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Darunavir, cobicistat, emtricitabine, and tenofovir alafenamide: Drug information

Darunavir, cobicistat, emtricitabine, and tenofovir alafenamide: Drug information
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ALERT: US Boxed Warning
Post treatment acute exacerbation of hepatitis B

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and hepatitis B virus (HBV) and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue darunavir/cobicistat/emtricitabine/tenofovir alafenamide. If appropriate, anti-hepatitis B therapy may be warranted.

Brand Names: US
  • Symtuza
Brand Names: Canada
  • Symtuza
Pharmacologic Category
  • Antiretroviral, Protease Inhibitor (Anti-HIV);
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV);
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HIV);
  • Cytochrome P-450 Inhibitor
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment: Oral: 1 tablet (darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 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: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use is not recommended.

End-stage renal disease on hemodialysis: One tablet (darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg) once daily; administer after hemodialysis on dialysis days (Ref).

Dosing: Liver Impairment: Adult

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

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

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Darunavir, cobicistat, emtricitabine, and tenofovir alafenamide: Pediatric drug information")

HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Product is a fixed-dose combination; use not recommended in other weight groups. Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.

Pediatric patients weighing ≥40 kg: Oral: Symtuza (darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg per tablet): One tablet 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

Pediatric patients weighing ≥40 kg:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use is not recommended.

End-stage renal disease on hemodialysis: Adolescents: One tablet (darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg) once daily; administer after hemodialysis on dialysis days (Ref).

Dosing: Liver Impairment: Pediatric

Pediatric patients weighing ≥40 kg:

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is not recommended (has not been studied).

Adverse Reactions

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

>10%

Dermatologic: Skin rash (8% to 15%)

Endocrine & metabolic: Increased serum cholesterol (2% to 17%)

Neuromuscular & skeletal: Decreased bone mineral density (16%)

1% to 10%:

Dermatologic: Pruritus (<2%), Stevens-Johnson syndrome (<2%)

Endocrine & metabolic: Diabetes mellitus (<2%), gynecomastia (<2%), increased LDL cholesterol (5% to 9%), increased serum glucose (≤6%), increased serum triglycerides (≤7%), lipodystrophy (<2%)

Gastrointestinal: Abdominal distress (2%), acute pancreatitis (<2%), anorexia (<2%), diarrhea (9%), dyspepsia (<2%), flatulence (2%), nausea (6%), vomiting (<2%)

Hepatic: Hepatitis (<2%), increased serum alanine aminotransferase (≤2%), increased serum aspartate aminotransferase (≤2%)

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

Immunologic: Immune reconstitution syndrome (<2%)

Nervous system: Abnormal dreams (<2%), fatigue (4%), headache (3%)

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

Renal: Increased serum creatinine (≤4%)

Contraindications

Concurrent use of alfuzosin, ranolazine, dronedarone, carbamazepine, phenobarbital, phenytoin, colchicine (in patients with renal/and or hepatic impairment), rifampin, lurasidone, pimozide, ergot derivatives (eg, dihydroergotamine, ergotamine, methylergonovine), cisapride, St John's wort, elbasvir/grazoprevir, lomitapide, lovastatin, simvastatin, sildenafil (for treatment of pulmonary arterial hypertension), midazolam (oral), ivabradine, naloxegol, and triazolam

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, cobicistat, emtricitabine, tenofovir alafenamide, or any component of the formulation; severe hepatic impairment (Child-Pugh class C); coadministration with amiodarone, apixaban, dabigatran, lidocaine (systemic), rivaroxaban, salmeterol, ticagrelor

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: Drug-induced hepatitis (including acute and cytolytic) has been reported with darunavir. 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 hepatic impairment occur.

• Hypersensitivity reactions: Protease inhibitors (PI) 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.

• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Renal toxicity: Renal toxicity (acute renal failure, Fanconi syndrome, and/or proximal renal tubulopathy) has been reported with use of tenofovir prodrugs; patients with impaired renal function and those with concurrent or recent nephrotoxic therapy (including nonsteroidal anti-inflammatory drug use) are at an increased risk. Discontinue use in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

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

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of HBV have been reported in patients coinfected with HIV-1 and HBV following discontinuation of antiretroviral therapy. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue darunavir/cobicistat/emtricitabine/tenofovir alafenamide therapy. If appropriate, anti-hepatitis B therapy may be warranted, especially in patients with advanced hepatic disease or cirrhosis (post-treatment exacerbation of hepatitis may lead to hepatic decompensation or liver failure). All patients with HIV-1 should be tested for HBV prior to initiation of treatment.

