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Darunavir: Drug information

Darunavir: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Darunavir: Patient drug information" and "Darunavir: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Prezista
Brand Names: Canada
  • APO-Darunavir;
  • AURO-Darunavir;
  • M-Darunavir [DSC];
  • Prezista [DSC]
Pharmacologic Category
  • Antiretroviral, Protease Inhibitor (Anti-HIV)
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment:

Note: Do not use darunavir and ritonavir or cobicistat plus abacavir and lamivudine in patients with a pre-antiretroviral therapy HIV RNA ≥100,000 copies/mL. Darunavir and ritonavir in combination with raltegravir should not be used in patients with CD4 count ≤200 cells/mm3 and HIV RNA ≥100,000 copies/mL (Ref).

Treatment naive: Oral: 800 mg once daily; coadministration with ritonavir 100 mg or cobicistat 150 mg once daily (Ref) is required.

Treatment experienced: Oral: Note: Genotypic testing is recommended in therapy experienced patients.

With no darunavir resistance-associated substitutions: 800 mg once daily; coadministration with ritonavir 100 mg or cobicistat 150 mg once daily (Ref) is required.

With ≥1 darunavir resistance-associated substitution: 600 mg twice daily; coadministration with ritonavir 100 mg twice daily is required.

If genotypic testing is not possible: 600 mg twice daily, coadministered with ritonavir 100 mg twice daily.

Pregnant patients: Oral: 600 mg twice daily, coadministered with ritonavir 100 mg twice daily. Product labeling notes 800 mg once daily coadministered with ritonavir 100 mg once daily should only be considered in patients already on a stable once daily regimen prior to pregnancy who are virologically suppressed (HIV-1 RNA less than 50 copies/mL), and in whom a change to twice daily dosing may compromise tolerability or compliance. However, current guidelines do not recommend once daily dosing during pregnancy (Ref).

HIV-1 infection, nonoccupational postexposure prophylaxis

HIV-1 infection, nonoccupational postexposure prophylaxis (off-label use): Oral: 800 mg plus ritonavir 100 mg once daily (in combination with other antiretroviral agents); initiate therapy within 72 hours of exposure and continue for 28 days (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: Oral: No dosage adjustment necessary for any degree of kidney impairment (limited clearance by the kidney) (Ref).

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

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

CRRT: Oral: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Oral: No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

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

Severe impairment (Child-Pugh class C): Use not recommended.

Dosing: Adjustment for Toxicity: Adult

Severe rash: Discontinue treatment.

New or worsening liver dysfunction: Consider interrupting or discontinuing treatment.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Darunavir: Pediatric drug information")

Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.

HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Coadministration with a boosting agent is required; use in combination with other antiretroviral agents. Darunavir resistance-associated viral mutations include: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V.

AIDSinfo recommendations (Ref): Oral:

Children 3 to 11 years weighing ≥10 kg: Note: Although FDA approved in this age group, the pediatric AIDSinfo guidelines do not recommend the use of manufacturer-labeled dosing (ie, once-daily dosing in children <12 years); clinical experience, robust pharmacokinetic data, and resistance profile evidence has shown once-daily dosing may be inadequate in this age group (Ref).

Treatment-naive patients or treatment-experienced patients without or with darunavir resistance-testing results that demonstrate at least one mutation associated with resistance (Ref):

Weight-directed dosing: Body weight 10 to 15 kg: Oral solution: Darunavir 20 mg/kg twice daily plus ritonavir 3 mg/kg twice daily; Note: Dosing for this weight-group is higher on a mg/kg basis than heavier children.

Fixed-dosing: Tablets, Oral solution (darunavir: 100 mg/mL): Note: Darunavir oral solution dose volume for some weight ranges are rounded for convenience.

10 kg to <11 kg: Darunavir 200 mg (2 mL) twice daily plus ritonavir 32 mg twice daily.

11 kg to <12 kg: Darunavir 220 mg (2.2 mL) twice daily plus ritonavir 32 mg twice daily.

12 kg to <13 kg: Darunavir 240 mg (2.4 mL) twice daily plus ritonavir 40 mg twice daily.

13 kg to <14 kg: Darunavir 260 mg (2.6 mL) twice daily plus ritonavir 40 mg twice daily.

14 kg to <15 kg: Darunavir 280 mg (2.8 mL) twice daily plus ritonavir 48 mg twice daily.

15 kg to <30 kg: Darunavir 375 mg (tablets or 3.8 mL) twice daily plus ritonavir 48 mg twice daily.

30 kg to <40 kg: Darunavir 450 mg (tablets or 4.6 mL) twice daily plus ritonavir 100 mg twice daily.

≥40 kg: Darunavir 600 mg (tablet or 6 mL) twice daily plus ritonavir 100 mg twice daily.

Children ≥12 years and Adolescents weighing 30 to <40 kg: Treatment-naive patients or treatment-experienced patients without or with mutations associated with darunavir resistance:

Twice-daily regimen: Darunavir 450 mg twice daily plus ritonavir 100 mg twice daily.

Once-daily regimen: Darunavir 675 mg (combination of tablets) once daily plus ritonavir 100 mg once daily; Note: Regimen not routinely suggested but has been recommended by some experts.

Children ≥12 years and Adolescents weighing ≥40 kg:

Treatment-naive patients or treatment-experienced patients without mutations associated with darunavir resistance: Darunavir 800 mg (tablet or combination of tablets) once daily plus ritonavir 100 mg once daily or cobicistat 150 mg once daily (Ref).

