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Atazanavir: Drug information

Atazanavir: Drug information
(For additional information see "Atazanavir: Patient drug information" and see "Atazanavir: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Reyataz
Brand Names: Canada
  • JAMP-Atazanavir;
  • MYLAN-Atazanavir;
  • Reyataz;
  • TEVA-Atazanavir
Pharmacologic Category
  • Antiretroviral, Protease Inhibitor (Anti-HIV)
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment: Oral:

Note: Do not use boosted atazanavir plus abacavir and lamivudine in patients with a pre-ART HIV RNA ≥100,000 copies/mL (Ref).

Antiretroviral-naive patients: Atazanavir 300 mg once daily plus ritonavir 100 mg or cobicistat 150 mg once daily or atazanavir 400 mg once daily in patients unable to tolerate ritonavir or cobicistat.

Antiretroviral-experienced patients: Atazanavir 300 mg once daily plus ritonavir 100 mg or cobicistat 150 mg once daily. Note: Unboosted atazanavir is not recommended in antiretroviral-experienced patients with prior virologic failure.

Pregnant patients, antiretroviral naive or experienced: Atazanavir 300 mg once daily plus ritonavir 100 mg once daily. Some experts recommend increasing the dose to atazanavir 400 mg once daily plus ritonavir 100 mg once daily in the second and third trimesters (Ref); the manufacturer recommends this dose increase only for antiretroviral-experienced pregnant patients in the second and third trimesters who are also receiving either tenofovir disoproxil fumarate or an H2 antagonist. Use is not recommended if both tenofovir disoproxil fumarate and an H2 antagonist are used (Ref). Postpartum dosage adjustment not needed. Observe patient for adverse events, especially within 2 months after delivery.

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

Dosing: Kidney Impairment: Adult

Note: Consider alternative therapy in patients at high risk for renal impairment or with preexisting renal disease (cases of chronic kidney disease have been reported postmarketing).

Atazanavir plus ritonavir:

Mild to severe impairment: No dosage adjustment necessary.

End-stage renal disease receiving intermittent hemodialysis: Note: In patients with end-stage renal disease managed with hemodialysis, atazanavir is not appreciably removed during hemodialysis. Only 2.1% of the dose was removed during a 4-hour dialysis session; however, mean AUC, peak, and trough serum concentrations were 25% to 43% lower (versus adults with normal renal function) when atazanavir was administered either prior to, or after hemodialysis; mechanism of the decrease is not currently known.

Antiretroviral-naive patients: Atazanavir 300 mg plus ritonavir 100 mg once daily

Antiretroviral-experienced patients: Not recommended.

Atazanavir plus cobicistat:

Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling. Coadministration with tenofovir disoproxil fumarate is not recommended in patients with CrCl <70 mL/minute or if patient is on a concomitant or recent nephrotoxic agent.

End-stage renal disease patients (treatment-experienced) requiring hemodialysis: Use is not recommended.

Dosing: Hepatic Impairment: Adult

Atazanavir: Antiretroviral-naive patients:

Mild impairment (Child-Pugh class A): Atazanavir 400 mg once daily

Moderate impairment (Child-Pugh class B): Atazanavir 300 mg once daily

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

Atazanavir plus ritonavir or cobicistat: Mild to severe impairment: Use is not recommended (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

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

HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to www.IASUSA.org for more information) when necessary. Use in combination with other ARV agents. Oral capsules and oral powder are not interchangeable; product-specific dosing should be used; the bioavailability of oral capsules was observed to be higher than that of oral powder (Ref).

Boosted regimen (preferred regimen):

Oral powder: Infants ≥3 months, Children, and Adolescents: Oral:

5 to <15 kg: Atazanavir 200 mg (4 packets) once daily plus ritonavir 80 mg once daily. In antiretroviral-naive patients weighing 5 to <10 kg unable to tolerate this dose, may use atazanavir 150 mg (3 packets) once daily plus ritonavir 80 mg once daily with close HIV viral load monitoring.

15 to <25 kg: Atazanavir 250 mg (5 packets) once daily plus ritonavir 80 mg once daily.

≥25 kg (who cannot swallow a capsule): Atazanavir 300 mg (6 packets) once daily plus ritonavir 100 mg once daily.

Oral capsule: Note: Recommended to use the capsule formulation in any child ≥15 kg who can swallow a capsule whole (Ref).

Children ≥6 years weighing ≥15 kg and Adolescents <18 years: Oral:

15 kg to <35 kg: Atazanavir 200 mg once daily plus ritonavir 100 mg once daily.

≥35 kg: Atazanavir 300 mg once daily plus ritonavir 100 mg once daily or cobicistat 150 mg once daily (Ref).

Adolescents ≥18 years: Oral: Atazanavir 300 mg once daily plus ritonavir 100 mg or cobicistat 150 mg once daily.

Unboosted regimen: Note: Boosted atazanavir dosing regimen is preferred; guidelines do not recommend unboosted regimens unless patient is ≥13 years and not receiving concurrent tenofovir (either alafenamide or disoproxil fumarate forms); closely monitor plasma concentrations to ensure adequate concentrations are achieved (Ref). Oral powder should not be used for unboosted regimens.

Antiretroviral-naive patients: Note: Data indicates that children and adolescents <18 years may require higher doses (mg/kg and mg/m2) than those predicted by adult dosing guidelines to achieve adequate levels for unboosted atazanavir therapy (Ref).

>6 to <13 years: Oral capsule: Oral: Atazanavir 520 mg/m2/dose once daily (Ref).

