for 1 day, followed by 300 mg once daily starting on day 2. Duration is based on recovery from neutropenia or immunosuppression.

Invasive fungal infection, prophylaxis in neutropenic patients (eg, patients with malignancy or post-hematopoietic stem cell transplant [HSCT]):

Note: Generally considered alternative therapy (Science 2014). 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; Boonsathorn 2019; Vicenzi 2018).

Weight-directed dosing:

Oral 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).

Oral delayed-release tablet: Very limited data available: Children ≥3 years and Adolescents ≤17 years: Oral: 5 to 7 mg/kg/dose twice daily on day 1, followed by 5 to 7 mg/kg/dose daily (Döring 2017b).

Fixed dosing: Limited data available: Note: Dosing for patients ≤12 years based on a population pharmacokinetic model built using 338 posaconazole concentrations from 117 patients; suggested doses result in ~60% of patients attaining a trough posaconazole concentration >0.7 mg/L; diarrhea, receipt of proton pump inhibitors, and suspension versus tablet all resulted in lower likelihood of target attainment (Boonsathorn 2019).

Oral suspension:

Infants ≥6 months and Children ≤6 years: Oral: Initial dosing: 200 mg/dose 3 times daily; monitor trough concentration; for trough concentration <0.7 mg/L, increase dose to 200 mg/dose 4 times daily (Boonsathorn 2019).

Children 7 to 12 years: Oral: Initial dosing: 300 mg/dose 3 times daily; monitor trough concentration; for trough concentration <0.7 mg/L, increase dose to 300 mg/dose 4 times daily (Boonsathorn 2019).

Adolescents: Oral: 200 mg/dose 3 times daily (Science 2014).

Oral delayed-release tablets (preferred if patient able to take tablet):

Children 7 to 12 years: Oral: Initial dosing: 200 mg/dose 3 times daily; monitor trough concentration; for trough concentration <0.7 mg/L, increase dose to 300 mg/dose 3 times daily (Boonsathorn 2019).

Adolescents: Oral: 300 mg/dose twice daily on day 1, followed by 300 mg/dose daily (Döring 2017b).

Note: Duration dependent upon indication for prophylaxis and clinical condition of patient, consult institutional protocols.

Invasive fungal infection, treatment (alternative/salvage):

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; Boonsathorn 2019; Vicenzi 2018).

Weight-directed dosing: Limited data available:

Oral 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 on day 1, 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 one patient with hypokalemia (Nickless 2019; Strommen 2018).

Fixed-dosing (Boonsathorn 2019):

Oral suspension:

Infants ≥6 months and Children <2 years: Oral: Initial dosing: 200 mg/dose 4 times daily; dose adjustments for low trough concentration were not recommended and considered of little value due to saturable absorption.

Children 2 to 6 years: Oral: Initial dosing: 200 mg/dose 4 times daily; monitor trough concentration; for trough concentration <1 mg/L: Consider dose increase to 300 mg/dose 4 times daily.

Children 7 to 12 years: Oral: Initial dosing: 300 mg/dose 4 times daily; monitor trough concentration; for trough concentration <1 mg/L, increase dose to 400 mg/dose 4 times daily.

Oral delayed-release tablets (preferred if patient able to take tablet): Children 7 to 12 years: Oral: Initial dosing: 200 mg/dose 3 times daily; monitor trough concentration; for trough concentration <1 mg/L, increase dose to 200 to 300 mg/dose 4 times daily.

Note: Dosing based on a population pharmacokinetic model built using 338 posaconazole concentrations from 117 patients; very few of the patients included received delayed-release tablets; suggested doses did not result in all modeled patients achieving trough concentration >1 mcg/mL; diarrhea, receipt of proton pump inhibitors, and suspension versus tablet all resulted in lower likelihood of target attainment (Boonsathorn 2019).

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

Reconstitution

IV: Equilibrate the refrigerated vial to room temperature. Contents of vial should be withdrawn and admixed with D5W, D5W with KCl 20 mEq, D5NS, D51/2NS, 1/2NS, or NS to achieve a concentration of 1 to 2 mg/mL. The admixed solution may be colorless to yellow. Color variations in this range do not affect potency. Admixture should be used immediately; may be stored for up to 24 hours between 2°C and 8°C (36°F and 46°F).

Administration

Oral:

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.

Tablets (delayed release): Swallow tablets whole; do not divide, crush, dissolve, or chew. Administer with food.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Oral 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.

Dietary Considerations

Tablets (delayed release): Take with food.

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.

Storage

Suspension: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Do not freeze.

