Ritonavir is an active pharmaceutical ingredient in the Protease Inhibitors group (J05AE). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised November 14, 2025[1]
Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infected patients (adults and children of 2 years of age and older).
How to take
GB
CACanada· Health Canada
3 products
Uses
CAOfficial regulatory label· revised April 15, 2025[2]
NORVIR (ritonavir) is indicated in combination with other antiretroviral agents for the treatment of HIV infection when therapy is warranted. 3 Pharmacokinetics). The safety and effectiveness of NORVIR in pediatric patients below the age of 2 years have not been established.
2 Geriatrics Geriatrics (> 65 years of age): Clinical studies of NORVIR did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects. In general, appropriate caution should be exercised in the administration and monitoring of NORVIR in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
How to take
USUnited States· FDA
2 products
Uses
USOfficial regulatory label· revised November 13, 2023[3]
1 INDICATIONS AND USAGE Ritonavir tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Ritonavir tablets are HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection ( 1 )
How to take
US
EUEuropean Union· EMA
2 products
Uses
EUOfficial regulatory label· revised May 8, 2026[4]
2).
How to take
EUOfficial regulatory label· revised May 8, 2026
Drug interactions
Known interactions involving Ritonavir. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PLGB410420031 · revised November 14, 2025
[2]Health Canada (DPD) · 02357593 · revised April 15, 2025
[3]FDA DailyMed · 11f757f1-cf48-47… · revised November 13, 2023 [PDF]
[4]European Medicines Agency · EMEA/H/C/004549 · revised May 8, 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.
Ritonavir should be administered by physicians who are experienced in the treatment of HIV infection. Posology Ritonavir dosed as a pharmacokinetic enhancer When ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors the Summary of Product Characteristics for the particular protease inhibitor must be consulted.
The following HIV-1 protease inhibitors have been approved for use with ritonavir as a pharmacokinetic enhancer at the noted doses. Adults Amprenavir 600 mg twice daily with ritonavir 100 mg twice daily. Atazanavir 300 mg once daily with ritonavir 100 mg once daily.
Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily. Lopinavir co-formulated with ritonavir (lopinavir/ritonavir) 400 mg/100 mg or 800 mg/200 mg. Saquinavir 1000 mg twice daily with ritonavir 100 mg twice daily in ART experienced patients.
Initiate treatment with saquinavir 500 mg twice daily with ritonavir 100 mg twice daily for the first 7 days, then saquinavir 1000 mg twice daily with ritonavir 100 mg twice daily in ART-naïve patients. Tipranavir 500 mg twice daily with ritonavir 200 mg twice daily.
Tipranavir with ritonavir should not be used in treatment-naïve patients. Darunavir 600 mg twice daily with ritonavir 100 mg twice daily in antiretroviral treatment (ART) experienced patients. Darunavir 800 mg once daily with ritonavir 100 mg once daily may be used in some ART experienced patients.
Refer to the darunavir Summary of Product Characteristics for further information on once daily dosing in ART experienced patients. Darunavir 800 mg once daily with ritonavir 100 mg once daily in ART-naïve patients. Children and adolescents Ritonavir is recommended for children 2 years of age and older.
For further dosage recommendations, refer to the product information of other protease inhibitors approved for co-administration with ritonavir. Special populations Renal impairment As ritonavir is primarily metabolised by the liver, ritonavir may be appropriate for use with caution as a pharmacokinetic enhancer in patients with renal insufficiency depending on the specific protease inhibitor with which it is co-administered.
However, since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not expected in patients with renal impairment. For specific dosing information in patients with renal impairment, refer to the Summary of Product Characteristics (SPC) of the co-administered protease inhibitor.
3). In the absence of pharmacokinetic studies in patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered PI may occur.
Specific recommendations for use of ritonavir as a pharmacokinetic enhancer in patients with hepatic impairment are dependent on the protease inhibitor with which it is co-administered. The SPC of the co-administered PI should be reviewed for specific dosing information in this patient population.
Ritonavir dosed as an antiretroviral agent Adults The recommended dose of Norvir powder for oral suspension is 600 mg (six sachets) twice daily by mouth and should be given with food. Gradually increasing the dose of ritonavir when initiating therapy may help to improve tolerance.
Treatment should be initiated at 300 mg (three sachets) twice daily for a period of three days and increased by 100 mg (one sachet) twice daily increments up to 600 mg twice daily over a period of no longer than 14 days. Patients should not remain on 300 mg twice daily for more than 3 days.
6 for details on preparing doses. Children and adolescents (2 years of age and above) The recommended dosage of Norvir powder for suspension in children is 350 mg/m² by mouth twice daily and should not exceed 600 mg twice daily. Norvir should be started at 250 mg/m² and increased at 2 to 3 day intervals by 50 mg/m² twice daily.