Treatment-experienced patients with at least one darunavir resistance-associated mutation: Darunavir 600 mg twice daily plus ritonavir 100 mg twice daily.

HIV-1 nonoccupational postexposure prophylaxis

HIV-1 nonoccupational postexposure prophylaxis (nPEP) (Ref): Note: Initiate therapy within 72 hours of exposure and continue for 28 days in combination with other antiretroviral agents; Oral:

Children ≥3 years weighing ≥10 kg:

10 to <11 kg: 200 mg twice daily plus ritonavir 32 mg twice daily.

11 to <12 kg: 220 mg twice daily plus ritonavir 32 mg twice daily.

12 to <13 kg: 240 mg twice daily plus ritonavir 40 mg twice daily.

13 to <14 kg: 260 mg twice daily plus ritonavir 40 mg twice daily.

14 to <15 kg: 280 mg twice daily plus ritonavir 48 mg twice daily.

15 to <30 kg: 375 mg twice daily plus ritonavir 48 mg twice daily.

30 to <40 kg: 450 mg twice daily plus ritonavir 100 mg twice daily.

≥40 kg: 600 mg twice daily plus ritonavir 100 mg twice daily.

Adolescents: 800 mg once daily plus ritonavir 100 mg once daily.

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

Dosing: Kidney Impairment: Pediatric

Children ≥3 years and Adolescents:

CrCl ≥30 mL/minute: No dosage adjustment required (Ref).

CrCl <30 mL/minute: There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Children ≥3 years and Adolescents:

Mild to moderate impairment: No dosage adjustment necessary; however, use with caution. Darunavir is primarily metabolized by the liver.

Severe impairment: Use not recommended.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency of adverse events is reported for adults (grades ≥2) for darunavir/ritonavir with a concomitant optimized background regimen in both treatment-naive and experienced patients, unless otherwise noted. Frequency, type, and severity of adverse events in pediatric patients are comparable to adult patients unless otherwise noted. Also see Ritonavir monograph.

>10%:

Dermatologic: Skin rash (children and adolescents: 5% to 19%; adults: 6% to 7%)

Endocrine & metabolic: Increased LDL cholesterol (children and adolescents: grade 3: 3%; adults: 8% to 14%), increased serum cholesterol (children and adolescents: grade 3: 1%; adults: 1% to 25%), increased serum glucose (≤11%)

Gastrointestinal: Diarrhea (children and adolescents: 11% to 24%; adults: 9% to 14%), nausea (children and adolescents: 4% to 25%; adults: 4% to 7%), vomiting (children and adolescents: 13% to 33%; adults: 2% to 5%)

1% to 10%:

Dermatologic: Pruritus (adolescents: 8%; adults: <2%), urticaria (<2%)

Endocrine & metabolic: Diabetes mellitus (≤2%), increased serum triglycerides (1% to 10%)

Gastrointestinal: Abdominal distention (2%), abdominal pain (5% to 10%), acute pancreatitis (<2%), anorexia (2% to 5%), decreased appetite (adolescents: 8%), dyspepsia (≤2%), flatulence (<2%), increased serum amylase (children and adolescents: grades 3/4: 1% to 4%; adults: 6% to 7%), increased serum lipase (children and adolescents: grade 3: 1%; adults: ≤3%)

Hepatic: Increased serum alanine aminotransferase (children and adolescents: grades 3/4: 1% to 3%; adults: ≤9%), increased serum alkaline phosphatase (≤1%), increased serum aspartate aminotransferase (children and adolescents: grade 3: 1%; adults: ≤7%)

Hypersensitivity: Angioedema (<2%), hypersensitivity reaction (<2%)

Immunologic: Immune reconstitution syndrome (<2%)

Nervous system: Abnormal dreams (<2%), asthenia (≤3%), fatigue (≤3%), headache (3% to 9%)

Neuromuscular & skeletal: Myalgia (<2%), osteonecrosis (<2%)

<1%:

Dermatologic: Stevens-Johnson syndrome

Hepatic: Hepatitis (including acute hepatitis, cytolytic hepatitis, and hepatotoxicity), hyperbilirubinemia

Postmarketing:

Dermatologic: Acute generalized exanthematous pustulosis, erythema multiforme (DHHS 2011), toxic epidermal necrolysis

Endocrine & metabolic: Hypercholesterolemia (DHHS 2011), redistribution of body fat

Genitourinary: Crystalluria

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms

Renal: Renal disease (crystal nephropathy)

Contraindications

Coadministration with drugs that are highly dependent on CYP3A for clearance and drugs for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index) (eg, alfuzosin, dronedarone, colchicine [in patients with renal and/or hepatic impairment], ranolazine, ergot derivatives [dihydroergotamine, ergonovine, ergotamine, methylergonovine], lurasidone, pimozide, midazolam (oral), triazolam, St. John's wort, elbasvir/grazoprevir, lomitapide, lovastatin, simvastatin, rifampin, sildenafil [for the treatment of pulmonary hypertension], ivabradine, naloxegol). Must be coadministered with ritonavir; refer to individual monograph for ritonavir for additional contraindication information.

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): Hypersensitivity to darunavir or any component of the formulation; severe (Child-Pugh class C) hepatic impairment; coadministration with amiodarone, apixaban, lidocaine (systemic), rivaroxaban.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular concerns: Possible higher risk of cardiovascular disease associated with the cumulative use of ritonavir-boosted darunavir; consider avoiding darunavir-based regimens in patients with high cardiac risk (HHS [ARV adult] 2023; Ryom 2018).