Tablets: Store between 20°C and 25°C (68°F and 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Injection: Store at 2°C to 8°C (36°F to 46°F).

Drug Interactions

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. Consider therapy modification

Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. 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. Consider therapy modification

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. Consider therapy modification

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

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. 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. Consider therapy modification

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

ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ALPRAZolam. Management: Consider using an alternative agent that is less likely to interact. If combined, monitor for increased therapeutic/toxic effects of alprazolam if combined with a strong CYP3A4 inhibitor. Consider therapy modification

Amphotericin B: Antifungal Agents (Azole Derivatives, Systemic) may diminish the therapeutic effect of Amphotericin B. Monitor therapy

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

Apixaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. 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, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. 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. Consider therapy modification

Astemizole: Posaconazole may increase the serum concentration of Astemizole. Avoid combination

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

Atazanavir: Posaconazole may increase the serum concentration of Atazanavir. Monitor therapy

AtorvaSTATin: Posaconazole may increase the serum concentration of AtorvaSTATin. Avoid combination

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

Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. 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. Consider therapy modification

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

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

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

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

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

Bictegravir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. Monitor therapy

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

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

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

Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. 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. 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. 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). 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. Consider therapy modification

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

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

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

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. Consider therapy modification

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

Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. 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. Consider therapy modification

Busulfan: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Busulfan. Isavuconazonium considerations are addressed in separate monographs. 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. 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. Consider therapy modification

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

Calcium Channel Blockers: Antifungal Agents (Azole Derivatives, Systemic) may enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Consider therapy modification

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

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

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

Cariprazine: 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 Consider therapy modification

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

Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. Consider therapy modification

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

Cisapride: Posaconazole may increase the serum concentration of Cisapride. Avoid combination

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

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

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

Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. 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. Consider therapy modification

Cortisone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cortisone. 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. Consider therapy modification

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of CycloSPORINE (Systemic). Management: Monitor cyclosporine serum concentrations and clinical cyclosporine closely with concurrent use of any strong CYP3A4 inhibitor. Cyclosporine dose reductions and/or prolongation of the dosing interval will likely be required. Consider therapy modification

CYP3A4 Substrates (High risk with Inhibitors): CYP3A4 Inhibitors (Strong) may decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

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

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. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. Consider therapy modification

Dapoxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. 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. Consider therapy modification

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. Consider therapy modification

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

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

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

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

Dihydroergotamine: Posaconazole may increase the serum concentration of Dihydroergotamine. Avoid combination

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. Consider therapy modification

Dofetilide: Posaconazole may increase the serum concentration of Dofetilide. Avoid combination

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

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

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. Prescribing information for at least one doxorubicin product recommends that these combinations be avoided. Consider therapy modification

Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy

Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Concurrent use of strong CYP3A4 inhibitors with dronedarone is contraindicated according to dronedarone prescribing information. Avoid combination

Drospirenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors. Consider therapy modification

Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. 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. Consider therapy modification

Efavirenz: May decrease the serum concentration of Posaconazole. 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. Consider therapy modification

Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Avoid combination

Eletriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. 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. Consider therapy modification

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

Enzalutamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Monitor therapy

Eplerenone: Posaconazole may increase the serum concentration of Eplerenone. 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. Consider therapy modification

Ergoloid Mesylates: Posaconazole may increase the serum concentration of Ergoloid Mesylates. Avoid combination

Ergonovine: Posaconazole may increase the serum concentration of Ergonovine. Avoid combination

Ergotamine: Posaconazole may increase the serum concentration of Ergotamine. 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 severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Consider therapy modification

Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. 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). Consider therapy modification

Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. Consider therapy modification

Etravirine: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Etravirine. Etravirine may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). This would be anticipated with itraconazole or ketoconazole. Monitor therapy

Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Management: Consider avoiding use of strong CYP3A4 inhibitors with everolimus. If combined, closely monitor for increased everolimus serum concentrations and toxicities. Everolimus dose reductions will likely be required. Consider therapy modification

Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. 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. 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. 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. Consider therapy modification

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. Avoid combination

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

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Consider therapy modification

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

Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. 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. Consider therapy modification

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

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

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

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. Consider therapy modification

GlipiZIDE: Posaconazole may enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. 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. Consider therapy modification

Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: The combination of halofantrine with a strong CYP3A4 inhibitor should be avoided whenever possible due to the risk for QTc interval prolongation. Avoid combination

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Posaconazole. Management: Avoid concurrent use of oral suspension with H2-antagonists whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Delayed-release posaconazole tablets may be less likely to interact. Consider therapy modification

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

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

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 and the posaconazole dose. See full Lexi Interact monograph for details. Consider therapy modification

Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Monitor therapy

Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. 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. Consider therapy modification

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

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

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. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. Avoid combination

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. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. Avoid combination

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. Consider therapy modification

Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. 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. 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. Consider therapy modification

Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, reduce lapatinib dose to 500 mg daily. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. 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. 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. Avoid combination

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

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

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

Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors. Consider therapy modification

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

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. Consider therapy modification

Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. 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. Consider therapy modification

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

Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. Monitor therapy

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

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

Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. 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. 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. Consider therapy modification

MedroxyPROGESTERone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. Monitor therapy

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

Methadone: Posaconazole may enhance the QTc-prolonging effect of Methadone. Posaconazole may increase the serum concentration of Methadone. Avoid combination

Methylergonovine: Posaconazole may increase the serum concentration of Methylergonovine. Avoid combination

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

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. 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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. Consider therapy modification

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

Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Consider therapy modification

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

Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Monitor therapy

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. Consider therapy modification

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. 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. Monitor therapy

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

PAZOPanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required if adverse reactions occur. Consider therapy modification

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. Consider therapy modification

Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily 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. Consider therapy modification

Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Monitor therapy

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

Piperaquine: CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Management: Avoid concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. If the combination cannot be avoided, frequent ECG monitoring is recommended due to the risk for QTc prolongation. 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. Monitor therapy

PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Reduce the adult starting dose of ponatinib to 30 mg daily during treatment with any strong CYP3A4 inhibitor. Consider therapy modification

Pralsetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pralsetinib. Avoid combination

Pranlukast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. Monitor therapy

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

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

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

Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Monitor therapy

Proton Pump Inhibitors: May decrease the serum concentration of Posaconazole. Management: Avoid coadministration of proton pump inhibitors (PPIs) 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. Consider therapy modification

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. Avoid combination

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

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

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

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

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

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. Avoid combination

Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Avoid combination

Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. Monitor therapy

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. Monitor therapy

Rifamycin Derivatives: Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Rifamycin Derivatives. Only rifabutin appears to be affected. Rifamycin Derivatives may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Avoid these combinations when possible. Voriconazole and isavuconazonium are considered contraindicated. Consider therapy modification

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

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

Riociguat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Riociguat. Monitor therapy

Ripretinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib. Monitor therapy

Ritonavir: Posaconazole may increase the serum concentration of Ritonavir. Monitor therapy

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

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

Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. 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. Consider therapy modification

Saccharomyces boulardii: Antifungal Agents (Systemic, Oral) may diminish the therapeutic effect of Saccharomyces boulardii. Avoid combination

Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. 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. 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. 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. Consider therapy modification

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. Monitor therapy

Sildenafil: Posaconazole may increase the serum concentration of Sildenafil. Management: Concurrent posaconazole is not recommended when sildenafil is used for treatment of pulmonary arterial hypertension. If sildenafil is used to treat erectile dysfunction, an initial dose of 25 mg is recommended with concurrent posaconazole. Consider therapy modification

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

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

Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Avoid combination

Sirolimus: Posaconazole may increase the serum concentration of Sirolimus. Avoid combination

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. Consider therapy modification

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

SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. Monitor therapy

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). Consider therapy modification

SUNItinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of 37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Consider therapy modification

Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. 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 during and at discontinuation of posaconazole. Consider therapy modification

Tacrolimus (Topical): Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Tacrolimus (Topical). Applicable Isavuconazonium considerations are addressed in separate monographs. 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. Consider therapy modification

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

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

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

Telithromycin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. Monitor therapy

Temsirolimus: Posaconazole may increase serum concentrations of the active metabolite(s) of Temsirolimus. Management: Consider temsirolimus dose reductions or alternatives to posaconazole. Monitor sirolimus concentrations in all patients receiving posaconazole or any systemic azole antifungal. Consider therapy modification

Terfenadine: Posaconazole may increase the serum concentration of Terfenadine. Avoid combination

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

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. 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. 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: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. 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. Avoid combination

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. 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. Consider therapy modification

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

Toremifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Consider therapy modification

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

TraMADol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. 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. Consider therapy modification

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

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

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

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

Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. Avoid combination

Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Monitor therapy

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. 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. Consider therapy modification

Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. If concomitant use is unavoidable, consider a vemurafenib dose reduction if clinically indicated. 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. Consider therapy modification

Verapamil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Verapamil. Management: Consider alternatives to this combination when possible. If combined, monitor for increased verapamil effects and toxicities (eg, hypotension, bradycardia). Consider therapy modification

Vilanterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilanterol. 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. Consider therapy modification

VinBLAStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinBLAStine. 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). Consider therapy modification

