Norvir Ritonavir 100 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
Ritonavir is used to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking these medications and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.
Read the full MedlinePlus article ↗- Ritonavir blocks an enzyme called protease that HIV needs to replicate. Without it, the virus can't make mature copies of itself. But ritonavir on its own isn't enough to fully con...
- What exactly does ritonavir do, and why do I have to take it with other HIV medicines?
- You're right — stomach side effects like diarrhea, nausea, vomiting, and abdominal pain are very common, especially when you first start. The good news is these often improve after...
- I've heard ritonavir causes a lot of stomach problems. What should I expect?
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Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
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UNII D9C330MD8B
Copovidone is a synthetic polymer made by combining two types of plastic-like molecules. It acts as a binder and film-former to help hold tablet ingredients together and improve how the medicine dissolves in your body.
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UNII 9XZ8H6N6OH
A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII G2M7P15E5P
Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.
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UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 7CV7WJK4UI
Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
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UNII 6W9PS8B71J
Sorbitan monolaurate is a natural oil-derived emulsifier made from sorbitol and lauric acid. It helps mix oils and water-based ingredients together in the medicine so the formula stays uniform and smooth.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $8.328 | $249.84 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $8.27 | $248.18 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $8.38 | $251.40 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ritonavir 100 mg 60687-0420-25 | American | 1 tablet | $0.607 | AB | Availability likely | save 93% |
| Ritonavir film coated 100 mg 69097-0655-02 | Cipla | 30 tablets | $0.607 | AB | Availability likely | save 93% |
| Norvir 100 mgthis 00074-2340-30 | AbbVie | 30 tablets | $8.328 | AB | Availability likely | — |
| Ritonavir 100 mg 31722-0597-12 | Camber | 120 tablets | — | AB | FDA listed | — |
| Ritonavir 100 mg 63629-5702-01 | Bryant | 15 tablets | — | AB | FDA listed | — |
| Ritonavir 100 mg 65162-0061-06 | Amneal | 60 tablets | — | — | FDA listed | — |
| Ritonavir 100 mg 65862-0687-01 | Aurobindo | 100 tablets | — | — | FDA listed | — |
| Ritonavir 100 mg 68071-3898-03 | NuCare | 3 tablets | — | AB | FDA listed | — |
| Ritonavir 100 mg 71335-2610-01 | Bryant | 15 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00074-2340-30 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (0074-2340-30) | 2022-08-16 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: DRUG-DRUG INTERACTIONS LEADING TO POTENTIALLY SERIOUS AND/OR LIFE THREATENING REACTIONS Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism of certain drugs. Review medications taken by patients prior to prescribing NORVIR or when prescribing other medications to patients already taking NORVIR [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )].
WARNING: DRUG-DRUG INTERACTIONS LEADING TO POTENTIALLY SERIOUS AND/OR LIFE THREATENING REACTIONS See full prescribing information for complete boxed warning Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism of certain drugs. Review medications taken by patients prior to prescribing NORVIR or when prescribing other medications to patients already taking NORVIR.
( 4 , 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE NORVIR tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. NORVIR oral powder is indicated in combination with other antiretroviral agents for the treatment of pediatric patients with HIV-1 infection. NORVIR tablets are HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection ( 1 ) NORVIR oral powder is indicated in combination with other antiretroviral agents for the treatment of pediatric patients with HIV-1 infection ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Adult patients: 600 mg twice-day with meals ( 2.2 ) Pediatrics patients: Do not exceed 600 mg twice daily dose with meals for children greater than one month of age. The dose is based on body surface area ( 2.3 ) Use NORVIR oral powder only for dosing increments of 100 mg ( 2.4 ) Follow the Instructions for Use for preparation and administration of NORVIR oral powder ( 2.4 ) Dose modification for NORVIR is necessary when used with other protease inhibitors ( 2.5 )
2.1General Administration Recommendations NORVIR must be used in combination with other antiretroviral agents. Administer NORVIR orally. Swallow NORVIR tablets whole.