• Fat redistribution: May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).

• Hepatotoxicity: Infrequent cases of drug-induced hepatitis (including acute and cytolytic) have been reported. Liver injury has been reported with use (including some fatalities), though generally in patients on multiple medications, with advanced HIV disease, hepatitis B/C coinfection, and/or immune reconstitution syndrome. Monitor patients closely; consider interrupting or discontinuing therapy if signs/symptoms of liver impairment occur.

• Hypersensitivity reactions: Protease inhibitors have been associated with a variety of hypersensitivity events (some severe), including rash, anaphylaxis (rare), angioedema, bronchospasm, erythema multiforme, Stevens-Johnson syndrome (rare), acute generalized exanthematous pustulosis, toxic epidermal necrolysis, and/or drug rash with eosinophilia and systemic symptoms (DRESS). Discontinue treatment if severe skin reactions develop. Severe skin reactions may be accompanied by fever, malaise, fatigue, arthralgias, hepatitis, oral lesions, blisters, conjunctivitis, and/or eosinophilia. Mild-to-moderate rash may occur early in treatment and resolve with continued therapy.

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.

• Sulfonamide allergy: Use with caution in patients with sulfonamide allergy (contains sulfa moiety).

Disease-related concerns:

• Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of antidiabetic agents may be required.

• Hemophilia A or B: Use with caution in patients with hemophilia A or B; increased bleeding during protease inhibitor (PI) therapy has been reported. In some patients, additional factor VIII was administered. In more than half the cases, PI therapy was continued or reintroduced if it had been discontinued.

• Hepatic impairment: May exacerbate preexisting hepatic dysfunction; use with caution in patients with underlying hepatic disease, such as hepatitis B or C or cirrhosis. Use is not recommended in severe impairment.

Special populations:

• Pediatric: Do not administer darunavir with ritonavir in pediatric patients younger than 3 years (toxicity and mortality observed in animal studies).

Other warnings/precautions:

• Administration: Must be administered with concomitant ritonavir and food to achieve the desired antiviral effect.

Warnings: Additional Pediatric Considerations

Do not use darunavir in children <3 years of age or weighing <10 kg; seizures and death associated with immaturity of the blood-brain barrier and immature hepatic metabolic pathways were observed in juvenile rats (HHS [pediatric] 2019). Although once daily dosing in treatment-naive pediatric patients or treatment-experienced pediatric patients with no darunavir resistance-associated viral mutations was FDA approved in February 2013, once daily dosing is not recommended for: Any patient <12 years or <40 kg, patients 12 to 18 years who are treatment-experienced with prior treatment failure, or patients ≥18 years with darunavir resistance-associated viral mutations (HHS [pediatric] 2019).

Darunavir can cause crystalluria but is not associated with nephrolithiasis. Some adverse effects have been reported more frequently in pediatric patients (6 to 18 years) than adults including: Vomiting (13% to 33% vs 2% to 5%); headache (9% vs 3% to 7%); pruritus (8% vs <2%); decreased appetite (8% vs 2%).

Dosage Forms: US

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

Suspension, Oral:

Prezista: 100 mg/mL (200 mL) [contains methylparaben sodium; strawberry cream flavor]

Tablet, Oral:

Prezista: 75 mg, 150 mg

Prezista: 600 mg [contains fd&c yellow #6 (sunset yellow)]

Prezista: 800 mg

Generic: 600 mg, 800 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Suspension (Prezista Oral)

100 mg/mL (per mL): $7.19

Tablets (Darunavir Oral)

600 mg (per each): $22.90 - $39.81

800 mg (per each): $46.15 - $79.62

Tablets (Prezista Oral)

75 mg (per each): $5.40

150 mg (per each): $10.79

600 mg (per each): $43.16

800 mg (per each): $86.33

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. [DSC] = Discontinued product

Suspension, Oral:

Prezista: 100 mg/mL ([DSC]) [contains methylparaben sodium]

Tablet, Oral:

Prezista: 75 mg [DSC], 150 mg [DSC]

Prezista: 600 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake]

Prezista: 800 mg [DSC]

Generic: 600 mg, 800 mg

Administration: Adult

Oral: Administer with food. Shake suspension prior to each dose; use provided oral dosing syringe to measure dose.

Administration: Pediatric

Coadministration with ritonavir and food is required (bioavailability is increased). Shake suspension well prior to each dose; use an oral dosing syringe to measure dose. Careful instructions to caregiver may be necessary when patient is receiving a combination of tablets to achieve dose. In patients taking darunavir once daily, if a dose of darunavir or ritonavir is missed by >12 hours, the next dose should be taken at the regularly scheduled time. If a dose of darunavir or ritonavir is missed by <12 hours, the dose should be taken immediately and then the next dose should be taken at the regularly scheduled time. In patients taking darunavir twice daily, if a dose of darunavir or ritonavir is missed by >6 hours, the next dose should be taken at the regularly scheduled time. If a dose of darunavir or ritonavir is missed by <6 hours, the dose should be taken immediately and then the next dose should be taken at the regularly scheduled time.

