ℹ️ Compiled from public regulatory records · Last regulator revision: June 1, 2026🚩 Report this page
Lopinavir
Active ingredient
Sold asKaletra
GB MHRAEU EMAUS FDACA Health Canada
Drug class
-
Availability
Prescription only
Routes
Oral
Markets covered
4
Products on record
10
FDA reports (12 mo)
91
Overview
Lopinavir is an active pharmaceutical ingredient. The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised April 17, 2026[1]
Lopinavir/ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV- 1) infected adults, adolescents and children above the age of 2 years. 1).
How to take
GB
EUEuropean Union· EMA
2 products
Uses
EUOfficial regulatory label· revised June 1, 2026[2]
Lopinavir/ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infected adults, adolescents and children above the age of 2 years. 1).
How to take
EU
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised June 5, 2021[3]
1 INDICATIONS AND USAGE Lopinavir and ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV1 infection in adults and pediatric patients 14 days and older.
Limitations of Use:
Genotypic or phenotypic testing and/or treatment history should guide the use of lopinavir and ritonavir. 4 )]. Lopinavir and ritonavir is an HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients (14 days and older).
( 1 )
How to take
CACanada· Health Canada
3 products
3 products on record with this regulator. Detailed label text (uses, dosage, side effects) is being ingested — the original document is linked under Sources [4].
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
Sources & citations
[1]MHRA (UK) · PLGB045692007 · revised April 17, 2026
[2]European Medicines Agency · EMEA/H/C/004025 · revised June 1, 2026
[3]FDA DailyMed · 115178c8-5ee2-4d… · revised June 5, 2021 [PDF]
[4]Health Canada (DPD) · 02243644 · revised March 12, 2026
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Lopinavir/ritonavir should be prescribed by physicians who are experienced in the treatment of HIV infection. Lopinavir/ritonavir tablets must be swallowed whole and not chewed, broken or crushed. Posology Adults and adolescents The standard recommended dosage of lopinavir/ritonavir tablets is 400/100 mg (two 200/50 mg) tablets twice daily taken with or without food.
In adult patients, in cases where once daily dosing is considered necessary for the management of the patient, lopinavir/ritonavir tablets may be administered as 800/200 mg (four 200/50 mg tablets) once daily with or without food. e.
8) compared to the recommended standard twice daily dosing. 4 m2. 4 m2 and able to swallow tablets, please refer to the dosing guideline tables below. 1). Before prescribing lopinavir/ritonavir 100/25 mg tablets, infants and young children should be assessed for the ability to swallow intact tablets.
For infants and young children unable to swallow tablets, more suitable formulations containing lopinavir/ritonavir should be checked for their availability. The following table contains dosing guidelines for lopinavir/ritonavir 100/25 mg tablets based on body weight and BSA.
4 4 tablets (400/100 mg) * weight based dosing recommendations are based on limited data If more convenient for patients, the lopinavir/ritonavir 200/50 mg tablets may also be considered alone or in combination with the lopinavir/ritonavir 100/25 mg tablet to achieve the recommended dose.
* Body surface area can be calculated with the following equation: BSA (m2) = √ (Height (cm) X Weight (kg) / 3600) Children less than 2 years of age The safety and efficacy of lopinavir/ritonavir in children aged less than 2 years have not yet been established.
2 but no recommendation on a posology can be made.
Concomitant Therapy:
Efavirenz or nevirapine The following table contains dosing guidelines for lopinavir/ritonavir tablets based on BSA when used in combination with efavirenz or nevirapine in children. Paediatric dosing guidelines with concomitant efavirenz or nevirapine Body Surface Area (m2) Recommended lopinavir/ritonavir dosing (mg) twice daily.
4 500/125 mg * The tablets must not be chewed, broken or crushed. 2). No data are available in patients with severe hepatic impairment. 3). Renal impairment Since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.
Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis. Pregnancy and postpartum • No dose adjustment is required for lopinavir/ritonavir during pregnancy and postpartum.
• Once daily administration of lopinavir/ritonavir is not recommended for pregnant women due to the lack of pharmacokinetic and clinical data. Method of administration Lopinavir/ritonavir tablets are administered orally and must be swallowed whole and not chewed, broken or crushed.