4 ml of liquid the concentration of the suspension is 10 mg/ml. †In some instances, the volumes and/or doses have been adjusted to ensure the recommended final dose and dosing volume.
Body surface area can be calculated with the following equation:
BSA (m2) = √(Height (cm) X Weight (kg) / 3600) To calculate the volume to be administered (in ml) for intermediate body surface areas not included in the above table, the body surface area should be multiplied by a factor of: 25 for a dose of 250 mg/m²; 30 for 300 mg/m²; and 35 for 350 mg/m².
6 for details on preparing doses. 2). Renal impairment Currently, there are no data specific to this patient population and therefore specific dosage recommendations cannot be made. The renal clearance of ritonavir is negligible; therefore, a decrease in the total body clearance is not expected in patients with renal impairment.
Because ritonavir is highly protein bound it is unlikely that it will be significantly removed by […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised November 14, 2025[1]
Summary of the safety profile Ritonavir dosed as a pharmacokinetic enhancer Adverse reactions associated with the use of ritonavir as a pharmacokinetic enhancer are dependent on the specific co-administered PI. For information on adverse reactions refer to the SPC of the specific co-administered PI.
Ritonavir dosed as an antiretroviral agent Adverse reactions from clinical trials and post-marketing experience in adult patients The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhoea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paraesthesia and oral paraesthesia) and fatigue/asthenia.
Tabulated list of adverse reactions The following adverse reactions of moderate to severe intensity with possible or probable relationship to ritonavir have been reported. 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 < 1/1,000); not known (cannot be estimated from the available data).
Events noted as having a frequency not known were identified via post-marketing surveillance Adverse reactions in clinical studies and post-marketing in adult patients System Order Class Frequency Adverse reaction Common Decreased white blood cells, decreased haemoglobin, decreased neutrophils, increased eosinophils, thrombocytopenia Blood and lymphatic system disorders Uncommon Increased neutrophils Adverse reactions in clinical studies and post-marketing in adult patients System Order Class Frequency Adverse reaction Immune system disorders Common Hypersensitivity, including urticaria and face oedema.
g. oliguria, elevated creatinine) Uncommon Not known Acute renal failure Nephrolithiasis Reproductive system and breast disorders Common Menorrhagia General disorders and administration site conditions Very common Fatigue including asthenia, flushing, feeling hot Adverse reactions in clinical studies and post-marketing in adult patients System Order Class Frequency Adverse reaction Common Fever, weight loss Common Increased amylase, decreased free and total thyroxine Investigations Uncommon Increased glucose, increased magnesium, increased alkaline phosphatase Description of selected adverse reactions Hepatic transaminase elevations exceeding five times the upper limit or normal, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir alone or in combination with other antiretrovirals.
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). Pancreatitis has been observed in patients receiving ritonavir therapy, including those who developed hypertriglyceridaemia.
In some cases fatalities have been observed. 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).
4). Paediatric populations The safety profile of Norvir in children 2 years of age and older is similar to that seen in adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised November 14, 2025[1]
Ritonavir is not a cure for HIV-1 infection or AIDS. Patients receiving ritonavir or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV-1 infection. When ritonavir is used as a pharmacokinetic enhancer with other PIs, full details on the warnings and precautions relevant to that particular PI should be considered, therefore the Summary of Product Characteristics for the particular PI must be consulted.
Ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer Patients with chronic diarrhoea or malabsorption Extra monitoring is recommended when diarrhoea occurs. The relatively high frequency of diarrhoea during treatment with ritonavir may compromise the absorption and efficacy (due to decreased compliance) of ritonavir or other concurrent medicinal products.
Serious persistent vomiting and/or diarrhoea associated with ritonavir use might also compromise renal function. It is advisable to monitor renal function in patients with renal function impairment. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
In some patients additional factor VIII was given. In more than a half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship has been evoked, although the mechanism of action has not been elucidated.
Haemophiliac patients should, therefore, be made aware of the possibility of increased bleeding.
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. 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.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised November 14, 2025[1]
1. When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the Summary of Product Characteristics of the co-administered protease inhibitor for contraindications. Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients with decompensated liver disease.
In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and CYP2D6- mediated biotransformations. The following medicines are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered medicinal product, resulting in increased exposure to the co-administered medicinal product and risk of clinically significant adverse effects.
The enzyme-modulating effect of ritonavir may be dose dependent. g. 5). Analgesics Pethidine, propoxyphene Increased plasma concentrations of norpethidine and propoxyphene. Thereby, increasing the risk of serious respiratory depression or haematologic abnormalities, or other serious adverse effects from these agents.
Thereby, increasing the risk of arrhythmias or other serious adverse effects from these agents. Antibiotic Fusidic Acid Increased plasma concentrations of fusidic acid and ritonavir. 5). Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine.
