Home › NDC Lookup › Ingredients › Lopinavir And Ritonavir › 31722-0603-12
Lopinavir and ritonavir 100 mg; 25 mg Tablet, Film Coated, 120-count — NDC 31722-0603-12 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Lopinavir and ritonavir 100 mg; 25 mg Tablet, Film Coated, 120-count — NDC 31722-603-12 (Billing 31722-0603-12)

by Camber Pharmaceuticals, Inc. · 120 TABLET, FILM COATED in 1 BOTTLE

This is a package of 120 tablets of Lopinavir and ritonavir 100 mg; 25 mg Tablet, Film Coated from Camber Pharmaceuticals, Inc., marketed since Jun 2021 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 31722-0603-12
🏷️ FDA NDC (as labeled) 31722-603-12 billing pads the product segment with a zero
This package
Contains120-count Pack sizes2 compare ↓
Also priced by: Part D plans $5.90/unit — full pricing hub ↓
Main listing for product 31722-603 · Also comes in: 60 tablets 31722-603-60
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 31722-603-12 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
31722 labeler · 603 product · 12 package
Package marketed since
Jun 7, 2021
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC)
0331722603607, 0331722556125
FDA record last changed
Oct 1, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 31722-603-12
Product NDC 31722-603
11-digit billing NDC 31722060312
RxCUI 597730, 746645
UNII O3J8G9O825, 2494G1JF75
UPC 0331722603607, 0331722556125
Application # ANDA091677
SPL Set ID 4e5005b8-f00c-4671-be09-bb927190760f
Established class (EPC) Cytochrome P450 3A Inhibitor; Protease Inhibitor
Mechanism of action HIV Protease Inhibitors; Cytochrome P450 3A Inhibitors; Cytochrome P450 2D6 Inhibitors; Cytochrome P450 2C19 Inducers; Cytochrome P450 3A Inducers; P-Glycoprotein Inhibitors; Breast Cancer Resistance Protein Inhibitors; Cytochrome P450 3A4 Inhibitors; Cytochrome P450 1A2 Inducers; Cytochrome P450 2C9 Inducers; Cytochrome P450 2B6 Inducers; UDP Glucuronosyltransferases Inducers; Organic Anion Transporting Polypeptide 1B1 Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-06-07
Route ORAL
Dosage form TABLET, FILM COATED
Substance LOPINAVIR; RITONAVIR
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 12109902550310
GPI class Lopinavir-Ritonavir
GCN Seq No 063355
GCN 99101
HICL code 021582
Ingredient (HICL) Lopinavir/Ritonavir
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W5
Therapeutic class — intermediate (HIC2) Antiviral Agents
HIC3 code W5M
Therapeutic class — specific (HIC3) Antivirals, Hiv-Specific, Protease Inhibitor Comb
AHFS code 08:18.08.08
AHFS class Hiv Protease Inhibitor Antiretrovirals
FDB label name LOPINAVIR-RITONAVR 100-25MG TB
FDB brand name Lopinavir-Ritonavir
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 063355
  • GCN: 99101
  • GPI-14 (Medi-Span): 12109902550310
  • HICL (First Databank): 021582
  • AHFS class code: 08:18.08.08
  • RxCUI (RxNorm): 597730
Why two NDCs? The FDA registers this code as 31722-603-12 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 31722-0603-12. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Protease Inhibitor class.

Pharmacologic class Protease Inhibitor
Drug family (ATC) Antivirals for treatment of HIV infections, combinations
How it works HIV Protease Inhibitors, P-Glycoprotein Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Cytochrome P450 3A Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name LOPINAVIR-RITONAVR 100-25MG TB Ingredient Lopinavir/Ritonavir
📗 Our plain-language guide HelloPharmacist
  • Lopinavir and ritonavir attacks HIV at a specific step in its life cycle. The virus needs an enzyme called protease to cut proteins into shapes it can use to build new, infectious...
  • What exactly is this medication doing for my HIV?
  • If you're taking the tablet form (Kaletra tablets or the generic lopinavir and ritonavir tablets), you can take it with or without food — that's flexible. Just be sure to swallow t...
  • Does it matter when I take my tablets — do I have to take them with food?
📖 Read our full Lopinavir and Ritonavir guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $5.90 $707.48 / 120 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
31722-0603-12 You're viewing this Main listing 120 TABLET, FILM COATED in 1 BOTTLE 2021-06-07 — Active
31722-0603-60 31722-603-60 60 TABLET, FILM COATED in 1 BOTTLE 2021-06-07 — Active

You're viewing the largest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This is a 120-count package — 120 tablet, film coated in 1 bottle.
How does this package differ from NDC 31722-0603-60?
Both are Lopinavir and ritonavir 100 mg; 25 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 120-count one, while NDC 31722-0603-60 is the 60 tablets package.
What NDC number is used to bill for this package of Lopinavir and ritonavir 100 mg; 25 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Kaletra 100 mg/1; 25 mg 00074-0522-60 AbbVie 60 tablets — AB Discontinued —
Kaletra 100 mg/1; 25 mg 00074-3008-60 AbbVie 60 tablets — AB FDA listed —
Lopinavir and ritonavir 100 mg/1; 25 mgthis 31722-0603-12 Camber 120 tablets — AB FDA listed —
Lopinavir and Ritonavir 100 mg/1; 25 mg 33342-0163-09 Macleods 60 tablets — AB FDA listed —
Lopinavir and Ritonavir 100 mg/1; 25 mg 42385-0933-60 Laurus 60 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2021
On the market since
Jun 2021
📍
2026
Currently FDA-listed
5 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color yellow
ShapeCapsule
ImprintH;L7
Size18 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • 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.
  • UNII 36SFW2JZ0W
    Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
  • UNII 0WZ8WG20P6
    Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

13 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerCamber Pharmaceuticals, Inc.
Application holderHETERO LABS LTD UNIT III
FDA applicationANDA091677 (ANDA)
Labeler code31722
First marketedJun 2021
Product typeHuman Prescription Drug
Portfolio603 products on file

More NDCs from Camber Pharmaceuticals, Inc. labeler code 31722

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 102 words ▾

1 INDICATIONS AND USAGE Lopinavir and ritonavir tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 14 days and older. Limitations of Use: • Genotypic or phenotypic testing and/or treatment history should guide the use of lopinavir and ritonavir tablets. The number of baseline lopinavir resistance-associated substitutions affects the virologic response to lopinavir and ritonavir tablets [see Microbiology (12.4)].

Lopinavir and ritonavir tablets are an HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients (14 days and older). (1)

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Tablets: May be taken with or without food, swallowed whole and not chewed, broken, or crushed. (2.1) Adults (2.3): • Total recommended daily dosage is 800/200 mg given once or twice daily. • Lopinavir and ritonavir tablets can be given as once daily or twice daily regimen. See Full Prescribing Information for details. • Lopinavir and ritonavir tablets once daily dosing regimen is not recommended in: • Adult patients with three or more of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V.

(12.4) • In combination with carbamazepine, phenobarbital, or phenytoin. (7.3) • In combination with efavirenz, nevirapine, or nelfinavir. (12.3) • In pregnant women.