Lopinavir/ritonavir tablets can be taken with or without food.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised April 17, 2026[1]
Summary of the safety profile The safety of lopinavir/ritonavir has been investigated in over 2600 patients in Phase II-IV clinical trials, of which over 700 have received a dose of 800/200 mg (6 capsules or 4 tablets) once daily. Along with nucleoside reverse transcriptase inhibitors (NRTIs), in some studies, lopinavir/ritonavir was used in combination with efavirenz or nevirapine.
The most common adverse reactions related to lopinavir/ritonavir therapy during clinical trials were diarrhoea, nausea, vomiting, hypertriglyceridaemia and hypercholesterolemia. The risk of diarrhoea may be greater with once daily dosing of lopinavir/ritonavir.
Diarrhoea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridaemia and hypercholesterolemia may occur later. Treatment emergent adverse events led to premature study discontinuation for 7% of subjects from Phase II-IV studies.
It is important to note that cases of pancreatitis have been reported in patients receiving lopinavir/ritonavir, including those who developed hypertriglyceridaemia. 4). Tabulated list of adverse reactions Adverse reactions from clinical trials and post-marketing experience in adult and paediatric patients: The following events have been identified as adverse reactions.
The frequency category includes all reported events of moderate to severe intensity, regardless of the individual causality assessment. The adverse reactions are displayed by system organ class. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100) rare (≥1/10,000 to <1/1000) and not known (cannot be estimated from the available data).
g. 5). Increased creatine phosphokinase (CPK), myalgia, myositis, and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors. 4). In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.
4). Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). The frequency […]
GBOfficial regulatory label· Warnings and precautions· revised April 17, 2026[1]
Patients with coexisting conditions Hepatic impairment The safety and efficacy of lopinavir/ritonavir has not been established in patients with significant underlying liver disorders. 3). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products. Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Elevated transaminases with or without elevated bilirubin levels have been reported in HIV-1 mono-infected and in individuals treated for post-exposure prophylaxis as early as 7 days after the initiation of lopinavir/ritonavir in conjunction with other antiretroviral agents.
In some cases the hepatic dysfunction was serious. Appropriate laboratory testing should be conducted prior to initiating therapy with lopinavir/ritonavir and close monitoring should be performed during treatment. Renal impairment Since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.
Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia type A and B treated with protease inhibitors.
In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship had been evoked, although the mechanism of action had not been elucidated.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding. Pancreatitis Cases of pancreatitis have been reported in patients receiving lopinavir/ritonavir, including those who developed hypertriglyceridaemia.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised April 17, 2026[1]
1. Severe hepatic insufficiency. Lopinavir/Ritonavir Mylan tablets contain lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Lopinavir/ritonavir should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events.
These medicinal products include:
Medicinal product class Medicinal products within class Rationale Concomitant medicinal product levels increased Alpha1- adrenoreceptor antagonist Alfuzosin Increased plasma concentrations of alfuzosin which may lead to severe hypotension.
5). 5). Antiarrhythmics Amiodarone, dronedarone Increased plasma concentrations of amiodarone and dronedarone. 5). Medicinal product class Medicinal products within class Rationale Antibiotic Fusidic Acid Increased plasma concentrations of fusidic acid.
5). 5). Anticancer Venetoclax Increased plasma concentrations of venetoclax. 5). Anti-gout Colchicine Increased plasma concentrations of colchicine. 5). Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine.
5). 5) Pimozide Increased plasma concentrations of pimozide. 5). Antipsychotics/ Neuroleptics Quetiapine Increased plasma concentrations of quetiapine which may lead to coma. 5). 5). Medicinal product class Medicinal products within class Rationale GI motility agent Cisapride Increased plasma concentrations of cisapride.
5). 5). 5). 5). 5). 5) Sildenafil Contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) only. Increased plasma concentrations of sildenafil. Thereby, increasing the potential for sildenafil- associated adverse events (which include hypotension and syncope).
5 for co-administration of sildenafil in patients with erectile dysfunction. 5) Sedatives/hypnotics Oral midazolam, triazolam Increased plasma concentrations of oral midazolam and triazolam. Thereby, increasing the risk of extreme sedation and respiratory depression from these agents.
