ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Isavuconazole (isavuconazonium sulfate): Drug information

Isavuconazole (isavuconazonium sulfate): Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
Brand Names: US
  • Cresemba
Brand Names: Canada
  • Cresemba
Pharmacologic Category
  • Antifungal Agent, Azole Derivative;
  • Antifungal Agent, Oral;
  • Antifungal Agent, Parenteral
Dosing: Adult

Note: Dosage expressed as milligrams of isavuconazonium sulfate; switching between the IV and oral formulations of isavuconazonium sulfate is acceptable; for maintenance dosing, it is not necessary to restart dosing with the initial dose regimen when switching between formulations.

Aspergillosis, invasive

Aspergillosis, invasive:

IV, Oral: Initial: 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses; Maintenance: 372 mg (isavuconazole 200 mg) once daily (Ref). Start maintenance dose 12 to 24 hours after the last loading dose.

Duration of therapy: Minimum of 6 to 12 weeks, although duration is highly dependent on degree/duration of immunosuppression, disease site, and evidence of disease improvement (Ref).

Candidiasis

Candidiasis:

Esophageal, fluconazole-refractory disease (alternative agent) (off-label use): Oral: 744 mg (isavuconazole 400 mg) as a single dose, then 186 mg (isavuconazole 100 mg) once daily for 14 to 28 days or 744 mg (isavuconazole 400 mg) once weekly for 4 weeks (Ref).

Mucormycosis, invasive

Mucormycosis, invasive: IV, Oral: Initial: 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses; Maintenance: 372 mg (isavuconazole 200 mg) once daily (Ref). Start maintenance dose 12 to 24 hours after the last loading dose.

Prophylaxis against invasive fungal infections

Prophylaxis against invasive fungal infections (alternative agent) (off-label use):

Hematology malignancy or hematopoietic cell transplant:

IV, Oral: Initial: 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses; Maintenance: 372 mg (isavuconazole 200 mg) once daily (Ref).

Duration of therapy: Varies based on degree and duration of immunosuppression (Ref).

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

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).

Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound): No dosage adjustment necessary (Ref).

CRRT: Not significantly dialyzable given high degree of protein binding (Ref). No initial dosage adjustment necessary; however, lower (and sometimes subtherapeutic) concentrations have been reported in critically ill patients receiving renal replacement therapy; monitor patient closely and utilize therapeutic drug monitoring if available (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Not significantly dialyzable given high degree of protein binding. No initial dosage adjustment necessary; however, potential adsorption to PIRRT equipment has been reported; monitor patient closely and utilize therapeutic drug monitoring if available (Ref).

Dosing: Hepatic Impairment: Adult

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Isavuconazole (isavuconazonium sulfate): Pediatric drug information")

Dosage guidance:

Dosing: Dosage expressed as milligrams of isavuconazonium sulfate; 372 mg isavuconazonium sulfate = 200 mg isavuconazole. Dosing is presented as weight-directed doses (mg isavuconazonium sulfate/kg) and fixed doses (mg isavuconazonium sulfate); use caution.

Clinical considerations: Switching between the IV and oral formulations of isavuconazonium sulfate is acceptable; the same dose and frequency can be used; additional loading doses are NOT necessary.

Aspergillosis, invasive

Aspergillosis, invasive: Note: Minimum duration of therapy is 6 to 12 weeks; duration should be individualized depending on degree and duration of immunosuppression, disease site, and evidence of improvement (Ref).

Intravenous:

Children <3 years: Initial (loading doses): IV: 15 mg isavuconazonium sulfate/kg/dose every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 15 mg isavuconazonium sulfate/kg/dose every 24 hours; maximum dose: 372 mg isavuconazonium sulfate/dose.

Children ≥3 years and Adolescents <18 years: IV: Initial (loading doses): 10 mg isavuconazonium sulfate/kg/dose every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last dosing dose): 10 mg isavuconazonium sulfate/kg/dose every 24 hours; maximum dose: 372 mg isavuconazonium sulfate/dose.

Adolescents ≥18 years: IV: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Oral:

Children ≥6 years and Adolescents <18 years:

16 to <18 kg: Oral: Initial (loading doses): 149 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 149 mg isavuconazonium sulfate every 24 hours.

18 to <25 kg: Oral: Initial (loading doses): 223.5 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 223.5 mg isavuconazonium sulfate every 24 hours.

25 to <32 kg: Oral: Initial (loading doses): 298 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 298 mg isavuconazonium sulfate every 24 hours.

≥32 kg: Oral: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Adolescents ≥18 years: Oral: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Candidiasis, esophageal

Candidiasis, esophageal (alternative agent): Limited data available: Multiple regimens reported: Patients with HIV: Adolescents: Oral: 744 mg isavuconazonium sulfate as a single dose, followed by 186 mg isavuconazonium sulfate every 24 hours or 372 mg isavuconazonium sulfate as a single dose, followed by 93 mg isavuconazonium sulfate every 24 hours or 744 mg isavuconazonium sulfate once weekly; treat for 14 to 21 days (Ref).

