Version July 2025
Nirmatrelvir/ritonavir includes ritonavir, a strong CYP3A inhibitor, which may lead to greater exposure of certain concomitant medications, resulting in potentially severe, life-threatening, or fatal events.
Prior to prescribing nirmatrelvir/ritonavir: 1) Review all medications taken by the patient to assess potential drug-drug interactions with a strong CYP3A inhibitor like nirmatrelvir/ritonavir and 2) Determine if concomitant medications require a dose adjustment, interruption, and/or additional monitoring.
Consider the benefit of nirmatrelvir/ritonavir treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed.
Dosage guidance:
Dosage form information: Three different packaging configurations (ie, dose packs) for nirmatrelvir/ritonavir are available. Selection of the appropriate dose pack configuration is based on kidney function. Prescriptions should specify the numeric dose (mg) of each active ingredient.
COVID-19, mild to moderate, treatment: Note: For patients at high risk of progression to severe COVID-19, including hospitalization or death (Ref).
Oral: Nirmatrelvir 300 mg with ritonavir 100 mg, administered together, twice daily for 5 days; initiate as soon as possible after COVID-19 diagnosis, and within 5 days of symptom onset. After initiating treatment with nirmatrelvir/ritonavir, if hospitalization is required, completion of 5-day course is at the health care provider's discretion (Ref).
Missed dose: If a dose is missed within 8 hours of usual administration time, the missed dose should be administered as soon as possible, and normal dosing schedule should resume. If a dose is missed by more than 8 hours, the missed dose should not be administered, and dosing should resume at the next scheduled administration time. Do not double the dose to make up for a missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Three different packaging configurations (ie, dose packs) for nirmatrelvir/ritonavir are available. One for use in patients with eGFR ≥60 mL/minute, one for use in patients with eGFR ≥30 to <60 mL/minute, and one for use in patients with eGFR <30 mL/minute or requiring hemodialysis. When prescribing nirmatrelvir/ritonavir, the numeric dose for each active ingredient should always be specified.
Altered kidney function:
eGFR ≥60 mL/minute: No dosage adjustment necessary.
eGFR ≥30 to <60 mL/minute: Oral: Nirmatrelvir 150 mg and ritonavir 100 mg, administered together, twice daily for 5 days.
eGFR <30 mL/minute: Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together, once on day 1, then nirmatrelvir 150 mg and ritonavir 100 mg, administered together, once daily for 4 more days to complete a 5-day course.
Hemodialysis, intermittent (thrice weekly): Minimally dialyzable (~7%): Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together, once on day 1, then nirmatrelvir 150 mg and ritonavir 100 mg, administered together, once daily for 4 more days to complete a 5-day course; when scheduled dose falls on a dialysis day, administer after dialysis.
Peritoneal dialysis: Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together, once on day 1, then nirmatrelvir 150 mg and ritonavir 100 mg, administered together, once daily for 4 more days to complete a 5-day course (Ref).
Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).
Refer to adult dosing.
(For additional information see "Nirmatrelvir and ritonavir: Pediatric drug information")
Dosage guidance:
Dosage form information: Three different packaging configurations (ie, dose packs) for nirmatrelvir/ritonavir are available; use caution. Selection of the appropriate dose pack configuration depends on kidney function. Prescriptions should specify the numeric dose (mg) of each active ingredient.
COVID-19, mild to moderate; treatment: Children ≥12 years and Adolescents, weighing ≥40 kg: Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together, twice daily for 5 days; initiate as soon as possible following COVID-19 diagnosis and within 5 days of symptom onset. Patients who require hospitalization due to severe or critical COVID-19 after initiating treatment outpatient should complete the full 5-day treatment course per health care providers' discretion (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥12 years and Adolescents, weighing ≥40 kg:
eGFR ≥60 mL/minute to <90 mL/minute: Oral: No dosage adjustment necessary (Ref).
eGFR 30 to <60 mL/minute: Oral: Nirmatrelvir 150 mg and ritonavir 100 mg, administered together twice daily for 5 days (Ref).
eGFR <30 mL/minute: Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together once on day 1, followed by nirmatrelvir 150 mg and ritonavir 100 mg once daily on days 2 through 5, administered together (Ref).
Hemodialysis: Oral: Nirmatrelvir 300 mg and ritonavir 100 mg, administered together once on day 1, followed by nirmatrelvir 150 mg and ritonavir 100 mg once daily on days 2 through 5, administered together. On days of hemodialysis, administer after hemodialysis (Ref).