Do not chew, break or crush NORVIR tablets. Take NORVIR with meals. Mix NORVIR oral powder with soft food such as apple sauce or vanilla pudding, or with liquid such as water, chocolate milk, or infant formula [see Dosage and Administration ( 2.4 ) and Instructions for Use ] .
When administered with food, the bitter aftertaste of NORVIR oral powder may be lessened. 2. 2 Dosage Recommendations in Adults Recommended Dosage for Treatment of HIV-1: The recommended dosage of NORVIR 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. Start NORVIR at no less than 300 mg twice daily and increase at 2 to 3 day intervals by 100 mg twice daily. Do not exceed the maximum dose of 600 mg twice daily upon completion of the titration [see Dosage and Administration ( 2.5 )] .
2. 3 Dosage Recommendations in Pediatric Patients NORVIR must be used in combination with other antiretroviral agents [see Dosage and Administration ( 2.1 ) ] . The recommended dosage of NORVIR in pediatric patients older than 1 month is 350 to 400 mg per m 2 twice daily by mouth to be taken with meals.
Do not exceed 600 mg twice daily. Start NORVIR at 250 mg per m 2 twice daily and increase at 2 to 3 day intervals by 50 mg per m 2 twice daily. If patients do not tolerate 400 mg per m 2 twice daily due to adverse events, use the highest tolerated dose for maintenance therapy in combination with other antiretroviral agents, or consider using alternative therapy [see Dosage and Administration ( 2.5 )] .
NORVIR powder should not be used for doses less than 100 mg or for incremental doses between 100 mg intervals. 2. 4 Preparation of NORVIR Oral Powder For details on the preparation and administration of NORVIR oral powder see Instructions for Use .
NORVIR oral powder should only be used for dosing increments of 100 mg. Prepare the dose using the required number of packets. For example, use one packet for doses of 100 mg and two packets for doses of 200 mg.
Pour and mix the entire contents of each packet over soft food or liquid. Administer all of the powder mixed with soft food or liquid within 2 hours of preparation. If not administered within 2 hours of preparation, discard the mixture and prepare a new dose.
The prescribed dose of NORVIR oral powder can be administered via a feeding tube after being mixed with water (see Instructions for Use ). Follow the instructions for the feeding tube to administer the medicine. 2.
5 Dose Modification due to Drug Interaction Reduce dose of NORVIR when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. Consult the full prescribing information and clinical study information of these protease inhibitors when they are co-administered with a reduced dose of ritonavir [see Warnings and Precautions ( 5.1 ) , and Drug Interactions ( 7 ) ] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS NORVIR Tablets White film-coated ovaloid tablets debossed with “NK” on one side providing 100 mg ritonavir. NORVIR Oral Powder Beige/pale yellow to yellow powder in child-resistant packet. Each packet contains 100 mg of ritonavir. Tablet: 100 mg ( 3 ) Oral Powder: 100 mg per packet ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS • Consult the prescribing information of the co-administered protease inhibitor for contraindication information for that product. • NORVIR is contraindicated in patients with known hypersensitivity (e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to ritonavir or any of its ingredients. • NORVIR is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . ○ Alpha 1- Adrenoreceptor Antagonist: alfuzosin ○ Antianginal: ranolazine ○ Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine ○ Antifungal: voriconazole ○ Anti-gout: colchicine ○ Antipsychotics: lurasidone, pimozide ○ Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine ○ GI Motility Agent: cisapride ○ HMG-CoA Reductase Inhibitors: lovastatin, simvastatin ○ Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ○ Non-opioid Analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine ○ PDE5 Inhibitor: sildenafil (Revatio ® ) when used for the treatment of pulmonary arterial hypertension ○ Sedative/Hypnotics: triazolam, orally administered midazolam • NORVIR is contraindicated with drugs that are potent CYP3A inducers where significantly reduced ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] . ○ Anticancer Agents: apalutamide ○ Herbal Products: St.