13 to <18 years: Oral capsule: Oral: Atazanavir 620 mg/m2/dose once daily (Ref).

Adolescents ≥18 years: Oral capsule: Oral: Atazanavir 400 mg once daily.

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

Dosing: Kidney Impairment: Pediatric

Mild to severe impairment: Infants ≥3 months, Children, and Adolescents: No dosage adjustment necessary.

End-stage renal disease receiving hemodialysis: Not appreciably removed during hemodialysis. Only 2.1% of the dose was removed during a 4-hour dialysis session; however, mean AUC, peak, and trough serum concentrations were 25% to 43% lower (versus adults with normal renal function) when atazanavir was administered either prior to, or after hemodialysis; mechanism of the decrease is not currently known.

Antiretroviral-naive patients: Adolescents ≥18 years: Atazanavir 300 mg plus ritonavir 100 mg once daily.

Antiretroviral-experienced patients: Infants ≥3 months, Children, and Adolescents: Do not use (Ref).

Dosing: Hepatic Impairment: Pediatric

Note: Patients with underlying hepatitis B or C or those with marked elevations in transaminases prior to treatment may be at increased risk of hepatic decompensation or further increases in transaminases with atazanavir therapy (monitor patients closely).

Unboosted regimens: Antiretroviral-naive patients:

Infants ≥3 months, Children, and Adolescents:

Mild impairment: There are no pediatric-specific dosage recommendations in the manufacturer's labeling; in adults, no dosage adjustment is recommended.

Moderate impairment: There are no pediatric-specific dosage recommendations in the manufacturer's labeling; in adults, dosage adjustment is recommended.

Severe impairment: Use not recommended.

Boosted regimens (with ritonavir): Infants, Children, and Adolescents: Mild to severe impairment: Use is not recommended (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse events reported in adults receiving combination antiretroviral therapy unless otherwise specified.

>10%:

Dermatologic: Skin rash (3% to 14%)

Endocrine & metabolic: Increased serum cholesterol (grades 3/4: 6% to 25%)

Gastrointestinal: Increased serum amylase (grades 3/4: infants and children: 33%; adults: 14%), nausea (3% to 14%), vomiting (children and adolescents: 12%; adults: 3% to 4%)

Hepatic: Increased serum bilirubin (grades 3/4: infants, children, adolescents, and adults: 16% to 58%), jaundice (children, adolescents, and adults: ≤15%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (grades 3/4: 6% to 11%)

Ophthalmic: Scleral icterus (children, adolescents, and adults: ≤15%)

Respiratory: Cough (children and adolescents: 21%)

Miscellaneous: Fever (children and adolescents: 18%; adults: 2%)

1% to 10%:

Cardiovascular: First-degree atrioventricular block (5% to 6%), increased serum creatinine kinase (adults: 8%), peripheral edema (children and adolescents: 7%), second-degree atrioventricular block (children and adolescents: <2%)

Endocrine & metabolic: Hypoglycemia (children and adolescents: grades 3/4: 4%), increased serum glucose (grades 3/4: 5%), increased serum triglycerides (grades 3/4: ≤8%)

Gastrointestinal: Abdominal pain (4%), diarrhea (children and adolescents: 9%; adults: 1% to 3%), increased serum lipase (grades 3/4: infants, children, and adults: ≤8%)

Hematologic & oncologic: Decreased hemoglobin (grades 3/4: ≤5%), decreased platelet count (grades 3/4: 2%), neutropenia (infants, children, and adolescents: grades 3/4: 9%)

Hepatic: Increased serum alanine aminotransferase (grades 3/4: infants, children, and adults: ≤9%), increased serum aspartate aminotransferase (grades 3/4: infants, children, and adults: ≤9%)

Nervous system: Depression (2%), dizziness (≤2%), headache (1% to 8%), insomnia (≤3%), peripheral neuropathy (≤4%)

Neuromuscular & skeletal: Limb pain (children and adolescents: 6%), myalgia (4%)

Respiratory: Nasal congestion (children and adolescents: 6%), oropharyngeal pain (children and adolescents: 6%), rhinorrhea (children and adolescents: 6%), wheezing (children and adolescents: 6%)

Postmarketing:

Cardiovascular: Complete atrioventricular block, edema, left bundle branch block, prolongation P-R interval on ECG (Soliman 2011), prolonged QT interval on ECG (Ly 2007), right bundle branch block (Gianotti 2007), torsades de pointes (Ly 2007)

Dermatologic: Alopecia, erythema multiforme, maculopapular rash (Walkty 2009), pruritus, Stevens-Johnson syndrome

Endocrine & metabolic: Diabetes mellitus

Gastrointestinal: Cholecystitis, cholelithiasis (Lin 2015), cholestasis, pancreatitis

Genitourinary Urolithiasis (Koblic 2011)

Hypersensitivity: Angioedema, drug reaction with eosinophilia and systemic symptoms

Immunologic: Immune reconstitution syndrome

Neuromuscular & skeletal: Arthralgia

Renal: Acute kidney injury (Hara 2015), chronic renal failure, interstitial nephritis (including granulomatous interstitial nephritis) (Varghese 2020), nephrolithiasis (Wang 2014)

Contraindications

Hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to atazanavir or any component of the formulation; concomitant use with drugs that are highly dependent on CYP3A or UGT1A1 for clearance and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events or strong CYP3A4 inducers that may lead to lower exposure and loss of atazanavir efficacy (eg, alfuzosin, amiodarone [when atazanavir is coadministered with ritonavir], apalutamide, carbamazepine, cisapride, elbasvir/grazoprevir, encorafenib, glecaprevir/pibrentasvir, ergot derivatives [dihydroergotamine, ergonovine, ergotamine, methylergonovine], indinavir, irinotecan, ivosidenib, lomitapide, lovastatin, lurasidone [when atazanavir is coadministered with ritonavir], midazolam [oral], nevirapine, phenobarbital, phenytoin, pimozide, quinidine [when atazanavir is coadministered with ritonavir], rifampin, sildenafil [when used for pulmonary artery hypertension (eg, Revatio)], simvastatin, St. John's wort, or triazolam).