• 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: Use is not recommended in patients with severe hepatic impairment (Child-Pugh class C).

• Renal impairment: Use is not recommended in patients with CrCl <30 mL/minute.

Special populations:

• Pediatric: Darunavir is not recommended in pediatric patients younger than 3 years (toxicity and mortality observed in animal studies).

Other warnings/precautions:

• False elevations in serum creatinine: Cobicistat may inhibit tubular secretion of creatinine without affecting glomerular filtration; use caution when interpreting serum creatinine values in patients with medical conditions or receiving drugs needing to be monitored with estimated CrCl. The elevation in serum creatinine usually occurs within 2 weeks of initiating therapy and is reversible after discontinuation. Patients who experience a confirmed increase in serum creatinine >0.4 mg/dL from baseline should have renal function monitored closely.

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]).

Darunavir can cause crystalluria but is not associated with nephrolithiasis (HHS [pediatric 2019]). Based on incidences reported with single entity products, 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 (8.3% vs not reported).

Emtricitabine-associated hyperpigmentation may occur at a higher frequency in pediatric patients compared to adults (children: 32%) (HHS [pediatric 2019]).

Through disruption in vitamin D metabolism, decreases in bone mineral density (BMD) have been observed with tenofovir alafenamide (TAF) after 48 weeks of treatment; however, the incidence and negative impact on BMD is less than that observed with tenofovir disoproxil fumarate (TDF). Additionally, TAF is associated with less renal toxicity than TDF but equal antiviral efficacy. A higher incidence of dyslipidemia has been reported with TAF than TDF. TAF is preferred over TDF whenever possible; do not use TAF and TDF concomitantly (HHS [pediatric 2019]).

Dosage Forms: US

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

Tablet, Oral:

Symtuza: Darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Symtuza Oral)

800-150-200-10 mg (per each): $188.68

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.

Tablet, Oral:

Symtuza: Darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg

Administration: Adult

Oral: Administer with food. Tablet may be split into 2 pieces with a tablet cutter in patients unable to swallow the tablet whole; administer entire dose immediately after splitting.

Administration: Pediatric

Oral: Administer with food. Tablet may be split into 2 pieces with a tablet cutter in patients unable to swallow the tablet whole; administer entire dose immediately after splitting.

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in adults and pediatric patients ≥40 kg who have no prior antiretroviral treatment history or who are virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable antiretroviral regimen for ≥6 months and have no known substitutions associated with resistance to darunavir or tenofovir.

Medication Safety Issues
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

Refer to individual components.

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 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 serum concentration of Acalabrutinib. Risk X: Avoid

Acrivastine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acrivastine. Risk C: Monitor

Acyclovir-Valacyclovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor

Adagrasib: CYP3A4 Inhibitors (Strong) may increase 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

Adefovir: May decrease therapeutic effects of Tenofovir Products. Adefovir may increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Adefovir. Risk X: Avoid

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

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

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

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

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

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

Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification

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

Aminoglycosides: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Aminoglycosides. Risk C: Monitor

Amiodarone: CYP3A4 Inhibitors (Strong) may increase 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 concentration of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor

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

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

Amphetamines: CYP2D6 Inhibitors (Moderate) may increase 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

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Risk D: Consider Therapy Modification

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

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure 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

ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase 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

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

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

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

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

Atidarsagene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Atidarsagene Autotemcel. Risk X: Avoid

Atogepant: CYP3A4 Inhibitors (Strong) may increase 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

Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider Therapy Modification

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

Atorvastatin: Cobicistat may increase serum concentration of Atorvastatin. Management: Avoid the combined use of atorvastatin with atazanavir/cobicistat. Atorvastatin dose should not exceed 20 mg daily when combined with other cobicistat-containing regimens. Risk D: Consider Therapy Modification

Atorvastatin: Darunavir may increase 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

Atrasentan: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atrasentan. Risk X: Avoid