Mucormycosis, invasive

Mucormycosis, invasive: Note: Treatment duration is highly individualized depending on degree and duration of immunosuppression, disease site, clinical resolution, and improvement on imaging studies; typically weeks to months or longer (Ref).

Intravenous:

Children <3 years: Initial (loading doses): IV: 15 mg isavuconazonium sulfate/kg/dose every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 15 mg isavuconazonium sulfate/kg/dose every 24 hours; maximum dose: 372 mg isavuconazonium sulfate/dose.

Children ≥3 years and Adolescents <18 years: IV: Initial (loading doses): 10 mg isavuconazonium sulfate/kg/dose every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last dosing dose): 10 mg isavuconazonium sulfate/kg/dose every 24 hours; maximum dose: 372 mg isavuconazonium sulfate/dose.

Adolescents ≥18 years: IV: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Oral:

Children ≥6 years and Adolescents <18 years:

16 to <18 kg: Oral: Initial (loading doses): 149 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 149 mg isavuconazonium sulfate every 24 hours.

18 to <25 kg: Oral: Initial (loading doses): 223.5 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 223.5 mg isavuconazonium sulfate every 24 hours.

25 to <32 kg: Oral: Initial (loading doses): 298 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 298 mg isavuconazonium sulfate every 24 hours.

≥32 kg: Oral: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Adolescents ≥18 years: Oral: Initial (loading doses): 372 mg isavuconazonium sulfate every 8 hours for 6 doses; maintenance (begin 12 to 24 hours after last loading dose): 372 mg isavuconazonium sulfate every 24 hours.

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Children and Adolescents: No dosage adjustment necessary in any degree of kidney impairment; less than 1% is eliminated by the kidney.

Hemodialysis: Children and Adolescents: Not readily dialyzable; no dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents:

Mild or moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use only when benefits outweigh risks; monitor closely.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are reported for adults, unless otherwise noted.

>10%:

Cardiovascular: Peripheral edema (15%)

Dermatologic: Pruritus (children, adolescents, and adults: 8% to 13%), skin rash (children, adolescents, and adults: 9% to 14%)

Endocrine & metabolic: Hypokalemia (19%)

Gastrointestinal: Abdominal pain (children, adolescents, and adults: 17% to 23%), constipation (14%), diarrhea (children, adolescents, and adults: 24% to 26%), nausea (children and adolescents: 13%; adults: 28%), vomiting (children, adolescents, and adults: 21% to 25%)

Hepatic: Increased liver enzymes (children, adolescents, and adults: 17% to 18%)

Nervous system: Fatigue (11%), headache (children, adolescents, and adults: 12% to 17%), insomnia (11%)

Respiratory: Dyspnea (17%)

1% to 10%:

Cardiovascular: Atrial fibrillation (<5%), atrial flutter (<5%), bradycardia (<5%), chest pain (9%), ECG changes (reduced QT interval) (<5%), hypotension (8%), palpitations (<5%), premature ventricular contractions (<5%), supraventricular extrasystole (<5%), supraventricular tachycardia (<5%), syncope (<5%), thrombophlebitis (<5%)

Dermatologic: Alopecia (<5%), dermatitis (<5%), erythema of skin (<5%), exfoliative dermatitis (<5%), urticaria (<5%)

Endocrine & metabolic: Hypoalbuminemia (<5%), hypoglycemia (<5%), hypomagnesemia (5%), hyponatremia (<5%)

Gastrointestinal: Abdominal distention (<5%), cholecystitis (<5%), cholelithiasis (<5%), decreased appetite (9%), dysgeusia (<5%), dyspepsia (6%), gastritis (<5%), gingivitis (<5%), stomatitis (<5%)

Genitourinary: Hematuria (<5%), proteinuria (<5%)

Hematologic & oncologic: Agranulocytosis (<5%), leukopenia (<5%), pancytopenia (<5%), petechia (<5%)

Hepatic: Hepatic failure (<5%), hepatitis (<5%), hepatomegaly (<5%), increased serum alanine aminotransferase (>3 × ULN: ≤4%; >10 × ULN: ≤1%), increased serum aspartate aminotransferase (>3 × ULN: ≤4%; >10 × ULN: ≤1%)

Hypersensitivity: Hypersensitivity reaction (<5%)

Local: Injection-site reaction (6%)

Nervous system: Anxiety (8%), chills (<5%), confusion (<5%), delirium (9%), depression (<5%), drowsiness (<5%), encephalopathy (<5%), falling (<5%), hallucination (<5%), hypoesthesia (<5%), malaise (<5%), migraine (<5%), paresthesia (<5%), peripheral neuropathy (<5%), seizure (<5%), stupor (<5%), tremor (<5%), vertigo (<5%)

Neuromuscular & skeletal: Back pain (10%), myositis (<5%), neck pain (<5%), ostealgia (<5%)

Ophthalmic: Optic neuropathy (<5%)

Otic: Tinnitus (<5%)

Renal: Kidney failure (10%)

Respiratory: Acute respiratory failure (7%), bronchospasm (<5%), tachypnea (<5%)

Frequency not defined:

Gastrointestinal: Cholestasis

Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin

Renal: Acute kidney injury

Respiratory: Cough

Postmarketing: Hypersensitivity: Anaphylaxis, infusion-related reaction

Contraindications

Hypersensitivity to isavuconazonium sulfate (eg, isavuconazole) or any component of the formulation; concurrent use of strong CYP3A4 inhibitors (eg, ketoconazole, high-dose ritonavir [400 mg every 12 hours]); concurrent use of strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s wort, long-acting barbiturates); familial short QT syndrome.