John's Wort (hypericum perforatum) NORVIR is contraindicated in patients with known hypersensitivity to ritonavir (e.g., 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS The following have been observed in patients receiving NORVIR: The concomitant use of NORVIR 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. ( 5.1 , 7.2 ) 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 ( 5.2 , 8.6 ) Pancreatitis: Fatalities have occurred; suspend therapy as clinically appropriate ( 5.3 ) Allergic Reactions/Hypersensitivity: Allergic reactions have been reported and include anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, bronchospasm and angioedema. Discontinue treatment if severe reactions develop ( 5.4 , 6.2 ) PR interval prolongation may occur in some patients.
Cases of second and third degree heart block have been reported. Use with caution with patients with preexisting conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease or when administering with other drugs that may prolong the PR interval ( 5.5 , 12.3 ) Total cholesterol and triglycerides elevations: Monitor prior to therapy and periodically thereafter ( 5.6 ) Patients may develop new onset or exacerbations of diabetes mellitus, hyperglycemia ( 5.7 ) Patients may develop immune reconstitution syndrome ( 5.8 ) Patients may develop redistribution/accumulation of body fat ( 5.9 ) Hemophilia: Spontaneous bleeding may occur, and additional factor VIII may be required ( 5.10 )
5.1Risk of Serious Adverse Reactions Due to Drug Interactions 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 of NORVIR, 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 NORVIR. Loss of therapeutic effect of NORVIR and possible development of resistance. When co-administering NORVIR with other protease inhibitors, see the full prescribing information for that protease inhibitor including important Warnings and Precautions.
See Table 3 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 NORVIR therapy; review concomitant medications during NORVIR therapy, and monitor for the adverse reactions associated with the concomitant medications [see Contraindications ( 4 ) and Drug Interactions ( 7 ) ] . 5.
2 Hepatotoxicity Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have occurred in patients receiving NORVIR alone or in combination with other antiretroviral drugs (see Table 2). There may be an increased risk for transaminase elevations in patients with underlying hepatitis B or C. Therefore, caution should be exercised when administering NORVIR to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis.
Increased AST/ALT monitoring should be considered in these patients, especially during the first three months of NORVIR treatment [see Use in Specific Populations ( 8.6 ) ] . 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.
5. 3 Pancreatitis Pancreatitis has been observe…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. Drug Interactions [see Warnings and Precautions ( 5.1 ) ] Hepatotoxicity [see Warnings and Precautions ( 5.2 ) ] Pancreatitis [see Warnings and Precautions ( 5.3 ) ] Allergic Reactions/Hypersensitivity [see Warnings and Precautions ( 5.4 ) ] When co-administering NORVIR with other protease inhibitors, see the full prescribing information for that protease inhibitor including adverse reactions. The most frequently reported adverse drug reactions among patients receiving NORVIR 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 ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 NORVIR alone and in combination with other antiretroviral agents was studied in 1,755 adult patients. Table 1 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 NORVIR in combined Phase II/IV studies.