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

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

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

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

Bedaquiline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bedaquiline. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Bedaquiline. Risk C: Monitor

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

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

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

Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor

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

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

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

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

Betibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Betibeglogene Autotemcel. Risk X: Avoid

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

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

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

Bosentan: Cobicistat may increase serum concentration of Bosentan. Bosentan may decrease serum concentration of Cobicistat. 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 serum concentration of Bosutinib. Risk X: Avoid

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

Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase 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 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

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider Therapy Modification

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

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

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

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

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

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

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

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

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

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

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

CarBAMazepine: Cobicistat may increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Cobicistat. Risk X: Avoid

CarBAMazepine: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

Cariprazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a strong CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification

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

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

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

Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ciclesonide (Oral Inhalation). Risk C: Monitor

Cidofovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Cidofovir. Risk C: Monitor

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

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

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

Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid

Clarithromycin: Cobicistat may decrease active metabolite exposure of Clarithromycin. Cobicistat may increase serum concentration of Clarithromycin. Management: Consider alternative antibiotics. Reduce clarithromycin dose by 50% in patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir with estimated creatinine clearance 50 to 60 mL/min. Closely monitor for clarithromycin toxicity. Risk D: Consider Therapy Modification

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

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

ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor

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

Clopidogrel: Cobicistat may decrease active metabolite exposure of Clopidogrel. Management: Consider alternatives to this combination when possible, as HIV treatment guidelines recommend that this combination not be coadministered. If coadministered, monitor closely for evidence of diminished antiplatelet response to clopidogrel. Risk D: Consider Therapy Modification

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

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

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

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

Codeine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Codeine. Risk C: Monitor

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

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

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

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

Crizotinib: CYP3A4 Inhibitors (Strong) may increase 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 increase adverse/toxic effects of CycloPHOSphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased. Protease Inhibitors may increase serum concentration of CycloPHOSphamide. Risk C: Monitor

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Strong) may increase 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 (Moderate): May decrease serum concentration of Cobicistat. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Cobicistat. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced cobicistat efficacy. Risk D: Consider Therapy Modification

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

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor

Dabrafenib: Cobicistat may increase serum concentration of Dabrafenib. Dabrafenib may decrease serum concentration of Cobicistat. Management: Consider alternatives to the combination of dabrafenib and cobicistat. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects and reduced cobicistat efficacy. Risk D: Consider Therapy Modification

Daclatasvir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification

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

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

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

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

Dasatinib: CYP3A4 Inhibitors (Strong) may increase 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 active metabolite exposure 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 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 serum concentration of Desipramine. Risk C: Monitor

Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Deutetrabenazine. Risk C: Monitor

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

DexAMETHasone (Systemic): Cobicistat may increase serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease serum concentration of Cobicistat. Management: Consider an alternative corticosteroid. Monitor patients receiving this combination closely for evidence of diminished response to the antiviral regimen as well as increased dexamethasone effects and toxicities. Risk D: Consider Therapy Modification

DexAMETHasone (Systemic): Darunavir may increase serum concentration of DexAMETHasone (Systemic). DexAMETHasone (Systemic) may decrease serum concentration of Darunavir. Management: Consider alternatives to this combination due to the potential for loss of darunavir efficacy and development of resistance. Monitor for decreased darunavir efficacy and increased dexamethasone adverse effects with any combined used. Risk D: Consider Therapy Modification

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

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

Diazoxide Choline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Diazoxide Choline. Risk C: Monitor

Didanosine: Darunavir may decrease 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 serum concentration of Dienogest. Risk C: Monitor

Digitoxin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Digitoxin. Risk C: Monitor

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

Digoxin: Cobicistat may increase serum concentration of Digoxin. Risk C: Monitor

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

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

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

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

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

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

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

Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Doxercalciferol. Risk C: Monitor

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

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

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

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

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

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

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

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

Ebastine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ebastine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ebastine. Risk C: Monitor

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

Efavirenz: Darunavir may increase serum concentration of Efavirenz. Efavirenz may decrease 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 serum concentration of Efonidipine. Risk C: Monitor

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

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

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix. Risk X: Avoid

Elbasvir and Grazoprevir: Cobicistat may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

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

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Eliglustat. Risk X: Avoid

Elivaldogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects 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