Thereby, increasing the risk of serious arrhythmias from these agents. 5). 4). Recommendations regarding use of ritonavir dosed as a pharmacokinetic enhancer with rifabutin are noted in section
This is not medical advice. Consult a qualified healthcare professional.
CAOfficial regulatory label· revised April 15, 2025[2]
1 Dosing Considerations Patients should be aware that frequently observed adverse events, such as mild to moderate gastrointestinal disturbances and paresthesias, may diminish as therapy is continued. In addition, patients initiating combination regimens with NORVIR and other antiretroviral agents may improve gastrointestinal tolerance by initiating NORVIR alone and subsequently adding the other antiretroviral agents before completing 2 weeks of NORVIR monotherapy.
The long-term effects of dose escalation on efficacy have not been established. Dose reduction of NORVIR is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. When NORVIR is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information and clinical study information of that protease inhibitor.
2 Recommended Dose and Dosage Adjustment Adult Patients The recommended dose of NORVIR is 600 mg (6 tablets) twice daily orally and should be taken with a meal. NORVIR tablets should be swallowed whole with water and not chewed, broken, or crushed.
Some patients experience nausea upon initiation of 600 mg twice daily dosing. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. NORVIR should be started at no less than 300 mg twice daily and increased by 100 mg twice daily increments up to 600 mg twice daily.
The titration period should not exceed 14 days. NORVIR (ritonavir) Page 8 of 65 Pediatric Patients (2 to 16 years of age) NORVIR should be used in combination with other antiretroviral agents. 3 Reconstitution Not applicable. 4 Administration NORVIR is administered orally.
5 Missed Dose If a dose of this medication has been missed, it should be taken as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not double doses.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised April 15, 2025[2]
1 Adverse Reaction Overview When NORVIR is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information of that protease inhibitor including Adverse Reactions. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.
The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful for identifying and approximating rates of adverse drug reactions in real-world use.
Adult Patients The safety of NORVIR alone and in combination with nucleoside reverse transcriptase inhibitors was studied in 1270 adult patients. Table 3 lists treatment-emergent adverse events (at least possibly related and of at least moderate intensity) that occurred in 2% or greater of adult patients receiving NORVIR alone or in combination with nucleoside reverse transcriptase inhibitors in Study M94-247 or Study M94-245 and in combination with saquinavir in Study M94-462.
In that study, 141 protease inhibitor-naïve, HIV- infected patients with mean baseline CD4 of 300 cells/microliter were randomized to 1 of 4 regimens of NORVIR + saquinavir, including NORVIR 400 mg twice daily + saquinavir 400 mg twice daily.
Overall, the most frequently reported adverse drug reactions among patients receiving NORVIR alone or in NORVIR (ritonavir) Page 15 of 65 combination with other antiretroviral drugs were gastrointestinal and neurological disturbances including diarrhea, nausea, vomiting, anorexia, abdominal pain (upper and lower), and neurological disturbances (including paresthesia and oral paresthesia), and fatigue/asthenia.
Similar adverse event profiles were reported in adult patients receiving NORVIR in other trials. 8 a. Includes those adverse events at least possibly related to study drug or of unknown relationship and excludes concurrent HIV conditions.
b. 4 months. c. 1 months. d. The median duration of treatment for patients in Study M94-462 was 48 weeks. e. The dose of NORVIR when co-administered with saquinavir was reduced to 400 mg twice daily.
Definitions:
N/A = Not available Other Common Clinical Trial Adverse Drug Reactions Table 4 includes other treatment-emergent adverse reactions (with possible or probable relationship to study drug) occurring in 1% of adult patients receiving NORVIR derived from cumulative data from combined Phase 2 to 4 studies.
2 Hepatobiliary disorders […]
CAOfficial regulatory label· Warnings and precautions· revised April 15, 2025[2]
and 9 DRUG INTERACTIONS for co-administration of sildenafil in patients with erectile dysfunction. c. See Table 6 for parenterally administered midazolam. Oral formulation of midazolam is not marketed in Canada. d. See Table 6 for coadministration of the maintenance dose of venetoclax.
NORVIR (ritonavir) Page 7 of 65 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • 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.
Patients who exhibit these signs or symptoms should be evaluated and NORVIR therapy should be discontinued if a diagnosis of pancreatitis is made (see 7 WARNINGS AND PRECAUTIONS). • Co-administration of NORVIR with certain non-sedating antihistamines, sedative hypnotics, or antiarrhythmics may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism of certain drugs (see 2 CONTRAINDICATIONS and 9 DRUG INTERACTIONS).
