Version May 2024
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:
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:
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: 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 (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.
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).
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.
Refer to adult dosing.
(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: 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 (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: 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.
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.
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.
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
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).
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).
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).
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)
No
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
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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)
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).
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).
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).
Candidiasis, esophageal, fluconazole-refractory disease; Prophylaxis against invasive fungal infections
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)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (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
Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
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): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). 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). Risk X: Avoid combination
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
Lonafarnib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lonafarnib. 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
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. For the 125 mg capsules: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily. Reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification
Pimavanserin: CYP3A4 Inhibitors (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 (Systemic): P-glycoprotein/ABCB1 Inhibitors 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
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.
Based on data from animal reproduction studies, in utero exposure to isavuconazonium sulfate may cause fetal harm.
It is not known if isavuconazonium sulfate is present breast milk.
The manufacturer recommends breastfeeding be discontinued during maternal isavuconazonium sulfate therapy.
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).
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).
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.
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).
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.
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