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection, coadministered with ritonavir and other antiretroviral agents, in adults and pediatric patients 3 years and older

Use: Off-Label: Adult

HIV-1 infection, nonoccupational postexposure prophylaxis

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

Prezista may be confused with Prezcobix

Pediatric patients: High-risk medication:

KIDs List: Darunavir, when used in patients <3 years of age or weighing <10 kg, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of seizures and death (strong recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate), CYP3A4 (strong)

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 (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider therapy modification

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

Adagrasib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Adagrasib. Management: Avoid use of adagrasib and strong CYP3A4 inhibitors until adagrasib concentrations have reached steady state (ie, after approximately 8 days of therapy). Risk D: Consider therapy modification

Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider therapy modification

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

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

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

Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25 mg and maximum dose to 12.5 mg in any 24-period when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider therapy modification

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

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

Amiodarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Amiodarone. Management: Consider alternatives to use of amiodarone and strong CYP3A4 inhibitors. If combined, monitor for increased amiodarone concentrations and toxicities. Risk D: Consider therapy modification

Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

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

Amoxapine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy

Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

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

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

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

ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification

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

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

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

Atidarsagene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Atidarsagene Autotemcel. Risk X: Avoid combination

Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended atogepant dose is 10 mg once daily with a concurrent strong CYP3A4 inhibitor. If used for treatment of chronic migraine, concurrent use of atogepant with strong CYP3A4 inhibitors should be avoided. Risk D: Consider therapy modification

Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Atomoxetine. Risk C: Monitor therapy

Atorvastatin: Darunavir may increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose necessary and limit the atorvastatin dose to 20 mg daily in patients taking darunavir. Monitor patients for signs and symptoms of myopathy at initiation of therapy and with any dose increase. Risk D: Consider therapy modification

Avacopan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk D: Consider therapy modification

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

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

Bedaquiline: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with strong CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline, including QTc interval prolongation. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination

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

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

Bosentan: Protease Inhibitors may increase the serum concentration of Bosentan. Management: Dose adjustment of bosentan and increased monitoring for bosentan toxicities is necessary when these agents are combined. See full drug interaction monograph for details. Risk D: Consider therapy modification

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

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

Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider therapy modification

Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification

Bromocriptine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification

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

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

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

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification

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

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

BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider therapy modification

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

Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Risk D: Consider therapy modification

Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Carvedilol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: Avoid this combination whenever possible. If combined, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

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

Clarithromycin: Protease Inhibitors may decrease serum concentrations of the active metabolite(s) of Clarithromycin. Protease Inhibitors may increase the serum concentration of Clarithromycin. Management: Do not exceed clarithromycin doses greater than 1,000 mg/day in patients taking protease inhibitors. If CrCL is 30 to 60 mL/min, reduced clarithromycin dose 50%. If CrCL is less than 30 mL/min, reduced clarithromycin dose 75%. Risk D: Consider therapy modification

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

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

ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

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

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

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

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

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

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

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

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

Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider therapy modification

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

Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors whenever possible. If combined use cannot be avoided, crizotinib dose reductions are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider therapy modification

CycloPHOSphamide: Protease Inhibitors may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased. Protease Inhibitors may increase the serum concentration of CycloPHOSphamide. Risk C: Monitor therapy

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

CYP3A4 Inducers (Strong): May decrease the serum concentration of Darunavir. Risk C: Monitor therapy

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

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

Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification

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

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

Darifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are combined. Risk D: Consider therapy modification

Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. For patients taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Risk D: Consider therapy modification

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

Delamanid: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Risk D: Consider therapy modification

Desipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Desipramine. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Risk C: Monitor therapy

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

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

Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

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

Didanosine: Darunavir may decrease the serum concentration of Didanosine. More specifically, this interaction is likely due to the effects of food (with which darunavir/ritonavir and darunavir/cobicistat are taken) on didanosine, which is supposed to be given on an empty stomach. Management: Didanosine should be administered 1 hour prior to or 2 hours after administration of darunavir/ritonavir or darunavir/cobicistat (which must be taken with food). Risk D: Consider therapy modification

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

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

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

DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Risk D: Consider therapy modification

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

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

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

Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy

Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy

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

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

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

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

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

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

Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider therapy modification

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

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

Efavirenz: Darunavir may increase the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of Darunavir. Management: Monitor for decreased concentrations and effects of darunavir and/or increased concentrations and effects of efavirenz when darunavir/ritonavir is combined with efavirenz. The use of darunavir/cobicistat in combination with efavirenz is not recommended. Risk D: Consider therapy modification

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

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

Elagolix: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider therapy modification

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

Elbasvir and Grazoprevir: Darunavir may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Administer elexacaftor/tezacaftor/ivacaftor in the morning, twice a week, 3 to 4 days apart, with no evening doses of ivacaftor alone. Specific dosing varies by age and weight. See full monograph for details. Risk D: Consider therapy modification

Eliglustat: Darunavir may increase the serum concentration of Eliglustat. Risk X: Avoid combination

Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination

Elvitegravir: Darunavir may increase the serum concentration of Elvitegravir. Management: When elvitegravir is combined with darunavir/ritonavir, the dose of elvitegravir should remain 150 mg once daily and the dose of darunavir/ritonavir should be 600 mg/100 mg twice daily. Avoid the combination of darunavir/cobicistat and elvitegravir. Risk D: Consider therapy modification

Encorafenib: Darunavir may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of Darunavir. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced darunavir efficacy and possible development of resistance. Risk D: Consider therapy modification

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

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

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

Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification

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

Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

Erythromycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased erythromycin effects and toxicities, including QTc interval prolongation. Risk D: Consider therapy modification

Estrogen Derivatives: Protease Inhibitors may decrease the serum concentration of Estrogen Derivatives. Protease Inhibitors may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider therapy modification