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider Therapy Modification

Encorafenib: Cobicistat may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Cobicistat. 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 cobicistat efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Encorafenib: Darunavir may increase serum concentration of Encorafenib. Encorafenib may decrease 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

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

Ensartinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ensartinib. Risk X: Avoid

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

Entrectinib: CYP3A4 Inhibitors (Strong) may increase 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

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

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

Erlotinib: CYP3A4 Inhibitors (Strong) may increase 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): Cobicistat may increase serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when cobicistat is combined with atazanavir or darunavir. If combined, monitor for increased erythromycin and cobicistat effects/toxicities. Risk D: Consider Therapy Modification

Esketamine (Injection): CYP3A4 Inhibitors (Strong) may increase serum concentration of Esketamine (Injection). Risk C: Monitor

Eslicarbazepine: May decrease serum concentration of Cobicistat. Management: Consider alternatives to eslicarbazepine in patients treated with cobicistat. If coadministration cannot be avoided, monitor for loss of virologic response. Risk D: Consider Therapy Modification

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

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

Eszopiclone: CYP3A4 Inhibitors (Strong) may increase 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

Ethosuximide: Cobicistat may increase serum concentration of Ethosuximide. Risk C: Monitor

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

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

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

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

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

Fedratinib: CYP3A4 Inhibitors (Strong) may increase 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 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 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 active metabolite exposure 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 active metabolite exposure 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 serum concentration of Finerenone. Risk X: Avoid

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

Flibanserin: CYP3A4 Inhibitors (Strong) may increase 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

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

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

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

Fluvastatin: Cobicistat may increase serum concentration of Fluvastatin. Risk C: Monitor

Fosamprenavir: Cobicistat may increase serum concentration of Fosamprenavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Risk X: Avoid

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

Fosphenytoin-Phenytoin: May decrease serum concentration of Cobicistat. Risk X: Avoid

Fosphenytoin-Phenytoin: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

Fostamatinib: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Fostamatinib. Risk C: Monitor

Fusidic Acid (Systemic): May increase serum concentration of Protease Inhibitors. Protease Inhibitors may increase 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

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

Ganciclovir-Valganciclovir: Tenofovir Products may increase serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase serum concentration of Tenofovir Products. Risk C: Monitor

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

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

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

Gepotidacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gepotidacin. Management: Avoid coadministration of gepotidacin and strong CYP3A4 inhibitors if possible. If coadministration cannot be avoided, conduct a baseline ECG, monitor closely for altered electrolytes, and correct electrolyte abnormalities as needed. Risk D: Consider Therapy Modification

Gilteritinib: CYP3A4 Inhibitors (Strong) may increase 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 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 serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid

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

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

Hormonal Contraceptives: Cobicistat may decrease serum concentration of Hormonal Contraceptives. Specifically, cobicistat may decrease serum concentrations of estrogens. Cobicistat may increase serum concentration of Hormonal Contraceptives. Specifically, cobicistat may increase serum concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with cobicistat. 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 serum concentration of HYDROcodone. Risk C: Monitor

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

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

Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase 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 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

Idelalisib: CYP3A4 Inhibitors (Strong) may increase 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 increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor

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

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

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

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

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

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

Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure 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 active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid

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

Istradefylline: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Itraconazole. Itraconazole may increase 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

Itraconazole: May increase serum concentration of Cobicistat. Cobicistat may increase serum concentration of Itraconazole. Management: Limit itraconazole to a maximum adult dose of 200 mg/day in patients treated with the elvitegravir/cobicistat/emtricitabine/tenofovir combination products. Dosing recommendations for other cobicistat-containing products are not available. Risk D: Consider Therapy Modification

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

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

Ketoconazole (Systemic): Darunavir may increase serum concentration of Ketoconazole (Systemic). Ketoconazole (Systemic) may increase 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

Ketoconazole (Systemic): May increase serum concentration of Cobicistat. Cobicistat may increase serum concentration of Ketoconazole (Systemic). Management: Limit ketoconazole to a maximum adult dose of 200 mg/day in patients being treated with the elvitegravir/cobicistat/emtricitabine/tenofovir combination product. Dosing recommendations for other cobicistat-containing products are not available. Risk D: Consider Therapy Modification