1 Serious Drug Interactions. 1 Dosing Considerations Patients should be aware that frequently observed adverse events, such as mild to moderate gastrointestinal disturbances and paresthesias, may diminish as therapy is continued. In addition, patients initiating combination regimens with NORVIR and other antiretroviral agents may improve gastrointestinal tolerance by initiating NORVIR alone and subsequently adding the other antiretroviral agents before completing 2 weeks of NORVIR monotherapy.
The long-term effects of dose escalation on efficacy have not been established. Dose reduction of NORVIR is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. When NORVIR is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information and clinical study information of that protease inhibitor.
2 Recommended Dose and Dosage Adjustment Adult Patients The recommended dose of NORVIR is 600 mg (6 tablets) twice daily orally and should be taken with a meal. NORVIR tablets should be swallowed whole with water and not chewed, broken, or crushed.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised April 15, 2025[2]
When NORVIR is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information of that protease inhibitor including contraindication information. , toxic epidermal necrosis (TEN) or Stevens Johnson syndrome (SJS)] to NORVIR or any of its ingredients (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
1 Serious Drug Interactions) because competition for primarily CYP3A by NORVIR could result in inhibition of the metabolism of these drugs and create the potential for serious and/or life-threatening reactions, such as cardiac arrhythmias, prolonged or increased sedation, and respiratory depression.
Voriconazole and St. John’s Wort are exceptions in that co-administration of NORVIR and voriconazole results in a significant reduction in plasma concentrations of voriconazole and possible loss of effect, and co-administration of NORVIR with St.
John’s Wort may lead to loss of virologic response and possible resistance to NORVIR. NORVIR (ritonavir) Page 5 of 65 Table 1 – Drugs that are Contraindicated with NORVIR Drug Class Drugs Within Class that are Contraindicated with NORVIR Clinical Comment Alpha1-Adrenoreceptor Antagonist alfuzosin Potential for serious reactions, such as hypotension (see Table 6).
Antianginal ranolazine Potential for serious and/or life-threatening reactions. Antiarrhythmics amiodarone, bepridila, dronedarone, flecainide, propafenone, quinidine Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias.
Antibiotic fusidic acid Potential of increased fusidic acid-associated adverse events, such as hepatitis or bone marrow suppression. Anticancer apalutamide Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of NORVIR and potential loss of virologic response.
In addition, exposure of apalutamide may increase with co-administration of NORVIR that may lead to serious adverse events including seizure and fracture. neratinib Potential for serious and/or life-threatening reactions including hepatotoxicity.
venetoclaxd Concomitant use of strong CYP3A inhibitors, such as NORVIR, and venetoclax may increase the risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase. Anticoagulant rivaroxaban Potential of increased rivaroxaban plasma concentrations which may lead to risk of increased bleeding.
Antifungal voriconazole Significant reduction in voriconazole plasma concentrations and possible loss of effect (see Table 7). Antigout colchicine Potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see Table 6).
Antihistamines astemizolea, terfenadinea Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. Antipsychotics lurasidone pimozide Potential for serious and/or life-threatening reactions. Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias.
NORVIR (ritonavir) Page 6 of 65 Drug Class Drugs Within Class that are Contraindicated with NORVIR Clinical Comment Ergot Derivatives dihydroergotamine, ergonovine, ergotaminea, methylergonovinea Potential for serious and/or life-threatening reactions, such as acute ergot toxicity characterized by vasospasm and tissue ischemia.
GI Motility Agent cisapridea Potential for serious and/or life-threatening reactions, such as cardiac arrhythmias. Herbal Products St. John’s wort (Hypericum perforatum) May lead to loss of virologic response and possible resistance to NORVIR or to the class of protease inhibitors.
Lipid-modifying agents HMG-CoA Reductase Inhibitors Microsomal triglyceride transfer protein (MTTP) Inhibitor lovastatin, simvastatin lomitapide Potential for serious reactions, such as risk of myopathy including rhabdomyolysis. Potential for serious reactions, such as hepatotoxicity.
Long Acting Beta- Adrenoceptor salmeterol May result in potential increased risk of cardiovascular adverse events associated with salmeterol. PDE5 Inhibitors sildenafilb, only when used for the treatment of pulmonary arterial hypertension (PAH) vardenafil, when used for the treatment of erectile dysfunction or PAH Potential increase in PDE5 inhibitor associated adverse reactions including hypotension, syncope, visual changes, and prolonged erection.
Potential increase in PDE5 inhibitor associated adverse reactions including hypotension, syncope, visual changes, and prolonged erection. Sedative/Hypnotics orally administered midazolamc, triazolam Potential for serious and/or life-threatening reactions, such as prolonged or increased sedation or respiratory depression.
a. Product no longer marketed in Canada. b. See 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS for co-administration of sildenafil in patients with erectile dysfunction. c. See Table 6 for parenterally administered midazolam. Oral formulation of midazolam is not marketed in Canada.
d. See Table 6 for coadministration of the maintenance dose of venetoclax. NORVIR (ritonavir) Page 7 of 65
This is not medical advice. Consult a qualified healthcare professional.