For caution on parenterally administered midazolam, see section
This is not medical advice. Consult a qualified healthcare professional.
Lopinavir/ritonavir should be prescribed by physicians who are experienced in the treatment of HIV infection. Lopinavir/ritonavir tablets must be swallowed whole and not chewed, broken or crushed. Posology 3 Adults and adolescents The standard recommended dosage of lopinavir/ritonavir tablets is 400/100 mg (two 200/50 mg) tablets twice daily taken with or without food.
In adult patients, in cases where once daily dosing is considered necessary for the management of the patient, lopinavir/ritonavir tablets may be administered as 800/200 mg (four 200/50 mg tablets) once daily with or without food. e.
8) compared to the recommended standard twice daily dosing. 4 m2. 4 m2 and able to swallow tablets, please refer to the dosing guideline tables below. 1). Before prescribing lopinavir/ritonavir 100/25 mg tablets, infants and young children should be assessed for the ability to swallow intact tablets.
For infants and young children unable to swallow tablets, more suitable formulations containing lopinavir/ritonavir should be checked for their availability. The following table contains dosing guidelines for lopinavir/ritonavir 100/25 mg tablets based on body weight and BSA.
4 4 tablets (400/100 mg) * weight based dosing recommendations are based on limited data If more convenient for patients, the lopinavir/ritonavir 200/50 mg tablets may also be considered alone or in combination with the lopinavir/ritonavir 100/25 mg tablet to achieve the recommended dose.
* Body surface area can be calculated with the following equation: BSA (m2) = √ (Height (cm) X Weight (kg) / 3600) Children less than 2 years of age The safety and efficacy of lopinavir/ritonavir in children aged less than 2 years have not yet been established.
2 but no recommendation on a posology can be made.
Concomitant Therapy:
Efavirenz or nevirapine The following table contains dosing guidelines for lopinavir/ritonavir tablets based on BSA when used in combination with efavirenz or nevirapine in children. 4 Paediatric dosing guidelines with concomitant efavirenz or nevirapine Body Surface Area (m2) Recommended lopinavir/ritonavir dosing (mg) twice daily*.
4 400/100 mg tablets * The tablets must not be chewed, broken or crushed. Lopinavir/Ritonavir Viatris 200/50 mg tablets may also be considered alone or in combination with the Lopinavir/Ritonavir Viatris 100/25 mg tablet to achieve the recommended dosage.
2). No data are available in patients with severe hepatic impairment. 3). Renal impairment Since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.
Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis. Pregnancy and postpartum • No dose adjustment is required for lopinavir/ritonavir during pregnancy and postpartum.
• Once daily administration of lopinavir/ritonavir is not recommended for pregnant women due to the lack of pharmacokinetic and clinical data. Method of administration Lopinavir/ritonavir tablets are administered orally and must be swallowed whole and not chewed, broken or crushed.
Lopinavir/ritonavir tablets can be taken with or without food.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised June 1, 2026[2]
Summary of the safety profile The safety of lopinavir/ritonavir has been investigated in over 2600 patients in Phase II-IV clinical trials, of which over 700 have received a dose of 800/200 mg (6 capsules or 4 tablets) once daily. Along with nucleoside reverse transcriptase inhibitors (NRTIs), in some studies, lopinavir/ritonavir was used in combination with efavirenz or nevirapine.
The most common adverse reactions related to lopinavir/ritonavir therapy during clinical trials were diarrhoea, nausea, vomiting, hypertriglyceridaemia and hypercholesterolemia. The risk of diarrhoea may be greater with once daily dosing of lopinavir/ritonavir.
Diarrhoea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridaemia and hypercholesterolemia may occur later. Treatment emergent adverse events led to premature study discontinuation for 7% of subjects from Phase II-IV studies.
It is important to note that cases of pancreatitis have been reported in patients receiving lopinavir/ritonavir, including those who developed hypertriglyceridaemia. 4). Tabulated list of adverse reactions Adverse reactions from clinical trials and post-marketing experience in adult and paediatric patients: The following events have been identified as adverse reactions.
The frequency category includes all reported events of moderate to severe intensity, regardless of the individual causality assessment. The adverse reactions are displayed by system organ class. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥1/10,000 to <1/1000) and not known (cannot be estimated from the available data).
g. 5). Increased creatine phosphokinase (CPK), myalgia, myositis, and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors. 4). In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.
4). Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). The […]
EUOfficial regulatory label· Warnings and precautions· revised June 1, 2026[2]
Patients with coexisting conditions Hepatic impairment The safety and efficacy of lopinavir/ritonavir has not been established in patients with significant underlying liver disorders. 3). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products. Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Elevated transaminases with or without elevated bilirubin levels have been reported in HIV-1 mono-infected and in individuals treated for post-exposure prophylaxis as early as 7 days after the initiation of 7 lopinavir/ritonavir in conjunction with other antiretroviral agents.
In some cases the hepatic dysfunction was serious. Appropriate laboratory testing should be conducted prior to initiating therapy with lopinavir/ritonavir and close monitoring should be performed during treatment. Renal impairment Since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.
Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia type A and B treated with protease inhibitors.
In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship had been evoked, although the mechanism of action had not been elucidated.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding. Pancreatitis Cases of pancreatitis have been reported in patients receiving lopinavir/ritonavir, including those who developed hypertriglyceridaemia.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised June 1, 2026[2]
1. Severe hepatic insufficiency. Lopinavir/Ritonavir Viatris tablets contain lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Lopinavir/ritonavir should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events.
These medicinal products include:
Medicinal product class Medicinal products within class Rationale Concomitant medicinal product levels increased Alpha1-adrenoreceptor antagonist Alfuzosin Increased plasma concentrations of alfuzosin which may lead to severe hypotension.
5). 5). Antiarrhythmics Amiodarone, dronedarone Increased plasma concentrations of amiodarone and dronedarone. 5). Antibiotic Fusidic Acid Increased plasma concentrations of fusidic acid. 5). 5). Venetoclax Increased plasma concentrations of venetoclax.
5). Anti-gout Colchicine Increased plasma concentrations of colchicine. 5). Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine. 5). 5) Antipsychotics/ Neuroleptics Pimozide Increased plasma concentrations of pimozide.
5). Quetiapine Increased plasma concentrations of quetiapine which may lead to coma. 5). 5). GI motility agent Cisapride Increased plasma concentrations of cisapride. 5). 5). 5). 5). 5) Sildenafil Contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) only.
Increased plasma concentrations of sildenafil. Thereby, increasing the potential for sildenafil- associated adverse events (which include hypotension and syncope). 5 for co-administration of sildenafil in patients with erectile dysfunction.
5) Sedatives/hypnotics Oral midazolam, triazolam Increased plasma concentrations of oral midazolam and triazolam. Thereby, increasing the risk of extreme sedation and respiratory depression from these agents. For caution on parenterally administered midazolam, see section
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised June 5, 2021[3]
2 DOSAGE AND ADMINISTRATION Tablets: May be taken with or without food, swallowed whole and not chewed, broken, or crushed. 3 ): Total recommended daily dosage is 800/200 mg given once or twice daily. Lopinavir and ritonavir can be given as once daily or twice daily regimen.
See Full Prescribing Information for details.
Lopinavir and ritonavir once daily dosing regimen is not recommended in:
Adult patients with three or more of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V. 4 ) In combination with carbamazepine, phenobarbital, or phenytoin.
3 ) In combination with efavirenz, nevirapine, or nelfinavir. 3 ) In pregnant women. 4 ): Lopinavir and ritonavir once daily dosing regimen is not recommended in pediatric patients. Twice daily dose is based on body weight or body surface area.
Concomitant Therapy in Adults and Pediatric Patients:
Dose adjustments of lopinavir and ritonavir may be needed when co-administering with efavirenz, nevirapine, or nelfinavir. 5 ): 400/100 mg twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions.
There are insufficient data to recommend a lopinavir and ritonavir dose for pregnant patients with any documented lopinavir and ritonavir -associated resistance substitutions. No dose adjustment of lopinavir and ritonavir is required for patients during the postpartum period.
1 General Administration Recommendations Lopinavir and ritonavir tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed. 3 Dosage Recommendations in Adults Lopinavir and ritonavir can be given in once daily or twice daily dosing regimen at dosages noted in Tables 1 and 2.