( 2.5, 8.1 , 12.3 ) Pediatric Patients (14 days and older) (2.4): • Lopinavir and ritonavir tablets once daily dosing regimen is not recommended in pediatric patients. • Twice daily dose is based on body weight or body surface area. Concomitant Therapy in Adults and Pediatric Patients : • Dose adjustments of lopinavir and ritonavir tablets may be needed when co-administering with efavirenz, nevirapine, or nelfinavir. (2.3, 2.4 , 7.3 ) • Lopinavir and ritonavir oral solution should not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days has been attained ( 2.4, 5.2 ) Pregnancy (2.5): • 400/100 mg twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions. • There are insufficient data to recommend a lopinavir and ritonavir tablets dose for pregnant patients with any documented lopinavir and ritonavir tablets-associated resistance substitutions. • No dose adjustment of lopinavir and ritonavir tablets are required for patients during the postpartum period.

2.1General Administration Recommendations Lopinavir and ritonavir tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed.

2.3Dosage Recommendations in Adults Lopinavir and ritonavir tablets can be given in once daily or twice daily dosing regimen at dosages noted in Tables 1 and 2. Lopinavir and ritonavir tablets once daily dosing regimen is not recommended in: • Adult patients with three or more of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V [see Microbiology (12.4)]. • In combination with carbamazepine, phenobarbital, or phenytoin [see Drug Interactions (7.3)]. • In combination with efavirenz, nevirapine, or nelfinavir [see Drug Interactions (7.3) and Clinical Pharmacology ( 12.3)]. • In pediatric patients younger than 18 years of age [see Dosage and Administration (2.4)]. • In pregnant women [see Dosage and Administration ( 2.5), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].

Table 1. Recommended Dosage in Adults - Lopinavir and Ritonavir Tablets Once Daily Regimen Lopinavir and Ritonavir Tablets Dosage Form Recommended Dosage 200 mg/50 mg Tablets 800 mg/200 mg (4 tablets) once daily Table 2. Recommended Dosage in Adults – Lopinavir and Ritonavir Tablets Twice Daily Regimen Lopinavir and Ritonavir Tablets Dosage Form Recommended Dosage 200 mg/50 mg Tablets 400 mg/100 mg (2 tablets) twice daily The dose of lopinavir and ritonavir tablets must be increased when administered in combination with efavirenz, nevirapine or nelfinavir.

Table 3 outlines the dosage recommendations for twice daily dosing when lopinavir and ritonavir tablets are taken in combination with these agents. Table 3. Recommended Dosage in Adults - Lopinavir and Ritonavir Tablets Twice Daily Regimen in Combination with Efavirenz, Nevirapine, or Nelfinavir Lopinavir and Ritonavir Tablets Dosage Form Recommended Dosage 200 mg/50 mg Tablets and 100 mg/25 mg Tablets 500 mg/125 m… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 93 words ▾

3 DOSAGE FORMS AND STRENGTHS • Lopinavir and Ritonavir Tablets USP, 200 mg lopinavir USP/50 mg ritonavir USP Yellow, film coated, ovaloid tablets debossed with ‘H’ on one side and ‘70’ on other side. • Lopinavir and Ritonavir Tablets USP, 100 mg lopinavir USP/25 mg ritonavir USP Yellow, capsule shaped, biconvex film coated tablets, debossed with ‘H’ on one side and ‘L7’ on other side. • Film coated Tablets: 200 mg lopinavir, USP and 50 mg ritonavir, USP (3) • Film coated Tablets: 100 mg lopinavir, USP and 25 mg ritonavir, USP (3)

⛔ Contraindications ~2 min read ▾

4 CONTRAINDICATIONS • Lopinavir and ritonavir tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir. • Lopinavir and ritonavir tablets are 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 o Alpha 1-Adrenoreceptor Antagonist: alfuzosin o Antianginal: ranolazine o Antiarrhythmic: dronedarone o Anti-gout: colchicine o Antipsychotics: lurasidone, pimozide o Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine o GI Motility Agent: cisapride o Hepatitis C direct acting antiviral: elbasvir/grazoprevir o HMG-CoA Reductase Inhibitors: lovastatin, simvastatin o triglyceride transfer protein (MTTP) Inhibitor: lomitapide o PDE5 Inhibitor: sildenafil (Revatio®) when used for the treatment of pulmonary arterial hypertension o Sedative/Hypnotics: triazolam, orally administered midazolam • Lopinavir and ritonavir tablets are contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance o Anticancer Agents: apalutamide o Antimycobacterial: rifampin o Herbal Products: St.

John's Wort (hypericum perforatum) • Lopinavir and ritonavir tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir. • Lopinavir and ritonavir tablets are 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)]. o Alpha 1-Adrenoreceptor Antagonist: alfuzosin o Antianginal: ranolazine o Antiarrhythmic: dronedarone o Anti-gout: colchicine o Antipsychotics: lurasidone, pimozide o Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine o GI Motility Agent: cisapride o Hepatitis C direct acting antiviral: elbasvir/grazoprevir o HMG-CoA Reductase Inhibitors: lovastatin, simvastatin o Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide o PDE5 Inhibitor: sildenafil (Revatio®) when used for the treatment of pulmonary arterial hypertension o Sedative/Hypnotics: triazolam, orally administered midazolam • Lopinavir and ritonavir tablets are contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see Drug Interactions (7.2) and Clinical Pharmacology (12.3 )]. o Anticancer Agents: apalutamide o Antimycobacterial: rifampin o Herbal Products: St.

John's Wort (hypericum perforatum) • Hypersensitivity to lopinavir and ritonavir tablets (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) or any of its ingredients, including ritonavir. (4) • Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma levels may result in serious and/or life-threatening events. (4) • Co-administration with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross resistance.

(4)

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS The following have been observed in patients receiving lopinavir and ritonavir: • The concomitant use of lopinavir and ritonavir and certain other drugs may result in known or potentially significant drug interactions. Consult the full prescribing information prior to and during treatment for potential drug interactions. ( 5.1, 7.3 ) • Toxicity in preterm neonates: Lopinavir and ritonavir oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities.

A safe and effective dose of lopinavir and ritonavir oral solution in this patient population has not been established. (2.4 , 5.2 ) • Pancreatitis: Fatalities have occurred; suspend therapy as clinically appropriate. (5.3 ) • Hepatotoxicity: Fatalities have occurred.

Monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations. ( 5.4, 8.6 ) • QT interval prolongation and isolated cases of torsade de pointes have been reported although causality could not be established. Avoid use in patients with congenital long QT syndrome, those with hypokalemia, and with other drugs that prolong the QT interval.

( 5.1, 5.5 , 12.3 ) • PR interval prolongation may occur in some patients. Cases of second and third degree heart block have been reported. Use with caution in patients with pre-existing conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease or when administering with other drugs that may prolong the PR interval.

( 5.1 , 5.6 , 12.3 ) • Patients may develop new onset or exacerbations of diabetes mellitus, hyperglycemia (5.7), immune reconstitution syndrome. (5.8), redistribution/accumulation of body fat. (5.10) • Total cholesterol and triglycerides elevations.

Monitor prior to therapy and periodically thereafter. (5.9) • Hemophilia: Spontaneous bleeding may occur, and additional factor VIII may be required. (5.11)

5.1Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of lopinavir and ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving lopinavir and ritonavir, may increase plasma concentrations of medications metabolized by CYP3A. Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of lopinavir and ritonavir, respectively. These interactions may lead to: • Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications. • Clinically significant adverse reactions from greater exposures of lopinavir and ritonavir. • Loss of therapeutic effect of lopinavir and ritonavir and possible development of resistance.