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

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use of moderate CYP3A4/5 inducers (eg, efavirenz, etravirine).

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic effects: Severe reactions (hepatic failure [including fatalities], hepatitis, and cholestasis) have been reported in patients with serious underlying medical conditions (eg, hematologic malignancy). Other reactions (elevations in AST, ALT, alkaline phosphatase and total bilirubin) have also been reported; these elevations are generally reversible and do not require discontinuation of therapy. Monitor liver function tests at baseline and periodically during therapy. If abnormal liver function tests develop, monitor closely for development of severe hepatic reactions. Discontinue therapy if clinical signs and symptoms of liver disease develop.

• Hypersensitivity: Anaphylactic reactions, with fatal outcome, have been reported with isavuconazonium sulfate. Discontinue isavuconazonium sulfate if a patient experiences an anaphylactic reaction. Serious hypersensitivity (eg, anaphylaxis) and severe skin reactions (eg, Stevens-Johnson syndrome) have been reported with other azole antifungal agents. Discontinue if a severe skin reaction occurs. There is no information regarding cross-sensitivity between isavuconazonium sulfate and other azoles. Use with caution in patients with hypersensitivity reactions to other azoles.

Disease-related concerns:

• Hepatic impairment: Use with caution and monitor for adverse effects in patients with severe hepatic impairment (Child-Pugh class C).

Dosage form specific issues:

• Drug particulates: Following dilution for IV infusion, may form precipitate from the insoluble isavuconazole. Use an infusion set with an in-line filter (pore size 0.2 to 1.2 micron) for IV administration.

• Infusion-related reactions: Infusion reactions (eg, hypotension, dizziness, chills, dyspnea, paresthesia and hypoesthesia) have been reported during IV administration. Discontinue the infusion if these reactions occur.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Dosage Forms: US

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

Capsule, Oral, as sulfate:

Cresemba: 186 mg (isavuconazole 100 mg), 74.5 mg (isavuconazole 40 mg) [contains disodium edta]

Solution Reconstituted, Intravenous, as sulfate [preservative free]:

Cresemba: 372 mg (isavuconazole 200 mg) (1 ea)

Generic Equivalent Available: US

No

Pricing: US

Capsules (Cresemba Oral)

74.5 mg (per each): $54.06

186 mg (per each): $134.85

Solution (reconstituted) (Cresemba Intravenous)

372 mg (per each): $459.47

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Capsule, Oral, as sulfate:

Cresemba: 186 mg (isavuconazole 100 mg) [contains disodium edta]

Solution Reconstituted, Intravenous, as sulfate:

Cresemba: 372 mg (isavuconazole 200 mg) (1 ea)

Administration: Adult

IV: Infuse over a minimum of 1 hour; must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron). Flush line with NS or D5W before and after infusion. Do not administer as an IV bolus injection. Do not mix or infuse with other medications.

NG tube: Administer within 1 hour of reconstitution. Once dose administered, flush nasogastric tube with three 5 mL rinses of water. Do not administer intact capsules through an NG tube.

Oral: Administer with or without food. The manufacturer recommends to swallow capsules whole; do not chew, crush, dissolve, or open. Administration of isavuconazonium sulfate by opening capsules and mixing contents with saline or tube feed formulations for administration via enteral feeding tubes has resulted in comparable isavuconazole concentrations to IV administration and intact capsule formulations. If capsules are opened, consider assessing serum concentrations to ensure absorption (Ref).

Administration: Pediatric

IV: Infuse over a minimum of 1 hour; must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron). Flush line with NS or D5W before and after infusion. Do not administer as an IV bolus injection. Do not mix or infuse with other medications.

Oral: Administer with or without food. The manufacturer recommends swallowing capsules whole and states not to chew, crush, dissolve, or open capsules, and recommends using the parenteral product enterally for patients who cannot swallow capsules. However, oral administration of isavuconazonium sulfate by opening capsules and mixing contents with an acidic beverage or soft food (eg, yogurt) has resulted in comparable isavuconazole concentrations to IV administration and administration of intact capsule formulations. If capsules are opened, consider assessing serum concentrations to ensure absorption (Ref).

Feeding tube administration:

Using parenteral formulation: Administer via nasogastric (NG) tube using an appropriate syringe within 1 hour of reconstitution. Once dose administered, flush NG tube with three 5 mL rinses of water.

