Most recent update(s): The National Institutes of Health’s COVID-19 guidelines recommend against the use of HIV protease inhibitors, such as lopinavir and ritonavir, for the treatment of COVID-19.
As part of our response to the evolving COVID-19 pandemic, published literature and guidelines from major health organizations are continuously monitored for potential content updates. At this time, only investigational medications with data determined to be of relatively high quality and/or consistently showing positive clinical outcomes to support dosing recommendations will be included in the Lexicomp monograph, outside of this Special Alert field.
Further information may be found at:
CDC: https://www.cdc.gov/coronavirus/2019-nCoV/index.html
NIH National Library of Medicine: https://clinicaltrials.gov/ct2/results?cond=Covid-19&term=lopinavir&cntry=&state=&city=&dist=&Search=Search
IDSA: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
HIV-1 infection, treatment (as a component of combination therapy): Oral:
Note: Lopinavir/ritonavir is not recommended as a component of initial therapy for the treatment of HIV (HHS [adults] 2019).
Patients receiving concomitant antiretroviral therapy without efavirenz, nelfinavir, or nevirapine:
Twice-daily dosing: Therapy-naive or therapy-experienced: Lopinavir 400 mg/ritonavir 100 mg twice daily.
Once-daily dosing: Therapy-naive or experienced patients with <3 lopinavir resistance-associated substitutions: Lopinavir 800 mg/ritonavir 200 mg once daily. Once-daily dosing is not recommended in those receiving efavirenz, fosamprenavir, nevirapine, nelfinavir, carbamazepine, phenobarbital, or phenytoin.
Pregnant patients (with no lopinavir-resistance-associated amino acid substitutions): Lopinavir 400 mg/ritonavir 100 mg twice daily. Once-daily dosing is not recommended. Tablets are recommended; avoid use of the oral solution. Alternately, the HHS perinatal guidelines recommend an increased dose of lopinavir 600 mg/ritonavir 150 mg twice daily, or lopinavir 500 mg/ritonavir 125 mg twice daily, during the second and third trimesters of pregnancy, especially in PI-experienced pregnant patients and patients with a baseline viral load >50 copies/mL. If standard doses are used, close monitoring is recommended (HHS [perinatal] 2020).
Dosage adjustment for combination therapy with efavirenz, nelfinavir, or nevirapine: Oral:
Twice-daily dosing: Therapy-naive and therapy-experienced patients:
Solution: Lopinavir 520 mg/ritonavir 130 mg (6.5 mL) twice daily
Tablet: Lopinavir 500 mg/ritonavir 125 mg twice daily
Once-daily dosing: Once-daily dosing not recommended.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, a decrease in clearance is not expected.
Hemodialysis: Avoid once-daily dosing in hemodialysis patients (HHS [adult] 2019).
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, lopinavir is primarily metabolized by the liver and its AUC may be increased ~30%; use with caution.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
(For additional information see "Lopinavir and ritonavir: Pediatric drug information")
Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary. Health care providers are reminded that lopinavir/ritonavir oral solution is highly concentrated. Dosage is based on patient body weight (mg/kg) or body surface area (mg/m2); use precaution during dose calculation; dosing is presented based on lopinavir component. To minimize the risk for medication errors, health care providers should pay special attention to accurate calculation of the dose, transcription of the medication order, dispensing information, dosing instructions, and proper measurement of the dose. Unlike in adults, once daily dosing is subtherapeutic and not recommended for use in pediatric patients (HHS [pediatric 2020]).
HIV-1 infection, treatment: Oral:
Note: Use in combination with other ARV agents. Use of tablets in patients <15 kg or <0.6 m2 is not recommended; oral solution preferable.
Infants (≥42 weeks PMA) (HHS [pediatric 2020]):
Patients not receiving concomitant efavirenz, nelfinavir, or nevirapine :
Lopinavir 16 mg/kg/dose or 300 mg/m2/dose twice daily.
Note: Infants who receive 300 mg/m2/dose twice daily may have lower trough concentrations compared to adults; evaluate infants and adjust dose for incremental growth at frequent intervals.
Patients with concomitant efavirenz, nelfinavir, or nevirapine : Dosage information does not exist; lopinavir/ritonavir is not recommended in infants who are receiving these agents.
Children and Adolescents:
Patients not receiving concomitant efavirenz, nelfinavir, or nevirapine:
Antiretroviral naive: Note: Higher dose (see below) recommended in antiretroviral-experienced patients who may have decreased sensitivity to lopinavir; some clinicians choose to initiate therapy with the higher dose in all patients due to lower trough concentrations observed with the lower dose (HHS [pediatric 2020]):
BSA-directed dosing: Children and Adolescents: Lopinavir 230 mg/m2/dose (maximum dose: 400 mg/dose) twice daily; others have suggested 300 mg/m2/dose twice daily if the oral solution is used. Note: For patients already receiving lopinavir and ritonavir, an immediate dosage reduction at 12 months of age is not recommended; patients are allowed to "grow into" the 230 mg/m2/dose dosage as they gain weight over time.
Alternate fixed dosing for patients weighing ≥15 kg who are able to swallow tablets: Dosing approximates lopinavir 230 mg/m2/dose:
BSA ≥0.6 to <0.9 m2: Lopinavir 200 mg twice daily.
BSA ≥0.9 to <1.4 m2: Lopinavir 300 mg twice daily.
BSA ≥1.4 m2: Lopinavir 400 mg twice daily.
Weight-directed dosing: Children and Adolescents: Dosing approximates lopinavir 230 mg/m2/dose:
<15 kg: Lopinavir 12 mg/kg/dose twice daily.
15 to 40 kg: Lopinavir 10 mg/kg/dose twice daily.
>40 kg: Lopinavir 400 mg twice daily.
Alternate fixed dosing for patients weighing ≥15 kg and able to swallow tablets: Dosing approximates lopinavir 230 mg/m2/dose:
≥15 to 25 kg: Lopinavir 200 mg twice daily.
>25 to 35 kg: Lopinavir 300 mg twice daily.
>35 kg: Lopinavir 400 mg twice daily.
Antiretroviral-experienced or suspected decreased sensitivity to lopinavir: Note: This dose is also used by some clinicians for initial therapy in all patients (HHS [pediatric 2020]):
BSA-directed dosing: Children and Adolescents: Lopinavir 300 mg/m2/dose (maximum dose: 400 mg/dose) twice daily.