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

Etravirine: Darunavir may decrease the serum concentration of Etravirine. Management: Avoid coadministration of etravirine and darunavir/cobicistat. No action is required if etravirine is combined with darunavir/ritonavir. Risk D: Consider therapy modification

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

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

Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider therapy modification

Felodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider therapy modification

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

Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in patients who are also receiving strong CYP3A4 inhibitors. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider therapy modification

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

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

Flecainide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Flecainide. Risk C: Monitor therapy

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

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

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

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider therapy modification

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

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

Fosphenytoin-Phenytoin: Darunavir may decrease the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

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

Fusidic Acid (Systemic): May increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Fusidic Acid (Systemic). Management: Avoid this combination if possible, due to the risk of increased concentrations of both agents which increases the risk of hepatotoxicity. If combined, monitor patients closely for adverse effects of both agents. Risk D: Consider therapy modification

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

Garlic: May decrease the serum concentration of Protease Inhibitors. Risk X: Avoid combination

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

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

Gilteritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. If the combination cannot be avoided, monitor more closely for evidence of gilteritinib toxicities. Risk D: Consider therapy modification

Glasdegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider therapy modification

Glecaprevir and Pibrentasvir: Darunavir may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination

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

Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for halofantrine toxicities, including QTc interval prolongation. Risk D: Consider therapy modification

Haloperidol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

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

Hormonal Contraceptives: Protease Inhibitors may decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification

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

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

Iboga: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iboga. Risk C: Monitor therapy

Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Risk X: Avoid combination

Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider therapy modification

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

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

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

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

Imipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Imipramine. Risk C: Monitor therapy

Indinavir: Darunavir may increase the serum concentration of Indinavir. Indinavir may increase the serum concentration of Darunavir. Risk X: Avoid combination

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

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

Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification

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

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

Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider therapy modification

Itraconazole: Darunavir may increase the serum concentration of Itraconazole. Itraconazole may increase the serum concentration of Darunavir. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving darunavir/ritonavir and monitor for increased itraconazole adverse effects during coadministration. Risk D: Consider therapy modification

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

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

Ivosidenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily and monitor for increased ivosidenib toxicities, including QTc interval prolongation. Risk D: Consider therapy modification

Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

Ketoconazole (Systemic): Darunavir may increase the serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase the serum concentration of Darunavir. Management: Limit the adult maximum ketoconazole dose to 200 mg/day in patients receiving darunavir/ritonavir and monitor closely for ketoconazole adverse effects. Risk D: Consider therapy modification

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

Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Larotrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Levomethadone: Darunavir may decrease the serum concentration of Levomethadone. More specifically, the combination of Darunavir and Ritonavir may decrease Methadone serum concentrations. Risk C: Monitor therapy

Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

Lofepramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy

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

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

Lopinavir: May decrease the serum concentration of Darunavir. Risk X: Avoid combination

Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider therapy modification

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

Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination

Lumacaftor and Ivacaftor: Darunavir may increase the serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease the serum concentration of Darunavir. Management: Consider alternatives. If combined, monitor for reduced darunavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider therapy modification

Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and strong CYP3A4 inhibitors. If coadministration with a strong CYP3A4 inhibitor cannot be avoided, reduce the lurbinectedin dose by 50%. Risk D: Consider therapy modification

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

Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider therapy modification

Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider therapy modification

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

Mavorixafor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mavorixafor. Management: Decrease the mavorixafor dose to 200 mg daily if combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

Mequitazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Methadone: Darunavir may decrease the serum concentration of Methadone. More specifically, the combination of Darunavir and Ritonavir may decrease Methadone serum concentrations. Risk C: Monitor therapy

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

Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoclopramide. Risk C: Monitor therapy

Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

Midazolam: Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam is contraindicated with protease inhibitors. Avoid use with nasal midazolam. Consider alternatives to use with other routes of midazolam (IV, IM) when possible. Consider use of lower midazolam doses if combined. Risk X: Avoid combination

Midostaurin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification

MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider therapy modification

Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

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

Nevirapine: Darunavir may increase the serum concentration of Nevirapine. Nevirapine may increase the serum concentration of Darunavir. Management: Avoid coadministration of darunavir/cobicistat and nevirapine. No action is required if darunavir/ritonavir is combined with nevirapine. Risk D: Consider therapy modification

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

NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification

Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Risk D: Consider therapy modification

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

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

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

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

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

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

Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy

Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Risk D: Consider therapy modification

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

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

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

Ombitasvir, Paritaprevir, and Ritonavir: May decrease the serum concentration of Darunavir. Management: These agents can be combined in treatment naive patients or those with no darunavir resistance if the darunavir dose is 800 mg daily, darunavir is administered at the same time as the combination product, and darunavir is given without ritonavir. Risk D: Consider therapy modification

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May decrease the serum concentration of Darunavir. Management: Avoid combination in treatment experienced patients with darunavir resistance substitution(s) or no baseline resistance information. In treatment naive patients or those with no darunavir resistance, darunavir 800 mg daily (without ritonavir) can be used. Risk D: Consider therapy modification

Omeprazole: Darunavir may decrease the serum concentration of Omeprazole. Risk C: Monitor therapy

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

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy

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

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

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

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

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

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

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

Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider therapy modification

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

Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider therapy modification

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

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

PARoxetine: Darunavir may decrease the serum concentration of PARoxetine. Risk C: Monitor therapy