Children ≥12 years and Adolescents, weighing ≥40 kg:
Mild or moderate impairment: No dosage adjustment necessary (Ref).
Severe impairment: Not recommended for use (has not been studied) (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults. Also see Ritonavir monograph.
1% to 10%: Gastrointestinal: Diarrhea (3%), dysgeusia (5%)
Postmarketing:
Cardiovascular: Bradycardia (Ref), hypertension, syncope (Ref)
Dermatologic: Pruritus (Ref), severe dermatological reaction (including Stevens-Johnson syndrome and toxic epidermal necrolysis), skin rash (Ref)
Gastrointestinal: Abdominal pain, nausea, pancreatitis (Ref), vomiting
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Nervous system: Headache, malaise
Respiratory: Dyspnea (Ref)
Significant hypersensitivity (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome) to nirmatrelvir, ritonavir, or any component of the formulation; coadministration with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions (eg, alfuzosin, amiodarone, colchicine, dihydroergotamine, dronedarone, eletriptan, eplerenone, ergotamine, finerenone, flecainide, flibanserin, ivabradine, lomitapide, lovastatin, lurasidone, methylergonovine, midazolam [oral], naloxegol, pimozide, propafenone, quinidine, ranolazine, sildenafil [when used for the treatment of pulmonary arterial hypertension], silodosin, simvastatin, tolvaptan, triazolam, ubrogepant, voclosporin); coadministration with strong CYP3A inducers. Note: For some strong CYP3A inducers (eg, apalutamide, carbamazepine, enzalutamide, lumacaftor/ivacaftor, phenobarbital, phenytoin, primidone, rifapentine, rifampin, St. John's wort), initiation of nirmatrelvir/ritonavir should be delayed after discontinuation of the CYP3A inducer due to the delayed offset of the CYP3A inducer.
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): Coadministration with ergonovine, fusidic acid, neratinib, rivaroxaban, salmeterol, vardenafil, venetoclax, voriconazole.
Concerns related to adverse effects:
• Hepatic effects: Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir; use with caution in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, serious skin reactions (including toxic epidermal necrosis and Stevens-Johnson syndrome), and other hypersensitivity reactions, have been reported. Discontinue therapy and initiate appropriate treatment if signs and symptoms of anaphylaxis or severe hypersensitivity occurs.
Disease-related concerns:
• Kidney impairment: Systemic exposure of nirmatrelvir is increased in patients with kidney impairment. Dosage adjustments are recommended in patients with eGFR <60 mL/minute including those on hemodialysis.
Other warnings/precautions:
• Risk of HIV-1 protease inhibitor drug resistance: Ritonavir is also an HIV-1 protease inhibitor. There may be a risk of HIV-1 developing resistance in patients with uncontrolled or undiagnosed HIV-1 infection.
• Viral rebound: Viral rebound and recurrence of COVID-19 symptoms have been reported in some patients after completing treatment. The frequency, mechanism, and clinical implications of these events are unclear. Viral rebound and recurrence of COVID-19 symptoms can occur in the absence of treatment. Concern for viral rebound and/or recurrence of symptoms should not be a reason to avoid antiviral therapy (NIH 2023).
Paxlovid dose pack intended for use in patients with eGFR <30 mL/minute or on hemodialysis: FDA approved February 2025; anticipated availability currently unknown. Information pertaining to this formulation within the monograph is pending revision. Paxlovid dose packs intended for use in patients with eGFR <30 mL/minute or on hemodialysis contain a total of 6 tablets of nirmatrelvir 150 mg and 5 tablets of ritonavir 100 mg in each carton. Each carton contains 1 blister card with all 11 tablets. Consult the prescribing information for additional information.
Dose packs intended for use in patients with eGFR ≥60 mL/minute contain a total of 20 tablets of nirmatrelvir 150 mg and 10 tablets of ritonavir 100 mg in each carton. Each carton contains 10 blister cards; each blister card contains 2 nirmatrelvir 150 mg tablets and 1 ritonavir 100 mg tablet.
Dose packs intended for use in patients with eGFR 30 to <60 mL/minute contain a total of 10 tablets of nirmatrelvir 150 mg and 10 tablets of ritonavir 100 mg in each carton. Each carton contains 10 blister cards; each blister card contains 1 nirmatrelvir 150 mg tablet and 1 ritonavir 100 mg tablet.