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

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

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

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

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

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

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

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

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

Levomethadone: Cobicistat may increase serum concentration of Levomethadone. Risk C: Monitor

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

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

Lofepramine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor

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

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

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

Lorlatinib: CYP3A4 Inhibitors (Strong) may increase 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 active metabolite exposure of Lovastatin. CYP3A4 Inhibitors (Strong) may increase serum concentration of Lovastatin. Risk X: Avoid

Lovotibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Lovotibeglogene Autotemcel. Risk X: Avoid

Lumacaftor and Ivacaftor: Darunavir may increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease 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

Lumacaftor and Ivacaftor: May decrease serum concentration of Cobicistat. Cobicistat may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced cobicistat efficacy. Lumacaftor/ivacaftor dose adjustments may be required; see full interact monograph for details. Risk D: Consider Therapy Modification

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

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

Manidipine: CYP3A4 Inhibitors (Strong) may increase 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 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 serum concentration of Mavacamten. Management: For patients on stable therapy with a strong CYP3A4 inhibitor initiate mavacamten at 2.5 mg daily. For patients initiating a strong CYP3A4 inhibitor during mavacamten therapy, dose reductions are recommended. See full mono for details. Risk D: Consider Therapy Modification

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

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

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

Methadone: Cobicistat may increase serum concentration of Methadone. Risk C: Monitor

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

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

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

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

Midazolam: Cobicistat may increase serum concentration of Midazolam. Management: Oral midazolam is contraindicated with cobicistat. 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

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

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

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

Mobocertinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mobocertinib. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Mobocertinib. Risk X: Avoid

Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Momelotinib. Risk C: Monitor

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

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

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

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

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

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

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

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

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

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

Nevirapine: Darunavir may increase serum concentration of Nevirapine. Nevirapine may increase 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 serum concentration of NiCARdipine. Risk C: Monitor

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

NIFEdipine: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Nilotinib. Management: Avoid if possible. If coadministration cannot be avoided, nilotinib dose adjustments are recommended and depend on the dosage form of nilotinib used and indication treated. See full monograph for details. Risk D: Consider Therapy Modification

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

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

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

Nirmatrelvir and Ritonavir: May increase serum concentration of Cobicistat. Risk C: Monitor

Nirmatrelvir and Ritonavir: May increase serum concentration of Tenofovir Alafenamide. Risk C: Monitor

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

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

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

Nonsteroidal Anti-Inflammatory Agents (Topical): May increase nephrotoxic effects of Tenofovir Products. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May increase nephrotoxic effects of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider Therapy Modification

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

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

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

Omaveloxolone: CYP3A4 Inhibitors (Strong) may increase 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 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 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 serum concentration of Omeprazole. Risk C: Monitor

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

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

OXcarbazepine: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

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

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

P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider Therapy Modification

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

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

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

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

Panobinostat: CYP3A4 Inhibitors (Strong) may increase 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

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

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

PAZOPanib: BCRP/ABCG2 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid

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

Pemigatinib: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Perhexiline. Risk C: Monitor

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

Pexidartinib: CYP3A4 Inhibitors (Strong) may increase 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: May decrease serum concentration of Cobicistat. Risk X: Avoid

PHENobarbital: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

Pimavanserin: CYP3A4 Inhibitors (Strong) may increase 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 metabolism of Pimecrolimus. Risk C: Monitor

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

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

Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase 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

Pitavastatin: Cobicistat may increase serum concentration of Pitavastatin. Risk C: Monitor

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

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

PONATinib: CYP3A4 Inhibitors (Strong) may increase 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 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

Pralsetinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase serum concentration of Pralsetinib. Management: Avoid concomitant use if possible. If combined, reduce the pralsetinib dose. If taking 400 mg or 300 mg once daily, reduce to 200 mg once daily. If taking 200 mg once daily, reduce to 100 mg once daily. Risk D: Consider Therapy Modification

Pravastatin: Darunavir may increase 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

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

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

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

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

Primidone: May decrease serum concentration of Cobicistat. Risk X: Avoid

Primidone: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

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

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

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

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

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

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

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

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

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

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

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

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

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

Regorafenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Regorafenib. Risk X: Avoid

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

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

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

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

Resmetirom: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Resmetirom. Risk X: Avoid

Retapamulin: CYP3A4 Inhibitors (Strong) may increase 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