See Table 12 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Drug Interactions (7)]. Consider the potential for drug interactions prior to and during lopinavir and ritonavir therapy; review concomitant medications during lopinavir and ritonavir therapy, and monitor for the adverse reactions associated with the concomitant medications [see Contraindications (4) and Drug Interactions (7)].

5.2Toxicity in Preterm Neonates Lopinavir and ritonavir oral solution contains the excipients alcohol and propylene glycol. When administered concomitantly with propylene glycol, alcohol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations. Preterm neonates may be at increased risk of propylene glycol-associated adverse events due to diminished ability to metabolize propylene glycol, thereby leading to accumulation and potential adverse events.

Postmarketing life-threatening cases of cardiac toxicity (including complete AV block, bradycardia, and cardiomyopathy), lactic… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. • QT Interval Prolongation, PR Interval Prolongation [see Warnings and Precautions ( 5.5 , 5.6 )] • Drug Interactions [see Warnings and Precautions (5.1)] • Pancreatitis [see Warnings and Precautions (5.3)] • Hepatotoxicity [see Warnings and Precautions (5.4)] Commonly reported adverse reactions to lopinavir and ritonavir included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Adults The safety of lopinavir and ritonavir has been investigated in about 2,600 patients in Phase II-IV clinical trials, of which about 700 have received a dose of 800/200 mg (6 capsules or 4 tablets) once daily.

Along with nucleoside reverse transcriptase inhibitors (NRTIs), in some studies, lopinavir and ritonavir was used in combination with efavirenz or nevirapine. In clinical studies the incidence of diarrhea in patients treated with either lopinavir and ritonavir capsules or tablets was greater in those patients treated once daily than in those patients treated twice daily. Any grade of diarrhea was reported by at least half of patients taking once daily lopinavir and ritonavir capsules or tablets.

At the time of treatment discontinuation, 4.2 to 6.3% of patients taking once daily lopinavir and ritonavir and 1.8 to 3.7% of those taking twice daily lopinavir and ritonavir reported ongoing diarrhea. Commonly reported adverse reactions to lopinavir and ritonavir included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia. Diarrhea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridemia and hypercholesterolemia may occur later.

The following have been identified as adverse reactions of moderate or severe intensity (Table 8): Table 8. Adverse Reactions of Moderate or Severe Intensity Occurring in at Least 0.1% of Adult Patients Receiving Lopinavir and Ritonavir in Combined Phase II/IV Studies (N=2,612) System Organ Class (SOC) and Adverse Reaction n % BLOOD AND LYMPHATIC SYSTEM DISORDERS anemia* 54 2.1 leukopenia and neutropenia* 44 1.7 lymphadenopathy* 35

1.3CARDIAC DISORDERS atherosclerosis such as myocardial infarction* 10 0.4 atrioventricular block* 3 0.1 tricuspid valve incompetence* 3

0.1 EAR AND LABYRINTH DISORDERS vertigo* 7

0.3 Tinnitus 6

0.2 ENDOCRINE DISORDERS hypogonadism* 16

0.81 EYE DISORDERS visual impairment* 8

0.3 GASTROINTESTINAL DISORDERS diarrhea* 510

19.5Nausea 269 10.3 vomiting* 177 6.8 abdominal pain (upper and lower)* 160 6.1 gastroenteritis and colitis* 66 2.5 dyspepsia 53 2.0 pancreatitis* 45

1.7Gastroesophageal Reflux Disease (GERD)* 40 1.5 hemorrhoids 39 1.5 flatulence 36 1.4 abdominal distension 34 1.3 constipation* 26 1.0 stomatitis and oral ulcers* 24 0.9 duodenitis and gastritis* 20 0.8 gastrointestinal hemorrhage including rectal hemorrhage* 13 0.5 dry mouth 9 0.3 gastrointestinal ulcer* 6 0.2 fecal incontinence 5

0.2 GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS fatigue including asthenia* 198

7.6HEPATOBILIARY DISORDERS hepatitis including AST, ALT, and GGT increases* 91 3.5 hepatomegaly 5 0.2 cholangitis 3 0.1 hepatic steatosis 3

0.1IMMUNE SYSTEM DISORDERS hypersensitivity including urticaria and angioedema* 70 2.7 immune reconstitution syndrome 3

0.1INFECTIONS AND INFESTATIONS upper respiratory tract infection* 363 13.9 lower respiratory tract infection* 202 7.7 skin infections including cellulitis, folliculitis, and furuncle* 86

3.3METABOLISM… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Co-administration of lopinavir and ritonavir can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of lopinavir. The potential for drug-drug interactions must be considered prior to and during therapy. (4, 5.1, 7, 12.3 )

7.1Potential for Lopinavir and Ritonavir to Affect Other Drugs Lopinavir/ritonavir is an inhibitor of 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 (> 3-fold) when co-administered with lopinavir and ritonavir. Thus, co-administration of lopinavir and ritonavir 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 12. Additionally, lopinavir and ritonavir induces glucuronidation. Published data suggest that lopinavir is an inhibitor of OATP1B1.

These examples are a guide and not considered a comprehensive list of all possible drugs that may interact with lopinavir/ritonavir. The healthcare provider should consult appropriate references for comprehensive information.

7.2Potential for Other Drugs to Affect Lopinavir Lopinavir/ritonavir is a CYP3A substrate; therefore, drugs that induce CYP3A may decrease lopinavir plasma concentrations and reduce lopinavir and ritonavir’s therapeutic effect. Although not observed in the lopinavir and ritonavir/ketoconazole drug interaction study, co-administration of lopinavir and ritonavir and other drugs that inhibit CYP3A may increase lopinavir plasma concentrations.

7.3Established and Other Potentially Significant Drug Interactions Table 12 provides a listing 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), Clinical Pharmacology (12.3)] for magnitude of interaction. Table 12.

Established and Other Potentially Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Lopinavir or Concomitant Drug Clinical Comments HIV-1 Antiviral Agents HIV-1 Protease Inhibitor: fosamprenavir/ritonavir ↓ amprenavir ↓ lopinavir An increased rate of adverse reactions has been observed with co-administration of these medications. Appropriate doses of the combinations with respect to safety and efficacy have not been established. HIV-1 Protease Inhibitor: indinavir* ↑ indinavir Decrease indinavir dose to 600 mg twice daily, when co­ administered with lopinavir and ritonavir400/100 mg twice daily.

Lopinavir and ritonavir once daily has not been studied in combination with indinavir. HIV-1 Protease Inhibitor: nelfinavir* ↑ nelfinavir ↑ M8 metabolite of nelfinavir ↓ lopinavir Lopinavir and ritonavir once daily in combination with nelfinavir is not recommended [see Dosage and Administration (2)]. HIV-1 Protease Inhibitor: ritonavir* ↑ lopinavir Appropriate doses of additional ritonavir in combination with lopinavir and ritonavirwith respect to safety and efficacy have not been established.