Dose packs intended for use in patients with eGFR <30 mL/minute or on hemodialysis contain a total of 6 tablets of nirmatrelvir 150 mg and 5 tablets of ritonavir 100 mg in each carton. Each carton contains 1 blister card with all 11 tablets.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet Therapy Pack, Oral:
Paxlovid: Nirmatrelvir 6 x 150 mg and ritonavir 5 x 100 mg (11 ea)
Paxlovid (150/100): Nirmatrelvir 10 x 150 mg and ritonavir 10 x 100 mg (2 ea, 4 ea [DSC], 20 ea)
Paxlovid (300/100): Nirmatrelvir 20 x 150 mg and ritonavir 10 x 100 mg (3 ea, 6 ea [DSC], 30 ea)
No
Tablet Therapy Pack (Paxlovid (150/100) Oral)
10 x 150 MG &10 x 100MG (per each): $89.77
Tablet Therapy Pack (Paxlovid (300/100) Oral)
20 x 150 MG &10 x 100MG (per each): $59.84
Tablet Therapy Pack (Paxlovid Oral)
6 x 150 MG &5 x 100MG (per each): $163.21
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Paxlovid (150/100): Nirmatrelvir 10 x 150 mg and ritonavir 10 x 100 mg (20 ea)
Paxlovid (300/100): Nirmatrelvir 20 x 150 mg and ritonavir 10 x 100 mg (30 ea)
Oral: Administer with or without food. Swallow tablets whole; do not chew, break, or crush. Nirmatrelvir must be coadministered with ritonavir; failure to correctly coadminister may result in insufficient nirmatrelvir plasma levels.
NG tube : The manufacturer of Paxlovid, Pfizer, had previously posted information on how to prepare and administer nirmatrelvir and ritonavir tablets via NG tube on the medical information section of their website. However, they have subsequently removed this information and now state they are unable to make any recommendations regarding alternate preparations for administration.
Enteral: Nirmatrelvir must be coadministered with ritonavir; failure to correctly coadminister may result in insufficient nirmatrelvir plasma concentrations (Ref).
Oral: Administer with or without food. Swallow tablets whole; do not chew, break, or crush (Ref).
Nasogastric: The manufacturer of Paxlovid, Pfizer, previously posted information on how to prepare and administer nirmatrelvir and ritonavir tablets via NG tube on the medical information section of their website. However, information was subsequently removed and replaced with a statement that recommendations regarding alternative preparations for administration cannot be provided.
Missed dose: If ≤8 hours since dose was due, the missed dose should be administered as soon as possible, and normal dosing schedule should resume. If >8 hours since dose was due, the dose should be skipped, and dosing should resume at the next scheduled administration time. Do not double the dose to make up for a missed dose (Ref).
COVID-19, treatment, mild to moderate: Treatment of mild to moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.
Limitations of use: Not approved for use as pre- or postexposure prophylaxis for prevention of COVID-19. In addition, not recommended for use in patients requiring hospitalization for COVID-19 (Ref).
Note: Medical conditions and factors associated with increased risk for progression to severe COVID-19 have been identified by the CDC and can be found at https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html. This list is not exhaustive and is updated as the science evolves. Consider the benefit:risk for an individual patient.
Three different packaging configurations (ie, dose packs) for nirmatrelvir/ritonavir are available. One for use in patients with normal kidney function or mild kidney impairment (eGFR ≥60 mL/minute), one for use in patients with moderate kidney impairment (eGFR ≥30 to <60 mL/minute), and one for use in patients with severe kidney impairment (eGFR <30 mL/minute) or requiring hemodialysis. When prescribing nirmatrelvir/ritonavir, the numeric dose for each active ingredient should always be specified.