4 ) ]. 3 )]. 3 )]. 4 )]. 3 )]. Table 1. Recommended Dosage in Adults -Lopinavir And Ritonavir Once Daily Regimen Lopinavir And Ritonavir Dosage Form Recommended Dosage 200 mg/50 mg Tablets 800 mg/200 mg (4 tablets) once daily Table 2. Recommended Dosage in Adults -Lopinavir And Ritonavir Twice Daily Regimen Lopinavir And Ritonavir Dosage Form Recommended Dosage 200 mg/50 mg Tablets 400 mg/100 mg (2 tablets) twice daily The dose of lopinavir and ritonavir must be increased when administered in combination with efavirenz, nevirapine or nelfinavir.
Table 3 outlines the dosage recommendations for twice daily dosing when lopinavir and ritonavir is taken in combination with these agents. Table 3. 4 Dosage Recommendations in Pediatric Patients Lopinavir and ritonavir tablets are not recommended for once daily dosing in pediatric patients younger than 18 years of age.
Lopinavir and ritonavir 100/25 mg tablets should be considered only in children who have reliably demonstrated the ability to swallow the intact tablet. Pediatric Dosage Calculations Calculate the appropriate dose of lopinavir and ritonavir for each individual pediatric patient based on body weight (kg) or body surface area (BSA) to avoid underdosing or exceeding the recommended adult dose.
Body surface area (BSA) can be calculated as follows:
The lopinavir and ritonavir dose can be calculated based on weight or BSA: Based on Weight : Patient Weight (kg) × Prescribed lopinavir dose (mg/kg) = Administered lopinavir dose (mg) Based on BSA: Patient BSA (m 2 ) × Prescribed lopinavir dose (mg/m 2 ) = Administered lopinavir dose (mg) Tablet Dosage Recommendation in Pediatric Patients Older than 6 Months to Less than 18 Years: Table 5 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for lopinavir and ritonavir tablets.
Table 5. 4 4 Concomitant Therapy: Efavirenz, Nevirapine, or Nelfinavir Dosing recommendations using tablets Table 7 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for lopinavir and ritonavir tablets when given in combination with efavirenz, nevirapine, or nelfinavir.
Table 7. 4 )] † Please refer to the individual product labels for appropriate dosing in children. 5 Dosage Recommendations in Pregnancy Administer 400/100 mg of lopinavir and ritonavir twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions.
3 )]. There are insufficient data to recommend dosing in pregnant women with any documented lopinavir-associated resistance substitutions. No dosage adjustment of lopinavir and ritonavir is required for patients during the postpartum period.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 91 reports total. [5]
USOfficial regulatory label· Adverse reactions· revised June 5, 2021[3]
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. 4 )] Commonly reported adverse reactions to lopinavir and ritonavir included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia.
1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Adverse Reactions in Adults The safety of lopinavir and ritonavir has been investigated in about 2,600 patients in Phase II-IV clinical trials, of which about 700 have received a dose of 800/200 mg (6 capsules or 4 tablets) once daily.
Along with nucleoside reverse transcriptase inhibitors (NRTIs), in some studies, lopinavir and ritonavir was used in combination with efavirenz or nevirapine. In clinical studies the incidence of diarrhea in patients treated with either lopinavir and ritonavir capsules or tablets was greater in those patients treated once daily than in those patients treated twice daily.
Any grade of diarrhea was reported by at least half of patients taking once daily lopinavir and ritonavir capsules or tablets. 7% of those taking twice daily lopinavir and ritonavir reported ongoing diarrhea. Commonly reported adverse reactions to lopinavir and ritonavir included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia.
Diarrhea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridemia and hypercholesterolemia may occur later. The following have been identified as adverse reactions of moderate or severe intensity (Table 8): Table 8.
3 constipation* 26. 7 *Represents a medical concept including several similar MedDRA PTs 1. Percentage of male population (N=2,038) 2. Percentage of female population (N=574) Laboratory Abnormalities in Adults The percentages of adult patients treated with combination therapy with Grade 3-4 laboratory abnormalities are presented in Table 9 (treatment-naïve patients) and Table 10 (treatment-experienced patients).