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

Pemigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification

Perhexiline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Perphenazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy

Pexidartinib: CYP3A4 Inhibitors (Strong) 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

PHENobarbital: Darunavir may decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy

Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pirtobrutinib. Management: Avoid concomitant use when possible. If combined, reduce the pirtobrutinib dose by 50 mg. If current dose is 50 mg, interrupt pirtobrutinib treatment during strong CYP3A4 inhibitor use. Risk D: Consider therapy modification

Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Risk C: Monitor therapy

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

PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Pralsetinib: CYP3A4 Inhibitors (Strong) 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

Pravastatin: Darunavir may increase the serum concentration of Pravastatin. This effect has been demonstrated with darunavir/ritonavir and may occur with darunavir/cobicistat. The individual contributions of darunavir, ritonavir, and cobicistat are unknown. Risk C: Monitor therapy

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

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

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

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

Primidone: Darunavir may decrease the serum concentration of Primidone. Risk C: Monitor therapy

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

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Propranolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Darunavir. Protease Inhibitors may increase the serum concentration of Darunavir. Risk X: Avoid combination

Protriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy

QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of original dose after starting a strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Risk D: Consider therapy modification

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

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

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

Quizartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor therapy

Ribociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily. Risk D: Consider therapy modification

Rifabutin: Darunavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Darunavir labeling recommends a decrease of at least 75%, to a maximum of 150 mg every other day for adults. Clinical guidelines recommend 150 mg/day when used with darunavir/ritonavir. Risk D: Consider therapy modification

RifAMPin: May decrease the serum concentration of Darunavir. Risk X: Avoid combination

Rifapentine: May decrease the serum concentration of Darunavir. Risk X: Avoid combination

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

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

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

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

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

Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. For clarithromycin, refer to more specific clarithromycin-rivaroxaban monograph recommendations. Risk C: Monitor therapy

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

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

Rosuvastatin: Protease Inhibitors may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy

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

Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider therapy modification

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

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

Saquinavir: May decrease the serum concentration of Darunavir. Risk X: Avoid combination

SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Selpercatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 40 mg twice/day, or from 160 mg twice/day to 80 mg twice/day. Risk D: Consider therapy modification

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

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

Sertraline: Darunavir may decrease the serum concentration of Sertraline. Risk C: Monitor therapy

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

Sildenafil: Protease Inhibitors may increase the serum concentration of Sildenafil. Management: Use of protease inhibitors and sildenafil for the treatment of PAH is contraindicated. If using sildenafil for the treatment of erectile dysfunction, limit the sildenafil dose to 25 mg and do not use more frequently than every 48 hours. Risk D: Consider therapy modification

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

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

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

Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification

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

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

Solifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit doses in pediatric patients to the recommended weight-based starting dose (and do not increase the dose) when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

St John's Wort: May decrease the serum concentration of Darunavir. Risk X: Avoid combination

SUFentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Risk D: Consider therapy modification

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

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

Tacrolimus (Systemic): Protease Inhibitors may enhance the nephrotoxic effect of Tacrolimus (Systemic). Protease Inhibitors may decrease the metabolism of Tacrolimus (Systemic). Management: Consider reducing the tacrolimus dose to 1 mg once or twice per week if coadministered with protease inhibitors that are strong inhibitors of CYP3A4. Monitor response, plasma concentrations (as appropriate), and for signs of toxicity. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to one-third of the original dose if starting posaconazole or voriconazole. Coadministration with nelfinavir is not generally recommended. Tacrolimus dose reductions or prolongation of dosing interval will likely be required. Risk D: Consider therapy modification

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

Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D: Consider therapy modification

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification

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

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

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

Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Tenofovir Disoproxil Fumarate: May increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

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

Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor therapy

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

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

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph for details. Risk D: Consider therapy modification

Thioridazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider therapy modification

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

Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy

Tipranavir: May decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Tipranavir. Risk X: Avoid combination

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

Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modification

Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

TraZODone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

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

Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider therapy modification

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

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

Trimipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy

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

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

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

Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are often needed when combined with strong CYP3A4 inhibitors. Specific adjustments vary based on upadacitinib indication. See full interact monograph for details. Risk D: Consider therapy modification

Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Valproate Products: Protease Inhibitors may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy

Vamorolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vamorolone. Management: Reduce the vamorolone dose to 4 mg/kg daily, with a maximum dose of 200 mg daily for patients weighing over 50 kg, when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

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

Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification

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

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

Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit the maximum vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Voriconazole: Darunavir may decrease the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Darunavir. Management: This combination should be avoided unless the risks of potentially altered drug concentrations are outweighed by potential benefits of therapy. Risk D: Consider therapy modification

Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Vortioxetine. Risk C: Monitor therapy

Warfarin: Darunavir may decrease the serum concentration of Warfarin. Darunavir may increase the serum concentration of Warfarin. Risk C: Monitor therapy

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

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

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

Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider therapy modification

Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Zuranolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuranolone. Management: Reduce the zuranolone dose to 30 mg once daily when used concomitantly with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Food Interactions

Absorption and bioavailability are increased when administered with food. Management: Take with meals.

Reproductive Considerations

Contraception is not required to initiate or continue antiretroviral therapy (ART).

Patients with HIV not planning to become pregnant may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. Consult drug interactions database for more detailed information specific to use of darunavir and specific contraceptives; particularly if efficacy of the contraceptive method is of primary importance.