HIV-1 Protease Inhibitor: saquinavir ↑ saquinavir The saquinavir dose is 1000 mg twice daily, when co­ administered with lopinavir and ritonavir 400/100 mg twice daily. Lopinavir and ritonavir once daily has not been studied in combination with saquinavir. HIV-1 Protease Inhibitor: tipranavir* ↓ lopinavir Co-administration with tipranavir (500 mg twice daily) and ritonavir (200 mg twice daily) is not recommended.

HIV CCR5 - Antagonist: maraviroc* ↑ maraviroc When co-administered, patients should receive 150 mg twice daily of maraviroc. For further details see complete prescribing information for ma… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding not recommended. ( 8.2 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lopinavir and ritonavir during pregnancy. Physicians are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263. Risk Summary Available data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects 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).

The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown. Methodological limitations of the APR include the use of MACDP as the external comparator group.

The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation (see Data). No treatment-related malformations were observed when lopinavir in combination with ritonavir was administered to pregnant rats or rabbits; however embryonic and fetal developmental toxicities occurred in rats administered maternally toxic doses. Clinical Considerations Dose Adjustments During Pregnancy and the Postpartum Period Administer 400/100 mg of lopinavir and ritonavir twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

There are insufficient data to recommend lopinavir and ritonavir dosing for pregnant patients with any documented lopinavir-associated resistance substitutions. No dose adjustment of lopinavir and ritonavir is required for patients during the postpartum period. Once daily lopinavir and ritonavir dosing is not recommended in pregnancy.

Avoid use of lopinavir and ritonavir oral solution during pregnancy due to the alcohol content. Lopinavir and ritonavir oral solution contains the excipients alcohol and propylene glycol. Data Human Data Lopinavir and ritonavir was evaluated in 12 HIV-infected pregnant women in an open-label pharmacokinetic trial [see Clinical Pharmacology (12.3)].

No new trends in the safety profile were identified in pregnant women dosed with lopinavir and ritonavir compared to the safety described in non-pregnant adults, based on the review of these limited data. Antiretroviral Pregnancy Registry Data: Based on prospective reports from the Antiretroviral Pregnancy Registry (APR) of over 3,000 exposures to lopinavir containing regimens (including over 1,000 exposed in the first trimester), there was no difference between lopinavir and overall birth defects compared with the background birth defect rate of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program.

The prevalence of birth defects in live births was 2.1% (95% CI:1.4%-3.0%) following first-trimester exposure to lopinavir-containing regimens and 3.0% (95% CI: 2.4%-3.8%) following second and third trimester exposure to lopinavir-containing regimens. Based on prospective reports from the APR of over 5,000 exposures to ritonavir containing regimens (including over 2,000 exposures in the first trimester) there was no difference between ritonavir and overall birth defects compared with the U.S. background rate (MACDP).

The prevalence of birth defects in live births was 2.2% (95% CI: 1.7%-2.8%) following first-trimester exposure to ritonavir-containing regimens and 2.9% (95% CI: 2.4%-3.6%) following second and third trimester exposure to ritonavir-containing regimens. For both lopinavir and ritonavir, sufficient numbers of first trimester exposures have been monitored to detect at least a 1.5 fold increase i… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lopinavir and ritonavir during pregnancy. Physicians are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263. Risk Summary Available data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects 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).

The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown. Methodological limitations of the APR include the use of MACDP as the external comparator group.

The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation (see Data). No treatment-related malformations were observed when lopinavir in combination with ritonavir was administered to pregnant rats or rabbits; however embryonic and fetal developmental toxicities occurred in rats administered maternally toxic doses. Clinical Considerations Dose Adjustments During Pregnancy and the Postpartum Period Administer 400/100 mg of lopinavir and ritonavir twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

There are insufficient data to recommend lopinavir and ritonavir dosing for pregnant patients with any documented lopinavir-associated resistance substitutions. No dose adjustment of lopinavir and ritonavir is required for patients during the postpartum period. Once daily lopinavir and ritonavir dosing is not recommended in pregnancy.

Avoid use of lopinavir and ritonavir oral solution during pregnancy due to the alcohol content. Lopinavir and ritonavir oral solution contains the excipients alcohol and propylene glycol. Data Human Data Lopinavir and ritonavir was evaluated in 12 HIV-infected pregnant women in an open-label pharmacokinetic trial [see Clinical Pharmacology (12.3)].

No new trends in the safety profile were identified in pregnant women dosed with lopinavir and ritonavir compared to the safety described in non-pregnant adults, based on the review of these limited data. Antiretroviral Pregnancy Registry Data: Based on prospective reports from the Antiretroviral Pregnancy Registry (APR) of over 3,000 exposures to lopinavir containing regimens (including over 1,000 exposed in the first trimester), there was no difference between lopinavir and overall birth defects compared with the background birth defect rate of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program.

The prevalence of birth defects in live births was 2.1% (95% CI:1.4%-3.0%) following first-trimester exposure to lopinavir-containing regimens and 3.0% (95% CI: 2.4%-3.8%) following second and third trimester exposure to lopinavir-containing regimens. Based on prospective reports from the APR of over 5,000 exposures to ritonavir containing regimens (including over 2,000 exposures in the first trimester) there was no difference between ritonavir and overall birth defects compared with the U.S. background rate (MACDP).

The prevalence of birth defects in live births was 2.2% (95% CI: 1.7%-2.8%) following first-trimester exposure to ritonavir-containing regimens and 2.9% (95% CI: 2.4%-3.6%) following second and third trimester exposure to ritonavir-containing regimens. For both lopinavir and ritonavir, sufficient numbers of first trimester exposures have been monitored to detect at least a 1.5 fold increase in risk of overall birth defects and a 2 fold increase in risk of birth defects i… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use The safety, efficacy, and pharmacokinetic profiles of lopinavir and ritonavir in pediatric patients below the age of 14 days have not been established. Lopinavir and ritonavir should not be administered once daily in pediatric patients. An open-label, multi-center, dose-finding trial was performed to evaluate the pharmacokinetic profile, tolerability, safety and efficacy of lopinavir and ritonavir oral solution containing lopinavir 80 mg/mL and ritonavir 20 mg/mL at a dose of 300/75 mg/m 2 twice daily plus two NRTIs in HIV-infected infants ≥14 days and < 6 months of age.

Results revealed that infants younger than 6 months of age generally had lower lopinavir AUC 12 than older children (6 months to 12 years of age), however, despite the lower lopinavir drug exposure observed, antiviral activity was demonstrated as reflected in the proportion of subjects who achieved HIV-1 RNA <400 copies/mL at Week 24 [see Adverse Reactions (6.2), Clinical Pharmacology (12.3), Clinical Studies (14.4)]. Safety and efficacy in pediatric patients > 6 months of age was demonstrated in a clinical trial in 100 patients.

The clinical trial was an open-label, multicenter trial evaluating the pharmacokinetic profile, tolerability, safety, and efficacy of lopinavir and ritonavir oral solution containing lopinavir 80 mg/mL and ritonavir 20 mg/mL in 100 antiretroviral naïve and experienced pediatric patients ages 6 months to 12 years. Dose selection for patients 6 months to 12 years of age was based on the following results. The 230/57.5 mg/m 2 oral solution twice daily regimen without nevirapine and the 300/75 mg/m 2 oral solution twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/100 mg twice daily regimen (without nevirapine) [see Adverse Reactions (6.2), Clinical Pharmacology (12.3), Clinical Studies (14.4)].