The most frequently reported adverse drug reactions among patients receiving NORVIR 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 1. Treatment-Emergent Adverse Reactions (With Possible or Probable Relationship to Study Drug) Occurring in greater than or equal to 1% of Adult Patients Receiving NORVIR in Combined Phase II/IV Studies (N = 1,755) Adverse Reactions n % Eye disorders Blurred vision 113
6.4 Gastrointestinal disorders Abdominal Pain (upper and lower)* 464
26.4 Diarrhea including severe with electrolyte imbalance* 1,192
67.9 Dyspepsia 201
11.5 Flatulence 142
8.1 Gastrointestinal hemorrhage* 41
2.3 Gastroesophageal reflux disease (GERD) 19
1.1 Nausea 1,007
57.4 Vomiting* 559
31.9 General disorders and administration site conditions Fatigue including asthenia* 811
46.2 Hepatobiliary disorders Blood bilirubin increased (including jaundice)* 25
1.4 Hepatitis (including increased AST, ALT, GGT)* 153
8.7 Immune system disorders Hypersensitivity including urticaria and face edema* 114
8.2 Metabolism and nutrition disorders Edema and peripheral edema* 110
6.3 Gout* 24
1.4 Hypercholesterolemia* 52
3.0 Hypertriglyceridemia* 158
9.0 Lipodystrophy acquired* 51
2.9 Musculoskeletal and connective tissue disorders Arthralgia and back pain* 326
18.6 Myopathy/creatine phosphokinase increased* 66
3.8 Myalgia 156
8.9 Nervous system disorders Dizziness* 274
15.6 Dysgeusia* 285
16.2 Paresthesia (including oral paresthesia)* 889
50.7 Peripheral neuropathy 178
10.1 Syncope* 58
3.3 Psychiatric disorders Confusion* 52
3.0 Disturbance in attention 44
2.5 Renal and urinary disorders Increased urination* 74
4.2 Respiratory, thoracic and mediastinal disorders Coughing* 380
21.7 Oropharyngeal Pain* 279
15.9 Skin and subcutaneous tissue disorders Acne* 67
3.8 Pruritus* 214
12.2 Rash (includes erythematous and maculopapular)* 475
27.1 Vascular disorders Flushing, feeling hot* 232
13.2 Hypertension* 58
3.3 Hypotension including orthostatic hypotension* 30
1.7Peripheral coldness* 21 1.2 * Represents a medical concept including several similar MedDRA PTs Laboratory Abnormalities in Adults Table 2 shows the percentage of adult patients wh…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS When co-administering NORVIR with other protease inhibitors (atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir), see the full prescribing information for that protease inhibitor including important information for drug interactions. Co-administration of NORVIR can alter the concentrations of other drugs. The potential for drug-drug interactions must be considered prior to and during therapy ( 4 , 5.1 , 7 , 12.3 )
7.1Potential for NORVIR to Affect Other Drugs Ritonavir is an inhibitor of cytochrome P450 3A (CYP3A) and may increase plasma concentrations of agents that are primarily metabolized by CYP3A. Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (greater than 3-fold) when co-administered with ritonavir. Thus, co-administration of NORVIR with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated.
Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring as shown in Table 3. Ritonavir also inhibits CYP2D6 to a lesser extent. Co-administration of substrates of CYP2D6 with ritonavir could result in increases (up to 2-fold) in the AUC of the other agent, possibly requiring a proportional dosage reduction.
Ritonavir also appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6 as well as other enzymes, including glucuronosyl transferase. These examples are a guide and not considered a comprehensive list of all possible drugs that may interact with ritonavir. The healthcare provider should consult appropriate references for comprehensive information.
7.2Established and Other Potentially Significant Drug Interactions Table 3 provides a list of established or potentially clinically significant drug interactions. Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), and Clinical Pharmacology ( 12.3 )] for magnitude of interaction. Table 3.
Established and Other Potentially Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Ritonavir or Concomitant Drug Clinical Comment HIV-Antiviral Agents HIV-1 Protease Inhibitor: atazanavir darunavir fosamprenavir ↑ amprenavir ↑ atazanavir ↑ darunavir See the complete prescribing information for fosamprenavir, atazanavir, darunavir for details on co-administration with ritonavir. HIV-1 Protease Inhibitor: indinavir ↑ indinavir Appropriate doses for this combination, with respect to efficacy and safety, have not been established.
HIV-1 Protease Inhibitor: saquinavir ↑ saquinavir See the complete prescribing information for saquinavir for details on co-administration of saquinavir and ritonavir. Saquinavir/ritonavir in combination with rifampin is not recommended due to the risk of severe hepatotoxicity (presenting as increased hepatic transaminases) if the three drugs are given together. HIV-1 Protease Inhibitor: tipranavir ↑ tipranavir See the complete prescribing information for tipranavir for details on co-administration of tipranavir and ritonavir.