1 General Administration Recommendations Ritonavir tablets must be used in combination with other antiretroviral agents. Ritonavir tablets are administered orally. Ritonavir tablets should be swallowed whole, and not chewed, broken or crushed.
Take ritonavir tablets with meals. 3) ] . Patients should also be aware that these adverse events (gastrointestinal or paresthesias) may diminish as therapy is continued. 3 Dosage Recommendations in Adults Recommended Dosage for Treatment of HIV-1: The recommended dosage of ritonavir is 600 mg twice daily by mouth to be taken with meals.
Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. Ritonavir tablets should be started at no less than 300 mg twice daily and increased at 2 to 3 day intervals by 100 mg twice daily.
6) ] . Pregnant Women Ritonavir oral solution is not recommended during pregnancy due to its ethanol content. 1) ] . 4 Dosage Recommendations in Pediatric Patients Ritonavir tablets must be used in combination with other antiretroviral agents [see Dosage and Administration (2) ] .
The recommended dosage of ritonavir tablets in pediatric patients older than 1 month is 350 to 400 mg per m 2 twice daily by mouth to be taken with meals and should not exceed 600 mg twice daily. Ritonavir tablets should be started at 250 mg per m 2 twice daily and increased at 2 to 3 day intervals by 50 mg per m 2 twice daily.
6) ] . 2) ]. Ritonavir oral solution contains the excipients ethanol and propylene glycol. Special attention should be given to accurate calculation of the dose of ritonavir oral solution, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors, and overdose.
This is especially important for young children. 2) and Overdosage (10) ]. When possible, dose should be administered using a calibrated dosing syringe. Table 1. 5 mL (600 mg) *The concentration of the oral solution is 80 mg per mL.
Body surface area (BSA) can be calculated as follows 1 :
Pediatric Dosage Guidelines for Oral Powder Ritonavir oral powder should be used only for dosing increments of 100 mg. Ritonavir powder should not be used for doses less than 100 mg or for incremental doses between 100 mg intervals.
Ritonavir oral solution is the preferred formulation for patients requiring doses less than 100 mg or incremental doses between 100 mg intervals. 6 Dose Modification due to Drug Interaction Dose reduction of ritonavir tablet is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir.
1) , and Drug Interactions (7) ].
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 2,003 reports total. [5]
Covid-19 337
Disease Recurrence 244
Product Prescribing Error 192
Drug Interaction 191
Dysgeusia 144
Off Label Use 138
Nausea 123
Vomiting 117
Diarrhoea 112
Toxicity To Various Agents 96
Incorrect Dose Administered 80
Pneumonia 70
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised November 13, 2023[3]
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. 5) ] When co-administering ritonavir with other protease inhibitors, see the full prescribing information for that protease inhibitor including adverse reactions.
1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. gov/medwatch. 1 Clinical Trial 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 practice.
Adverse Reactions in Adults The safety of ritonavir alone and in combination with other antiretroviral agents was studied in 1,755 adult patients. Table 2 lists treatment-emergent Adverse Reactions (with possible or probable relationship to study drug) occurring in greater than or equal to 1% of adult patients receiving ritonavir in combined Phase II/IV studies.
The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia.
Table 2. 2 Laboratory Abnormalities in Adults Table 3 shows the percentage of adult patients who developed marked laboratory abnormalities. Table 3. Percentage of Adult Patients, by Study and Treatment Group, with Chemistry and Hematology Abnormalities Occurring in greater than 3% of Patients Receiving Ritonavir - Indicates no events reported.
5 Adverse Reactions in Pediatric Patients Ritonavir has been studied in 265 pediatric patients greater than 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients.
Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in greater than or equal to 2% of pediatric patients enrolled in ritonavir clinical trials. Laboratory Abnormalities in Pediatric Patients The following Grade 3 to 4 laboratory abnormalities occurred in greater than 3% of pediatric patients who received treatment with ritonavir either alone or in combination with reverse transcriptase inhibitors: neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia (4%), and elevated AST (3%).
2 Postmarketing Experience The following adverse events (not previously mentioned in the labeling) have been reported during post-marketing use of 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 ritonavir exposure.
Body as a Whole Dehydration, usually associated with gastrointestinal symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency has been reported. Syncope, orthostatic hypotension, and renal insufficiency have also been reported without known dehydration.
Co-administration of ritonavir with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. 6) ] .
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded. Endocrine System Cushing’s syndrome and adrenal suppression have been reported when ritonavir has been co-administered with fluticasone propionate or budesonide.
Nervous System There have been postmarketing reports of seizure. Also, see Cardiovascular System. Renal and Urinary Disorders Nephrolithiasis Skin and subcutaneous tissue disorders Toxic epidermal necrolysis (TEN) has been reported.