Using capsules: Isavuconazonium sulfate administration via enteral feeding tubes (eg, gastrostomy tube, gastrojejunostomy [GJ] tube) has been described; open capsules and mix contents with water, saline, or tube feed formulations (eg, 372 mg isavuconazonium sulfate in 10 mL saline). In some cases, isavuconazole concentrations were found to be comparable to those achieved with IV administration; however, in one pharmacokinetic study, opening capsules resulted in lower concentrations compared to IV administration. The manufacturer recommends against using capsules for feeding tube administration; parenteral formulation is preferred. If capsules opened and administered via enteral tube, assess serum concentrations to ensure absorption (Ref).

Use: Labeled Indications

Aspergillosis: Treatment of invasive aspergillosis in adults and pediatric patients ≥1 year of age (injection) or adults and pediatric patients ≥6 years of age and ≥16 kg (capsule).

Mucormycosis: Treatment of invasive mucormycosis in adults and pediatric patients ≥1 year of age (injection) or adults and pediatric patients ≥6 years of age and ≥16 kg (capsule).

Use: Off-Label: Adult

Candidiasis, esophageal, fluconazole-refractory disease; Prophylaxis against invasive fungal infections

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (moderate), OCT1, OCT2, P-glycoprotein/ABCB1; Induces CYP2B6 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor therapy

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider therapy modification

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification

ALfentanil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification

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

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

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

ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modification

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

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

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

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

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Astemizole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Astemizole. Management: Avoid concomitant use of astemizole and moderate CYP3A4 inhibitors whenever possible. If combined, monitor closely for increased astemizole toxicities, especially for QTc interval prolongation. Risk D: Consider therapy modification

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

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

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

Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider therapy modification

Avapritinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor therapy

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider therapy modification

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

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) 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 CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification

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

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

BuPROPion: CYP2B6 Inducers (Weak) may decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

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

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

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

Capivasertib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider therapy modification

Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cariprazine. Risk C: Monitor therapy

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

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Cisapride: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cisapride. Management: Consider alternatives to this combination. Prescribing information for some moderate CYP3A4 inhibitors state coadministration with cisapride is contraindicated, while some others recommend monitoring and dose titration. Risk D: Consider therapy modification

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

Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider therapy modification

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

Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider therapy modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification

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

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

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

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

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor therapy

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

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

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

Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider therapy modification

Daridorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

Deflazacort: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification

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

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

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

Dofetilide: MATE1/2-K Inhibitors may increase the serum concentration of Dofetilide. Risk X: Avoid combination

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

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

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

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

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

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

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

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

Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor therapy

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider therapy modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider therapy modification

Enasidenib: May decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Risk X: Avoid combination

Entrectinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Entrectinib. Management: Avoid moderate CYP3A4 inhibitors if possible. If needed, reduce entrectinib dose to 50 mg/day if starting dose 200 mg; to 100 mg/day if starting dose 300 mg; to 200 mg if starting dose 400 mg or 600 mg. Risk D: Consider therapy modification

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider therapy modification

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

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

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

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

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

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

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

Everolimus: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Everolimus. Management: Afinitor: For TSC-associated SEGA or TSC-associated seizures reduce everolimus dose 50%. For other Afinitor indications, reduce everolimus dose to 2.5 mg/day, increase to 5 mg/day if tolerated. Zortress: Monitor for increased everolimus concentrations. Risk D: Consider therapy modification

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

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

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider therapy modification

Fexinidazole: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Avoid use of fexinidazole and moderate CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification

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

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination

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

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

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

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

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider therapy modification

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

Gepirone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider therapy modification

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

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

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

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification

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

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

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider therapy modification

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

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

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

Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy

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

Itraconazole: May increase the serum concentration of Isavuconazonium Sulfate. Risk X: Avoid combination

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

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider therapy modification

Ivosidenib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities, including QTc prolongation. Risk D: Consider therapy modification

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

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

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

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

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

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification

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

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

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

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

Levomethadone: Isavuconazonium Sulfate may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy

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

Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

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

Lopinavir: May increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, lopinavir/ritonavir may increase isavuconazole serum concentrations. Isavuconazonium Sulfate may decrease the serum concentration of Lopinavir. Management: Consider alternatives to this combination. If coadministered, use caution and monitor for increased isavuconazonium effects and toxicities as well as reduced concentrations and effects of lopinavir/ritonavir. Risk D: Consider therapy modification

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

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: US labeling recommends reducing lurasidone dose by 50% with a moderate CYP3A4 inhibitor and initiating 20 mg/day, max 80 mg/day. Some non-US labels recommend initiating lurasidone 20 mg/day, max 40 mg/day. Avoid concurrent use of grapefruit products. Risk D: Consider therapy modification

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Risk D: Consider therapy modification

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

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

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

Mavacamten: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor. For those stable on mavacamten who are initiating a moderate CYP3A4 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification

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

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

MetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Methadone: Isavuconazonium Sulfate may decrease the serum concentration of Methadone. Risk C: Monitor therapy

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

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

Midazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider therapy modification

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

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

Mitapivat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider therapy modification

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

Mobocertinib: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mobocertinib. Management: Avoid use of moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification

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

Mycophenolate: Isavuconazonium Sulfate may increase the serum concentration of Mycophenolate. Risk C: Monitor therapy

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

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

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

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

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider therapy modification

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

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

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

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

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

Nirmatrelvir and Ritonavir: Isavuconazonium Sulfate may increase the serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase the serum concentration of Isavuconazonium Sulfate. Risk C: Monitor therapy

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

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

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

Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider therapy modification

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

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

Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider therapy modification

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

OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy

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

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

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

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

Palovarotene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider therapy modification

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

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

Pemigatinib: CYP3A4 Inhibitors (Moderate) 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 moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification

Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification

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

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy

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

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

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

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

Pralsetinib: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification

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

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

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

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

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

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

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider therapy modification

Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Red Yeast Rice. Risk C: Monitor therapy

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

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

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

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

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

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

Rimegepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider therapy modification

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

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

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

Rivaroxaban: Inhibitors of CYP3A4 (Moderate) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Management: No action is needed in patients with normal renal function. Do not use this combination in patients with estimated creatinine clearance 15 to 80 mL/min unless prospective benefits outweigh the risks. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Selpercatinib: CYP3A4 Inhibitors (Moderate) 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 80 mg twice/day, or from 160 mg twice/day to 120 mg twice/day. Risk D: Consider therapy modification

Selumetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification

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

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

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

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

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

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

Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider therapy modification

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification

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

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

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification

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

St John's Wort: May decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, St Johns Wort may decrease isavuconazole serum concentrations. Risk X: Avoid combination

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

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

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider therapy modification

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

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

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

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

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

Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider therapy modification

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

Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor therapy

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

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

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

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

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

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider therapy modification

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

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

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

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

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider therapy modification

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

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

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

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

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

Triazolam: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification

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

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

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

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

Vardenafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

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

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

VinCRIStine: Isavuconazonium Sulfate may increase the serum concentration of VinCRIStine. Risk X: Avoid combination

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

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

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

Voclosporin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

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

Reproductive Considerations

Evaluate pregnancy status prior to use; patients who could become pregnant should use effective contraception during therapy and for 28 days after the last isavuconazonium sulfate dose.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to isavuconazonium sulfate may cause fetal harm.

Breastfeeding Considerations

It is not known if isavuconazonium sulfate is present breast milk.

The manufacturer recommends breastfeeding be discontinued during maternal isavuconazonium sulfate therapy.

Monitoring Parameters

Hypersensitivity reactions with initial doses, LFTs (eg AST, ALT, alkaline phosphatase, total bilirubin) at baseline and periodically during therapy. Infusion-related reactions (eg hypotension, dyspnea, chills, dizziness, paresthesias, hypoesthesia) during IV infusion.

Routine therapeutic drug monitoring is not recommended; consider assessing serum drug concentrations if there is concern for toxicity, therapeutic failure, or possibility of impaired drug absorption (Adamsick 2019; Andes 2018; McCreary 2020; MSG-ERC [Johnson 2020]; Schmitt-Hoffman 2009).

Reference Range

Optimal drug concentrations have not been established; however, most adult patients achieve levels >1 mg/L with standard dosing regimens; an upper limit associated with toxicity has not been determined (Andes 2018; Desai 2017).

Mechanism of Action

Isavuconazonium sulfate is a prodrug that is rapidly hydrolyzed in the blood to active isavuconazole. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vss: Isavuconazole: IV: ~450 L.

Protein binding: Isavuconazole: >99% (primarily to albumin).

Metabolism: Isavuconazonium sulfate (prodrug) is rapidly hydrolyzed in the blood by esterases to active isavuconazole and an inactive cleavage product. Isavuconazole is metabolized by CYP3A4, CYP 3A5, and UGT.

Bioavailability: Oral: Isavuconazole: 98%.

Half-life elimination: IV: Isavuconazole: 130 hours.

Time to peak: Isavuconazole:

IV: Children and Adolescents: Median range: 1.07 to 1.08 hours (range: 1.02 to 1.35 hours) (Arrieta 2021).

Oral:

Children ≥6 years and Adolescents: Median range: 3.98 to 4 hours (range: 1.98 to 8.03 hours) (Arrieta 2021).

Adults: 2 to 3 hours.

Excretion: Urine (<1% as unchanged isavuconazole); feces (33% as unchanged isavuconazole) (Townsend 2018).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Patients with mild and moderate hepatic impairment had 40% and 48% lower isavuconazole Cl values, respectively, compared with healthy subjects, resulting in 64% and 84% increased drug exposure, respectively. In addition, patients with moderate hepatic impairment had 30% lower Cmax, compared with healthy subjects.