Non-Nucleoside Reverse Transcriptase Inhibitor: delavirdine ↑ ritonavir Appropriate doses of this combination with respect to safety and efficacy have not been established. HIV-1 CCR5 – antagonist: maraviroc ↑ maraviroc See the complete prescribing information for maraviroc for details on co-administration of maraviroc and ritonavir-containing protease inhibitors. Integrase Inhibitor: raltegravir ↓ raltegravir The effects of ritonavir on raltegravir with ritonavir dosage regimens greater than 100 mg twice daily have not been evaluated, however raltegravir concentrations may be decreased with ritonavir coadministration.
Other Agents Alpha 1- Adrenoreceptor Antagonist: alfuzosin ↑ alfuzosin Contraindicated d…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS When co-administering NORVIR with other protease inhibitors, see the full prescribing information for the co-administered protease inhibitor including important information for use in special populations. Lactation: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission ( 8.2 ).
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to NORVIR during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Prospective pregnancy data from the Antiretroviral Pregnancy Registry (APR) are not sufficient to adequately assess the risk of birth defects or miscarriage.
Available data from the APR show no difference in the rate of overall birth defects for ritonavir compared to the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [see Data]. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with oral administration of ritonavir to pregnant rats and rabbits. During organogenesis in the rat and rabbit, systemic exposure (AUC) was approximately 1/3 lower than human exposure at the recommended daily dose.
In the rat pre- and post-natal developmental study, maternal systemic exposure to ritonavir was approximately 1/2 of the exposure in humans at the recommended daily dose, based on a body surface area conversion factor [see Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data Based on prospective reports to the APR of approximately 6100 live births following exposure to ritonavir-containing regimens (including over 2800 live births exposed in the first trimester and over 3200 live births exposed in the second and third trimesters), there was no difference in the rate of overall birth defects for ritonavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP.
The prevalence of birth defects in live births was 2.3% (95% CI: 1.7%-2.9%) following first-trimester exposure to ritonavir-containing regimens and 2.9% (95% CI: 2.3%-3.5%) following second and third trimester exposure to ritonavir-containing regimens. While placental transfer of ritonavir and fetal ritonavir concentrations are generally low, detectable levels have been observed in cord blood samples and neonate hair. Animal Data Ritonavir was administered orally to pregnant rats (at 0, 15, 35, and 75 mg/kg/day) and rabbits (at 0, 25, 50, and 110 mg/kg/day) during organogenesis (on gestation days 6 through 17 and 6 through 19, respectively).
No evidence of teratogenicity due to ritonavir was observed in rats and rabbits at doses producing systemic exposures (AUC) equivalent to approximately 1/3 lower than human exposure at the recommended daily dose. Developmental toxicity observed in rats (early resorptions, decreased fetal body weight and ossification delays and developmental variations) occurred at a maternally toxic dose, at an exposure equivalent to approximately 1/3 lower than human exposure at the recommended daily dose. A slight increase in the incidence of cryptorchidism was also noted in rats (at a maternally toxic dose) at an exposure approximately 1/5 lower than human exposure at the recommended daily dose.
Developmental toxicity was observed in rabbits (resorptions, decreased litter size and decreased fetal weights) at maternally toxic doses approximately 1.8 times higher than the recommended daily dose, based on a body…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to NORVIR during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Prospective pregnancy data from the Antiretroviral Pregnancy Registry (APR) are not sufficient to adequately assess the risk of birth defects or miscarriage.
Available data from the APR show no difference in the rate of overall birth defects for ritonavir compared to the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [see Data]. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with oral administration of ritonavir to pregnant rats and rabbits. During organogenesis in the rat and rabbit, systemic exposure (AUC) was approximately 1/3 lower than human exposure at the recommended daily dose.
In the rat pre- and post-natal developmental study, maternal systemic exposure to ritonavir was approximately 1/2 of the exposure in humans at the recommended daily dose, based on a body surface area conversion factor [see Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Human Data Based on prospective reports to the APR of approximately 6100 live births following exposure to ritonavir-containing regimens (including over 2800 live births exposed in the first trimester and over 3200 live births exposed in the second and third trimesters), there was no difference in the rate of overall birth defects for ritonavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP.