Weight-directed dosing: Children and Adolescents: Dosing approximates lopinavir 300 mg/m2/dose:
<15 kg: Lopinavir 13 mg/kg/dose twice daily.
15 to 45 kg: Lopinavir 11 mg/kg/dose twice daily.
>45 kg: Lopinavir 400 mg twice daily.
Weight-band dosing for children and adolescents weighing ≥15 kg and able to swallow tablets: Dosing approximates lopinavir 300 mg/m2/dose:
15 to 20 kg: 200 mg twice daily.
>20 to 30 kg: 300 mg twice daily.
>30 kg: 400 mg twice daily.
Patients with concomitant efavirenz, nelfinavir, or nevirapine (or treatment-experienced patients not receiving these agents who have suspected decreased susceptibility to lopinavir):
BSA-directed dosing: Children and Adolescents: Lopinavir 300 mg/m2/dose twice daily; maximum dose: Oral solution: 520 mg/dose; Tablet: 500 mg/dose.
Alternate fixed dosing for patients who are able to swallow tablets: Dosing approximates lopinavir 300 mg/m2/dose:
BSA ≥0.6 to <0.8 m2: Lopinavir 200 mg twice daily.
BSA ≥0.8 to < 1.2 m2: Lopinavir 300 mg twice daily.
BSA ≥1.2 to < 1.7 m2: Lopinavir 400 mg twice daily.
BSA ≥1.7 m2: Lopinavir 500 mg twice daily.
Weight-directed dosing: Children and Adolescents: Dosing approximates lopinavir ~300 mg/m2/dose:
<15 kg: Lopinavir 13 mg/kg/dose twice daily.
≥15 to 45 kg: Lopinavir 11 mg/kg/dose twice daily.
>45 kg:
Oral solution: Lopinavir 520 mg (6.5 mL) twice daily.
Tablets: Lopinavir 500 mg twice daily.
Fixed dosing for children and adolescents weighing ≥15 kg who are able to swallow tablets:
≥15 to 20 kg: Lopinavir 200 mg twice daily.
>20 to 30 kg: Lopinavir 300 mg twice daily.
>30 to 45 kg: Lopinavir 400 mg twice daily.
>45 kg: Lopinavir 500 mg twice daily; Note: Alternatively, lopinavir 600 mg twice daily (3 tablets of the 200/50 mg lopinavir/ritonavir) can be used for ease of dosing (HHS [pediatric 2020]).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (HHS [nPEP] 2016): Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other antiretroviral agents. Oral:
Infants (≥42 weeks PMA): Oral solution: 300 mg/m2/dose or 16 mg/kg/dose twice daily.
Children:
Weight-directed dosing: Oral solution:
<15 kg: Lopinavir 12 mg/kg/dose twice daily.
15 to 40 kg: Lopinavir 10 mg/kg/dose twice daily.
>40 kg: Lopinavir 400 mg twice daily.
Fixed dosing: Patients weighing ≥15 kg and able to swallow tablets: Tablets:
≥15 to 25 kg: Lopinavir 200 mg twice daily.
>25 to 35 kg: Lopinavir 300 mg twice daily.
>35 kg: Lopinavir 400 mg twice daily.
Adolescents: Not recommended; other antiretroviral agents should be used.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, a decrease in clearance is not expected based on pharmacokinetics.
Infants, Children, and Adolescents: Use caution in hepatic impairment (metabolized primarily by the liver).
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, lopinavir AUC may be increased ~30% in patients with mild to moderate hepatic impairment; use with caution.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Kaletra: Lopinavir 80 mg and ritonavir 20 mg per 1 mL (160 mL) [contains ethanol 42.4%, menthol, propylene glycol; cotton candy flavor]]
Tablet:
Kaletra:
Lopinavir 100 mg and ritonavir 25 mg
Lopinavir 200 mg and ritonavir 50 mg
No
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Kaletra capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021226s049lbl.pdf#page=53
Kaletra oral solution, tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021251s059,021906s054lbl.pdf#page=53
Solution: Must be administered with food; if using didanosine, take didanosine 1 hour before or 2 hours after lopinavir/ritonavir. Administer using calibrated dosing cup or syringe. Contains ethanol and propylene glycol; not recommended for use with polyurethane feeding tubes (potential incompatibility); silicone and polyvinyl chloride feeding tubes may be used.
Tablet: May be taken with or without food. Swallow whole, do not break, crush, or chew. May be taken with didanosine when taken without food.
Oral:
Oral solution: Administer with food to enhance bioavailability and decrease kinetic variability; use a calibrated oral dosing syringe to measure and administer the oral solution; contains ethanol and propylene glycol; not recommended for use with polyurethane feeding tubes (potential incompatibility); silicone and polyvinyl chloride feeding tubes may be used. Note: Dose must be accurately measured and administered to pediatric patients as oral solution is very concentrated and a fatal accidental overdose has been reported.
Methods to improve poor palatability of the oral solution include numbing the taste buds with ice chips before or after drug administration, or administering the medication with sweet or tangy foods, chocolate syrup, or peanut butter to help mask the taste; flavoring the solution prior to dispensing may also help improve palatability (HHS [pediatric 2020]).
Tablets: May be administered without regard to meals; swallow tablets whole, do not crush, break, or chew; crushing tablets was shown to decrease AUC of lopinavir and ritonavir by 45% and 47%, respectively (Best 2011).
HIV-1 infection, treatment: Treatment of HIV-1 infection in adults and pediatric patients 14 days and older in combination with other antiretroviral agents.
Note: Lopinavir/ritonavir is not recommended as a component of initial therapy for the treatment of HIV (HHS [adults] 2019).
Potential for dispensing errors between Kaletra and Keppra (levETIRAcetam)
Children’s doses are based on weight and calculated by milligrams of lopinavir. Care should be taken to accurately calculate the dose. The oral solution contains lopinavir 80 mg and ritonavir 20 mg per one mL. Children <12 years of age (and ≤40 kg) who are not taking certain concomitant antiretroviral medications will receive <5 mL of solution per dose.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Data presented for short- and long-term combination antiretroviral therapy in both protease inhibitor experienced and naïve patients. Adverse reactions are for adults unless otherwise specified.