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

  • (AE) United Arab Emirates: Cresemba;
  • (AR) Argentina: Cresemba;
  • (AT) Austria: Cresemba;
  • (AU) Australia: Cresemba;
  • (BE) Belgium: Cresemba;
  • (BG) Bulgaria: Cresemba;
  • (BR) Brazil: Cresemba;
  • (CH) Switzerland: Cresemba;
  • (CL) Chile: Cresemba;
  • (CO) Colombia: Cresemba;
  • (CZ) Czech Republic: Cresemba;
  • (DE) Germany: Cresemba;
  • (EC) Ecuador: Cresemba;
  • (EE) Estonia: Cresemba;
  • (ES) Spain: Cresemba;
  • (FI) Finland: Cresemba;
  • (FR) France: Cresemba;
  • (GB) United Kingdom: Cresemba;
  • (GR) Greece: Cresemba;
  • (HU) Hungary: Cresemba;
  • (IE) Ireland: Cresemba;
  • (IN) India: Cresemba | Isavufic | Isuvaz;
  • (IT) Italy: Cresemba;
  • (JO) Jordan: Cresemba;
  • (JP) Japan: Cresemba;
  • (KR) Korea, Republic of: Cresemba;
  • (LT) Lithuania: Cresemba;
  • (LU) Luxembourg: Cresemba;
  • (LV) Latvia: Cresemba;
  • (MX) Mexico: Cresemba;
  • (MY) Malaysia: Cresemba;
  • (NL) Netherlands: Cresemba;
  • (NO) Norway: Cresemba;
  • (PE) Peru: Cresemba;
  • (PR) Puerto Rico: Cresemba;
  • (PT) Portugal: Cresemba;
  • (QA) Qatar: Cresemba;
  • (RO) Romania: Cresemba;
  • (RU) Russian Federation: Cresemba;
  • (SA) Saudi Arabia: Cresemba;
  • (SE) Sweden: Cresemba;
  • (SG) Singapore: Cresemba;
  • (SI) Slovenia: Cresemba;
  • (SK) Slovakia: Cresemba;
  • (TW) Taiwan: Cresemba
  1. Adamsick ML, Elshaboury RH, Gift T, Mansour MK, Kotton CN, Gandhi RG. Therapeutic drug concentrations of isavuconazole following the administration of isavuconazonium sulfate capsules via gastro-jejunum tube: a case report. Transpl Infect Dis. 2019;21(2):e13048. doi:10.1111/tid.13048 [PubMed 30636363]
  2. American Academy of Pediatrics (AAP) Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. doi:10.1542/peds.99.2.268 [PubMed 9024461]
  3. Andes D, Kovanda L, Desai A, Kitt T, Zhao M, Walsh TJ. Isavuconazole concentration in real-world practice: consistency with results from clinical trials. Antimicrob Agents Chemother. 2018;62(7):e00585-18. doi:10.1128/AAC.00585-18 [PubMed 29735569]
  4. Arrieta AC, Neely M, Day JC, et al. Safety, tolerability, and population pharmacokinetics of intravenous and oral isavuconazonium sulfate in pediatric patients. Antimicrob Agents Chemother. 2021;65(8):e0029021. doi:10.1128/AAC.00290-21 [PubMed 34031051]
  5. Ashkenazi-Hoffnung L, Bilavsky E, Levy I, et al. Isavuconazole as successful salvage therapy for mucormycosis in pediatric patients. Pediatr Infect Dis J. 2020;39(8):718-724. doi:10.1097/INF.0000000000002671 [PubMed 32251256]
  6. Barg AA, Malkiel S, Bartuv M, Greenberg G, Toren A, Keller N. Successful treatment of invasive mucormycosis with isavuconazole in pediatric patients. Pediatr Blood Cancer. 2018;65(10):e27281. doi:10.1002/pbc.27281 [PubMed 29932282]
  7. Biagi M, Butler D, Tan X, et al. Pharmacokinetics and dialytic clearance of isavuconazole during in vitro and in vivo continuous renal replacement therapy. Antimicrob Agents Chemother. 2019;63(12):e01085-19. doi:10.1128/AAC.01085-19 [PubMed 31527035]
  8. Bogler Y, Stern A, Su Y, et al. Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. Med Mycol. 2021;59(10):970-979. doi:10.1093/mmy/myab025 [PubMed 34036319]
  9. Bose P, McCue D, Wurster S, et al. Isavuconazole as primary antifungal prophylaxis in patients with acute myeloid leukemia or myelodysplastic syndrome: an open-label, prospective, phase 2 study. Clin Infect Dis. 2021;72(10):1755-1763. doi:10.1093/cid/ciaa358 [PubMed 32236406]
  10. Bury D, Wolfs TFW, Ter Heine R, et al. Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube. J Antimicrob Chemother. 2023;78(12):2886-2889. doi:10.1093/jac/dkad324 [PubMed 37864491]
  11. Candidiasis (Mucocutaneous). In: US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf. Updated May 26, 2020. Accessed June 16, 2021.
  12. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology (ECMM) in cooperation with the Mycoses Study Group Education and Research Consortium (MSG-ERC). Lancet Infect Dis. 2019;19(12):e405-e421. doi:10.1016/S1473-3099(19)30312-3 [PubMed 31699664]
  13. Cornely OA, Böhme A, Schmitt-Hoffmann A, Ullmann AJ. Safety and pharmacokinetics of isavuconazole as antifungal prophylaxis in acute myeloid leukemia patients with neutropenia: results of a phase 2, dose escalation study. Antimicrob Agents Chemother. 2015 Apr;59(4):2078-2085. [PubMed 25624327]