The prevalence of birth defects in live births was 2.3% (95% CI: 1.7%-2.9%) following first-trimester exposure to ritonavir-containing regimens and 2.9% (95% CI: 2.3%-3.5%) following second and third trimester exposure to ritonavir-containing regimens. While placental transfer of ritonavir and fetal ritonavir concentrations are generally low, detectable levels have been observed in cord blood samples and neonate hair. Animal Data Ritonavir was administered orally to pregnant rats (at 0, 15, 35, and 75 mg/kg/day) and rabbits (at 0, 25, 50, and 110 mg/kg/day) during organogenesis (on gestation days 6 through 17 and 6 through 19, respectively).
No evidence of teratogenicity due to ritonavir was observed in rats and rabbits at doses producing systemic exposures (AUC) equivalent to approximately 1/3 lower than human exposure at the recommended daily dose. Developmental toxicity observed in rats (early resorptions, decreased fetal body weight and ossification delays and developmental variations) occurred at a maternally toxic dose, at an exposure equivalent to approximately 1/3 lower than human exposure at the recommended daily dose. A slight increase in the incidence of cryptorchidism was also noted in rats (at a maternally toxic dose) at an exposure approximately 1/5 lower than human exposure at the recommended daily dose.
Developmental toxicity was observed in rabbits (resorptions, decreased litter size and decreased fetal weights) at maternally toxic doses approximately 1.8 times higher than the recommended daily dose, based on a body surface area conversion factor. In pre-and postnatal development study in rats, ritonavir was administered at doses of 0, 15, 35, and 60 mg/kg/day from gestation day 6 through postnatal day 20. At doses of 60 mg/kg/day, no developmental toxicity was noted with ritonavir dosage equivalent to 1/2 of the recommended daily dose, based on a body surface area con…
🧒 Pediatric Use ▾
8.4Pediatric Use In HIV-infected patients age greater than 1 month to 21 years, the antiviral activity and adverse event profile seen during clinical trials and through postmarketing experience were similar to that for adult patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of NORVIR did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE Acute Overdosage - Human Overdose Experience Human experience of acute overdose with NORVIR is limited. One patient in clinical trials took NORVIR 1500 mg per day for two 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 ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice. Management of Overdosage 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. If indicated, elimination of unabsorbed drug should be achieved by gastric lavage; usual precautions should be observed to maintain the airway. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug.
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. A Certified Poison Control Center should be consulted for up-to-date information on the management of overdose with NORVIR.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Ritonavir is an antiretroviral drug [see Microbiology ( 12.4 ) ] .
12.2Pharmacodynamics Cardiac Electrophysiology QTcF interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg once-daily) controlled crossover study in 45 healthy adults, with 10 measurements over 12 hours on Day 3. The maximum mean (95% upper confidence bound) time-matched difference in QTcF from placebo after baseline correction was 5.5 (7.6) milliseconds (msec) for 400 mg twice-daily ritonavir. Ritonavir 400 mg twice daily resulted in Day 3 ritonavir exposure that was approximately 1.5 fold higher than observed with ritonavir 600 mg twice-daily dose at steady state.
PR interval prolongation was also noted in subjects receiving ritonavir in the same study on Day 3. The maximum mean (95% confidence interval) difference from placebo in the PR interval after baseline correction was 22 (25) msec for 400 mg twice-daily ritonavir [see Warnings and Precautions ( 5.6 )] .
12.3Pharmacokinetics The pharmacokinetics of ritonavir have been studied in healthy volunteers and HIV-infected patients (CD 4 greater than or equal to 50 cells per μL). See Table 4 for ritonavir pharmacokinetic characteristics. Absorption The absolute bioavailability of ritonavir has not been determined.