>10%:
Endocrine & metabolic: Increased gamma-glutamyl transferase (grade 3/4: 10% to 29%)
Gastrointestinal: Diarrhea (children and adults: 12% to 20%; greater with once-daily dosing), dysgeusia (children: 22%), vomiting (children: 21%; adults: 7%)
Hepatic: Increased serum alanine aminotransferase (grade 3/4: children and adults: 1% to 11%)
Respiratory: Upper respiratory tract infection (14%)
1% to 10%:
Cardiovascular: Hypertension (2%)
Dermatologic: Dermatitis (≤2%, including seborrheic dermatitis), night sweats (2%), pruritus (1%), skin infection (3%, including cellulitis, folliculitis, furuncle), skin rash (4%, including eczema and maculopapular rash)
Endocrine & metabolic: Altered serum glucose (1%; including diabetes mellitus), amenorrhea (≤2%), decreased serum sodium (grade 3/4: children: 3%), heavy menstrual bleeding (≤2%), hypercholesterolemia (7%), hypertriglyceridemia (6%), hypophosphatemia (grade 3/4: ≤2%), increased serum glucose (grade 3/4: ≤5%), increased serum sodium (grade 3/4: children: 3%), increased uric acid (grade 3/4: ≤5%), lipodystrophy (acquired: 2%, including facial wasting), weight loss (2%)
Gastrointestinal: Abdominal distension (1%), abdominal pain (6%), colitis (≤3%), constipation (1%), decreased appetite (2%), dyspepsia (2%), flatulence (1%), gastroenteritis (≤3%), gastroesophageal reflux disease (2%), hemorrhoids (2%), increased serum amylase (grade 3/4: children and adults: 3% to 8%), increased serum lipase (grade 3/4: 1% to 5%), nausea (10%), pancreatitis (2%)
Genitourinary: Erectile dysfunction (2%)
Hematologic & oncologic: Anemia (2%), leukopenia (≤2%), lymphadenopathy (1%), neutropenia (≤2%; grade 3/4: 1% to 5%), thrombocytopenia (grade 3/4: children: 4%)
Hepatic: Hepatitis (4%), increased serum aspartate aminotransferase (grade 3/4: children and adults: 1% to 10%), increased serum bilirubin (grade 3/4: children 3%; adults 1%)
Hypersensitivity: Hypersensitivity (3%, including angioedema)
Nervous system: Anxiety (4%), dizziness (2%), fatigue (8%, including asthenia), headache (6%; including migraine), insomnia (4%), neuropathy (≤2%), peripheral neuropathy (≤2%)
Neuromuscular & skeletal: Increased creatinine phosphokinase in blood specimen (grade 3/4: 4% to 5%), musculoskeletal pain (6%; including arthralgia and back pain), myalgia (2%), myopathy (1%; including asthenia and muscle spasm)
Renal: Decreased creatinine clearance (grade 3/4: 2% to 3%), renal failure syndrome (1%)
Respiratory: Lower respiratory tract infection (8%)
<1%:
Cardiovascular: Acute myocardial infarction, atherosclerotic disease, atrioventricular block, capillary leak syndrome (capillaritis), cerebrovascular accident, deep vein thrombosis, tricuspid regurgitation, vasculitis
Dermatologic: Alopecia
Endocrine & metabolic: Decreased libido, lactic acidosis, weight gain
Gastrointestinal: Ageusia, cholangitis, duodenitis, fecal incontinence, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, increased appetite, oral mucosa ulcer, stomatitis, xerostomia
Genitourinary: Hematuria, hypogonadism
Hematologic & oncologic: Rectal hemorrhage
Hepatic: Hepatomegaly, liver steatosis
Immunologic: Immune reconstitution syndrome
Nervous system: Abnormal dreams, seizure, vertigo
Neuromuscular & skeletal: Osteonecrosis, rhabdomyolysis, tremor
Ophthalmic: Visual impairment
Otic: Tinnitus
Renal: Nephritis
Postmarketing:
Cardiovascular: Bradycardia, prolongation P-R interval on ECG, prolonged QT interval on ECG, torsades de pointes
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Exacerbation of diabetes mellitus, redistribution of body fat
Hepatic: Hepatic insufficiency
Neuromuscular & skeletal: Lipotrophy
Renal: Nephrolithiasis
Hypersensitivity (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to lopinavir, ritonavir, or any component of the formulation; coadministration with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions or with potent CYP3A inducers where significantly decreased lopinavir levels may be associated with a potential for loss of virologic response and resistance and cross-resistance to develop (eg, alfuzosin, apalutamide, cisapride, colchicine [patients with renal and/or hepatic impairment], dronedarone, elbasvir/grazoprevir, ergot derivatives [eg, dihydroergotamine, ergotamine, methylergonovine], lomitapide, lovastatin, lurasidone, oral midazolam, pimozide, ranolazine, rifampin, sildenafil [when used to treat pulmonary arterial hypertension], simvastatin, St John's wort, triazolam).
Canadian labeling: Additional contraindications (not in US labeling):
Tablets, oral solution: Coadministration with apalutamide, astemizole (not available in Canada), fusidic acid, salmeterol, terfenadine (not available in Canada), vardenafil, venetoclax (during dose initiation and the ramp-up phase).
Oral solution: Pregnancy; hepatic or renal failure; coadministration with disulfiram or metronidazole.
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction and prolong the QTc and/or PR interval; second- and third-degree AV block and torsade de pointes have been observed. Use with caution in patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease or cardiomyopathies. Avoid use in combination with QTc- or PR-interval prolonging drugs or in patients with hypokalemia or congenital long QT syndrome.
• Cardiovascular concerns: Possible higher risk of myocardial infarction associated with the cumulative use of lopinavir/ritonavir; consider avoiding lopinavir/ritonavir-based regimens in patients with high cardiac risk (Bavinger 2013; HHS [adult] 2019).
• Fat redistribution: May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).
• Hepatotoxicity: May cause hepatitis and/or exacerbate pre-existing hepatic dysfunction; use with caution in patients with underlying hepatic disease, such as hepatitis B or C, cirrhosis, or unspecified hepatic impairment. Consider more frequent liver function test monitoring during therapy initiation in patients with preexisting hepatic dysfunction.
• 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) later in therapy; further evaluation and treatment may be required.
• Increased cholesterol: Increases in total cholesterol and triglycerides have been reported; screening should be done prior to therapy and periodically throughout treatment.
Disease-related concerns:
• Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of diabetes, DKA, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors. Consider monitoring for these conditions. In some patients who discontinued protease inhibitors, hyperglycemia persisted.