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

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use of apixaban and rivaroxaban (when atazanavir is coadministered with ritonavir); ticagrelor.

Warnings/Precautions

Concerns related to adverse effects:

• Elevated bilirubin: Asymptomatic elevations in bilirubin (unconjugated) occur commonly during therapy and are reversible upon discontinuation of treatment. Consider alternative therapy if jaundice or scleral icterus associated with bilirubin elevations present cosmetic concerns. Evaluate alternative etiologies if transaminase elevations also occur (dose reduction is not recommended because long-term efficacy has not been established).

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

• Hypersensitivity reactions: Protease inhibitors have been associated with a variety of hypersensitivity events (some severe), including rash, anaphylaxis (rare), angioedema, bronchospasm, erythema multiforme, Stevens-Johnson syndrome (rare), and/or toxic skin eruptions (including DRESS [drug rash, eosinophilia and systemic symptoms] syndrome). Discontinue treatment if severe rash develops.

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

• Nephrolithiasis/cholelithiasis: Cases have been reported in postmarketing surveillance; some associated with complications and/or requiring hospitalization. Consider temporary or permanent discontinuation of therapy if symptoms develop.

Disease-related concerns:

• Conduction abnormalities: May prolong PR interval; ECG monitoring should be considered in patients with preexisting conduction abnormalities or with medications which prolong AV conduction (dosage adjustment required with some agents); rare cases of second-degree AV block have been reported.

• Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors.

• Hemophilia A or B: Use with caution in patients with hemophilia A or B; increased bleeding during protease inhibitor therapy has been reported.

• Hepatic impairment: Protease inhibitors may cause hepatitis and/or exacerbate preexisting hepatic dysfunction; use with caution in patients with transaminase elevations prior to therapy or underlying hepatic disease, such as hepatitis B or C or cirrhosis; monitor closely at baseline and during treatment. Not recommended in patients with severe hepatic impairment. In combination with ritonavir, is not recommended in patients with any degree of hepatic impairment.

• Renal impairment: Cases of chronic kidney disease, including granulomatous interstitial nephritis, have been reported in postmarketing surveillance; consider alternative therapy in patients at high risk for renal impairment or with preexisting renal disease. Renal laboratory testing (serum creatinine, estimated CrCl, and urinalysis with microscopic examination) should be performed prior to initiation and throughout treatment. Not recommended for use in treatment-experienced patients with ESRD on hemodialysis. Consider therapy discontinuation in patients with progressive kidney disease.

Dosage form specific issues:

• Oral powder: Contains phenylalanine; avoid or use with caution in patients with phenylketonuria. Oral powder is not recommended for use in children <5 kg.

Special populations:

• Pediatric: Do not use in children <3 months of age due to potential for kernicterus.

Warnings: Additional Pediatric Considerations

Skin rash may occur with atazanavir use, usually mild to moderate; maculopapular; reported incidence lower in pediatric patients (grades 2 to 4: 14%) than adults (all grades: 20%); median onset: 7.3 weeks; treatment may be continued if rash is mild to moderate (rash may resolve; median duration: 1.4 weeks); discontinue therapy in cases of severe rash. May cause cough; reported incidence in pediatric patients: 21%. May cause fever; higher incidence observed in pediatric patients compared to adults (18% vs 2%).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as sulfate:

Reyataz: 150 mg [DSC], 200 mg, 300 mg [contains fd&c blue #2 (indigotine,indigo carmine)]

Generic: 150 mg, 200 mg, 300 mg

Packet, Oral, as sulfate:

Reyataz: 50 mg (30 ea) [contains aspartame; orange-vanilla flavor]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Capsules (Atazanavir Sulfate Oral)

150 mg (per each): $25.05 - $27.80

200 mg (per each): $25.05 - $27.80

300 mg (per each): $50.09 - $55.08

Capsules (Reyataz Oral)

200 mg (per each): $29.27

300 mg (per each): $57.98

Pack (Reyataz Oral)

50 mg (per each): $9.04

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

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as sulfate:

Reyataz: 150 mg [DSC], 200 mg, 300 mg [contains fd&c blue #2 (indigotine,indigo carmine)]

Generic: 150 mg, 200 mg, 300 mg

Administration: Adult

Administer with food. Administer atazanavir 2 hours before or 1 hour after didanosine buffered formulations, didanosine enteric-coated capsules, other buffered medications, or antacids. Administer atazanavir (with ritonavir) simultaneously with, or at least 10 hours after, H2-receptor antagonists; administer atazanavir (without ritonavir) at least 2 hours before or at least 10 hours after H2-receptor antagonist. Administer atazanavir (with ritonavir) 12 hours after proton pump inhibitor.

Additional formulation specific information:

Oral capsules: Swallow capsules whole, do not open.

Oral powder: Mixing with food: Using a spoon, mix the recommended number of oral powder packets with a minimum of one tablespoon of food (such as applesauce or yogurt) in a small container. Feed the mixture to the patient. Add an additional one tablespoon of food to the container, mix, and feed the patient the residual mixture.