The Health and Human Services (HHS) perinatal HIV guidelines consider darunavir (when combined with low-dose ritonavir boosting) a preferred protease inhibitor for patients with HIV who are not yet pregnant but are trying to conceive. Darunavir (when combined with low-dose cobicistat boosting) is not recommended for use in patients who are planning to become pregnant.

Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.

Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).

Pregnancy Considerations

Darunavir has a low level of transfer across the human placenta.

No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm birth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction. The risk of hepatic dysfunction and gestational diabetes may be increased in pregnant patients taking protease inhibitors. Consider performing the standard glucose screening test earlier in pregnancy in patients who initiated protease inhibitor therapy prior to conception.

The Health and Human Services (HHS) perinatal HIV guidelines consider darunavir (when combined with low-dose ritonavir boosting) a preferred protease inhibitor for pregnant patients with HIV who are antiretroviral naive (initial therapy), who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking darunavir may continue if viral suppression is effective and the regimen is well tolerated. Darunavir (when combined with low-dose ritonavir boosting) can be used when early (acute/recent) HIV infection is detected during pregnancy. Use is part of a preferred regimen in patients previously treated with long-acting cabotegravir for preexposure prophylaxis (PrEP); genotyping may be required prior to treatment. Use is part of an alternative regimen in patients not previously treated with long-acting cabotegravir for PrEP.

Darunavir serum concentrations are decreased during pregnancy; therefore, ritonavir-boosted twice-daily dosing should be used. Product labeling provides guidance for use of once-daily darunavir dosing (combined with low-dose ritonavir boosting) in patients who are pregnant; however, the current HHS perinatal guidelines do not recommend once-daily dosing during pregnancy.

Darunavir (when combined with low-dose cobicistat boosting) is not recommended for use during pregnancy. Exposure to darunavir is decreased in pregnant patients when combined with cobicistat. If pregnancy occurs during therapy, consideration should be given to changing to a preferred or alternative regimen. If continued in patients who are virologically suppressed, frequent viral load monitoring is recommended.

ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.

Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.

Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).

Breastfeeding Considerations

It is not known if darunavir is present in breast milk.

Darunavir (when combined with low-dose ritonavir boosting) is a recommended component of an initial regimen when early (acute/recent) HIV infection is detected in patients who are breastfeeding. Breastfeeding should be interrupted and not continued if infection is confirmed. Milk may be expressed and stored while waiting for confirmation.

Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.

Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2023).

Dietary Considerations

Absorption increased with food. Take with meals.

Monitoring Parameters

Viral load, CD4, baseline genotypic and/or phenotypic testing in treatment-experienced patients (if possible); serum glucose; transaminase levels prior to and during therapy (increase monitoring in patients at risk for liver impairment), cholesterol, triglycerides

Mechanism of Action

Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

Pharmacokinetics (Adult Data Unless Noted)

All kinetic parameters derived in the presence of ritonavir coadministration; pharmacokinetic data in pediatric patients (6 to 18 years) reported to be similar to adult data.

Absorption: Increased ~40% with food

Protein binding: ~95%; primarily to alpha1 acid glycoprotein (AAG)

Metabolism: Hepatic, via CYP3A to minimally active metabolites

Bioavailability: Absolute oral: 82% (darunavir 600 mg single dose with ritonavir twice daily); bioavailability is increased 30% to 40% with food

Half-life elimination: ~15 hours

Time to peak, plasma: 2.5 to 4 hours

Excretion: Feces (~80%, 41% as unchanged drug); urine (~14%, 8% as unchanged drug)