A prospective multicenter, open-label trial evaluated the pharmacokinetic profile, tolerability, safety and efficacy of high-dose lopinavir and ritonavir with or without concurrent NNRTI therapy (Group 1: 400/100 mg/m 2 twice daily + ≥ 2 NRTIs; Group 2: 480/120 mg/m2 twice daily + ≥ 1 NRTI + 1 NNRTI) in 26 children and adolescents ≥ 2 years to < 18 years of age who had failed prior therapy. Patients also had saquinavir mesylate added to their regimen. This strategy was intended to assess whether higher than approved doses of lopinavir and ritonavir could overcome protease inhibitor cross-resistance.

High doses of lopinavir and ritonavir exhibited a safety profile similar to those observed in previous trials; changes in HIV-1 RNA were less than anticipated; three patients had HIV-1 RNA <400 copies/mL at Week 48. CD4+ cell count increases were noted in the eight patients who remained on treatment for 48 weeks [see Adverse Reactions (6.2), Clinical Pharmacology (12.3)]. A prospective multicenter, randomized, open-label study evaluated the efficacy and safety of twice-daily versus once-daily dosing of lopinavir and ritonavir tablets dosed by weight as part of combination antiretroviral therapy (cART) in virologically suppressed HIV-1 infected children (n=173).

Children were eligible when they were aged < 18 years, ≥ 15 kg in weight, receiving cART that included lopinavir and ritonavir tablets, HIV-1 ribonucleic acid (RNA) < 50 copies/mL for at least 24 weeks and able to swallow tablets. At week 24, efficacy (defined as the proportion of subjects with plasma HIV-1 RNA less than 50 copies per mL) was significantly higher in subjects receiving twice daily dosing compared to subjects receiving once daily dosing. The safety profile was similar between the two treatment arms although there was a greater incidence of diarrhea in the once daily treated subjects.

🧓 Geriatric Use 67 words ▾

8.5Geriatric Use Clinical studies of lopinavir and ritonavir did not include sufficient numbers of subjects aged 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 lopinavir and ritonavir in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE Overdoses with lopinavir and ritonavir oral solution have been reported. One of these reports described fatal cardiogenic shock in a 2.1 kg infant who received a single dose of 6.5 mL of lopinavir and ritonavir oral solution (520 mg lopinavir, approximately 10-fold above the recommended lopinavir dose) nine days prior. The following events have been reported in association with unintended overdoses in preterm neonates: complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure [see Warnings and Precautions (5.2)].

Healthcare professionals should be aware that lopinavir and ritonavir oral solution is highly concentrated and therefore, should pay special attention to accurate calculation of the dose of lopinavir and ritonavir, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors and overdose. This is especially important for infants and young children. Lopinavir and ritonavir oral solution contains alcohol and propylene glycol.

Ingestion of the product over the recommended dose by an infant or a young child could result in significant toxicity and could potentially be lethal. Human experience of acute overdosage with lopinavir and ritonavir is limited. Treatment of overdose with lopinavir and ritonavir should consist 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 lopinavir and ritonavir. If indicated, elimination of unabsorbed drug should be achieved by gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug.

Since lopinavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the drug. However, dialysis can remove both alcohol and propylene glycol in the case of overdose with lopinavir and ritonavir oral solution.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Lopinavir and ritonavir is a fixed-dose combination of HIV-1 antiviral drugs lopinavir [see Microbiology (12.4)] and ritonavir. As co-formulated in lopinavir and ritonavir, ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir.

12.2Pharmacodynamics Cardiac Electrophysiology The effect of lopinavir and ritonavir on QTcF interval was evaluated in a placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 39 healthy adults. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline-correction were 5.3 (8.1) and 15.2 (18.0) mseconds (msec) for 400/100 mg twice daily and supratherapeutic 800/200 mg twice daily lopinavir and ritonavir, respectively. Lopinavir and ritonavir 800/200 mg twice daily resulted in a Day 3 mean C max approximately 2-fold higher than the mean C max observed with the approved once daily and twice daily lopinavir and ritonavir doses at steady state.

The maximum mean (95% upper confidence bound) difference from placebo in the PR interval after baseline-correction were 24.9 (21.5, 28.3) and 31.9 (28.5, 35.3) msec for 400/100 mg twice daily and supratherapeutic 800/200 mg twice daily lopinavir and ritonavir, respectively [see Warnings and Precautions ( 5.5, 5.6 )].

12.3Pharmacokinetics The pharmacokinetic properties of lopinavir are summarized in Table 13. The steady-state pharmacokinetic parameters of lopinavir are summarized in Table 14. Under fed conditions, lopinavir concentrations were similar following administration of lopinavir and ritonavir tablets to capsules with less pharmacokinetic variability.

Under fed conditions (500 kcal, 25% from fat), lopinavir concentrations were similar following administration of lopinavir and ritonavir capsules and oral solution. Table 13. Pharmacokinetic Properties of Lopinavir Absorption T max (hr) a 4.4 ±

0.8Effect of meal (relative to fasting) Tablet Oral solution ↑ 19% b ↑ 130% b Distribution % Bound to human plasma proteins > 98 V d /F a (L)

16.9Metabolism Metabolism CYP3A Elimination Major route of elimination hepatic t 1/2 (h) a 6.9 ± 2.2 % of dose excreted in urine 10.4 ± 2.3 % of dose excreted in feces 82.6 ± 2.5 a. lopinavir and ritonavir tablet b. Changes in AUC values Table 14. Steady-State Pharmacokinetic Parameters of Lopinavir, Mean ± SD Pharmacokinetic Parameter Twice Daily a Once Daily b C max (mcg/mL) 9.8 ± 3.7 11.8 ±

3.7C min (mcg/mL) 5.5 ± 2.7 1.7 ±

1.6AUC tau (mcg•h/mL) 92.6 ± 36.7 154.1 ± 61.4 a. 19 HIV-1 subjects, lopinavir and ritonavir 400/100 mg twice daily b. 24 HIV-1 subjects, lopinavir and ritonavir 800/200 mg + emtricitabine 200 mg + tenofovir DF 300 mg Specific Populations Gender, Race and Age No gender or race related pharmacokinetic differences have been observed in adult patients.

Lopinavir pharmacokinetics have not been studied in elderly patients. Pediatric Patients The 230/57.5 mg/m 2 twice daily regimen without nevirapine and the 300/75 mg/m 2 twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/100 mg twice daily regimen without nevirapine. Table 15.