Mixing with a beverage such as milk or water in a small drinking cup: Using a spoon, mix the recommended number of oral powder packets with a minimum of 30 mL of the beverage in a drinking cup. Have the patient drink the mixture. Add an additional 15 mL more of beverage to the cup, mix, and have the patient drink the residual mixture. If water is used, food should also be taken at the same time.

Administer the entire dosage of oral powder (mixed in the food or beverage) within one hour of preparation (may leave the mixture at room temperature during this one hour period). Ensure that the patient eats or drinks all the food or beverage that contains the powder. Additional food may be given after consumption of the entire mixture. Administer ritonavir immediately following oral powder administration.

Administration: Pediatric

Oral: Administer with food to enhance absorption.

Oral capsules: Swallow capsules whole; do not open.

Oral powder:

Mixing with food: Using a spoon, mix the recommended number of oral powder packets with a minimum of 1 tablespoon of food (such as applesauce or yogurt) in a small container. Feed the mixture to the patient. Add an additional 1 tablespoon of food to the container, mix, and feed the patient the residual mixture.

Mixing with a beverage such as milk or water in a small drinking cup: Using a spoon, mix the recommended number of oral powder packets with a minimum of 30 mL of the beverage in a drinking cup. Have the patient drink the mixture. Add an additional 15 mL more of beverage to the cup, mix, and have the patient drink the residual mixture. If water is used, food should also be taken at the same time.

Mixing with liquid infant formula using an oral dosing syringe and a small medicine cup: Using a spoon, mix the recommended number of oral powder packets with 10 mL of prepared liquid infant formula in the medicine cup. Draw up the full amount of the mixture into an oral syringe and administer into either right or left inner cheek of infant. Pour another 10 mL of formula into the medicine cup to rinse off remaining oral powder in cup. Draw up residual mixture into the syringe and administer into either right or left inner cheek of infant. Administration of atazanavir and infant formula using an infant bottle is not recommended because full dose may not be delivered.

Administer the entire dosage of oral powder (mixed in the food or beverage) within 1 hour of preparation (may leave the mixture at room temperature during this 1 hour period). Ensure that the patient eats or drinks all the food or beverage that contains the powder. Additional food may be given after consumption of the entire mixture. Administer ritonavir immediately following oral powder administration.

Concomitant administration with medications affecting gastric pH:

Coadministration with didanosine buffered or enteric-coated formulations: Infants ≥3 months, Children, and Adolescents: Administer atazanavir 2 hours before or 1 hour after didanosine buffered or enteric-coated formulations.

Coadministration with H2-receptor antagonists: Boosted regimens:

Antiretroviral-naive patients: Infants ≥3 months, Children, and Adolescents: Daily dose of atazanavir plus ritonavir given simultaneously with, or at least 10 hours after, the H2-receptor antagonist; dosage of H2-receptor antagonist must be limited to the equivalent of 40 mg dose of famotidine twice daily in adults.

Antiretroviral-experienced patients: Infants ≥3 months, Children, and Adolescents: Daily dose of atazanavir plus ritonavir given simultaneously with, or at least 10 hours after, the H2-receptor antagonist; dosage of H2-receptor antagonist must be limited to the equivalent of a 20 mg dose of famotidine twice daily in adults.

Coadministration with proton pump inhibitor: Antiretroviral-naive patients: Infants ≥3 months, Children, and Adolescents: Daily dose of atazanavir plus ritonavir given 12 hours after the proton pump inhibitor; dosage of proton pump inhibitor must be limited to the equivalent of a 20 mg dose of omeprazole/day in adults.

Use: Labeled Indications

HIV-1 infection, treatment:

Treatment of HIV-1 infection in combination with other antiretroviral agents in patients ≥3 months of age weighing ≥5 kg (US labeling) or ≥6 years of age weighing ≥20 kg (Canadian labeling).

Limitations of use:

Not recommended for use in pediatric patients <3 months of age due to the risk of kernicterus.

Use in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions.

Medication Safety Issues
Pediatric patients: High-risk medication:

KIDs List: Atazanavir, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of kernicterus unless pharmacogenetic testing used (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP2C8 (weak), CYP3A4 (strong), OATP1B1/1B3 (SLCO1B1/1B3), UGT1A1

Drug Interactions

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

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

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

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

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

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

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

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

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

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

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

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

Amiodarone: Atazanavir may increase the serum concentration of Amiodarone. Risk X: Avoid combination

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

Antacids: May decrease the absorption of Atazanavir. Management: Administer antacids 1 to 2 hours before or 2 hours after atazanavir to minimize the risk of a clinically significant interaction. Risk D: Consider therapy modification

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

Apalutamide: Atazanavir may increase the serum concentration of Apalutamide. Apalutamide may decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

Atorvastatin: Atazanavir may increase the serum concentration of Atorvastatin. Management: Use of atorvastatin and atazanavir/cobicistat is not recommended. Use the lowest atorvastatin dose necessary and titrate carefully in patients taking atazanavir or atazanavir/ritonavir due to the increased risk of myopathy, including rhabdomyolysis. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Belinostat: UGT1A1 Inhibitors may increase the serum concentration of Belinostat. Risk X: Avoid combination

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

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

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

Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification

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

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

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

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

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

Bictegravir: Atazanavir may increase the serum concentration of Bictegravir. Risk C: Monitor therapy

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

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

Bosentan: May decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Bosentan. Management: Concurrent use of unboosted atazanavir (without ritonavir or cobicistat) and bosentan is not recommended. Bosentan dose adjustments and increased monitoring are recommended when used together with boosted atazanavir. See interaction monograph for details. Risk D: Consider therapy modification