Table 9. 75 x 10 9 /L 1% 3% 5% 2% 1% 1 ULN = upper limit of the normal range; N/A = Not Applicable. 2 Criterion for Study 730 was >5x ULN (AST/ALT). Table 10. 75 x 10 9 /L 1% 2% 4% 3% 4% Hemoglobin <80 g/L 1% 1% 1% 1% 2% 1 ULN = upper limit of the normal range; N/A = Not Applicable.
2 Includes clinical laboratory data from patients receiving 400/100 mg twice daily (n = 29) or 533/133 mg twice daily (n = 28) for 84 weeks. Patients received lopinavir and ritonavir in combination with NRTIs and efavirenz. 3 Includes clinical laboratory data from patients receiving 400/100 mg twice daily (n = 36) or 400/200 mg twice daily (n = 34) for 144 weeks.
Patients received lopinavir and ritonavir in combination with NRTIs and nevirapine. 4 Criterion for Study 802 was >5x ULN (AST/ALT). Adverse Reactions in Pediatric Patients Lopinavir and ritonavir oral solution dosed up to 300/75 mg/m2 has been studied in 100 pediatric patients 6 months to 12 years of age.
The adverse reaction profile seen during Study 940 was similar to that for adult patients. Dysgeusia (22%), vomiting (21%), and diarrhea (12%) were the most common adverse reactions of any severity reported in pediatric patients treated with combination therapy for up to 48 weeks in Study 940.
A total of 8 patients experienced adverse reactions of moderate to severe intensity. The adverse reactions meeting these criteria and reported for the 8 subjects include: hypersensitivity (characterized by fever, rash and jaundice), pyrexia, viral infection, constipation, hepatomegaly, pancreatitis, vomiting, alanine aminotransferase increased, dry skin, rash, and dysgeusia.
Rash was the only event of those listed that occurred in 2 or more subjects (N = 3). Lopinavir and ritonavir oral solution dosed at 300/75 mg/m2 has been studied in 31 pediatric patients 14 days to 6 months of age. The adverse reaction profile in Study 1030 was similar to that observed in older children and adults.
No adverse reaction was reported in greater than 10% of subjects. Adverse drug reactions of moderate to severe intensity occurring in 2 or more subjects included decreased neutrophil count (N=3), anemia (N=2), high potassium (N=2), and low sodium (N=2).
Lopinavir and ritonavir oral solution and soft gelatin capsules dosed at higher than recommended doses including 400/100 mg/m2 (without concomitant NNRTI) and 480/120 mg/m2 (with concomitant NNRTI) have been studied in 26 pediatric patients 7 to 18 years of age in Study 1038.
Patients also had saquinavir mesylate added to their regimen at Week 4. Rash (12%), blood cholesterol abnormal (12%) and blood triglycerides abnormal (12%) were the only adverse reactions reported in greater than 10% of subjects. Adverse drug reactions of moderate to severe intensity occurring in 2 or more subjects included rash (N=3), blood triglycerides abnormal (N=3), and electrocardiogram QT prolonged (N=2).
Both subjects with QT prolongation had additional predisposing conditions such as electrolyte abnormalities, concomitant medications, or pre-existing cardiac abnormalities. Laboratory Abnormalities in Pediatric Patients The percentages of pediatric patients treated with combination therapy including lopinavir and ritonavir with Grade 3-4 laboratory abnormalities are presented in Table 11.
Table 11. 40 x 109/L 2% 1 ULN = upper limit of the normal range. 2 Subjects with Grade 3-4 amylase confirmed by elevations in pancreatic amylase. 2 Postmarketing Experience The following adverse reactions have been reported during postmarketing use of lopinavir and ritonavir.
Because these reactions are reported voluntarily from a population of unknown size, it is not possible to reliably estimate their frequency or establish a causal relationship to lopinavir and ritonavir exposure. 10 )]. Cardiovascular Bradyarrhythmias.
6 )]. Renal and Urinary Disorders Nephrolithiasis Skin and Appendages Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome and erythema multiforme.
USOfficial regulatory label· Warnings and precautions· revised June 5, 2021[3]
5 WARNINGS AND PRECAUTIONS The following have been observed in patients receiving lopinavir and ritonavir: The concomitant use of lopinavir and ritonavir and certain other drugs may result in known or potentially significant drug interactions.