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase active metabolite exposure of Revefenacin. Risk X: Avoid

Revumenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Revumenib. Management: If combined use is required, decrease revumenib dose for patients weighing 40 kg or more to 160 mg orally twice/day; for patients weighing less than 40 kg to 95 mg/m2 twice daily. Risk D: Consider Therapy Modification

Ribociclib: CYP3A4 Inhibitors (Strong) may increase 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 in advanced or metastatic breast cancer; reduce ribociclib dose to 200 mg daily in early breast cancer. Risk D: Consider Therapy Modification

Rifabutin: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

RifAMPin: May decrease serum concentration of Cobicistat. Risk X: Avoid

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

RifAMPin: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

Rifapentine: May decrease serum concentration of Cobicistat. Risk X: Avoid

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

Rifapentine: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

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

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

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

Riociguat: Inhibitors of CYP3A4 (Strong) and BCRP may increase serum concentration of Riociguat. Management: Consider a riociguat starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving strong CYP3A4 and BCRP inhibitors. Monitor for hypotension when these agents are combined and reduce the riociguat dose as needed. Risk D: Consider Therapy Modification

Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ripretinib. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ripretinib. Risk C: Monitor

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

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

Ritonavir: Cobicistat may increase therapeutic effects of Ritonavir. Specifically, cobicistat and ritonavir have overlapping effects on the CYP3A4-mediated metabolism of other drugs. Risk X: Avoid

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

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

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

Rosuvastatin: Darunavir may increase serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at the lowest dose and titrate slowly. Monitor for increased rosuvastatin toxicities when combined. The dose of rosuvastatin should not exceed 20 mg daily when used with darunavir/cobicistat. Risk D: Consider Therapy Modification

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

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

Salmeterol: Cobicistat may increase serum concentration of Salmeterol. Risk X: Avoid

Saquinavir: Cobicistat may increase serum concentration of Saquinavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Risk X: Avoid

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

SAXagliptin: CYP3A4 Inhibitors (Strong) may increase 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

Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor

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

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

Sildenafil: Cobicistat may increase serum concentration of Sildenafil. Management: Use of cobicistat 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 serum concentration of Silodosin. Risk X: Avoid

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

Simvastatin: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Simvastatin. CYP3A4 Inhibitors (Strong) may increase serum concentration of Simvastatin. Risk X: Avoid

Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase 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 (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification

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

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

Sofpironium: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Sofpironium. Risk C: Monitor

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

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

St John's Wort: May decrease serum concentration of Cobicistat. Risk X: Avoid

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

St John's Wort: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

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

Suzetrigine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Suzetrigine. Risk X: Avoid

Tacrolimus (Systemic): CYP3A4 Inhibitors (Strong) may increase 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 (Systemic): Protease Inhibitors may increase nephrotoxic effects of Tacrolimus (Systemic). Protease Inhibitors may decrease 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 (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor

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

Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor

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

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure 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 serum concentration of Tamsulosin. Risk X: Avoid

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

Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Taurursodiol. Risk X: Avoid

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

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

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

Tenofovir Disoproxil Fumarate: May increase adverse/toxic effects of Cobicistat. More specifically, cobicistat may impair proper tenofovir disoproxil fumarate monitoring and dosing. Risk C: Monitor

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

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

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

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

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Thioridazine. Risk X: Avoid

Thiotepa: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Thiotepa. CYP3A4 Inhibitors (Strong) may increase 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 active metabolite exposure of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ticagrelor. Risk X: Avoid

Tilidine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Tilidine. Risk C: Monitor

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

Tipranavir: Cobicistat may increase serum concentration of Tipranavir. However, the magnitude of this change is unclear, and dosing recommendations for this combination are not available. Risk X: Avoid

Tipranavir: May decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid

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

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

Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid

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

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

TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of TraMADol. Risk C: Monitor

TraZODone: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inhibitors when possible. If combined, monitor for increased tretinoin concentrations and toxicities (eg, pseudotumor cerebri, hypercalcemia). Risk D: Consider Therapy Modification

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

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

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

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

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

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

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

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

Upadacitinib: CYP3A4 Inhibitors (Strong) may increase 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 concentration of Valbenazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Valproic Acid and Derivatives: Protease Inhibitors may decrease serum concentration of Valproic Acid and Derivatives. Risk C: Monitor