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

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

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

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

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the 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 the serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider therapy modification

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

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

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

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

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

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

Buprenorphine: May decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Buprenorphine. Management: Buprenorphine is not recommended in patients taking atazanavir without ritonavir. In patients taking atazanavir with ritonavir or cobicistat, monitor for opioid excess if coadministered with buprenorphine and consider buprenorphine dose reductions. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

CarBAMazepine: May decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of CarBAMazepine. Risk X: Avoid combination

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

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

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

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

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

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

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

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

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification

Clarithromycin: Atazanavir may decrease serum concentrations of the active metabolite(s) of Clarithromycin. Atazanavir may increase the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of Atazanavir. Management: Decrease clarithromycin dose 50% and do not exceed 1,000 mg per day. Decrease clarithromycin dose 75% in patients with CrCL less than 30 mL/min. Use alternative antimicrobial therapy if treating infections other than Mycobacterium avium complex. Risk D: Consider therapy modification

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

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

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

Clopidogrel: Atazanavir may diminish the antiplatelet effect of Clopidogrel. Atazanavir may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Coadministration of clopidogrel and atazanavir is not recommended and alternative should be sought if possible. If combined, monitor closely for evidence of diminished antiplatelet response to clopidogrel. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Daprodustat: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Daprodustat. Risk C: Monitor therapy

Dapsone (Systemic): May enhance the adverse/toxic effect of Atazanavir. Specifically, the risk of hyperbilirubinemia may be increased. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

Didanosine: May decrease the serum concentration of Atazanavir. Specifically, the buffered formulation of didanosine may decrease atazanavir absorption. Atazanavir may decrease the serum concentration of Didanosine. Reported with enteric coated didanosine capsules. Management: To avoid therapeutic failure of atazanavir, atazanavir should be administered 2 hours before or 1 hour after didanosine. This recommendation applies to both buffered didanosine products and enteric coated didanosine products. Risk D: Consider therapy modification

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

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

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

Disulfiram: Atazanavir may diminish the therapeutic effect of Disulfiram. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

Efavirenz: May decrease the serum concentration of Atazanavir. Management: Only use atazanavir/ritonavir (400/100 mg daily with food) an efavirenz (600 mg daily on empty stomach at bedtime) in treatment-naive patients. Use in treatment-experienced patients, or other combination of atazanavir and efavirenz, are not recommended. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Eliglustat: CYP3A4 Inhibitors (Strong) may increase the 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

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

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

Elvitegravir: Atazanavir may increase the serum concentration of Elvitegravir. Specifically, atazanavir/ritonavir may increase the concentration of elvitegravir. Management: When elvitegravir is combined with atazanavir/ritonavir, the dose of elvitegravir should be reduced to 85 mg once daily and the dose of atazanavir/ritonavir should be 300 mg/100 mg once daily. Avoid the use of atazanavir/cobicistat and elvitegravir. Risk D: Consider therapy modification

Encorafenib: May decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Encorafenib. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

Etravirine: Atazanavir may increase the serum concentration of Etravirine. Etravirine may decrease the serum concentration of Atazanavir. Management: The combination of etravirine and atazanavir should be avoided unless atazanavir is boosted with ritonavir. The use of cobicistat instead of ritonavir has not been evaluated and is not recommended. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

Fluvastatin: Atazanavir may increase the serum concentration of Fluvastatin. Management: When used with atazanavir/cobicistat, initiate fluvastatin at the lowest recommended dose and monitor clinical response (particularly any evidence of toxicity) to dose titration. Risk D: Consider therapy modification

Fosamprenavir: Atazanavir may increase serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Atazanavir. Management: Consider alternatives to this combination. Safe and effective doses of fosamprenavir and atazanavir have not been established for concurrent use. Risk D: Consider therapy modification

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

Fosphenytoin-Phenytoin: Atazanavir may decrease the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information. Risk D: Consider therapy modification

Hormonal Contraceptives: Atazanavir may decrease the serum concentration of Hormonal Contraceptives. Specifically, atazanavir/ritonavir may decrease concentrations of estrogens. Atazanavir may increase the serum concentration of Hormonal Contraceptives. Specifically, atazanavir alone may increase concentrations of estrogens and atazanavir alone or boosted may increase concentrations of progestins. Management: Dose adjustment of hormonal contraceptives or use of alternative or additional nonhormonal contraceptive may be needed when combined with atazanavir. See full interact monograph for details. Atazanavir/cobicistat with drospirenone is contraindicated. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

Indinavir: Atazanavir may enhance the adverse/toxic effect of Indinavir. Indinavir may enhance the adverse/toxic effect of Atazanavir. Specifically, the risk for hyperbilirubinemia may be increased when these agents are combined. Risk X: Avoid combination

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

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Atazanavir. Management: Avoid use in treatment-experienced patients. In treatment-naive patients, administer boosted atazanavir 12 hours after the PPI and the PPI dose should not exceed the equivalent of 20 mg omeprazole. Monitor for reduced atazanavir efficacy. Risk D: Consider therapy modification

Irinotecan Products: Atazanavir may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid combination

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

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

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

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

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

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

Ivosidenib: Atazanavir may increase the serum concentration of Ivosidenib. Ivosidenib may decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

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

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

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

LamoTRIgine: Atazanavir may decrease the serum concentration of LamoTRIgine. Specifically, the use of ritonavir-boosted atazanavir may decrease the serum concentration of lamotrigine. Risk C: Monitor therapy