• 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: Use with caution; lopinavir concentrations may be increased.
• Pancreatitis: Use with caution in patients with increased triglycerides; pancreatitis has been observed. Patients with history of pancreatitis or advanced HIV-1 disease may be at increased risk. Monitor for clinical symptoms (nausea, vomiting, abdominal pain) and serum lipase and amylase.
Special populations:
• Pediatric: Safety, efficacy, and pharmacokinetic profiles of lopinavir and ritonavir have not been established for neonates <14 days of age. Neonates <14 days of age, particularly preterm neonates, are at risk for developing propylene glycol toxicity with use of the lopinavir/ritonavir oral solution. Oral solution contains ethanol and propylene glycol; ethanol competitively inhibits propylene glycol metabolism. Postmarketing reports in preterm neonates following use of the oral solution include cardiotoxicity (complete AV block, bradycardia, cardiomyopathy), lactic acidosis, CNS depression, respiratory complications, acute renal failure, and death. The oral solution should not be used in the immediate postnatal period, including full-term neonates age <14 days or preterm neonates until 14 days after their due date, unless the infant is closely monitored and benefits clearly outweigh risk. Once-daily dosing (oral solution or tablets) is not an approved regimen for children <18 years of age.
Dosage form specific issues:
• Oral solution: The oral solution is highly concentrated and contains large amounts of ethanol (42.4%) and propylene glycol (15.3%). Monitor patients with renal impairment or with decreased ability to metabolize propylene glycol (eg, patients of Asian origin) for propylene glycol toxicity (eg, seizures tachycardia, lactic acidosis, hyperosmolarity, stupor, hemolysis). Health care providers should pay special attention to accurate calculation, measurement, and administration of dose. Overdose (or cumulative ethanol or propylene glycol content in medications) in a child may lead to lethal ethanol or propylene glycol toxicity.
Other warnings/precautions:
• Appropriate use: Once-daily dosing is not recommended in patients with ≥3 of the following lopinavir-resistance-associated amino acid substitutions in protease (L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V); those receiving efavirenz, fosamprenavir, nevirapine, or nelfinavir, carbamazepine, phenobarbital, phenytoin, or in children <18 years of age.
Serious cardiac, renal, CNS, or respiratory problems have been reported in preterm neonates receiving lopinavir/ritonavir oral solution. The oral solution contains 42.4% ethanol (v/v) and 15.3% propylene glycol (w/v). Ethanol competitively inhibits propylene glycol metabolism, which may lead to propylene glycol toxicity due to impaired elimination in neonates. Preterm neonates are at an increased risk of adverse events from propylene glycol toxicity, including cardiotoxicity (complete AV block, bradycardia, cardiomyopathy), lactic acidosis, CNS depression, respiratory complications, transient symptomatic adrenal insufficiency, acute renal failure, and death. Avoid oral solution in neonates if the patient is either PNA <14 days old or PMA <42 weeks. Toxicities have been reported with the use of products containing propylene glycol in all ages, including hyperosmolality, lactic acidosis, seizures, and respiratory depression. Due to concentration of ethanol in oral solution, an overdose in a small pediatric patient (particularly neonate or infant) may cause potentially lethal alcohol toxicity. Treatment for overdose should be supportive and include general poisoning management; activated charcoal may help remove unabsorbed medication; dialysis unlikely to be of benefit; however, dialysis can remove alcohol and propylene glycol. In neonates and infants 14 days to 6 months of age, the total amounts of ethanol and propylene glycol delivered from all medications should be considered to avoid toxicity. Neonates and young infants should be closely monitored for increases in serum osmolality, serum creatinine, and other signs of propylene glycol toxicity (eg, CNS depression, seizures, cardiac arrhythmias, hemolysis); in neonates particularly, symptoms should be distinguished from sepsis (HHS [pediatric 2020]).
A fatal accidental overdose occurred in a 2.1 kg, 44-day old infant (born at 30 weeks GA) with HIV who received a single dose of 6.5 mL (520 mg) of lopinavir/ritonavir oral solution. The infant died of cardiogenic shock 9 days later. Health care providers are reminded that lopinavir/ritonavir oral solution is highly concentrated. To minimize the risk for medication errors, health care providers should pay special attention to accurate calculation of the dose, transcription of the medication order, dispensing information, dosing instructions, and proper measurement of the dose. Pediatric tablets containing lopinavir 100 mg and ritonavir 25 mg (ie, half the amount in regular tablets) are available; caution should be taken so that dosing and dispensing errors do not occur.
May cause diarrhea (5% to 28%; children: 12%); in one adult study, incidence of diarrhea was higher in patients receiving once-daily dosing compared to twice-daily dosing. Children may have a higher incidence of vomiting (21% vs ≤6%). May cause taste perversion in children (incidence: 22%). Dyslipidemia has been reported, the incidence of dyslipidemia is estimated at 10% to 20% in young children and 45% to 75% in older children and adolescents with prolonged history of antiretroviral use; cholesterol and triglycerides may be of most concern (HHS [pediatric 2020]).
Refer to individual components.