Substrate of CYP1A2 (Minor), CYP2B6 (Minor), CYP2D6 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Weak), CYP3A4 (Strong), ENT1 and CNT3, MRP2, OATP1B1/1B3, P-glycoprotein; Induces CYP1A2 (Weak), CYP2B6 (Moderate), CYP2C19 (Weak), UGT1A1;
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
Acoramidis: UGT1A1 Inducers may decrease serum concentration of Acoramidis. Risk X: Avoid
Acrivastine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acrivastine. 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
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
Albendazole: Nirmatrelvir and Ritonavir may decrease serum concentration of Albendazole. 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: Nirmatrelvir and Ritonavir may increase serum concentration of Aliskiren. Risk X: Avoid
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
ALPRAZolam: Nirmatrelvir and Ritonavir may increase serum concentration of ALPRAZolam. Management: Reduce the alprazolam dose by 50% when a patient is started on nirmatrelvir/ritonavir and alprazolam together, or when nirmatrelvir/ritonavir is initiated in a patient already treated with alprazolam. Risk D: Consider Therapy Modification
Amiodarone: Nirmatrelvir and Ritonavir may increase serum concentration of Amiodarone. Risk X: Avoid
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase serum concentration of AmLODIPine. Risk C: Monitor
Antihepaciviral Combination Products: Nirmatrelvir and Ritonavir may increase serum concentration of Antihepaciviral Combination Products. Antihepaciviral Combination Products may increase serum concentration of Nirmatrelvir and Ritonavir. 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: 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
Artesunate: Nirmatrelvir and Ritonavir may decrease active metabolite exposure of Artesunate. Nirmatrelvir and Ritonavir may increase serum concentration of Artesunate. Risk C: Monitor
Asciminib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Asciminib. 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
Atorvastatin: Nirmatrelvir and Ritonavir may increase serum concentration of Atorvastatin. Management: Consider temporarily discontinuing atorvastatin during treatment with nirmatrelvir/ritonavir. It is not necessary to hold atorvastatin either prior to or after completion of nirmatrelvir/ritonavir treatment. Risk D: Consider Therapy Modification
Atovaquone: Nirmatrelvir and Ritonavir may decrease serum concentration of Atovaquone. Risk C: Monitor
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 (Systemic): Nirmatrelvir and Ritonavir may increase serum concentration of Betamethasone (Systemic). Risk C: Monitor
Bictegravir: UGT1A1 Inducers may decrease serum concentration of Bictegravir. Risk C: Monitor
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: Nirmatrelvir and Ritonavir may increase serum concentration of Bosentan. Management: Consider alternative COVID-19 treatments in patients taking bosentan. If nirmatrelvir and ritonavir must be used, discontinue bosentan at least 36 hours before initiation of nirmatrelvir and ritonavir. Monitor for increased bosentan toxicities. 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 (Oral Inhalation): Nirmatrelvir and Ritonavir may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
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): Nirmatrelvir and Ritonavir may increase serum concentration of Budesonide (Topical). Management: Consider the risks of systemic corticosteroid adverse effects versus the benefits of coadministration. Monitor patients for systemic corticosteroid adverse effects if combined. Risk D: Consider Therapy Modification
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Buprenorphine. Risk C: Monitor
BuPROPion: Nirmatrelvir and Ritonavir may decrease serum concentration of BuPROPion. 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
Cabotegravir: Nirmatrelvir and Ritonavir may decrease serum concentration of Cabotegravir. Risk X: Avoid
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
Canagliflozin: Nirmatrelvir and Ritonavir may decrease serum concentration of Canagliflozin. 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: Nirmatrelvir and Ritonavir may increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Nirmatrelvir and Ritonavir. 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
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
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: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transporters may increase serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider Therapy Modification
Clarithromycin: Protease Inhibitors may increase serum concentration of Clarithromycin. Protease Inhibitors may decrease active metabolite exposure of Clarithromycin. Management: Do not exceed clarithromycin doses greater than 1,000 mg/day in patients taking protease inhibitors. If CrCL is 30 to 60 mL/min, reduced clarithromycin dose 50%. If CrCL is less than 30 mL/min, reduced clarithromycin dose 75%. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clobetasone: Nirmatrelvir and Ritonavir may increase serum concentration of Clobetasone. Risk C: Monitor
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase serum concentration of ClonazePAM. Risk C: Monitor
Clopidogrel: Nirmatrelvir and Ritonavir may decrease antiplatelet effects of Clopidogrel. Nirmatrelvir and Ritonavir may decrease active metabolite exposure of Clopidogrel. Management: Avoid coadministration of clopidogrel and nirmatrelvir/ritonavir when possible. Consider using alternative COVID-19 therapy or an alternative antiplatelet such as prasugrel if clinically appropriate. Risk D: Consider Therapy Modification
Clorazepate: Nirmatrelvir and Ritonavir may increase serum concentration of Clorazepate. Risk C: Monitor