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

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

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

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

Lenacapavir: Atazanavir may increase the serum concentration of Lenacapavir. Management: Concomitant use of atazanavir/cobicistat or atazanavir/ritonavir with lenacapavir is not recommended. Use of atazanavir alone may result in increases in lenacapavir concentrations, but concomitant use is allowed. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lurasidone: Atazanavir may increase the serum concentration of Lurasidone. Management: Decrease lurasidone dose 50% if adding atazanavir. Start lurasidone 20 mg daily and increase to no more than 80 mg daily in patients already taking atazanavir. Use of ritonavir- or cobicistat-boosted atazanavir with lurasidone is contraindicated. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

Minocycline (Systemic): May decrease the serum concentration of Atazanavir. Risk C: Monitor therapy

Minoxidil (Systemic): Atazanavir may increase the serum concentration of Minoxidil (Systemic). Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

Nevirapine: Atazanavir may increase the serum concentration of Nevirapine. Nevirapine may decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

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

Ombitasvir, Paritaprevir, and Ritonavir: Atazanavir may increase the serum concentration of Ombitasvir, Paritaprevir, and Ritonavir. Specifically, the paritaprevir component may increase significantly. Risk X: Avoid combination

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: Atazanavir may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the paritaprevir component may increase significantly. Management: These agents can be combined if the atazanavir dose is 300 mg daily, atazanavir is administered in the morning at the same time as the ombitasvir/paritaprevir/ritonavir/dasabuvir combination product, and atazanavir is given without additional ritonavir. Risk D: Consider therapy modification

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

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

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

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

OXcarbazepine: May decrease the serum concentration of Atazanavir. Risk C: Monitor therapy

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

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

PACLitaxel (Conventional): Atazanavir may increase the serum concentration of PACLitaxel (Conventional). Management: Use of paclitaxel or other narrow therapeutic index CYP2C8 substrates with atazanavir without concurrent ritonavir is not recommended. If paclitaxel is used with ritonavir-boosted atazanavir, monitor for increased paclitaxel exposure. Risk X: Avoid combination

PACLitaxel (Protein Bound): Atazanavir may increase the serum concentration of PACLitaxel (Protein Bound). Management: Use of paclitaxel or other narrow therapeutic index CYP2C8 substrates with atazanavir without concurrent ritonavir is not recommended. If paclitaxel is used with ritonavir-boosted atazanavir, monitor for increased paclitaxel exposure. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

PHENobarbital: Atazanavir may decrease the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

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

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

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

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

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

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

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

Pravastatin: Atazanavir may increase the serum concentration of Pravastatin. Risk C: Monitor therapy

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

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

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

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

Primidone: May decrease the serum concentration of Atazanavir. Atazanavir may decrease the serum concentration of Primidone. Risk X: Avoid combination

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

Protease Inhibitors: Atazanavir may increase the serum concentration of Protease Inhibitors. Risk X: Avoid combination

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

QuiNIDine: Atazanavir may increase the serum concentration of QuiNIDine. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination

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

Rifabutin: Atazanavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Atazanavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Clinical guidelines recommend rifabutin 150 mg daily (with or without ritonavir). Atazanavir labeling recommends a decrease of at least 75%, to 150 mg every other day or 150 mg 3 times per week for adults. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

Rosuvastatin: Atazanavir may increase the serum concentration of Rosuvastatin. Rosuvastatin may increase the serum concentration of Atazanavir. Management: Initiate rosuvastatin at 5 mg daily and do not exceed rosuvastatin 10 mg daily if coadministered with atazanavir/ritonavir. If combined, monitor for signs and symptoms of myopathy and rhabdomyolysis and for increased atazanavir toxicities. Risk D: Consider therapy modification

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

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

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

Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Risk X: Avoid combination

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

Saquinavir: May increase the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Saquinavir. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tegoprazan: May decrease the serum concentration of Atazanavir. Risk X: Avoid combination

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

Tenofovir Disoproxil Fumarate: May decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and use of H2-blockers require dose changes. See Lexi Interact monograph. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Voriconazole: Atazanavir may decrease the serum concentration of Voriconazole. Atazanavir may increase the serum concentration of Voriconazole. Voriconazole may decrease the serum concentration of Atazanavir. Management: Voriconazole should not be used in a patient who is being treated with ritonavir-boosted atazanavir unless the benefits of the combination outweigh the potential risks. Extra monitoring for both loss of effectiveness and toxicity is warranted. Risk D: Consider therapy modification

Voxilaprevir: Atazanavir may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination

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

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

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

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

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

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

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

Food Interactions

Bioavailability of atazanavir increased when taken with food. Management: Administer with food.

Reproductive Considerations

Patients with HIV not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. Consult drug interactions database for more detailed information specific to use of atazanavir and combination oral contraceptives. Contraception is not required to initiate or continue antiretroviral therapy.

The Health and Human Services (HHS) perinatal HIV guidelines consider atazanavir (when combined with low-dose ritonavir boosting) an alternative protease inhibitor for patients with HIV who are not yet pregnant but are trying to conceive. Atazanavir (when combined with low-dose cobicistat boosting) is not recommended for patients who are planning to become pregnant.

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

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

Pregnancy Considerations

Atazanavir has a low level of transfer across the human placenta with cord blood concentrations reported as 13% to 21% of maternal serum concentrations at delivery.

An increased risk of teratogenic effects has not been observed based on information collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm birth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction. Hyperbilirubinemia or hypoglycemia may occur in neonates following in utero exposure to atazanavir, although data are conflicting (monitor). The risk of hepatic dysfunction and gestational diabetes may be increased in pregnant patients taking protease inhibitors. Consider performing the standard glucose screening test earlier in pregnancy in patients who initiated protease inhibitor therapy prior to conception.