Lopinavir Pharmacokinetic Data from Pediatric Clinical Trials, Mean ± SD C max ( mcg/mL) C min ( mcg/mL) AUC 12 ( mcg•hr/m ) Age ≥ 14 Days to < 6 Weeks Cohort (N = 9): 5.17 ± 1.84 a 1.40 ± 0.48 a 43.39 ± 14.80 a Age ≥ 6 Weeks to < 6 Months Cohort (N = 18): 9.39 ± 4.91 a 1.95 ± 1.80 a 74.50 ± 37.87 a Age ≥ 6 Months to ≤ 12 years Cohort (N = 24): 8.2 ± 2.9 b 3.4 ± 2.1 b 72.6 ± 31.1 b 10.0 ± 3.3 c 3.6 ± 3.5 c 85.8 ± 36.9 c a. lopinavir and ritonavir oral solution 300/75 mg/m 2 twice daily without concomitant NNRTI therapy b. lopinavir and ritonavir oral solution 230/57.5 mg/m 2 twice daily without nevirapine (n=12) c. lopinavir and ritonavir oral solution 300/75 mg/m 2 twice daily with nevirapine (n=12) Pregn… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 41 words ▾

12.1Mechanism of Action Lopinavir and ritonavir is a fixed-dose combination of HIV-1 antiviral drugs lopinavir [see Microbiology (12.4)] and ritonavir. As co-formulated in lopinavir and ritonavir, ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Lopinavir and ritonavir film coated tablets USP are available in the following strengths and package sizes: Lopinavir and Ritonavir Tablets USP, 200 mg/50 mg Yellow film coated, ovaloid tablets debossed with ‘H’ on one side and ‘70’ on other side. Bottles of 60 tablets (NDC 31722-556-60) Bottles of 120 tablets (NDC 31722-556-12) Blister pack of 80 (8x10) Unit dose tablets (Alu-Alu) (NDC 31722-556-31) Blister pack of 80 (8x10) Unit dose tablets (Alu-PVC/PVdC) (NDC 31722-556-32) Recommended Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense in original container or USP equivalent tight container (250 mL or less). For patient use: exposure of this product to high humidity outside the original container or USP equivalent tight container (250 mL or less) for longer than 2 weeks is not recommended. Lopinavir and Ritonavir Tablets USP, 100 mg/25 mg Yellow, capsule shaped, biconvex film coated tablets, debossed with ‘H’ on one side and ‘L7’ on other side Bottles of 60 tablets (NDC 31722-603-60) Bottles of 120 tablets (NDC 31722-603-12) Recommended Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense in original container or USP equivalent tight container (100 mL or less). For patient use: exposure of this product to high humidity outside the original container or USP equivalent tight container (100 mL or less) for longer than 2 weeks is not recommended.

📋 Description ~1 min read ▾

11 DESCRIPTION Lopinavir and Ritonavir Tablets, USP is a co-formulation of lopinavir USP and ritonavir USP. Lopinavir USP is an inhibitor of the HIV-1 protease. As co-formulated in lopinavir and ritonavir, ritonavir USP inhibits the CYP3A-mediated metabolism of lopinavir USP, thereby providing increased plasma levels of lopinavir USP.

Lopinavir USP is chemically designated as [1 S -[1 R *, ( R *),3 R *,4 R *]]- N -[4-[[(2,6-dimethylphenoxy) acetyl]amino]-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl]tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2 H )-pyrimidineacetamide. Its molecular formula is C 37 H 48 N 4 O 5 , and its molecular weight is 628.80. Lopinavir USP is a white to off-white powder.

It is practically insoluble in water, freely soluble in methanol, ethanol and in isopropyl alcohol. Lopinavir USP has the following structural formula: Ritonavir USP is chemically designated as 2,4,7,12-tetraazatridecan-13-oic acid, 10-hydroxy-2-methyl-5-(1-methylethyl)-1-[2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-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 720.94.

Ritonavir USP is a white to off-white powder. It is freely soluble in methanol, methylene chloride, sparingly soluble in acetonitrile and practically insoluble in water. Ritonavir USP has the following structural formula: Lopinavir and ritonavir film coated tablets USP are available for oral administration in two strengths: • Yellow tablets containing 200 mg of lopinavir USP and 50 mg of ritonavir USP • Yellow tablets containing 100 mg of lopinavir USP and 25 mg of ritonavir USP The yellow, 200 mg lopinavir/50 mg ritonavir, tablets contain the following inactive ingredients: colloidal silicon dioxide, copovidone, sodium stearyl fumarate, sorbitan monolaurate and opadry yellow which contains colloidal anhydrous silica, hypromellose, hydroxypropyl cellulose, iron oxide yellow, polyethylene glycol, polysorbate 80, talc and titanium dioxide.

The yellow, 100 mg lopinavir/25 mg ritonavir, tablets contain the following inactive ingredients: colloidal silicon dioxide, copovidone, sodium stearyl fumarate, sorbitan monolaurate and opadry yellow which contains colloidal anhydrous silica, hypromellose, hydroxypropyl cellulose, iron oxide yellow, polyethylene glycol, polysorbate 80, talc and titanium dioxide. lopiandritotabstructure1 lopiandritotabstructure2

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) General Administration Information [see Dosage and Administration ( 2)]: • Advise patients to pay special attention to accurate administration of their dose to minimize the risk of accidental overdose or underdose of lopinavir and ritonavir tablets. • Advise caregivers to inform their healthcare provider if the child’s weight changes in order to make sure that the child’s lopinavir and ritonavir tablets dose is adjusted as needed. • Inform patients and caregivers that lopinavir and ritonavir tablets may be taken with or without food but lopinavir and ritonavir oral solution should be taken with food to enhance absorption. • Advise patients to remain under the care of a healthcare provider while using lopinavir and ritonavir tablets and to take lopinavir and ritonavir tablets in combination with other antiretroviral drugs as prescribed. • Advise patients not to alter the dose or discontinue therapy without consulting with their healthcare provider.

If a dose of lopinavir and ritonavir tablets 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. • Inform patients that it is important to take lopinavir and ritonavir tablets on a regular dosing schedule as directed and to avoid missing doses as that can result in development of resistance. • Inform patients that there may be a greater chance of developing diarrhea with the once daily regimen as compared with the twice daily regimen. • Inform patients that lopinavir and ritonavir tablets are not a cure for HIV-1 infection and that they may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections.

Drug Interactions Inform patients that lopinavir and ritonavir tablets may interact with some drugs; therefore, patients should be advised to report to their healthcare provider the use of any prescription, non-prescription medication or herbal products such as St. John’s Wort [see Contraindications (4), Warnings and Precautions (5.1) and Drug Interactions (7)]. Pancreatitis Advise patients that pancreatitis has been observed in patients receiving lopinavir and ritonavir tablets and to alert their healthcare provider if they experience symptoms such as nausea, vomiting or abdominal pain [see Warnings and Precautions (5.3)].

Skin Rash Inform patients that skin rash ranging in severity from mild to toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, erythema multiforme, urticaria, and angioedema have been reported in patients receiving lopinavir and ritonavir tablets or its components lopinavir and/or ritonavir. Advise patients to contact their healthcare provider if they develop a rash while taking lopinavir and ritonavir tablets [see Adverse Reactions (6.1)]. Hepatotoxicity Pre-existing liver disease including Hepatitis B or C can worsen with use of lopinavir and ritonavir tablets.

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 lopinavir and ritonavir tablets 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 (5.4)]. QT and PR Interval Prolongation Advise patients that lopinavir and ritonavir tablets may produce changes in the electrocardiogram (e.g., PR and/or QT prolongation) and 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 , 5.6)].

Diabetes Mellitus/Hyperglycemia Advise patients that new onset of diabetes or exacerbation of pre-e… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 45 words ▾

8.3Females and Males of Reproductive Potential Contraception Use of lopinavir and ritonavir may reduce the efficacy of combined hormonal contraceptives. Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception [see Drug Interactions (7.3)].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetic properties of lopinavir are summarized in Table 13. The steady-state pharmacokinetic parameters of lopinavir are summarized in Table 14. Under fed conditions, lopinavir concentrations were similar following administration of lopinavir and ritonavir tablets to capsules with less pharmacokinetic variability.