After a 100 mg tablet dose of NORVIR, peak concentrations of ritonavir were achieved approximately 3 hours and 4 hours after dosing under fasting conditions and moderate-fat (857 KCal; 31% fat, 13% protein, and 56% carbohydrate) meal, respectively. Effect of Food on Oral Absorption The bioavailability of NORVIR tablet and oral powder is decreased under fed conditions as compared to fasted conditions. Following the administration of a 100 mg tablet dose of NORVIR, C max and AUC inf of ritonavir were decreased by 21-23% under moderate fat (857 Kcal, 30% from fat) or high fat conditions (917 Kcal, 60% calories from fat) relative to fasting conditions.
Following the administration of a 100 mg dose of NORVIR oral powder, C max and AUC inf of ritonavir were decreased by 23-49% under moderate fat (617 Kcal, 29% calories from fat) or high fat conditions (917 Kcal, 60% calories from fat) relative to fasting conditions. Metabolism Nearly all of the plasma radioactivity after a single oral 600 mg dose of 14 C-ritonavir oral solution (n = 5) was attributed to unchanged ritonavir. Five ritonavir metabolites have been identified in human urine and feces.
The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of parent drug; however, the concentrations of this metabolite in plasma are low. In vitro studies utilizing human liver microsomes have demonstrated that cytochrome P450 3A (CYP3A) is the major isoform involved in ritonavir metabolism, although CYP2D6 also contributes to the formation of M–2. Elimination In a study of five subjects receiving a 600 mg dose of 14 C-ritonavir oral solution, 11.3 ± 2.8% of the dose was excreted into the urine, with 3.5 ± 1.8% of the dose excreted as unchanged parent drug.
In that study, 86.4 ± 2.9% of the dose was excreted in the feces with 33.8 ± 10.8% of the dose excreted as unchanged parent drug. Upon multiple dosing, ritonavir accumulation is less than predicted from a single dose possibly due to a time and dose-related increase in clearance. Table 4.
Ritonavir Pharmacokinetic Characteristics Parameter N Values (Mean ± SD) V β /F ‡ 91 0.41 ±
0.25L/kg t ½ 3 - 5 h CL/F SS † 10 8.8 ±
3.2L/h CL/F ‡ 91 4.6 ±
1.6 L/h CL R 62 <
0.1 L/h RBC/Plasma Ratio
0.14Percent Bound* 98 to 99% † SS = steady state; patients taking ritonavir 600 mg q12h. ‡ Single ritonavir 600 mg dose. * Primarily bound to human serum albumin and alpha-1 acid glycoprotein over the ritonavir concentration range of 0.01 to 30 µg/mL. Special Populations Gender, Race and Age No age-related pharmacokinetic differences have been observed in adult patients (18 to 63 years). Ritonavir…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Ritonavir is an antiretroviral drug [see Microbiology ( 12.4 ) ] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING The package sizes, strengths, and storage and handling recommendations for NORVIR (ritonavir) tablets and oral powder are shown in the table below. NORVIR Tablets, 100 mg Ritonavir NORVIR Oral Powder, 100 mg Packet Presentation White film-coated ovaloid tablets debossed with “NK” on one side providing 100 mg ritonavir. beige/pale yellow to yellow powder, in packets containing 100 mg of ritonavir Packaging Size Bottles containing 30 tablets 30 foil/laminate, child-resistant packets per carton NDC Number 0074-2340-30 0074-3399-30 Recommended Storage Store at or below 30°C (86°F).
Exposure to temperatures up to 50°C (122°F) for seven days permitted. Dispense in original container or USP equivalent tight container (60 mL or less). For patient use: exposure of this product to high humidity outside the original or USP equivalent tight container (60 mL or less) for longer than 2 weeks is not recommended.
Store at or below 30°C (86°F).
📋 Description ▾
11 DESCRIPTION NORVIR (ritonavir) is an inhibitor of HIV protease with activity against the Human Immunodeficiency Virus (HIV). Ritonavir is chemically designated as 10-Hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12- tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]. Its molecular formula is C 37 H 48 N 6 O 5 S 2 , and its molecular weight is 720.95.
Ritonavir has the following structural formula: Ritonavir is a white-to-light-tan powder. Ritonavir has a bitter metallic taste. It is freely soluble in methanol and ethanol, soluble in isopropanol and practically insoluble in water.