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

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

Vinflunine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Avoid combination

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

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

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

Voxelotor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inhibitors. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. Consider therapy modification

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. Consider therapy modification

Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. 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). Consider therapy modification

Adverse Reactions

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

>10%:

Cardiovascular: Thrombophlebitis (intravenous via peripheral venous catheter: 60%), hypertension (8% to 18%), peripheral edema (12% to 16%), lower extremity edema (oral: 15%), hypotension (oral: 14%), tachycardia (oral: 12%)

Central nervous system: Headache (8% to 28%), rigors (oral: ≤20%), fatigue (3% to 17%), insomnia (oral: 1% to 17%), chills (10% to 16%), dizziness (oral: 11%)

Dermatologic: Skin rash (3% to 24%), pruritus (oral: 11%)

Endocrine & metabolic: Hypokalemia (oral: ≤30%), hypomagnesemia (10% to 18%), hyperglycemia (oral: 11%)

Gastrointestinal: Diarrhea (10% to 42%), nausea (9% to 38%), vomiting (7% to 29%), abdominal pain (5% to 27%), constipation (8% to 21%), anorexia (oral: 2% to 15%), stomatitis (oral: 14%), decreased appetite (10% to 12%), upper abdominal pain (6% to 11%)

Hematologic & oncologic: Thrombocytopenia (≤29%), anemia (2% to 25%), neutropenia (oral: 4% to 23%), petechia (8% to 11%)

Hepatic: Increased serum alanine aminotransferase (oral: ≤17%)

Neuromuscular & skeletal: Musculoskeletal pain (oral: 16%), arthralgia (oral: 11%)

Respiratory: Cough (3% to 24%), dyspnea (1% to 20%), epistaxis (14% to 17%), pharyngitis (oral: 12%)

Miscellaneous: Fever (21% to 45%)

1% to 10%:

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

Central nervous system: Paresthesia (<5%), pain (oral: 1%)

Dermatologic: Diaphoresis (oral: 2%)

Endocrine & metabolic: Hypocalcemia (9%), adrenocortical insufficiency (<5%), dehydration (oral: 1%), weight loss (oral: 1%)

Gastrointestinal: Dyspepsia (10%), pancreatitis (<5%), oral candidiasis (oral: 1%)

Genitourinary: Vaginal hemorrhage (oral: 10%)

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

Hepatic: Hyperbilirubinemia (≤10%), hepatic insufficiency (<5%), hepatitis (<5%), hepatomegaly (<5%), increased liver enzymes (<5%), jaundice (<5%), increased serum aspartate aminotransferase (≤4%), increased serum alkaline phosphatase (oral: ≤3%)

Hypersensitivity: Hypersensitivity reaction (<5%)

Infection: Herpes simplex infection (oral: 3%)

Neuromuscular & skeletal: Back pain (oral: 10%), asthenia (oral: 2% to 10%)

Renal: Acute renal failure (<5%)

Respiratory: Pneumonia (oral: 3%)

<1%, postmarketing, and/or case reports: Cholestasis, prolonged QT interval on ECG, pseudoaldosteronism

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 liver function tests 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 suspension total daily doses of 800 mg. Monitor liver function tests 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 tablets or 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 intravenous 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 patients undergoing concurrent continuous venovenous hemofiltration (CVVH), the use of standard doses of intravenous posaconazole has been used without SBECD accumulation (Morris 2015).

• Oral formulations: The delayed-release tablet and oral suspension are not to be used interchangeably due to dosing differences for each formulation.

• 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.

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 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 or injection, consider alternative antifungal therapy or closely monitor for breakthrough fungal infections.

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

For invasive aspergillosis (treatment or prolonged prophylaxis), IDSA recommends monitoring serum trough concentrations in patients receiving posaconazole oral suspension; further studies are needed to address whether therapeutic drug monitoring is helpful or necessary with delayed-release tablets or IV formulations of posaconazole (IDSA [Patterson 2016]). In general, 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 (Dekkers 2016).

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat fungal infections.

• It is used to prevent fungal infections

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Constipation

• Cough

• Lack of appetite

• Joint pain

• Back pain

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Abnormal heartbeat

• Chest pain

• Fast heartbeat

• Severe dizziness

• Passing out

• Vision changes

• Severe diarrhea

• Severe nausea

• Severe vomiting

• Shortness of breath

• Swelling of arms or legs

• Chills

• Sore throat

• Severe headache

• Nosebleed

• Bruising

• Bleeding

• Abnormal vaginal bleeding

• Severe loss of strength and energy

• Mouth irritation

• Mouth sores

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.