USOfficial regulatory label· Warnings and precautions· revised November 13, 2023[3]
5 WARNINGS AND PRECAUTIONS The following have been observed in patients receiving ritonavir: The concomitant use of 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.
2 ) Toxicity in preterm neonates: Ritonavir oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities. 2 ) Hepatotoxicity: Fatalities have occurred. 4) Allergic Reactions/Hypersensitivity: Allergic reactions have been reported and include anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, bronchospasm and angioedema.
2) PR interval prolongation may occur in some patients. Cases of second and third degree heart block have been reported. 1 Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving ritonavir, may increase plasma concentrations of medications metabolized by CYP3A.
Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of 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 ritonavir.
Loss of therapeutic effect of ritonavir and possible development of resistance. When co-administering ritonavir with other protease inhibitors, see the full prescribing information for that protease inhibitor including important Warnings and Precautions.
See Table 4 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 ritonavir therapy; review concomitant medications during ritonavir therapy, and monitor for the adverse reactions associated with the concomitant medications [see Contraindications (4) and Drug Interactions (7) ].
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised November 13, 2023[3]
4 CONTRAINDICATIONS When co-administering ritonavir tablets with other protease inhibitors, see the full prescribing information for that protease inhibitor including contraindication information. , toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to ritonavir or any of its ingredients.
3) ] . 3) ] .
Anticancer Agents: apalutamide Herbal Products:
St. , toxic epidermal necrolysis, Stevens-Johnson syndrome) or any of its ingredients (4) Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations may be associated with serious and/or life-threatening events (4) Co-administration with drugs that significantly reduce ritonavir (4)
This is not medical advice. Consult a qualified healthcare professional.
Ritonavir Viatris should be prescribed by physicians who are experienced in the treatment of HIV infection. Posology When ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors the Summary of Product Characteristics (SmPC) for the particular protease inhibitor must be consulted.
The following HIV-1 protease inhibitors have been approved for use with ritonavir as a pharmacokinetic enhancer at the noted doses. Adults Atazanavir 300 mg once daily with ritonavir 100 mg once daily. Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily.
Lopinavir co-formulated with ritonavir (lopinavir/ritonavir) 400 mg/100 mg or 800 mg/200 mg. Tipranavir 500 mg twice daily with ritonavir 200 mg twice daily. Tipranavir with ritonavir should not be used in treatment-naïve patients. Darunavir 600 mg twice daily with ritonavir 100 mg twice daily in antiretroviral treatment (ART) experienced patients.
Darunavir 800 mg once daily with ritonavir 100 mg once daily may be used in some ART experienced patients. Refer to the darunavir SmPC for further information on once daily dosing in ART experienced patients. Darunavir 800 mg once daily with ritonavir 100 mg once daily in ART-naïve patients.
3 Children and adolescents Ritonavir is recommended for children 2 years of age and older. For further dose recommendations, refer to the SmPC of other protease inhibitors approved for co-administration with ritonavir. 2). Renal impairment As ritonavir is primarily metabolised by the liver, ritonavir may be appropriate for use with caution as a pharmacokinetic enhancer in patients with renal insufficiency depending on the specific protease inhibitor with which it is co-administered.
However, since the renal clearance of ritonavir is negligible, a decrease in the total body clearance of ritonavir is not expected in patients with renal impairment. 3). In the absence of pharmacokinetic studies in patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered protease inhibitor may occur.
Specific recommendations for use of ritonavir as a pharmacokinetic enhancer in patients with hepatic impairment are dependent on the protease inhibitor with which it is co-administered. The SmPC of the co-administered protease inhibitor should be reviewed for specific dosing information in this patient population.
Paediatric population The safety and efficacy of ritonavir in children aged below 2 years has not been established. 2 but no recommendation on a posology can be made. 2). Ritonavir Viatris film-coated tablets should be swallowed whole and not chewed, broken or crushed.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised May 8, 2026[4]
Summary of the safety profile Adverse reactions associated with the use of ritonavir as a pharmacokinetic enhancer are dependent on the specific co-administered protease inhibitor. For information on adverse reactions refer to the SmPC of the specific co-administered protease inhibitor.
Adverse reactions from clinical studies and post-marketing experience in adult patients The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhoea, nausea, 24 vomiting, abdominal pain (upper and lower)), neurological disturbances (including paraesthesia and oral paraesthesia) and fatigue/asthenia.
Tabulated list of adverse reactions The following adverse reactions of moderate to severe intensity with possible or probable relationship to ritonavir have been reported. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); not known (cannot be estimated from the available data).