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

  • (AR) Argentina: Resisvir;
  • (AT) Austria: Darunavir accord | Darunavir krka | Darunavir mylan | Darunavir ratiopharm | Darunavir sandoz | Darunavir stada | Prezista;
  • (AU) Australia: Prezista;
  • (BE) Belgium: Darunavir krka | Darunavir mylan | Darunavir sandoz | Prezista;
  • (BF) Burkina Faso: Prezista;
  • (BG) Bulgaria: Darunavir mylan;
  • (BR) Brazil: Prezista;
  • (CH) Switzerland: Darunavir mepha | Darunavir mylan | Darunavir sandoz | Prezista;
  • (CL) Chile: Civaspan | Prezista;
  • (CN) China: Prezista;
  • (CO) Colombia: Darivih | Daruhet | Darunavir | Darunax | Daruvir | Durart | Furthas | Predaru | Prenavir | Prezista | Protinavir | Sarux;
  • (CZ) Czech Republic: Darunavir krka | Darunavir mylan | Darunavir sandoz | Darunavir teva;
  • (DE) Germany: Darunasta | Darunavir accord | Darunavir al | Darunavir amarox | Darunavir beta | Darunavir Glenmark | Darunavir heumann | Darunavir hexal | Darunavir hormosan | Darunavir mylan | Darunavir puren | Darunavir ratiopharm | Darunavir tillomed | Darunavir Zentiva | Prezista;
  • (EC) Ecuador: Antivirox | Daruhet | Darunavir etanolato | Darunax | Prezista;
  • (EE) Estonia: Darunavir krka | Prezista;
  • (EG) Egypt: Prezista;
  • (ES) Spain: Darunavir aurovitas | Darunavir dr. reddys | Darunavir kern pharma | Darunavir mylan | Darunavir sandoz | Darunavir stada | Darunavir tarbis | Prezista;
  • (ET) Ethiopia: Darunavir;
  • (FI) Finland: Darunavir accord | Darunavir krka | Darunavir medical valley | Darunavir mylan | Darunavir sandoz | Darunavir stada | Prezista;
  • (FR) France: Darunavir accord | Darunavir arrow | Darunavir biogaran | Darunavir eg | Darunavir krka | Darunavir mylan | Darunavir reddy pharma | Darunavir sandoz | Darunavir teva | Darunavir Zentiva | Prezista;
  • (GB) United Kingdom: Prezista;
  • (GR) Greece: Darunavir mylan | Dodefar;
  • (HR) Croatia: Prezista;
  • (HU) Hungary: Darunavir alvogen | Darunavir sandoz;
  • (ID) Indonesia: Prezista;
  • (IE) Ireland: Darunavir accord | Darunavir clonmel | Darunavir krka | Darunavir mylan | Darunavir rowex | Prezista;
  • (IN) India: Daruvir | Virem;
  • (IT) Italy: Darunavir accord | Darunavir aurobindo | Darunavir dr. reddys | Darunavir eg | Darunavir Krka d.d. | Darunavir mylan | Darunavir sandoz | Darunavir teva | Darunavir tillomed | Darunavir Zentiva | Prezista;
  • (KE) Kenya: Prezista;
  • (KR) Korea, Republic of: Prezista | Prezistanaive;
  • (LT) Lithuania: Darunavir mylan | Prezista;
  • (LU) Luxembourg: Prezista;
  • (LV) Latvia: Darunavir krka | Darunavir mylan;
  • (MX) Mexico: Altlegr | Civine | Prezista;
  • (NG) Nigeria: Prezista;
  • (NL) Netherlands: Darunavir aurobindo | Darunavir Glenmark | Darunavir mylan | Darunavir sandoz | Darunavir teva | Darunavir xiromed | Prezista;
  • (NO) Norway: Darunavir accord | Darunavir krka;
  • (NZ) New Zealand: Darunavir mylan | Darunavir viatris | Prezista;
  • (PE) Peru: Daruna | Durart | Prezista;
  • (PL) Poland: Darunavir mylan | Darunavir sandoz | Darunavir teva | Darunavir Zentiva;
  • (PR) Puerto Rico: Prezista;
  • (PT) Portugal: Darunavir accord | Darunavir farmoz | Darunavir generis | Darunavir krka | Darunavir mylan | Darunavir sandoz | Prezista;
  • (PY) Paraguay: Prezista | Resisvir;
  • (QA) Qatar: Prezista;
  • (RO) Romania: Darunavir alvogen | Darunavir aurobindo | Darunavir mylan | Darunavir sandoz | Prezista;
  • (RU) Russian Federation: Darunavir | Darunavir canon | Darunavir nanolek | Darunavir tl | Kemeruvir | Prezista;
  • (SA) Saudi Arabia: Prezista;
  • (SE) Sweden: Darunavir accord | Darunavir krka | Darunavir mylan | Darunavir sandoz | Darunavir stada | Darunavir teva | Prezista;
  • (SG) Singapore: Prezista;
  • (SI) Slovenia: Darunavir krka | Darunavir mylan | Prezista;
  • (SK) Slovakia: Darunavir krka | Darunavir mylan | Prezista;
  • (TN) Tunisia: Prezista;
  • (TR) Turkey: Prezista;
  • (UA) Ukraine: Danavir | Darunavir krka | Presista;
  • (UG) Uganda: Durart | Prezista;
  • (UY) Uruguay: Resisvir;
  • (ZA) South Africa: Danavir | Nuradar | Paranvir | Prezista;
  • (ZM) Zambia: Prezista;
  • (ZW) Zimbabwe: Prezista
  1. Centers for Disease Control and Prevention (CDC), US Department of Health and Human Services (HHS). Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV-United States, 2016. https://stacks.cdc.gov/view/cdc/38856. Published April 18, 2016. Accessed July 11, 2016.
  2. 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.
  3. Mar-Darunavir (darunavir) tablets [product monograph]. Ottawa, Ontario, Canada: Marcan Pharmaceuticals Inc; January 2023.
  4. Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]
  5. Prezista (darunavir) [prescribing information]. Horsham, PA: Janssen Products LP; October 2022.
  6. Prezista (darunavir) [prescribing information]. Horsham, PA: Janssen Products LP; March 2023.
  7. Prezista (darunavir) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; March 2023.
  8. Public Health Agency of Canada (PHAC), Canadian Guidelines on Sexually Transmitted Infection. Last modified December 2013. Available at http://www.phac-aspc.gc.ca/std-mts/sti-its/index-eng.php. Accessed December 30, 2015.
  9. Punyawudho B, Singkham N, Thammajaruk N, et al. Therapeutic drug monitoring of antiretroviral drugs in HIV-infected patients. Expert Rev Clin Pharmacol. 2016;9(12):1583-1595. [PubMed 27626677]
  10. Refer to manufacturer’s labeling.
  11. Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018;5(6):e291-e300. doi:10.1016/S2352-3018(18)30043-2 [PubMed 29731407]
  12. Tybost (cobicistat) [prescribing information]. Foster City, CA: Gilead Sciences Inc; October 2019.
  13. US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new. Updated March 23, 2023. Accessed May 16, 2023.
  14. US Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Updated April 16, 2019. Accessed July 11, 2019.
  15. US Department of Health and Human Services (HHS) Panel on COVID-19 Treatment Guidelines. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://covid19treatmentguidelines.nih.gov. Updated October 9, 2020. Accessed October 16, 2020.
  16. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new. Updated January 31, 2023. Accessed February 23, 2023.
Topic 8842 Version 496.0

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