CloZAPine: CYP3A4 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobicistat: Nirmatrelvir and Ritonavir may increase serum concentration of Cobicistat. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: Nirmatrelvir and Ritonavir may increase serum concentration of Colchicine. Risk X: Avoid
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
Corticosteroids (Nasal): Nirmatrelvir and Ritonavir may increase serum concentration of Corticosteroids (Nasal). Risk C: Monitor
Corticosteroids (Ophthalmic): Nirmatrelvir and Ritonavir may increase serum concentration of Corticosteroids (Ophthalmic). Risk C: Monitor
Corticosteroids (Topical): Nirmatrelvir and Ritonavir may increase serum concentration of Corticosteroids (Topical). Risk C: Monitor
Cortisone: Nirmatrelvir and Ritonavir 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: CYP2B6 Inducers (Moderate) may increase active metabolite exposure of CycloPHOSphamide. Risk C: Monitor
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): Nirmatrelvir and Ritonavir may increase serum concentration of CycloSPORINE (Systemic). Management: Consider avoiding this combination if possible and using alternative anti-COVID-19 therapy if appropriate. If coadministration is required, consider reducing cyclosporine dose by 80% and monitoring cyclosporine concentrations closely. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor
Cyproterone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cyproterone. Risk C: Monitor
Dabigatran Etexilate: Nirmatrelvir and Ritonavir may increase serum concentration of Dabigatran Etexilate. Risk C: Monitor
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider Therapy Modification
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
Deferasirox: Nirmatrelvir and Ritonavir may decrease serum concentration of Deferasirox. Risk C: Monitor
Deflazacort: Nirmatrelvir and Ritonavir may increase active metabolite exposure of Deflazacort. Management: Consider reducing the deflazacort dose to one-third the recommended dose during coadministration with nirmatrelvir and ritonavir. 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
DexAMETHasone (Systemic): Nirmatrelvir and Ritonavir may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
Diamorphine: Nirmatrelvir and Ritonavir may decrease serum concentration of Diamorphine. Risk C: Monitor
DiazePAM: Nirmatrelvir and Ritonavir may increase serum concentration of DiazePAM. Nirmatrelvir and Ritonavir may decrease serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
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: Nirmatrelvir and Ritonavir may increase serum concentration of Digoxin. Management: Reduce the digoxin dose by approximately 30% to 50%, or reduce the dosing frequency, when these agents are combined. Monitor digoxin levels closely and adjust digoxin dose as needed. Risk D: Consider Therapy Modification
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
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
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: May increase adverse/toxic effects of Nirmatrelvir and Ritonavir. Efavirenz may decrease serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may decrease concentration of nirmatrelvir. Efavirenz may increase serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may increase concentration of ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Efavirenz. Risk C: Monitor
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: 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: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider Therapy Modification
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider Therapy Modification
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: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Eluxadoline: Nirmatrelvir and Ritonavir may increase serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily and monitor patients for increased eluxadoline effects/toxicities (eg, impaired mental or physical abilities needed to drive a car or operate machinery, constipation, abdominal pain). 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): CYP3A4 Inhibitors (Strong) may increase serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased erythromycin effects and toxicities, including QTc interval prolongation. Risk D: Consider Therapy Modification
Esketamine (Injection): CYP3A4 Inhibitors (Strong) may increase serum concentration of Esketamine (Injection). 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
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: Nirmatrelvir and Ritonavir may decrease serum concentration of Etravirine. Risk C: Monitor
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: Nirmatrelvir and Ritonavir may increase serum concentration of Flecainide. Risk X: Avoid
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
Flurazepam: Nirmatrelvir and Ritonavir may increase serum concentration of Flurazepam. Risk C: Monitor
Fluticasone (Nasal): Nirmatrelvir and Ritonavir may increase serum concentration of Fluticasone (Nasal). Management: Use of nasal fluticasone together with a strong CYP3A4 inhibitor is not recommended. Consider an alternative nasal corticosteroid, when possible. Risk D: Consider Therapy Modification
Fluticasone (Oral Inhalation): Nirmatrelvir and Ritonavir may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may decrease serum concentration of Fosphenytoin-Phenytoin. 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 Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir 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
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: Nirmatrelvir and Ritonavir 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: CYP3A4 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: Nirmatrelvir and Ritonavir may decrease serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may decrease concentrations of estrogens. Nirmatrelvir and Ritonavir may increase serum concentration of Hormonal Contraceptives. Specifically, nirmatrelvir and ritonavir may increase concentrations of progestins. Management: Use additional nonhormonal forms of contraception (back-up method) when estrogen-containing hormonal contraceptives are combined with nirmatrelvir/ritonavir. 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): Nirmatrelvir and Ritonavir may increase serum concentration of Hydrocortisone (Systemic). 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