Events noted as having frequency not known were identified via post-marketing surveillance. Table 6. g. oliguria, elevated creatinine) Uncommon Acute renal failure Not known Nephrolithiasis Reproductive system and breast disorders Common Menorrhagia General disorders and administration site conditions Very common Fatigue including asthenia, flushing, feeling hot Common Fever, weight loss Investigations Common Increased amylase, decreased free and total thyroxin Uncommon Increased glucose, increased magnesium, increased alkaline phosphatase Description of selected adverse reactions Hepatic transaminase elevations exceeding five times the upper limit or normal, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir alone or in combination with other antiretrovirals.
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). Pancreatitis has been observed in patients receiving ritonavir therapy, including those who developed hypertriglyceridaemia.
In some cases fatalities have been observed. 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).
4). Paediatric population The safety profile of ritonavir in children 2 years of age and older is similar to that seen in adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 26 professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised May 8, 2026[4]
General Ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors. Full details on the warnings and precautions relevant to that particular protease inhibitor should be considered, therefore the SmPC for the particular protease inhibitor must be consulted.
Ritonavir is not a cure for HIV-1 infection or AIDS. Patients receiving ritonavir or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV-1 infection. Therefore, patients should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases.
Patients with co-existing conditions Patients with chronic diarrhoea or malabsorption Extra monitoring is recommended when diarrhoea occurs. The relatively high frequency of diarrhoea during treatment with ritonavir may compromise the absorption and efficacy (due to decreased compliance) of ritonavir or other concurrent medicinal products.
Serious persistent vomiting and/or diarrhoea associated with ritonavir use might also compromise renal function. It is advisable to monitor renal function in patients with renal function impairment. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors.
In some patients additional factor VIII was given. In more than a half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship has been evoked, although the mechanism of action has not been elucidated.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding. 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 7 this to any particular treatment. For monitoring of blood lipids and glucose, reference is made to established HIV treatment guidelines.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised May 8, 2026[4]
1. Ritonavir should not be given to patients with decompensated liver disease. In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and CYP2D6- mediated biotransformations. 1). The following medicinal products are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered medicinal product, resulting in increased exposure to the co-administered medicinal product and risk of clinically significant adverse events.
Table 2. 5). Analgesics Pethidine, propoxyphene Increased plasma concentrations of norpethidine and propoxyphene. Thereby, increasing the risk of serious respiratory depression or haematologic abnormalities, or other serious adverse effects from these agents.
Thereby, increasing the risk of arrhythmias or other serious adverse effects from these agents. Antibiotic Fusidic acid Increased plasma concentrations of fusidic acid and ritonavir. Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine.
Thereby, increasing the risk of serious arrhythmias from these agents. 5). 5). Clozapine, pimozide Increased plasma concentrations of clozapine and pimozide. Thereby, increasing the risk of serious haematologic abnormalities, or other serious adverse effects from these agents.
Quetiapine Increased plasma concentrations of quetiapine which may lead to coma. 5). Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine Increased plasma concentrations of ergot derivatives leading to acute ergot toxicity, including vasospasm and ischaemia.
GI motility agent Cisapride Increased plasma concentrations of cisapride. Thereby, increasing the risk of serious arrhythmias from this agent. 5). 5). 4. 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.
4. 5). Sedatives/hypnotics Clorazepate, diazepam, estazolam, flurazepam, oral midazolam and triazolam Increased plasma concentrations of clorazepate, diazepam, estazolam, flurazepam, oral midazolam and triazolam. Thereby, increasing the risk of extreme sedation and respiratory depression from these agents.
). 5).
This is not medical advice. Consult a qualified healthcare professional.
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.
2). 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 active 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 must be considered. 2). 8). Medication error Special attention should be given to the accurate calculation of the dose of Norvir, transcription of the medication order, dispensing information and dosing instructions to minimise the risk for medication errors and underdose.
This is especially important for infants and young children. Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported 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 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 atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving medicinal products known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving ritonavir.
1). Interactions […]
Some patients experience nausea upon initiation of 600 mg twice daily dosing. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. NORVIR should be started at no less than 300 mg twice daily and increased by 100 mg twice daily increments up to 600 mg twice daily.
The titration period should not exceed 14 days. NORVIR (ritonavir) Page 8 of 65 Pediatric Patients (2 to 16 years of age) NORVIR should be used in combination with other antiretroviral agents. 3 Reconstitution Not applicable. 4 Administration NORVIR is administered orally.
5 Missed Dose If a dose of this medication has been missed, it should be taken as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not double doses.
5 OVERDOSAGE Acute Overdosage Human Overdose Experience Human experience of acute overdose with NORVIR is limited. One patient in clinical trials took NORVIR 1500 mg/day for 2 days. The patient reported paresthesias which resolved after the dose was decreased.