  14. Cornu M, Bruno B, Loridant S, et al. Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report. BMC Pharmacol Toxicol. 2018;19(1):81. doi:10.1186/s40360-018-0273-7 [PubMed 30522521]
  15. Cresemba (isavuconazonium) [prescribing information]. Northbrook, IL: Astellas Pharma US Inc; December 2023.
  16. Cresemba (isavuconazonium) [product monograph]. Blainville, Quebec, Canada: Avir Pharma Inc; April 2022.
  17. Desai AV, Kovanda LL, Hope WW, et al. Exposure-response relationships for isavuconazole in patients with invasive aspergillosis and other filamentous fungi. Antimicrob Agents Chemother. 2017;61(12):e01034-17. doi:10.1128/AAC.01034-17 [PubMed 28923872]
  18. Decembrino N, Perruccio K, Zecca M, et al. A case series and literature review of isavuconazole use in pediatric patients with hemato-oncologic diseases and hematopoietic stem cell transplantation. Antimicrob Agents Chemother. 2020;64(3):e01783-19. doi:10.1128/AAC.01783-19 [PubMed 31871077]
  19. De Leonardis F, Novielli C, Giannico B, Mariggiò MA, Castagnola E, Santoro N. Isavuconazole treatment of cerebral and pulmonary aspergillosis in a pediatric patient with acute lymphoblastic leukemia: case report and review of literature. J Pediatr Hematol Oncol. 2020;42(6):e469-e471. doi:10.1097/MPH.0000000000001508 [PubMed 31094909]
  20. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  21. Falci DR, Pasqualotto AC. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections. Infect Drug Resist. 2013;6:163-174. [PubMed 24187505]
  22. Ferdjallah A, Nelson KM, Meyer K, Jennissen CA, Ebens CL. Isavuconazonium sulfate use in multi-modal management of invasive mucormycosis in four pediatric allogeneic hematopoietic cell transplant patients. J Pediatr Pharmacol Ther. 2021;26(8):863-867. doi:10.5863/1551-6776-26.8.863 [PubMed 34790078]
  23. Fernández Ledesma B, Mendoza-Palomar N, Melendo Pérez S, et al. Isavuconazole use and TDM in real-world pediatric practice. Antimicrob Agents Chemother. 2023;67(12):e0082923. doi:10.1128/aac.00829-23 [PubMed 37962334]
  24. Fontana L, Perlin DS, Zhao Y, et al. Isavuconazole prophylaxis in patients with hematologic malignancies and hematopoietic cell transplant recipients. Clin Infect Dis. 2020;70(5):723-730. doi:10.1093/cid/ciz282 [PubMed 30958538]
  25. Garner LM, Echols CD, Wilson WS. Enteral tube administration of isavuconazole in a pediatric patient. Pediatr Blood Cancer. 2021;68(9):e29108. doi:10.1002/pbc.29108 [PubMed 33991386]
  26. Gatti M, Campoli C, Belotti T, et al. Real-world comparison of isavuconazole and voriconazole in terms of the need for dosage adjustments guided by clinical pharmacological advice during primary prophylaxis of invasive fungal infections in pediatric patients with hemato-oncological malignancies. Ther Drug Monit. 2022;44(5):641-650. doi:10.1097/FTD.0000000000000980 [PubMed 35344524]
  27. Johnson MD, Lewis RE, Dodds Ashley ES, et al. Core recommendations for antifungal stewardship: a statement of the Mycoses Study Group Education and Research Consortium. J Infect Dis. 2020;222(suppl 3):S175-S198. doi:10.1093/infdis/jiaa394 [PubMed 32756879]
  28. Kauffman CA. Esophageal candidiasis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed September 23, 2021.
  29. Kovanda LL, Desai AV, Lu Q, et al. Isavuconazole population pharmacokinetic analysis using nonparametric estimation in patients with invasive fungal disease (results from the VITAL study). Antimicrob Agents Chemother. 2016;60(8):4568-4576. doi:10.1128/AAC.00514-16 [PubMed 27185799]
  30. Lahmer T, Batres Baires G, Heilmaier M, et al. Influence of sustained low-efficiency dialysis treatment on isavuconazole plasma levels in critically ill patients. Antimicrob Agents Chemother. 2019;63(11):e01162-19. doi:10.1128/AAC.01162-19 [PubMed 31427296]
  31. Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760-769. doi:10.1016/S0140-6736(15)01159-9 [PubMed 26684607]
  32. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al; VITAL and FungiScope Mucormycosis Investigators. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828-837. doi:10.1016/S1473-3099(16)00071-2 [PubMed 26969258]
  33. McCarthy MW, Moriyama B, Petraitiene R, Walsh TJ, Petraitis V. Clinical pharmacokinetics and pharmacodynamics of isavuconazole. Clin Pharmacokinet. 2018;57(12):1483-1491. doi:10.1007/s40262-018-0673-2 [PubMed 29725999]
  34. McCreary EK, Davis MR, Narayanan N, et al. Utility of triazole antifungal therapeutic drug monitoring: insights from the Society of Infectious Diseases Pharmacists: endorsed by the Mycoses Study Group Education and Research Consortium. Pharmacotherapy. 2023;43(10):1043-1050. doi:10.1002/phar.2850 [PubMed 37459118]