Under fed conditions (500 kcal, 25% from fat), lopinavir concentrations were similar following administration of lopinavir and ritonavir capsules and oral solution. Table 13. Pharmacokinetic Properties of Lopinavir Absorption T max (hr) a 4.4 ±

0.8Effect of meal (relative to fasting) Tablet Oral solution ↑ 19% b ↑ 130% b Distribution % Bound to human plasma proteins > 98 V d /F a (L)

16.9Metabolism Metabolism CYP3A Elimination Major route of elimination hepatic t 1/2 (h) a 6.9 ± 2.2 % of dose excreted in urine 10.4 ± 2.3 % of dose excreted in feces 82.6 ± 2.5 a. lopinavir and ritonavir tablet b. Changes in AUC values Table 14. Steady-State Pharmacokinetic Parameters of Lopinavir, Mean ± SD Pharmacokinetic Parameter Twice Daily a Once Daily b C max (mcg/mL) 9.8 ± 3.7 11.8 ±

3.7C min (mcg/mL) 5.5 ± 2.7 1.7 ±

1.6AUC tau (mcg•h/mL) 92.6 ± 36.7 154.1 ± 61.4 a. 19 HIV-1 subjects, lopinavir and ritonavir 400/100 mg twice daily b. 24 HIV-1 subjects, lopinavir and ritonavir 800/200 mg + emtricitabine 200 mg + tenofovir DF 300 mg Specific Populations Gender, Race and Age No gender or race related pharmacokinetic differences have been observed in adult patients.

Lopinavir pharmacokinetics have not been studied in elderly patients. Pediatric Patients The 230/57.5 mg/m 2 twice daily regimen without nevirapine and the 300/75 mg/m 2 twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/100 mg twice daily regimen without nevirapine. Table 15.

Lopinavir Pharmacokinetic Data from Pediatric Clinical Trials, Mean ± SD C max ( mcg/mL) C min ( mcg/mL) AUC 12 ( mcg•hr/m ) Age ≥ 14 Days to < 6 Weeks Cohort (N = 9): 5.17 ± 1.84 a 1.40 ± 0.48 a 43.39 ± 14.80 a Age ≥ 6 Weeks to < 6 Months Cohort (N = 18): 9.39 ± 4.91 a 1.95 ± 1.80 a 74.50 ± 37.87 a Age ≥ 6 Months to ≤ 12 years Cohort (N = 24): 8.2 ± 2.9 b 3.4 ± 2.1 b 72.6 ± 31.1 b 10.0 ± 3.3 c 3.6 ± 3.5 c 85.8 ± 36.9 c a. lopinavir and ritonavir oral solution 300/75 mg/m 2 twice daily without concomitant NNRTI therapy b. lopinavir and ritonavir oral solution 230/57.5 mg/m 2 twice daily without nevirapine (n=12) c. lopinavir and ritonavir oral solution 300/75 mg/m 2 twice daily with nevirapine (n=12) Pregnancy The C 12h values of lopinavir were lower during the second and third trimester by approximately 40% as compared to post-partum in 12 HIV-infected pregnant women received lopinavir and ritonavir 400 mg/100 mg twice daily.

Yet this decrease is not considered clinically relevant in patients with no documented lopinavir and ritonavir-associated resistance substitutions receiving 400 mg/100 mg twice daily [see Use in Specific Populations (8.1)]. Renal Impairment Lopinavir pharmacokinetics have not been studied in patients with renal impairment; however, since the renal clearance of lopinavir is negligible, a decrease in total body clearance is not expected in patients with renal impairment. Hepatic Impairment Multiple dosing of lopinavir and ritonavir 400/100 mg twice daily to HIV-1 and HCV co-infected patients with mild to moderate hepatic impairment (n = 12) resulted in a 30% increase in lopinavir AUC and 20% increase in C max compared to HIV-1 infected subjects with normal hepatic function (n = 12).

Additionally, the plasma protein binding of lopinavir was statistically significantly lower in both mild and moderate hepatic impairment compared to controls (99.09 vs. 99.31%, respectively). Lopinavir and ritonavir has not been studied in patients with severe hepatic impairment [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6)].

Drug Interactions Lop… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 158 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology The effect of lopinavir and ritonavir on QTcF interval was evaluated in a placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 39 healthy adults. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline-correction were 5.3 (8.1) and 15.2 (18.0) mseconds (msec) for 400/100 mg twice daily and supratherapeutic 800/200 mg twice daily lopinavir and ritonavir, respectively. Lopinavir and ritonavir 800/200 mg twice daily resulted in a Day 3 mean C max approximately 2-fold higher than the mean C max observed with the approved once daily and twice daily lopinavir and ritonavir doses at steady state.

The maximum mean (95% upper confidence bound) difference from placebo in the PR interval after baseline-correction were 24.9 (21.5, 28.3) and 31.9 (28.5, 35.3) msec for 400/100 mg twice daily and supratherapeutic 800/200 mg twice daily lopinavir and ritonavir, respectively [see Warnings and Precautions ( 5.5, 5.6 )].

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Adult Patients without Prior Antiretroviral Therapy Study 863: Lopinavir and Ritonavir Capsules twice daily + stavudine + lamivudine compared to nelfinavir three times daily + stavudine + lamivudine Study 863 was a randomized, double-blind, multicenter trial comparing treatment with lopinavir and ritonavir capsules (400/100 mg twice daily) plus stavudine and lamivudine versus nelfinavir (750 mg three times daily) plus stavudine and lamivudine in 653 antiretroviral treatment naïve patients. Patients had a mean age of 38 years (range: 19 to 84), 57% were Caucasian, and 80% were male.

Mean baseline CD4+ cell count was 259 cells/mm3 (range: 2 to 949 cells/mm 3 ) and mean baseline plasma HIV-1 RNA was 4.9 log 10 copies/mL (range: 2.6 to 6.8 log 10 copies/mL). Treatment response and outcomes of randomized treatment are presented in Table 21. Table 21.

Outcomes of Randomized Treatment Through Week 48 (Study 863) Outcome Lopinavir and Ritonavir +d4T+3TC (N =326) Nelfinavir+d4T+3TC (N = 327) Responder 1 75% 62% Virologic failure 2 Rebound Never suppressed through Week 48 9% 7% 2% 25% 15% 9% Death 2% 1% Discontinued due to adverse events 4% 4% Discontinued for other reasons 3 10% 8% 1 Patients achieved and maintained confirmed HIV-1 RNA < 400 copies/mL through Week 48. 2 Includes confirmed viral rebound and failure to achieve confirmed < 400 copies/mL through Week 48.

3 Includes lost to follow-up, patient's withdrawal, non-compliance, protocol violation and other reasons. Overall discontinuation through Week 48, including patients who discontinued subsequent to virologic failure, was 17% in the lopinavir and ritonavir arm and 24% in the nelfinavir arm. Through 48 weeks of therapy, there was a statistically significantly higher proportion of patients in the lopinavir and ritonavir arm compared to the nelfinavir arm with HIV-1 RNA < 400 copies/mL (75% vs.

62%, respectively) and HIV-1 RNA < 50 copies/mL (67% vs. 52%, respectively). Treatment response by baseline HIV-1 RNA level subgroups is presented in Table 22.