A post-marketing case of renal failure with eosinophilia has been reported with NORVIR overdose. Management of Overdosage Administration of activated charcoal may be used to aid in removal of unabsorbed drug. Treatment of overdose with NORVIR consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
There is no specific antidote for overdose with NORVIR. Since ritonavir is extensively metabolized by the liver and is highly protein-bound, dialysis is unlikely to be beneficial in significant removal of the drug. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 2 - Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form/Strength/Composition Non-medicinal Ingredients oral film-coated tablets/100 mg copovidone, colloidal silicon dioxide/colloidal anhydrous silica, dibasic calcium phosphate anhydrous/calcium hydrogen phosphate For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764- 7669).
NORVIR (ritonavir) Page 9 of 65 Route of Administration Dosage Form/Strength/Composition Non-medicinal Ingredients anhydrous, sorbitan monolaurate/sorbitan laurate, sodium stearyl fumarate The film coating ingredients include colloidal silicon dioxide/colloidal silica anhydrous, hydroxypropyl cellulose, hypromellose, polyethylene glycol 400/macrogol type 400, polyethylene glycol 3350/macrogol type 3350, polysorbate 80, talc and titanium dioxide E171.
NORVIR is available as 100 mg film-coated tablets. NORVIR film-coated tablets are supplied as follows: - white oval tablets debossed with the code “NK” on one side. Each bottle contains 30 tablets. 7 WARNINGS AND PRECAUTIONS Please see 3 WARNINGS AND PRECAUTIONS BOX.
Drug-Drug Interactions When NORVIR is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information of that protease inhibitor including Warning and Precautions. NORVIR is an inhibitor of cytochrome P450 3A (CYP3A) both in vitro and in vivo.
NORVIR also inhibits CYP2D6 in vitro, but to a lesser extent than CYP3A. Initiation of NORVIR, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving NORVIR, may increase plasma concentrations of medications metabolized by CYP3A.
Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations […]
2 Toxicity in Preterm Neonates Ritonavir oral solution contains the excipients ethanol and propylene glycol. 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 an 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/ritonavir oral solution which also contains the excipients ethanol and propylene glycol.
Ritonavir oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities. However, if the benefit of using 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 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 Hepatotoxicity Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir alone or in combination with other antiretroviral drugs (see Table 3).
There may be an increased risk for transaminase elevations in patients with underlying hepatitis B or C. Therefore, caution should be exercised when administering ritonavir to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.
6) ] . There have been postmarketing reports of hepatic dysfunction, including some fatalities. These have generally occurred in patients taking multiple concomitant medications and/or with advanced AIDS. 4 Pancreatitis Pancreatitis has been observed in patients receiving ritonavir therapy, including those who developed hypertriglyceridemia.
In some cases fatalities have been observed. 7) ] . 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.
Patients who exhibit these signs or symptoms should be evaluated and ritonavir therapy should be discontinued if a diagnosis of pancreatitis is made. 5 Allergic Reactions/Hypersensitivity Allergic reactions including urticaria, mild skin eruptions, bronchospasm, and angioedema have been reported.
Cases of anaphylaxis, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome have also been reported. Discontinue treatment if severe reactions develop. 6 PR Interval Prolongation Ritonavir prolongs the PR interval in some patients.
Post marketing cases of second or third degree atrioventricular block have been reported in patients. Ritonavir should be used with caution in patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, cardiomyopathies, as these patients may be at increased risk for developing cardiac conduction abnormalities.
The impact on the PR interval of co-administration of 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 ritonavir with these drugs should be undertaken with caution, particularly with those drugs metabolized by CYP3A.
3) ] . 1) ] . Triglyceride and cholesterol testing should be performed prior to initiating ritonavir therapy and at periodic intervals during therapy. Lipid disorders should be managed as clinically appropriate, taking into account any potential drug-drug interactions with ritonavir and HMG CoA reductase inhibitors [see Contraindications (4) and Drug Interactions (7) ] .
8 Diabetes Mellitus/Hyperglycemia New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-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 ritonavir.
9 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy, including 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 jiroveci pneumonia, 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.
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 There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, 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.
12 Resistance/Cross-resistance Varying degrees of cross-resistance among protease inhibitors have been observed. 4) ] . 13 Laboratory Tests Ritonavir has been shown to increase triglycerides, cholesterol, SGOT (AST), SGPT (ALT), GGT, CPK, and uric acid.
Appropriate laboratory testing should be performed prior to initiating ritonavir therapy and at periodic intervals or if any clinical signs or symptoms occur during therapy.
Lipid disorders should be managed as clinically appropriate. 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.
2). 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 active 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 must be considered. 2). 8). Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported 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 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 atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving medicinal products known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving ritonavir.
1). 8 Interactions with other medicinal products HIV-protease inhibitors co-administered with Ritonavir The interaction profiles of HIV-protease inhibitors, co-administered […]