  35. McCreary EK, Nguyen MH, Davis MR, et al. Achievement of clinical isavuconazole blood concentrations in transplant recipients with isavuconazonium sulphate capsules administered via enteral feeding tube. J Antimicrob Chemother. Published online July 25, 2020. doi:10.1093/jac/dkaa274 [PubMed 32710097]
  36. Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America (IDSA). Clin Infect Dis. 2016;63(4):e1-e60. doi:10.1093/cid/ciw326. http://cid.oxfordjournals.org/content/early/2016/06/22/cid.ciw326.full.pdf+html. Accessed August 8, 2016. [PubMed 27365388]
  37. Peixoto D, Gagne LS, Hammond SP, et al. Isavuconazole treatment of a patient with disseminated mucormycosis. J Clin Microbiol. 2014; 52(3):1016-1019. [PubMed 24403304]
  38. Perez L, Corne P, Pasquier G, et al. Population pharmacokinetics of isavuconazole in critical care patients with COVID-19-associated pulmonary aspergillosis and Monte Carlo simulations of high off-label doses. J Fungi (Basel). 2023;9(2):211. doi:10.3390/jof9020211 [PubMed 36836325]
  39. Refer to the manufacturer's labeling.
  40. Risum M, Vestergaard MB, Weinreich UM, Helleberg M, Vissing NH, Jørgensen R. Therapeutic drug monitoring of isavuconazole: serum concentration variability and success rates for reaching target in comparison with voriconazole. Antibiotics (Basel). 2021;10(5):487. doi:10.3390/antibiotics10050487 [PubMed 33922419]
  41. Ross JA, Karras NA, Tegtmeier B, et al. Safety of isavuconazonium sulfate in pediatrics patients with hematologic malignancies and hematopoietic cell transplantation with invasive fungal infections: a real world experience. J Pediatr Hematol Oncol. 2020;42(4):261-265. doi:10.1097/MPH.0000000000001787 [PubMed 32218096]
  42. Salas MQ, Mussetti A, Muñóz C, et al. Isavuconazole prophylaxis against invasive fungal infections in allogeneic stem cell transplantation: a single-center experience. Hematol Transfus Cell Ther. 2021:S2531-1379(21)00024-9. doi:10.1016/j.htct.2021.01.002 [PubMed 33583766]
  43. Schmitt-Hoffmann A, Roos B, Spickermann J, et al. Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557. Antimicrob Agents Chemother. 2009;53(11):4885-4890. doi:10.1128/AAC.00319-09 [PubMed 19667286]
  44. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. doi:10.1097/PCC.0b013e31819a383c [PubMed 19188870]
  45. Spivey J, Wrenn R, Liu B, Maziarz E, Kram B. Characterization of isavuconazole serum concentrations after enteral feeding tube administration in a hospitalized cohort: a case series. J Clin Pharm Ther. 2021;46(2):528-531. doi:10.1111/jcpt.13317 [PubMed 33247433]
  46. Taplitz RA, Kennedy EB, Bow EJ, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol. 2018;36(30):3043-3054. doi:10.1200/JCO.18.00374 [PubMed 30179565]
  47. Townsend RW, Akhtar S, Alcorn H, et al. Phase I trial to investigate the effect of renal impairment on isavuconazole pharmacokinetics. Eur J Clin Pharmacol. 2017;73(6):669-678. doi:10.1007/s00228-017-2213-7 [PubMed 28271239]
  48. Townsend R, Kato K, Hale C, et al. Two phase 1, open-label, mass balance studies to determine the pharmacokinetics of 14 C-labeled isavuconazonium sulfate in healthy male volunteers. Clin Pharmacol Drug Dev. 2018;7(2):207-216. doi:10.1002/cpdd.376 [PubMed 28750160]
  49. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed May 1, 2020.
  50. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents With HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new. Updated April 12, 2022. Accessed June 20, 2022.
  51. Viljoen J, Azie N, Schmitt-Hoffmann AH, Ghannoum M. A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and efficacy of three dosing regimens of isavuconazole compared with fluconazole in patients with uncomplicated esophageal candidiasis. Antimicrob Agents Chemother. 2015;59(3):1671-1679. doi:10.1128/AAC.04586-14 [PubMed 25561337]
  52. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. doi:10.1111/j.1525-139X.2007.00280.x [PubMed 17555487]
  53. Zurl C, Waller M, Schwameis F, et al. Isavuconazole treatment in a mixed patient cohort with invasive fungal infections: outcome, tolerability and clinical implications of isavuconazole plasma concentrations. J Fungi (Basel). 2020;6(2):90. doi:10.3390/jof6020090 [PubMed 32580296]
Topic 100324 Version 291.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