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
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
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Albendazole: Ritonavir may decrease the serum concentration of Albendazole. Risk C: Monitor therapy
Alfentanil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfentanil. Management: If use of alfentanil and strong CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
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: Ritonavir may increase the serum concentration of Amiodarone. Management: Ritonavir US prescribing information lists this combination as contraindicated. Amiodarone use should be avoided with lopinavir/ritonavir, but if the combination must be used, monitor closely for increased amiodarone serum concentrations and effects. Risk X: Avoid combination
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihepaciviral Combination Products: Lopinavir may increase the serum concentration of Antihepaciviral Combination Products. Specifically, the serum concentrations of the paritaprevir component may increase significantly. Risk X: Avoid combination
Apalutamide: May decrease the serum concentration of Lopinavir. Risk X: Avoid combination
Apixaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Apixaban. Management: US labeling recommends a 50% apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily, and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian labeling lists any combined use as contraindicated. Risk D: Consider therapy modification
Aprepitant: CYP3A4 Inhibitors (Strong) may increase 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, 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
Artesunate: Ritonavir may decrease serum concentrations of the active metabolite(s) of Artesunate. Ritonavir may increase the serum concentration of Artesunate. 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
Atazanavir: Lopinavir may enhance the arrhythmogenic effect of Atazanavir. Specifically, the PR interval may be further prolonged. Atazanavir may decrease the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of Atazanavir. Lopinavir may increase the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant is 10 mg once daily when coadministered with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant when coadministered with OATP1B1/1B3 inhibitors is 10 mg once daily or 30 mg once daily. Risk D: Consider therapy modification
Atorvastatin: Lopinavir may increase the serum concentration of Atorvastatin. Management: Consider the risks and benefits of this combination. If coadministered, use the lowest dose of atorvastatin necessary and monitor patients for signs and symptoms of myopathy, especially at initiation of therapy and with any dose increase. Risk D: Consider therapy modification
Atorvastatin: Ritonavir may increase the serum concentration of Atorvastatin. Management: Use lowest atorvastatin dose needed. If ritonavir is combined with another protease inhibitor, see the drug interaction monograph for that protease inhibitor. Consider temporarily discontinuing atorvastatin during treatment with nirmatrelvir/ritonavir. Risk D: Consider therapy modification
Atovaquone: Ritonavir may decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
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
Bedaquiline: Lopinavir may increase serum concentrations of the active metabolite(s) of Bedaquiline. Lopinavir may increase the serum concentration of Bedaquiline. Management: Consider alternatives to this combination. Concomitant use should only occur if the benefit of coadministration outweighs the risk. If combined, monitor for increased bedaquiline effects/toxicities (eg, QTc interval prolongation). Risk D: Consider therapy modification
Benidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
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
Bictegravir: UGT1A1 Inducers may decrease the serum concentration of Bictegravir. Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Risk X: Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosentan: Protease Inhibitors may increase the serum concentration of Bosentan. Management: Dose adjustment of bosentan and increased monitoring for bosentan toxicities is necessary when these agents are combined. See full drug interaction monograph for details. Risk D: Consider therapy modification
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider therapy modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
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
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Buprenorphine. Risk C: Monitor therapy
BuPROPion: CYP2B6 Inducers (Moderate) may decrease the serum concentration of BuPROPion. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider therapy modification
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
Cabotegravir: UGT1A1 Inducers may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination
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
Canagliflozin: Ritonavir may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 200 mg/day in patients tolerating 100 mg/day. A further increase to 300 mg/day can be considered in patients with an estimated glomerular filtration rate (GFR) of 60 mL/min/1.73 m2 or greater. Risk D: Consider therapy modification
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
Capmatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Capmatinib. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of CarBAMazepine. Management: Do not use a once daily lopinavir/ritonavir regimen together with carbamazepine. If used with a twice daily lopinavir/ritonavir regimen, monitor for reduced lopinavir/ritonavir effectiveness. Also monitor for increased carbamazepine effects/toxicities. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of CarBAMazepine. Management: Consider avoiding this combination due to the potential for decreased ritonavir concentrations and the possible development of resistance. If combined, monitor for increased carbamazepine concentrations and effects and decreased ritonavir effects. Risk D: Consider therapy modification
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
Cat's Claw: May increase the serum concentration of Ritonavir. Risk C: Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: Avoid this combination whenever possible. If combined, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilnidipine. Risk C: Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. Risk C: Monitor therapy
Cisapride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cisapride. Risk X: Avoid combination
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
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider therapy modification
Clarithromycin: Protease Inhibitors may decrease serum concentrations of the active metabolite(s) of Clarithromycin. Protease Inhibitors may increase the serum concentration of Clarithromycin. Management: Do not exceed clarithromycin doses greater than 1,000 mg/day in patients taking protease inhibitors. If CrCL is 30 to 60 mL/min, reduced clarithromycin dose 50%. If CrCL is less than 30 mL/min, reduced clarithromycin dose 75%. Risk D: Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clobetasone: Ritonavir may increase the serum concentration of Clobetasone. Risk X: Avoid combination
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: Ritonavir may diminish the antiplatelet effect of Clopidogrel. Ritonavir may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy
Clorazepate: Ritonavir may increase the serum concentration of Clorazepate. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: May enhance the therapeutic effect of Ritonavir. Specifically, cobicistat and ritonavir have overlapping effects on the CYP3A4-mediated metabolism of other drugs. Risk X: Avoid combination
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: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. 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
Cyclophosphamide: CYP2B6 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) 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 Ritonavir. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lopinavir. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ritonavir. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ritonavir. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lopinavir. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ritonavir. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lopinavir. 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
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
Darolutamide: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Darolutamide. Risk C: Monitor therapy
Darunavir: Lopinavir may decrease the serum concentration of Darunavir. Risk X: Avoid combination
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
Deferasirox: Ritonavir may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing. 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
Delavirdine: May increase the serum concentration of Ritonavir. Management: Consider alternatives to this combination. Safe and effective doses for coadministration have not been determined according to ritonavir prescribing information. Risk D: Consider therapy modification
Delavirdine: May increase the serum concentration of Lopinavir. Management: Consider alternatives to this combination. Safe and effective doses for coadministration have not been determined according to lopinavir/ritonavir prescribing information. Risk D: Consider therapy modification
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy
DexAMETHasone (Systemic): May decrease the serum concentration of Lopinavir. Management: Consider alternative corticosteroids for coadministration with lopinavir/ritonavir due to the potential for dexamethasone to decrease lopinavir/ritonavir efficacy and result in the development of resistance. Risk D: Consider therapy modification
DiazePAM: Ritonavir may increase the serum concentration of DiazePAM. Ritonavir may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
Didanosine: Lopinavir may decrease the serum concentration of Didanosine. This interaction refers only to lopinavir/ritonavir oral solution, which must be taken with food, and is principally the result of a food-didanosine interaction. Management: Didanosine should be administered 1 hour prior to or 2 hours after administration of lopinavir/ritonavir oral solution (which must be taken with food). Didanosine and lopinavir/ritonavir tablets can be administered together. Risk D: Consider therapy modification
Digoxin: Ritonavir may increase the serum concentration of Digoxin. Management: Reduce the digoxin dose by approximately 30% to 50%, or reduce the dosing frequency, when these agents are combined. Monitor digoxin levels closely and adjust digoxin dose as needed. Risk D: Consider therapy modification
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase 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: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination
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 (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
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
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Lopinavir. Management: Avoid once daily use of lopinavir/ritonavir with efavirenz. Avoid use of this combination in patients less than 6 months of age. Lopinavir/ritonavir dose adjustments are required for patients taking twice daily lopinavir/ritonavir. See full monograph. Risk D: Consider therapy modification
Efonidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Efonidipine. Risk C: Monitor therapy
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. Risk X: Avoid combination
Elbasvir and Grazoprevir: Lopinavir 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: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. 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
Eluxadoline: Ritonavir may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with ritonavir and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
Elvitegravir: Lopinavir may increase the serum concentration of Elvitegravir. Specifically, lopinavir/ritonavir may increase the concentration of elvitegravir. Management: When elvitegravir is combined with lopinavir/ritonavir, the dose of elvitegravir should be reduced to 85 mg once daily and the dose of lopinavir/ritonavir should be 400 mg/100 mg twice daily. Risk D: Consider therapy modification
Encorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Once the CYP3A4 inhibitor is discontinued for 3 to 5 half-lives, resume prior dose. Risk D: Consider therapy modification
Enfortumab Vedotin: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Entrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Entrectinib. Management: Avoid strong CYP3A4 inhibitors during treatment with entrectinib when possible. If combined in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters, reduce dose to 100 mg/day. Avoid if BSA is less than 1.5 square meters. Risk D: Consider therapy modification
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). Risk C: Monitor therapy
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
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etravirine: Ritonavir may decrease the serum concentration of Etravirine. Management: Avoid concomitant use of etravirine with antiviral doses of ritonavir; use with ritonavir-boosted fosamprenavir or with ritonavir-boosted tipranavir is also not recommended. Risk D: Consider therapy modification
Everolimus: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Everolimus. Risk X: Avoid combination
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: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Finerenone. Risk X: Avoid combination
Flecainide: Ritonavir may increase the serum concentration of Flecainide. 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
Flurazepam: Ritonavir may increase the serum concentration of Flurazepam. 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
Fosamprenavir: May decrease the serum concentration of Lopinavir. Specifically, amprenavir (the active metabolite of fosamprenavir) may decrease the serum concentration of lopinavir. Lopinavir may decrease the serum concentration of Fosamprenavir. Specifically, lopinavir/ritonavir may decrease the serum concentration of amprenavir (the active metabolite of fosamprenavir) Risk X: Avoid combination
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fosphenytoin: May decrease the serum concentration of Lopinavir. Lopinavir may decrease the serum concentration of Fosphenytoin. Management: Avoid once-daily administration of lopinavir/ritonavir if used together with phenytoin. If twice daily lopinavir/ritonavir is coadministered with phenytoin, monitor phenytoin levels and response to both agents. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Fosphenytoin. Management: Consider avoiding when possible. Dose adjustments may be required. Monitor phenytoin concentrations, and for therapeutic response to fosphenytoin and ritonavir, particularly with any dose adjustments. Risk D: Consider therapy modification
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Fusidic Acid (Systemic): Ritonavir may increase the serum concentration of Fusidic Acid (Systemic). Fusidic Acid (Systemic) may increase the serum concentration of Ritonavir. 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
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: Lopinavir may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: Ritonavir 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: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Haloperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: Protease Inhibitors may decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
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: May increase the serum concentration of Lopinavir. Management: Coadministration of indinavir and lopinavir/ritonavir once daily regimens have not been studied. If indinavir is coadministered with twice daily lopinavir/ritonavir, decrease the indinavir dose to 600 mg twice daily. Risk D: Consider therapy modification
Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid combination
Isradipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider therapy modification
Itraconazole: Lopinavir may increase the serum concentration of Itraconazole. Management: Itraconazole doses greater than 200 mg/day are not recommended in combination with lopinavir/ritonavir. Risk D: Consider therapy modification
Itraconazole: Ritonavir may increase the serum concentration of Itraconazole. Management: Limit the adult maximum itraconazole dose to 200 mg/day in patients receiving ritonavir. Risk D: Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily and monitor for increased ivosidenib toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ketamine: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Ketamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of Ketoconazole (Systemic). Management: Ketoconazole doses greater than 200 mg/day are not recommended in combination with lopinavir/ritonavir. Risk D: Consider therapy modification
Ketoconazole (Systemic): Ritonavir may increase the serum concentration of Ketoconazole (Systemic). Management: Limit the adult maximum ketoconazole dose to 200 mg/day in patients receiving ritonavir. Risk D: Consider therapy modification
Lacidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacidipine. Risk C: Monitor therapy
LamoTRIgine: Lopinavir may decrease the serum concentration of LamoTRIgine. Management: For patients taking lopinavir/ritonavir without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, reduce lapatinib dose to 500 mg daily. 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
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Risk X: Avoid combination
Letermovir: May increase the serum concentration of UGT1A1 Inducers. Risk X: Avoid combination
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomethadone: Lopinavir may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomethadone: Ritonavir may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: Ritonavir may increase the serum concentration of Lopinavir. 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
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurbinectedin. Risk X: Avoid combination
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
Mebendazole: Ritonavir may decrease the serum concentration of Mebendazole. Risk C: Monitor therapy
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
Meptazinol: Ritonavir may increase the serum concentration of Meptazinol. Risk X: Avoid combination
Methadone: Lopinavir may enhance the QTc-prolonging effect of Methadone. Lopinavir may decrease the serum concentration of Methadone. More specifically, the combination of Lopinavir and Ritonavir may decrease Methadone serum concentrations. Risk C: Monitor therapy
Methadone: Ritonavir may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
MetroNIDAZOLE (Systemic): Ritonavir may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Specifically, the combination of ritonavir oral solution or ritonavir soft gelatin capsule, both of which contain alcohol, and metronidazole may result in a disulfiram-like reaction. Risk X: Avoid combination
MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Lopinavir. Specifically, the use of topical metronidazole with lopinavir/ritonavir solution (which contains 42% alcohol) may result in a disulfiram-like reaction. Risk C: Monitor therapy
Midazolam: Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam is contraindicated with protease inhibitors. Avoid use with nasal midazolam. Consider alternatives to use with other routes of midazolam (IV, IM) when possible. Consider use of lower midazolam doses if combined. Risk X: Avoid combination
Midostaurin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider therapy modification
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirtazapine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mitapivat. Risk X: Avoid combination
Mobocertinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Nasal). Risk C: Monitor therapy
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Topical). Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. 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
Nefazodone: May increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of Nefazodone. Risk C: Monitor therapy
Nelfinavir: May decrease the serum concentration of Lopinavir. Lopinavir may increase the serum concentration of Nelfinavir. Concentrations of the nelfinavir M8 metabolite may also be increased. Management: Avoid once daily use of lopinavir/ritonavir with nelfinavir. Avoid use of this combination in patients less than 6 months of age. Lopinavir/ritonavir dose adjustments are required for patients taking twice daily lopinavir/ritonavir. See full monograph. Risk D: Consider therapy modification
Nelfinavir: Ritonavir may increase the serum concentration of Nelfinavir. Management: Consider alternatives to this combination. Safe and effective doses for coadministration have not been determined according to the nelfinavir prescribing information. Risk D: Consider therapy modification
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Risk X: Avoid combination
Nevirapine: May decrease the serum concentration of Lopinavir. Management: Avoid once daily use of lopinavir/ritonavir with nevirapine. Avoid use of this combination in patients less than 6 months of age. Lopinavir/ritonavir dose adjustments are required for patients taking twice daily lopinavir/ritonavir. See full monograph. Risk D: Consider therapy modification
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Risk D: Consider therapy modification
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Nirmatrelvir: May increase the serum concentration of Ritonavir. Risk C: Monitor therapy
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
OLANZapine: Ritonavir may decrease the serum concentration of OLANZapine. 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
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Risk C: Monitor therapy
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
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
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: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
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: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Lopinavir. Management: Increased doses of lopinavir may be necessary when using these agents in combination. Do not use a once daily lopinavir/ritonavir regimen together with phenobarbital. Increase monitoring of therapeutic response in all patients using this combination. Risk D: Consider therapy modification
PHENobarbital: Ritonavir may decrease the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Ritonavir. Management: Consider avoiding this combination due to the potential for decreased ritonavir concentrations and the possible development of resistance. If combined, monitor for decreased phenobarbital and ritonavir concentrations and effects during coadministration. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Lopinavir. Lopinavir may decrease the serum concentration of Phenytoin. Management: Avoid once-daily administration of lopinavir/ritonavir if used together with phenytoin. If twice daily lopinavir/ritonavir is coadministered with phenytoin, monitor phenytoin levels and response to both agents. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Phenytoin. Management: Consider avoiding when possible. Dose adjustments may be required. Monitor phenytoin concentrations, and for therapeutic response to phenytoin and ritonavir, particularly with any dose adjustments. Risk D: Consider therapy modification
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
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. Risk X: Avoid combination
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: Ritonavir may decrease the serum concentration of Primidone. Primidone may decrease the serum concentration of Ritonavir. Management: Consider avoiding this combination due to the potential for decreased ritonavir concentrations and the possible development of resistance. If combined, monitor for decreased phenobarbital and ritonavir concentrations and effects during coadministration. Risk D: Consider therapy modification
Primidone: May decrease the serum concentration of Lopinavir. Management: Avoid once-daily administration of lopinavir/ritonavir if used together with phenobarbital. If lopinavir/ritonavir twice daily is combined with phenobarbital, monitor closely for decreased efficacy of lopinavir/ritonavir. Risk D: Consider therapy modification
Proguanil: Ritonavir may decrease the serum concentration of Proguanil. Risk C: Monitor therapy
Propafenone: Ritonavir may increase the serum concentration of Propafenone. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of original dose after starting a strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Risk D: Consider therapy modification
QuiNIDine: Ritonavir 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: Ritonavir may decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. Ritonavir may increase the serum concentration of QuiNINE. Risk X: Avoid combination
QuiNINE: Lopinavir may decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. Risk X: Avoid combination
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
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
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: Lopinavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Lopinavir may increase the serum concentration of Rifabutin. Management: Reduce rifabutin doses. Clinical guidelines recommend 150 mg daily. Lopinavir/ritonavir prescribing information recommends a decrease of at least 75% (ie, to 150 mg every other day or 3 times per week). Risk D: Consider therapy modification
Rifabutin: Ritonavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Ritonavir may increase the serum concentration of Rifabutin. Management: Ritonavir labeling recommends reducing rifabutin doses by at least 75% (ie, 150 mg every other day or 3 times per week). Clinical practice guidelines recommend rifabutin 150 mg daily if combined with ritonavir-boosted protease inhibitors. Risk D: Consider therapy modification
RifAMPin: May enhance the adverse/toxic effect of Lopinavir. Specifically, the risk of hepatocellular toxicity may be increased. RifAMPin may decrease the serum concentration of Lopinavir. Risk X: Avoid combination
RifAMPin: May increase the serum concentration of Ritonavir. RifAMPin may decrease the serum concentration of Ritonavir. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
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 P-glycoprotein 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 P-gp inhibitors. Monitor for hypotension when these agents are combined and reduce the riociguat dose as needed. Risk D: Consider therapy modification
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 the serum concentration of Ripretinib. Risk C: Monitor therapy
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RisperiDONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritonavir: May increase the serum concentration of Lopinavir. Risk X: Avoid combination
Rivaroxaban: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Rivaroxaban. Risk X: Avoid combination
Roflumilast: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast. Risk C: Monitor therapy
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rosuvastatin: Lopinavir may increase the serum concentration of Rosuvastatin. Management: Limit rosuvastatin doses to 10 mg daily if coadministered with lopinavir/ritonavir. 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 Inducers may decrease serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saquinavir: Lopinavir may enhance the QTc-prolonging effect of Saquinavir. Risk C: Monitor therapy
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
Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination
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
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 (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
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
St John's Wort: May decrease the serum concentration of Lopinavir. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Ritonavir. 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): Ritonavir may increase the serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose reductions may be needed with concurrent ritonavir. Monitor tacrolimus concentrations closely to determine dose; doses of tacrolimus 0.5 mg to 1 mg every week may be adequate. Risk D: Consider therapy modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: Ritonavir may increase the serum concentration of Tadalafil. Management: In patients treated for pulmonary arterial hypertension avoid initiating ritonavir in patients taking tadalafil; dose adjustments are required. For ED or BPH treatment, decrease tadalafil max dose and frequency. See full monograph for details. Risk D: Consider therapy modification