Table 22. Proportion of Responders Through Week 48 by Baseline Viral Load (Study 863) Baseline Viral Load (HIV-1 RNA copies/mL) Lopinavir and Ritonavir +d4T+3TC Nelfinavir +d4T+3TC <400 copies/mL 1 <50 copies/mL 2 n <400 copies/mL 1 <50 copies/mL 2 n < 30,000 74% 71% 82 79% 72% 87 ³ 30,000 to < 100,000 81% 73% 79 67% 54% 79 ³ 100,000 to < 250,000 75% 64% 83 60% 47% 72 ³ 250,000 72% 60% 82 44% 33% 89 1 Patients achieved and maintained confirmed HIV-1 RNA < 400 copies/mL through Week 48. 2 Patients achieved HIV-1 RNA < 50 copies/mL at Week 48.

Through 48 weeks of therapy, the mean increase from baseline in CD4+ cell count was 207 cells/mm 3 for the lopinavir and ritonavir arm and 195 cells/mm 3 for the nelfinavir arm. Study 730: Lopinavir and Ritonavir Tablets once daily + tenofovir DF + emtricitabine compared to Lopinavir and Ritonavir Tablets twice daily + tenofovir DF + emtricitabine Study 730 was a randomized, open-label, multicenter trial comparing treatment with lopinavir and ritonavir 800/200 mg once daily plus tenofovir DF and emtricitabine versus lopinavir and ritonavir 400/100 mg twice daily plus tenofovir DF and emtricitabine in 664 antiretroviral treatment-naïve patients.

Patients were randomized in a 1:1 ratio to receive either lopinavir and ritonavir 800/200 mg once daily (n = 333) or lopinavir and ritonavir 400/100 mg twice daily (n = 331). Further stratification within each group was 1:1 (tablet vs. capsule). Patients administered the capsule were switched to the tablet formulation at Week 8 and maintained on their randomized dosing schedule.

Patients were administered emtricitabine 200 mg once daily and tenofovir DF 300 mg once daily. Mean age of patients enrolled was 39 years (range: 19 to 71); 75% were Caucasian, and 78% were male. Mean baseline CD4+ cell count was 216 cells/mm 3 (range: 20 to 775 cells/mm 3 ) and mean baseline plasma HIV-1 RNA was 5.0 log 10 copies/mL (range: 1.7 to 7.0 l… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Lopinavir/ritonavir combination was evaluated for carcinogenic potential by oral gavage administration to mice and rats for up to 104 weeks. Results showed an increase in the incidence of benign hepatocellular adenomas and an increase in the combined incidence of hepatocellular adenomas plus carcinoma in both males and females in mice and males in rats at doses that produced approximately 1.6 to 2.2 times (mice) and 0.5 times (rats) the human exposure (based on AUC 0 to 24hr measurement) at the recommended dose of 400/100 mg lopinavir and ritonavir twice daily.

Administration of lopinavir/ritonavir did not cause a statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or rats. Carcinogenicity studies in mice and rats have been carried out on ritonavir. In male mice, there was a dose dependent increase in the incidence of both adenomas and combined adenomas and carcinomas in the liver.

Based on AUC measurements, the exposure at the high dose was approximately 4-fold for males that of the exposure in humans with the recommended therapeutic dose (400/100 mg lopinavir and ritonavir twice daily). There were no carcinogenic effects seen in females at the dosages tested. The exposure at the high dose was approximately 9-fold for the females that of the exposure in humans.

There were no carcinogenic effects in rats. In this study, the exposure at the high dose was approximately 0.7-fold that of the exposure in humans with the 400/100 mg lopinavir and ritonavir twice daily regimen. Based on the exposures achieved in the animal studies, the significance of the observed effects is not known.

Mutagenesis Neither lopinavir nor ritonavir was found to be mutagenic or clastogenic in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the mouse lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human lymphocytes. Impairment of Fertility Lopinavir in combination with ritonavir at a 2:1 ratio produced no effects on fertility in male and female rats at levels of 10/5, 30/15 or 100/50 mg/kg/day. Based on AUC measurements, the exposures in rats at the high doses were approximately 0.7-fold for lopinavir and 1.8-fold for ritonavir of the exposures in humans at the recommended therapeutic dose (400/100 mg twice daily).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Lopinavir/ritonavir combination was evaluated for carcinogenic potential by oral gavage administration to mice and rats for up to 104 weeks. Results showed an increase in the incidence of benign hepatocellular adenomas and an increase in the combined incidence of hepatocellular adenomas plus carcinoma in both males and females in mice and males in rats at doses that produced approximately 1.6 to 2.2 times (mice) and 0.5 times (rats) the human exposure (based on AUC 0 to 24hr measurement) at the recommended dose of 400/100 mg lopinavir and ritonavir twice daily.

Administration of lopinavir/ritonavir did not cause a statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or rats. Carcinogenicity studies in mice and rats have been carried out on ritonavir. In male mice, there was a dose dependent increase in the incidence of both adenomas and combined adenomas and carcinomas in the liver.

Based on AUC measurements, the exposure at the high dose was approximately 4-fold for males that of the exposure in humans with the recommended therapeutic dose (400/100 mg lopinavir and ritonavir twice daily). There were no carcinogenic effects seen in females at the dosages tested. The exposure at the high dose was approximately 9-fold for the females that of the exposure in humans.

There were no carcinogenic effects in rats. In this study, the exposure at the high dose was approximately 0.7-fold that of the exposure in humans with the 400/100 mg lopinavir and ritonavir twice daily regimen. Based on the exposures achieved in the animal studies, the significance of the observed effects is not known.

Mutagenesis Neither lopinavir nor ritonavir was found to be mutagenic or clastogenic in a battery of in vitro and in vivo assays including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli , the mouse lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human lymphocytes. Impairment of Fertility Lopinavir in combination with ritonavir at a 2:1 ratio produced no effects on fertility in male and female rats at levels of 10/5, 30/15 or 100/50 mg/kg/day. Based on AUC measurements, the exposures in rats at the high doses were approximately 0.7-fold for lopinavir and 1.8-fold for ritonavir of the exposures in humans at the recommended therapeutic dose (400/100 mg twice daily).

📄 Recent Major Changes 3 words ▾

Contraindications (4) 12/2019

📄 Package Label / Principal Display Panel 24 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Lopinavir and Ritonavir Tablets USP, 200 mg/50 mg -Label Lopinavir and Ritonavir Tablets USP, 100 mg/25 mg- Label lopiandritotablabel200mg-50mg lopiandritotablabel100mg-25mg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Lopinavir and Ritonavir — the ingredient across all brands.

Top reported reactions

Drug Interaction1,337
Depression1,136
Nausea789
Drug Exposure During Pregnancy780
Diarrhoea775
Foetal Exposure During Pregnancy753
Anxiety713

Age at onset

Neonate121
Infant49
Child17
Adolescent2
Adult1,245
Elderly78

Reporter sex

13,474 reports
Male · 63%
Female · 37%
Unknown · 1%

Serious outcomes

Hospitalization5,002
Reports over time (by year) — tap or hover for the count & year
2021 2022 2024 2026 863 55
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Camber Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 60 tablets (31722-0603-60). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Camber Pharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 31722-0601-31 · Camber 31722-0605-31 · Camber →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.