Use of unboosted atazanavir is not recommended during pregnancy. The Health and Human Services (HHS) perinatal HIV guidelines consider atazanavir (when combined with low-dose ritonavir boosting) an alternative protease inhibitor for pregnant patients with HIV who are antiretroviral-naive (initial therapy), who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking atazanavir may continue if viral suppression is effective and the regimen is well tolerated. Atazanavir (when combined with low-dose cobicistat boosting) is not recommended for use during pregnancy. If pregnancy occurs during therapy, consideration should be given to changing to a preferred or alternative regimen. If continued in patients who are virologically suppressed, frequent viral load monitoring, is recommended.

Pharmacokinetic studies suggest that standard dosing during pregnancy may provide decreased plasma concentrations and some experts recommend increased doses during the second and third trimesters; however, the manufacturer notes that dose adjustment is not required unless using concomitant H2-receptor blockers or tenofovir disoproxil fumarate in antiretroviral-experienced patients who are pregnant. Therapeutic drug monitoring may be useful. Atazanavir is not recommended in treatment-experienced pregnant patients taking both H2-receptor blockers and tenofovir disoproxil fumarate.

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

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

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

Breastfeeding Considerations

Atazanavir is present in breast milk.

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

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

Dietary Considerations

Must be taken with food; enhances absorption.

Monitoring Parameters

Viral load, CD4, serum glucose; liver function tests (prior to initiation and as clinically indicated in patients with existing liver disease), bilirubin (as clinically indicated); drug levels (with certain concomitant medications), ECG monitoring in patients with preexisting prolonged PR interval or with concurrent AV nodal blocking drugs; serum creatinine, estimated CrCL, and urinalysis with microscopic examination (prior to initiation and as clinically indicated).

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid; enhanced with food

Distribution: CSF: Plasma concentration ratio (range): 0.0021 to 0.0226

Protein binding: 86%; binds to both alpha1-acid glycoprotein and albumin (similar affinity)

Metabolism: Hepatic, primarily by cytochrome P450 isoenzyme CYP3A; also undergoes biliary elimination; major biotransformation pathways include mono-oxygenation and deoxygenation; minor pathways for parent drug or metabolites include glucuronidation, N-dealkylation, hydrolysis and oxygenation with dehydrogenation; 2 minor inactive metabolites have been identified

Half-life elimination: Unboosted therapy: 7 to 8 hours; Boosted therapy (with ritonavir): 9 to 18 hours; 12 hours in patients with hepatic impairment

Time to peak, plasma: 2 to 3 hours

Excretion: Feces (79%, 20% of total dose as unchanged drug); urine (13%, 7% of total dose as unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The mean Cmax was 9% lower, AUC was 19% higher, and Cmin was 96% higher in subjects with severe renal impairment not undergoing hemodialysis.