Consult the full prescribing information prior to and during treatment for potential drug interactions. 3 ) Toxicity in preterm neonates: Lopinavir and ritonavir oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities.
A safe and effective dose of lopinavir and ritonaviroral solution in this patient population has not been established. 2) Pancreatitis: Fatalities have occurred; suspend therapy as clinically appropriate. 3 ) Hepatotoxicity: Fatalities have occurred.
Monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations. 6 ) QT interval prolongation and isolated cases of torsade de pointes have been reported although causality could not be established.
Avoid use in patients with congenital long QT syndrome, those with hypokalemia, and with other drugs that prolong the QT interval. 3 ) PR interval prolongation may occur in some patients. Cases of second and third degree heart block have been reported.
Use with caution in patients with pre-existing conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease or when administering with other drugs that may prolong the PR interval. 7 ), immune reconstitution syndrome.
8 ), redistribution/accumulation of body fat. 10 ) Total cholesterol and triglycerides elevations. Monitor prior to therapy and periodically thereafter. 9 ) Hemophilia: Spontaneous bleeding may occur, and additional factor VIII may be required.
1 Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of lopinavir and ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving lopinavir and ritonavir, may increase plasma concentrations of medications metabolized by CYP3A.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised June 5, 2021[3]
, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir. 3 )]. 3 )]. o Anticancer Agents: apalutamide o Antimycobacterial: rifampin o Herbal Products: St.
, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) or any of its ingredients, including ritonavir. ( 4 ) Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma levels may result in serious and/or lifethreatening events.
( 4 ) Co-administration with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross resistance. ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
In most of these cases patients have had a prior history of pancreatitis and/or concurrent therapy with other medicinal products associated with pancreatitis. Marked triglyceride elevation is a risk factor for development of pancreatitis.
Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis. Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
8). Immune Reconstitution Inflammatory Syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymtomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jiroveci pneumonia.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the reported time to onset is more variable and can occur many months after initiation of treatment.
Osteonecrosis Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. PR interval prolongation Lopinavir/ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Rare reports of 2nd or 3rd degree atroventricular block in patients with underlying structural heart disease and pre- existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving lopinavir/ritonavir.
1). Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment.
For monitoring of blood lipids and glucose, reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate. Interactions with medicinal products Lopinavir/Ritonavir Mylan tablets contain lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A.
Lopinavir/ritonavir is likely to increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A. These […]
In most of these cases patients have had a prior history of pancreatitis and/or concurrent therapy with other medicinal products associated with pancreatitis. Marked triglyceride elevation is a risk factor for development of pancreatitis.
Patients with advanced HIV disease may be at risk of elevated triglycerides and pancreatitis. Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should occur.
8). Immune Reconstitution Inflammatory Syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymtomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jiroveci pneumonia.
Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the reported time to onset is more variable and can occur many months after initiation of treatment.
Osteonecrosis Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART).
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement. PR interval prolongation 8 Lopinavir/ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects.
Rare reports of 2nd or 3rd degree atroventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving lopinavir/ritonavir.
1). Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment.
For monitoring of blood lipids and glucose, reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate. Interactions with medicinal products Lopinavir/Ritonavir Viatris tablets contain lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A.
Lopinavir/ritonavir is likely to increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A. […]
Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of lopinavir and ritonavir, respectively.
These interactions may lead to:
Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications. Clinically significant adverse reactions from greater exposures of lopinavir and ritonavir.
Loss of therapeutic effect of lopinavir and ritonavir and possible development of resistance. See Table 12 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Drug Interactions ( 7 )].
Consider the potential for drug interactions prior to and during lopinavir and ritonavir therapy; review concomitant medications during lopinavir and ritonavir therapy, and monitor for the adverse reactions associated with the concomitant medications [see Contraindications ( 4 ) and Drug Interactions ( 7 )].
2 Toxicity in Preterm Neonates Lopinavir and ritonavir oral solution contains the excipients ethanol, approximately 42% (v/v) and propylene glycol, approximately 15% (w/v). When administered concomitantly with propylene glycol, ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations.