Indinavir: Nirmatrelvir and Ritonavir may increase adverse/toxic effects of Indinavir. Specifically, the risk for nephrolithiasis may be increased with this combination. Indinavir may increase serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Indinavir. 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: May increase serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Isavuconazonium Sulfate. Risk C: Monitor
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: May increase serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving nirmatrelvir/ritonavir. 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): May increase serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Ketoconazole (Systemic). Risk C: Monitor
Lacidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lacidipine. Risk C: Monitor
LamoTRIgine: Nirmatrelvir and Ritonavir may decrease serum concentration of LamoTRIgine. 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
Letermovir: UGT1A1 Inducers may decrease serum concentration of Letermovir. 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: Nirmatrelvir and Ritonavir may decrease serum concentration of Levomethadone. 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
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
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: Nirmatrelvir and Ritonavir may increase serum concentration of Lovastatin. Risk X: Avoid
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
Mebendazole: Nirmatrelvir and Ritonavir may decrease serum concentration of Mebendazole. Risk C: Monitor
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
Meptazinol: Nirmatrelvir and Ritonavir may increase serum concentration of Meptazinol. Risk X: Avoid
Methadone: Nirmatrelvir and Ritonavir may decrease serum concentration of Methadone. Risk C: Monitor
Methoxyflurane: CYP2B6 Inducers (Moderate) may increase metabolism of Methoxyflurane. Specifically, this increased metabolism may lead to increased production of nephrotoxic metabolites. Risk X: Avoid
MethylPREDNISolone: Nirmatrelvir and Ritonavir may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Midazolam: Protease Inhibitors may increase serum concentration of Midazolam. Management: Oral midazolam is contraindicated with protease inhibitors. Avoid use with nasal midazolam. Consider alternatives to use with other routes of midazolam (IV, IM) when possible. Consider use of lower midazolam doses if combined. Risk X: Avoid
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
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
Neratinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Neratinib. Risk X: Avoid
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
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
OLANZapine: Nirmatrelvir and Ritonavir may decrease serum concentration of OLANZapine. 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
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
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
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
Parecoxib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Paricalcitol. Risk C: Monitor
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
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: Nirmatrelvir and Ritonavir may decrease serum concentration of PHENobarbital. PHENobarbital may decrease serum concentration of Nirmatrelvir and Ritonavir. 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
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: 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
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
Primidone: Nirmatrelvir and Ritonavir may decrease serum concentration of Primidone. Primidone may decrease active metabolite exposure of Nirmatrelvir and Ritonavir. Risk X: Avoid
Proguanil: Nirmatrelvir and Ritonavir may decrease serum concentration of Proguanil. Risk C: Monitor
Propafenone: Nirmatrelvir and Ritonavir may increase serum concentration of Propafenone. Risk X: Avoid
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: Nirmatrelvir and Ritonavir may increase serum concentration of QuiNIDine. Risk X: Avoid
QuiNINE: May increase serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may decrease serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The effects of nirmatrelvir and ritonavir on quinine are unclear. Risk X: Avoid
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: Nirmatrelvir and Ritonavir may increase serum concentration of Red Yeast Rice. 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: Nirmatrelvir and Ritonavir may increase serum concentration of Rifabutin. Nirmatrelvir and Ritonavir may increase active metabolite exposure of Rifabutin. Management: Decrease the rifabutin dose by at least 75%, to a maximum of 150 mg every other day or 3 times weekly, during coadministration with nirmatrelvir and ritonavir. Monitor for increased rifabutin adverse effects (eg, rash, urine discoloration, neutropenia). Risk D: Consider Therapy Modification
Rifapentine: May decrease serum concentration of Nirmatrelvir and Ritonavir. 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 P-glycoprotein 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 P-gp 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: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
Ritonavir: Nirmatrelvir and Ritonavir may increase serum concentration of Ritonavir. Risk C: Monitor
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: Nirmatrelvir and Ritonavir may increase serum concentration of Rosuvastatin. Risk C: Monitor