NORVIR tablets are available for oral administration in a strength of 100 mg ritonavir with the following inactive ingredients: copovidone, anhydrous dibasic calcium phosphate, sorbitan monolaurate, colloidal silicon dioxide, and sodium stearyl fumarate. The following are the ingredients in the film coating: hypromellose, titanium dioxide, polyethylene glycol 400, hydroxypropyl cellulose, talc, polyethylene glycol 3350, colloidal silicon dioxide, and polysorbate 80. NORVIR oral powder is beige/pale yellow to yellow and is available for oral administration as a packet containing 100 mg of ritonavir with the following inactive ingredients: copovidone, sorbitan monolaurate, and colloidal silicon dioxide.
The following structural formula for Ritonavir is chemically designated as 10-Hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12- tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]. Its molecular formula is C37H48N6O5S2, and its molecular weight is 720.95.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ) General Administration Information [see Dosage and Administration ( 2 )] : Advise patients and caregivers to pay special attention to accurate preparation and administration of their dose to minimize the risk of accidental overdose or underdose of NORVIR. For Norvir oral powder, advise patients or caregivers to read and follow the Instructions for Use for preparing the correct dose.
Advise caregivers to inform their healthcare provider if their child’s weight changes in order to make sure that the child’s NORVIR dose is adjusted as needed. Advise patients to take NORVIR with meals. For adult patients taking NORVIR tablets, the maximum dose of 600 mg twice daily by mouth with meals should not be exceeded.
Advise patients to remain under the care of a physician while using NORVIR and to take NORVIR and other concomitant antiretroviral therapy every day as prescribed. NORVIR must always be used in combination with other antiretroviral drugs. Advise patients not to alter the dose or discontinue therapy without consulting with their healthcare provider.
If a dose of NORVIR is missed patients should take the dose as soon as possible and then return to their normal schedule. However, if a dose is skipped the patient should not double the next dose. Continued NORVIR therapy at a dose of 600 mg twice daily following loss of viral suppression may increase the likelihood of cross-resistance to other protease inhibitors.
NORVIR is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using NORVIR. Drug Interactions NORVIR may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St.
John's Wort. Instruct patients receiving combined hormonal contraception to use an effective alternative contraceptive method or an additional barrier method during therapy with NORVIR because hormonal levels may decrease [see Drug Interactions ( 7.2 ) , Use in Specific Populations ( 8.3 ) ]. Hepatotoxicity Pre-existing liver disease including Hepatitis B or C can worsen with use of NORVIR.
This can be seen as worsening of transaminase elevations or hepatic decompensation. Advise patients that their liver function tests will need to be monitored closely especially during the first several months of NORVIR treatment and that they should notify their healthcare provider if they develop the signs and symptoms of worsening liver disease including loss of appetite, abdominal pain, jaundice, and itchy skin [see Warnings and Precautions ( 5.2 ) ] . Pancreatitis Pancreatitis, including some fatalities, has been observed in patients receiving NORVIR therapy.
Advise patients to notify their healthcare provider of signs and symptoms (nausea, vomiting, and abdominal pain) that might be suggestive of pancreatitis [see Warnings and Precautions ( 5.3 ) ] . Allergic Reactions/Hypersensitivity Skin rashes ranging in severity from mild to Stevens-Johnson syndrome have been reported in patients receiving NORVIR. Advise patients to contact their healthcare provider if they develop a rash while taking NORVIR [see Warnings and Precautions ( 5.4 ) ] .
PR Interval Prolongation NORVIR may produce changes in the electrocardiogram (e.g., PR prolongation). Advise patients to consult their healthcare provider if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm or loss of consciousness [see Warnings and Precautions ( 5.5 ) ] . Lipid Disorders Advise patients that treatment with NORVIR therapy can result in substantial increases in the concentration of total cholesterol and triglycerides [see Warnings and Precautions ( 5.6 ) ] .
Diabet…