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
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
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. Risk X: Avoid combination
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Risk C: Monitor therapy
Telithromycin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. Risk C: Monitor therapy
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
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Alafenamide: Ritonavir may increase the serum concentration of Tenofovir Alafenamide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: Lopinavir may enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Tepotinib: Inhibitors of CYP3A4 (Strong) and P-glycoprotein may increase the serum concentration of Tepotinib. Risk X: Avoid combination
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
Theophylline Derivatives: Ritonavir may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease 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
Thyroid Products: Ritonavir may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
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: Protease Inhibitors may increase the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Protease Inhibitors. 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
Topotecan: P-glycoprotein/ABCB1 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: Ritonavir may decrease serum concentrations of the active metabolite(s) of TraMADol. Ritonavir 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: When used together with a strong CYP3A4 inhibitor, the recommended dose of upadacitinib is 15 mg/day. Coadministration of the upadacitinib 30 mg/day dose together with a strong CYP3A4 inhibitor is not recommended. 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
Vardenafil: Ritonavir may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 72-hour period if combined with ritonavir. Avoid concomitant use of Staxyn (vardenafil) and ritonavir. 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
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. 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
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors 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
Vitamin K Antagonists (eg, warfarin): Ritonavir may decrease the serum concentration of Vitamin K Antagonists. 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: Ritonavir may increase the serum concentration of Voriconazole. Ritonavir may decrease the serum concentration of Voriconazole. Management: Concurrent voriconazole and high-dose ritonavir (adult doses of 400 mg every 12 hrs or greater) is contraindicated. Voriconazole with lower-dose ritonavir should be avoided unless benefits outweigh risk of inadequate voriconazole concentrations. Risk D: Consider therapy modification
Voriconazole: Lopinavir may decrease the serum concentration of Voriconazole. Management: This combination should be avoided unless the risks of potentially subtherapeutic voriconazole concentrations are outweighed by potential benefits of therapy. Risk D: Consider therapy modification
Voxilaprevir: Lopinavir may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Warfarin: Lopinavir may decrease 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
Zidovudine: Lopinavir may decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Zidovudine: Ritonavir may decrease the serum concentration of Zidovudine. 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
Moderate- to high-fat meals increase the Cmax and AUC of lopinavir/ritonavir oral solution; no significant changes observed with oral tablets. Management: Take oral solution with food; take tablet with or without food.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommend (except in special circumstances) lopinavir combined with ritonavir for patients living with HIV who are not yet pregnant but are trying to conceive.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in patients of all genders who are living with HIV and planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception.
Health care providers caring for couples planning a pregnancy when one or both partners are living with HIV may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Lopinavir has a low level of transfer across the human placenta; fetal exposure is increased with ritonavir.
Based on information collected by the Antiretroviral Pregnancy Registry, an increased risk of teratogenic effects has not been observed in humans. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, 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. However, regimens containing lopinavir/ritonavir may be more closely associated with preterm delivery compared to others. 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 infection 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 mitochondrial dysfunction. The risk of hepatic dysfunction and gestational diabetes may be increased in pregnant patients taking protease inhibitors. Consider performing the standard glucose screening test earlier in pregnancy in patients who initiated protease inhibitor therapy prior to conception.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommended (except in special circumstances) lopinavir combined with ritonavir for pregnant patients living 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). Patients who become pregnant while taking lopinavir combined with ritonavir may continue if viral suppression is effective and the regimen is well tolerated.
Pharmacokinetic studies suggest that standard dosing during pregnancy may provide decreased plasma concentrations; dose adjustments are required in patients during the second and third trimesters of pregnancy. Although there is an abundance of data related to the use of lopinavir/ritonavir during pregnancy, the HHS perinatal HIV guidelines consider lopinavir/ritonavir to be an alternative protease inhibitor for initial therapy in antiretroviral-naive patients who are pregnant due to the need for twice daily dosing, the increased incidence of diarrhea and nausea, and an association with preterm delivery. Lopinavir/ritonavir is not recommended for use in pregnant patients with lopinavir-associated resistance substitutions. In addition, once-daily dosing is not recommended during pregnancy and use of the oral solution should be avoided (due to alcohol and propylene glycol content).
ART is recommended for all patients who are pregnant and living with HIV to maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART should be continued postpartum for all patients living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant patients who are living with HIV and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2020).
Lopinavir and ritonavir are present in breast milk.
The Health and Human Services (HHS) perinatal HIV guidelines state breast milk concentrations of lopinavir are low to undetectable and concentrations in breastfed infants would not be clinically significant. Also refer to the ritonavir monograph for additional information.
Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is 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 who are living with HIV. Information is available for counseling and managing patients living with HIV who are considering breastfeeding (HHS [perinatal] 2020).
Solution must be taken with food. Tablet may be taken with or without food
Prior to therapy, consider genotypic or phenotypic testing for lopinavir resistance-associated substitutions.
Triglycerides and cholesterol (prior to initiation then periodically thereafter), LFTs, electrolytes, basic HIV monitoring, viral load and CD4 count, glucose
A coformulation of lopinavir and ritonavir. The lopinavir component binds to the site of HIV-1 protease activity and inhibits the 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. The ritonavir component inhibits the CYP3A metabolism of lopinavir, allowing increased plasma levels of lopinavir.
Ritonavir: See Ritonavir monograph.
Lopinavir:
Protein binding: 98% to 99%; binds to both alpha-1 acid glycoprotein and albumin; higher affinity for alpha-1 acid glycoprotein; decreased with mild-to-moderate hepatic dysfunction
Metabolism: Hepatic via CYP3A4; 13 metabolites identified; may induce its own metabolism
Half-life elimination: 5 to 6 hours
Time to peak, plasma: ~4 hours
Excretion: Feces (83%, 20% as unchanged drug); urine (10%; <3% as unchanged drug)
Clearance: (Apparent oral): 6 to 7 L/hour
Hepatic function impairment: Lopinavir is principally metabolized and eliminated by the liver. Multiple dosing of lopinavir 400 mg/ritonavir 100 mg twice daily to patients coinfected with HIV-1 and hepatitis C virus with mild to moderate hepatic impairment resulted in a 30% increase in lopinavir AUC and a 20% increase in Cmax compared with patients infected with HIV-1 with normal hepatic function.
Solution (Kaletra Oral)
400-100 mg/5 mL (per mL): $3.84
Solution (Lopinavir-Ritonavir Oral)
400-100 mg/5 mL (per mL): $3.26
Tablets (Kaletra Oral)
100-25 mg (per each): $5.12
200-50 mg (per each): $10.24
Tablets (Lopinavir-Ritonavir Oral)
100-25 mg (per each): $4.61
200-50 mg (per each): $9.22
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.