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
Sacituzumab Govitecan: UGT1A1 Inducers may decrease active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid
Salmeterol: Nirmatrelvir and Ritonavir may increase serum concentration of Salmeterol. 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
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
Sildenafil: Protease Inhibitors may increase serum concentration of Sildenafil. Management: Use of protease inhibitors and sildenafil for the treatment of PAH is contraindicated. If using sildenafil for the treatment of erectile dysfunction, limit the sildenafil dose to 25 mg and do not use more frequently than every 48 hours. Risk D: Consider Therapy Modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Silodosin. Risk X: Avoid
Simeprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: Nirmatrelvir and Ritonavir may increase serum concentration of Simvastatin. Management: Discontinue simvastatin at least 12 hours prior to initiating nirmatrelvir and ritonavir, and do not restart simvastatin until 5 days after completing nirmatrelvir and ritonavir treatment. Risk X: Avoid
Sirolimus (Conventional): Nirmatrelvir and Ritonavir may increase serum concentration of Sirolimus (Conventional). Management: Consider avoiding this combination, if possible, through use of alternative anti-COVID-19 therapy. If combined, hold sirolimus during nirmatrelvir/ritonavir treatment and for at least 2 to 3 days after completion. Monitor sirolimus levels closely. 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
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 Nirmatrelvir and Ritonavir. 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): Nirmatrelvir and Ritonavir may increase serum concentration of Tacrolimus (Systemic). Management: Consider avoiding this combination, if possible, through use of alternative anti-COVID-19 therapy. If combined, hold tacrolimus during nirmatrelvir/ritonavir treatment and for at least 2 to 3 days after completion. Monitor tacrolimus levels closely. Risk D: Consider Therapy Modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Tadalafil: Nirmatrelvir and Ritonavir may increase serum concentration of Tadalafil. Management: In patients treated for pulmonary arterial hypertension avoid initiating nirmatrelvir and ritonavir in patients taking tadalafil. For ED or BPH treatment, decrease tadalafil max dose and frequency. See full monograph for details. Risk D: Consider Therapy Modification
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
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 Alafenamide: Nirmatrelvir and Ritonavir may increase serum concentration of Tenofovir Alafenamide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. 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
Theophylline Derivatives: Nirmatrelvir and Ritonavir may decrease serum concentration of Theophylline Derivatives. Risk C: Monitor
Thioridazine: CYP2D6 Inhibitors (Weak) may increase serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider Therapy Modification
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
Thyroid Products: Nirmatrelvir and Ritonavir may decrease therapeutic effects of Thyroid Products. Risk C: Monitor
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
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: 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 (Systemic): Nirmatrelvir and Ritonavir may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Triazolam. Risk X: Avoid
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: Nirmatrelvir and Ritonavir 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 nirmatrelvir/ritonavir. Avoid concomitant use of vardenafil orally disintegrating tablets and nirmatrelvir/ritonavir. 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
Vitamin K Antagonists: Nirmatrelvir and Ritonavir may decrease serum concentration of Vitamin K Antagonists. Nirmatrelvir and Ritonavir may increase serum concentration of Vitamin K Antagonists. 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: Nirmatrelvir and Ritonavir may decrease serum concentration of Voriconazole. Nirmatrelvir and Ritonavir may increase serum concentration of Voriconazole. Management: Consider avoiding this combination if possible. NIH COVID-19 treatment guidelines state voriconazole may be continued in patients treated with nirmatrelvir and ritonavir, but patients should be monitored for adverse effects. Risk D: Consider Therapy Modification
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Voxilaprevir. Risk X: Avoid
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
Zidovudine: Nirmatrelvir and Ritonavir may decrease serum concentration of Zidovudine. Risk C: Monitor
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
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
Ritonavir may reduce the efficacy of combination hormonal contraceptives (CHCs). Patients using CHCs should use an effective alternative contraceptive or an additional barrier contraceptive during treatment with ritonavir. Consult drug interactions database for more detailed information specific to use of ritonavir and contraceptives.
Both nirmatrelvir (Chuang 2023) and ritonavir cross the placenta.
Outcome data following maternal use of ritonavir-boosted nirmatrelvir during pregnancy are limited (Garmeau 2022; Lin 2023a; Lin 2023b; Loza 2022; Toure 2024; Wong 2024b; Zhuang 2023). Ritonavir has been highly studied in pregnant patients (Chourasia 2023); refer to the Ritonavir monograph for information related to ritonavir and pregnancy.
The risk of severe morbidity and mortality from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Symptomatic pregnant patients may require ICU admission, mechanical ventilation, or ventilatory support (ECMO). Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2024; NIH 2023).