Vamorolone: CYP3A4 Inhibitors (Strong) may increase 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

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification

Vardenafil: Cobicistat may increase serum concentration of Vardenafil. Management: Limit the dose of vardenafil tablets to a single 2.5 mg dose within a 72-hour period if combined with cobicistat. Avoid concomitant use of vardenafil orally disintegrating tablets and cobicistat. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification

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

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

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

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

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

Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Vinflunine. Risk X: Avoid

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

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

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

Voriconazole: Darunavir may decrease serum concentration of Voriconazole. Voriconazole may increase 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

Voriconazole: May increase serum concentration of Cobicistat. Cobicistat may increase serum concentration of Voriconazole. Management: Careful consideration of the risk/benefit ratio for voriconazole use is recommended prior to its use in patients who are being treated with cobicistat-containing products. If coadministered, monitor for voriconazole and cobicistat toxicity. Risk D: Consider Therapy Modification

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

Warfarin: Cobicistat may increase serum concentration of Warfarin. Risk C: Monitor

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

Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase 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

Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Zavegepant. Risk X: Avoid

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

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

Zopiclone: CYP3A4 Inhibitors (Strong) may increase 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 serum concentration of Zuclopenthixol. Risk C: Monitor

Zuranolone: CYP3A4 Inhibitors (Strong) may increase 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 of darunavir are increased when administered with food. Management: Take with meals.

Reproductive Considerations

This fixed-dose combination of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is not recommended for patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2024).

Refer to individual monographs for additional information.

Pregnancy Considerations

This fixed-dose combination of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is not recommended as initial therapy for pregnant patients with HIV who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking this fixed-dose combination may continue if viral suppression is effective and the regimen is well tolerated; however, concentrations may be significantly reduced during the second and third trimesters. Consider changing to a preferred or alternative regimen if pregnancy occurs during therapy. Frequent viral load monitoring (every 1 to 2 months) is recommended if continued in patients who are virologically suppressed (HHS [perinatal] 2024).

Refer to individual monographs for additional information.

Breastfeeding Considerations

Darunavir, emtricitabine and tenofovir are present in breast milk; it is not known if cobicistat is present in breast milk (HHS [perinatal] 2024).

Refer to individual monographs for additional information.

Dietary Considerations

Take with food.

Monitoring Parameters

CD4 count, HIV RNA plasma levels; serum creatinine, urine glucose, urine protein (prior to initiation and as clinically indicated during therapy); serum phosphorus (in patients with chronic kidney disease); hepatic function tests (prior to initiation and as clinically indicated), HBV testing (prior to the initiation of antiretroviral therapy); serum glucose.

Mechanism of Action

Darunavir 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. Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Inhibition of CYP3A-mediated metabolism by cobicistat increases the systemic exposure of CYP3A substrates (eg, darunavir). Emtricitabine is a cytidine analogue and tenofovir alafenamide is converted intracellularly to tenofovir (adenosine nucleotide analog) and subsequently phosphorylated by cellular kinases to the active moiety, tenofovir diphosphate. Emtricitabine and tenofovir alafenamide interfere with HIV viral RNA-dependent DNA polymerase activities resulting in inhibition of viral replication.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

  1. Eron JJ, Orkin C, Gallant J, et al; AMBER study group. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018;32(11):1431-1442. doi: 10.1097/QAD.0000000000001817. [PubMed 29683855]
  2. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Updated December 18, 2019. Accessed December 18, 2019.
  3. 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]
  4. Orkin C, Molina JM, Negredo E, et al; EMERALD study group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018;5(1):23-34. doi: 10.1016/S2352-3018(17)30179-0. [PubMed 28993180]
  5. Ryom L, Lundgren JD, El-Sadr W, et al; D:A:D study group. 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]
  6. Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) [prescribing information]. Horsham, PA: Janssen Products LP; March 2023.
  7. Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) [product monograph]. Toronto, Ontario, Canada: Janssen Inc; March 2023.
  8. 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.
  9. 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. https://aidsinfo.nih.gov/guidelines/html/2/pediatric-treatment-guidelines/0. Updated September 12, 2019. Accessed November 6, 2019.
  10. 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 December 19, 2024. Accessed December 30, 2024.
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