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

  • (AE) United Arab Emirates: Reyataz;
  • (AR) Argentina: Reyataz | Suravir;
  • (AT) Austria: Atazanavir Krka | Reyataz;
  • (AU) Australia: Atazanavir mylan | Reyataz;
  • (BE) Belgium: Atazanavir Krka | Atazanavir mylan | Reyataz;
  • (BG) Bulgaria: Atazanavir mylan | Reyataz;
  • (BR) Brazil: Reyataz | Sulfato de atazanavir;
  • (CH) Switzerland: Atazanavir mepha | Reyataz;
  • (CL) Chile: Atazanavir | Reyataz | Tozar;
  • (CN) China: Reyataz;
  • (CO) Colombia: Ancef | Atazanavir | Hivatax | Reyataz | Reyavir | Tamsuride | Tavirapin | Virazan | Zanavir;
  • (CZ) Czech Republic: Reyataz;
  • (DE) Germany: Atazam | Atazanavir | Atazanavir Accord | Atazanavir al | Atazanavir beta | Atazanavir heumann | Atazanavir hexal | Atazanavir medicopharm | Atazanavir mylan | Reyataz;
  • (EC) Ecuador: Ancef | Convirox;
  • (EE) Estonia: Reyataz;
  • (EG) Egypt: Reyataz;
  • (ES) Spain: Atazanavir Accord | Atazanavir mylan | Atazanavir reddy | Atazanavir stada | Atazanavir teva | Reyataz;
  • (FI) Finland: Atazanavir Accord | Atazanavir Krka | Atazanavir stada | Reyataz;
  • (FR) France: Atazanavir | Atazanavir arrow | Atazanavir biogaran | Atazanavir Krka | Atazanavir mylan | Atazanavir sandoz | Atazanavir teva | Atazanavir zentiva | Reyataz;
  • (GB) United Kingdom: Atazanavir | Atazanavir mylan | Atazanavir sandoz | Reyataz;
  • (GR) Greece: Reyataz;
  • (HK) Hong Kong: Reyataz;
  • (HU) Hungary: Reyataz;
  • (ID) Indonesia: Reyataz;
  • (IE) Ireland: Atazanavir Accord | Atazanavir Krka | Atazanavir mylan | Atazanavir Rowex | Reyataz;
  • (IN) India: Atavir | Atazor;
  • (IT) Italy: Atazanavir Accord | Atazanavir eg | Atazanavir Krka | Atazanavir mylan | Atazanavir reddy | Atazanavir sandoz | Reyataz;
  • (JP) Japan: Reyataz;
  • (KE) Kenya: Atazanavir | Atazor;
  • (KR) Korea, Republic of: Reyataz;
  • (LU) Luxembourg: Reyataz;
  • (LV) Latvia: Atazanavir mylan | Atazanavir sandoz | Atazanavir teva | Reyataz;
  • (MX) Mexico: Anxeliataz | Atazanavir | Ductrazol | Kyroy | Reyataz | Trivaltor | Viver;
  • (MY) Malaysia: Atavir | Atazor | Reyataz;
  • (NL) Netherlands: Atazanavir Accord | Atazanavir aurobindo | Atazanavir Krka | Atazanavir mylan | Atazanavir teva | Reyataz;
  • (NO) Norway: Atazanavir Accord | Atazanavir Krka | Reyataz;
  • (NZ) New Zealand: Atazanavir | Atazanavir mylan | Atazanavir Sulphat;
  • (PE) Peru: Atazanavir | Reyataz;
  • (PL) Poland: Atazanavir mylan | Atazanavir zentiva;
  • (PR) Puerto Rico: Atazanavir | Reyataz;
  • (PT) Portugal: Atazanavir Accord | Atazanavir farmoz | Atazanavir Generis | Atazanavir Krka | Atazanavir mylan | Atazanavir teva | Atazanavir zentiva | Reyataz;
  • (QA) Qatar: Reyataz;
  • (RO) Romania: Atazanavir mylan | Reyataz;
  • (RU) Russian Federation: Atazanavir | Atazanavir canon | Atazanavir nanolek | Atazanavir tl | Atazor | Reyataz | Simanod;
  • (SA) Saudi Arabia: Reyataz;
  • (SE) Sweden: Atazanavir Accord | Atazanavir Krka | Atazanavir mylan | Atazanavir stada | Atazanavir teva | Reyataz;
  • (SG) Singapore: Reyataz;
  • (SI) Slovenia: Reyataz;
  • (TH) Thailand: Atazanavir | Atazanavir sandoz | Reyataz;
  • (TW) Taiwan: Reyataz;
  • (UA) Ukraine: Atazor;
  • (UY) Uruguay: Reyataz;
  • (ZA) South Africa: Aspen atazanavir | Atazanavir cipla | Atazor;
  • (ZM) Zambia: Atazor;
  • (ZW) Zimbabwe: Atazanavir mylan
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  2. Atazanavir capsules [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; April 2021.
  3. Evotaz (atazanavir and cobicistat) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; July 2020.
  4. Gianotti N, Guffanti M, Galli L, et al. Electrocardiographic changes in HIV-infected, drug-experienced patients being treated with atazanavir. AIDS. 2007;21(12):1648-1651. doi:10.1097/QAD.0b013e32826fbc6a [PubMed 17630564]
  5. Hara M, Suganuma A, Yanagisawa N, Imamura A, Hishima T, Ando M. Atazanavir nephrotoxicity. Clin Kidney J. 2015;8(2):137-142. doi:10.1093/ckj/sfv015 [PubMed 25815168]
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  7. HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. April 2019. http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf.
  8. Kiser JJ, Rutstein RM, Samson P, et al. Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. AIDS. 2011;25(12):1489-1496. [PubMed 21610486]
  9. Koblic PM, Gold WL, la Porte CJ, Lee TC. Medication-based urolithiasis and atazanavir. CMAJ. 2011;183(11):E748-E751. doi:10.1503/cmaj.100019 [PubMed 21444613]
  10. Lin KY, Liao SH, Liu WC, et al. Cholelithiasis and nephrolithiasis in hiv-positive patients in the era of combination antiretroviral therapy. PLoS One. 2015;10(9):e0137660. doi:10.1371/journal.pone.0137660 [PubMed 26360703]
  11. Ly T, Ruiz ME. Prolonged QT interval and torsades de pointes associated with atazanavir therapy. Clin Infect Dis. 2007;44(6):e67-e68. doi:10.1086/511875 [PubMed 17304444]
  12. Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]
  13. Molina JM, Andrade-Villanueva J, Echevarria J, et al, “Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1-Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study,” J Acquir Immune Defic Syndr, 2010, 53(3):323-32. [PubMed 20032785]
  14. Reyataz (atazanavir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; November 2023.
  15. Reyataz (atazanavir) [product monograph]. Montreal, Canada: Bristol-Myers Squibb Canada; August 2023.
  16. Soliman EZ, Lundgren JD, Roediger MP, et al. Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations. AIDS. 2011;25(3):367-377. doi:10.1097/QAD.0b013e328341dcc0 [PubMed 21150558]
  17. Tybost (cobicistat) [prescribing information]. Foster City, CA: Gilead Sciences Inc; September 2021.
  18. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Perinatal_GL.pdf. Updated January 31, 2023. Accessed February 23, 2023.
  19. Varghese V, Rodriguez R, Self S, Velez JCQ. Atazanavir crystal-induced chronic granulomatous interstitial nephritis. Kidney Int Rep. 2020;5(7):1106-1110. doi:10.1016/j.ekir.2020.04.007 [PubMed 32647771]
  20. Walkty A, Smith D, Lopko B, Kasper K. Severe skin rash associated with atazanavir. Can J Infect Dis Med Microbiol. 2009;20(1):e10-e12. doi:10.1155/2009/721956 [PubMed 20190882]
  21. Wang LC, Osterberg EC, David SG, Rosoff JS. Recurrent nephrolithiasis associated with atazanavir use. BMJ Case Rep. 2014;2014:bcr2013201565. doi:10.1136/bcr-2013-201565 [PubMed 24403382]
Topic 9353 Version 488.0

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