Preterm neonates may be at increased risk of propylene glycol-associated adverse events due to diminished ability to metabolize propylene glycol, thereby leading to accumulation and potential adverse events. Postmarketing life-threatening cases of cardiac toxicity (including complete AV block, bradycardia, and cardiomyopathy), lactic acidosis, acute renal failure, CNS depression and respiratory complications leading to death have been reported, predominantly in preterm neonates receiving lopinavir and ritonavir oral solution.
Lopinavir and ritonavir oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities. A safe and effective dose of Lopinavir and ritonavir oral solution in this patient population has not been established.
However, if the benefit of using Lopinavir and ritonavir oral solution to treat HIV infection in infants immediately after birth outweighs the potential risks, infants should be monitored closely for increases in serum osmolality and serum creatinine, and for toxicity related to Lopinavir and ritonavir oral solution including: hyperosmolality, with or without lactic acidosis, renal toxicity, CNS depression (including stupor, coma, and apnea), seizures, hypotonia, cardiac arrhythmias and ECG changes, and hemolysis.
4 ) and Overdosage ( 10)]. 3 Pancreatitis Pancreatitis has been observed in patients receiving lopinavir and ritonavir therapy, including those who developed marked triglyceride elevations. In some cases, fatalities have been observed.
9)]. Patients with advanced HIV-1 disease may be at increased risk of elevated triglycerides and pancreatitis, and patients with a history of pancreatitis may be at increased risk for recurrence during lopinavir and ritonavir therapy.
Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis occur. Patients who exhibit these signs or symptoms should be evaluated and lopinavir and ritonavir and/or other antiretroviral therapy should be suspended as clinically appropriate.
4 Hepatotoxicity Patients with underlying hepatitis B or C or marked elevations in transaminase prior to treatment may be at increased risk for developing or worsening of transaminase elevations or hepatic decompensation with use of lopinavir and ritonavir.
There have been postmarketing reports of hepatic dysfunction, including some fatalities. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications in the setting of underlying chronic hepatitis or cirrhosis.
A causal relationship with lopinavir and ritonavir therapy has not been established. Elevated transaminases with or without elevated bilirubin levels have been reported in HIV-1 mono-infected and uninfected patients as early as 7 days after the initiation of lopinavir and ritonavir in conjunction with other antiretroviral agents.
In some cases, the hepatic dysfunction was serious; however, a definitive causal relationship with lopinavir and ritonavir therapy has not been established. Appropriate laboratory testing should be conducted prior to initiating therapy with lopinavir and ritonavir and patients should be monitored closely during treatment.
6) ]. 5 QT Interval Prolongation Postmarketing cases of QT interval prolongation and torsade de pointes have been reported although causality of lopinavir and ritonavir could not be established. 3 )]. 6 PR Interval Prolongation Lopinavir/ritonavir prolongs the PR interval in some patients.
Cases of second or third degree atrioventricular block have been reported. Lopinavir and ritonavir should be used with caution in patients with underlying structural heart disease, pre-existing conduction system abnormalities, ischemic heart disease or cardiomyopathies, as these patients may be at increased risk for developing cardiac conduction abnormalities.
The impact on the PR interval of co-administration of lopinavir and ritonavir with other drugs that prolong the PR interval (including calcium channel blockers, beta-adrenergic blockers, digoxin and atazanavir) has not been evaluated.
As a result, co-administration of lopinavir and ritonavir with these drugs should be undertaken with caution, particularly with those drugs metabolized by CYP3A. 3 )]. 7 Diabetes Mellitus/Hyperglycemia New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during post-marketing surveillance in HIV-1 infected patients receiving protease inhibitor therapy.
Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases.
Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established. Consider monitoring for hyperglycemia, new onset diabetes mellitus or an exacerbation of diabetes mellitus in patients treated with lopinavir and ritonavir.
8 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including lopinavir and ritonavir. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis) which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.
1 )]. Triglyceride and cholesterol testing should be performed prior to initiating lopinavir and ritonavir therapy and at periodic intervals during therapy. 3 )]. 10 Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.
The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. 11 Patients with Hemophilia Increased bleeding, including spontaneous skin hematomas and hemarthrosis have been reported in patients with hemophilia type A and B treated with protease inhibitors.
In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship between protease inhibitor therapy and these events has not been established.