In general, the treatment of COVID-19 infection during pregnancy is the same as in nonpregnant patients. However, because data for most therapeutic agents in pregnant patients are limited, treatment options should be evaluated as part of a shared decision-making process (NIH 2023). Pregnancy is a risk factor for severe COVID-19. The use of ritonavir-boosted nirmatrelvir is recommended and can be initiated in nonhospitalized pregnant patients who test positive for COVID-19 or are highly suspected of being positive. Evaluate potential drug interactions prior to prescribing (ACOG 2024; NIH 2023). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
Data collection to monitor maternal and infant outcomes following exposure to COVID-19 during pregnancy is ongoing. Health care providers are encouraged to enroll patients exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists pregnancy registry (1-877-311-8972; https://mothertobaby.org/join-study/).
Nirmatrelvir and ritonavir are present in breast milk.
Data related to the presence of ritonavir-boosted nirmatrelvir in breast milk are available from 8 lactating patients. Patients voluntarily provided breast milk at specified times over a 12-hour dosing interval following a standard oral dose of nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 days to a human milk biorepository. The maximum breast milk concentrations were 55.6 ng/mL (ritonavir) and 1,107 ng/mL (nirmatrelvir) occurring 4 hours after the dose. The mean breast milk concentrations were 22.48 ng/mL (ritonavir) and 729 ng/mL (nirmatrelvir). Using mean concentrations, authors of the study calculated the estimated exposure of ritonavir to the breastfeeding infant to be 0.0024 mg/kg/12 hours (relative infant dose [RID] 0.19%, based on a maternal dose of 1.27 mg/kg/12 hours) and the estimated exposure of nirmatrelvir to be 0.054 mg/kg/12 hours (RID 1.43%, based on a maternal dose of 3.83 mg/kg/12 hours). Adverse events were not reported in the infants (all but one were exclusively breastfed) (Dai 2024). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
Outcome data following the use of ritonavir-boosted nirmatrelvir in lactating patients are limited (Dai 2024; Lin 2023a).
Breast milk has not been found to be a source of COVID-19 infection and maternal infection is not a contraindication to breastfeeding. The decision to breastfeed during treatment for COVID-19 should be evaluated as part of a shared decision-making process. Breastfeeding can continue if ritonavir-boosted nirmatrelvir is needed for the management of COVID-19. However, lactating patients with COVID-19 infection can transmit the virus through respiratory droplets and all precautions should be taken to avoid spreading the virus to the infant (eg, hand hygiene, mask wearing); alternatively, breast milk can be expressed and fed to the infant by someone without confirmed or suspected COVID-19 (ACOG 2024; NIH 2023).
Information related to COVID-19 and breastfeeding is available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).
Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro; also known as 3C-like protease or nsp5 protease); inhibition of Mpro prevents processing of polyprotein precursors, resulting in inhibition of viral replication. Ritonavir is a pharmacokinetic enhancer with no activity against SARS-CoV-2 Mpro. Ritonavir inhibits CYP3A-mediated metabolism of nirmatrelvir, resulting in increased nirmatrelvir plasma concentrations.
Distribution: Vz/F: Nirmatrelvir (when given with ritonavir): 104.7 L; Ritonavir: 112.4 L.
Protein binding: Nirmatrelvir (when given with ritonavir): 69%; Ritonavir: 98% to 99%.
Metabolism: Nirmatrelvir (when given with ritonavir): Minimal; Ritonavir: Hepatic via CYP3A4 (major) and CYP2D6 (minor).
Half-life elimination: Nirmatrelvir (when given with ritonavir): 6.05 hours; Ritonavir: 6.15 hours.
Time to peak: Nirmatrelvir (when given with ritonavir): 3 hours; Ritonavir: 3.98 hours.
Excretion: Nirmatrelvir (when given with ritonavir): Feces (27.5%); urine (55%); Ritonavir: Feces (86.4%); urine (3.5%).
Altered kidney function: Following a single oral dose of nirmatrelvir/ritonavir 100 mg/100 mg, Cmax and AUC were 30% and 24% higher in subjects with eGFR ≥60 to <90 mL/minute, 38% and 87% higher in subjects with eGFR ≥30 to <60 mL/minute, and 48% and 204% higher in subjects with eGFR <30 mL/minute. In subjects with eGFR <30 mL/minute or requiring hemodialysis, administration of nirmatrelvir/ritonavir 300 mg/100 mg once on day 1 followed by nirmatrelvir/ritonavir 150 mg/100 mg once daily on days 2 to 5 resulted in comparable exposures on day 1 and at steady state (AUC0-24 and Cmax) compared to subjects with normal kidney function receiving nirmatrelvir/ritonavir 300 mg/100 mg twice daily for 5 days.
