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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
KALETRA (NDA-021251)
(LOPINAVIR; RITONAVIR)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/23/2026 (SUPPL-60)
4 Contraindications
Additions and/or revisions underlined:
Non-opioid Analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine
7 Drug Interactions
Extensive changes to table 12; please refer to label for complete information
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
Who should not take KALETRA?
Do not take KALETRA if you or your child:
are allergic to lopinavir, ritonavir, or any of the ingredients in KALETRA. See the end of this Medication Guide for a complete list of ingredients in KALETRA.
take any of the following medicines:
alfuzosin
- suzetrigine
…
Before taking KALETRA, tell your healthcare provider about all of your medical conditions, including if you or your child:
…
Talk to your healthcare provider about the following risks to your baby from breastfeeding during treatment with KALETRA:
The HIV-1 virus may pass to your baby if your baby does not have HIV-1.
The HIV-1 virus may become harder to treat if your baby has HIV-1.
Your baby may get side effects from KALETRA.
10/21/2020 (SUPPL-59)
6 Adverse Reactions
6.2 Postmarketing Experience(Additions underlined)
…
Renal and Urinary Disorders
Nephrolithiasis
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(Additions underlined)
…
What are the possible side effects of KALETRA?
KALETRA can cause serious side effects, including:
…
Kidney stones
…
12/19/2019 (SUPPL-58)
4 Contraindications
(Additions underlined)
• KALETRA is 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)].
- Anticancer Agents: apalutamide
7 Drug Interactions
Potential for KALETRA to Affect Other Drugs(Newly added information)
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.
(Table 12 updated to add several drug interactions; see label for complete information)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide(addition underlined)
Do not take KALETRA if you:
• if you take any of the following medicines:
- apalutamide
08/21/2019 (SUPPL-57)
4 Contraindications
Section has been revised from a chart format to a bulleted line listing.
Addition of the lipid modifying agent lomitapide
7 Drug Interactions
7.3 Established and Other Potentially Significant Drug InteractionsAddition of the following drug-drug interaction information to Table 12 Established and Other Potentially Significant Drug Interactions:
anticancer agents: neratinib and abemaciclib
lipid modifying agent: Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide
hepatitis C direct acting antivirals: glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEWho should not take KALETRA? Do not take KALETRA if you:
if you take any of the following medicines:
Addition of ‘lomitapide’
11/15/2018 (SUPPL-56)
7 Drug Interactions
7.3 Established and Other Potentially Significant Drug Interactions(added ibrutinib to the list of Anticancer Agents under Table 13, please refer to label to vie Table 13)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(reformatted and revised to be consistent with changes to the USPI, please refer to label)
10/13/2017 (SUPPL-55)
8 Use in Specific Populations
8.1 Pregnancy(extensive additions; please refer to label)
(additions underlined)
Risk Summary
The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Because of the potential for: 1) HIV transmission (in HIV-negative infants), 2) developing viral resistance (in HIV- positive infants), and 3) adverse reactions in the breastfed infant, instruct mothers not to breastfeed if they are receiving KALETRA.
(new subsection added)
Contraception
Use of KALETRA 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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(additions underlined)
Advise the patient to read the FDA-approved patient labeling (Medication Guide)
General Administration Information :
- Advise patients to pay special attention to accurate administration of their dose to minimize the risk of accidental overdose or underdose of KALETRA.
- Advise patients and caregivers that the oral solution should be administered using the calibrated dosing cup (supplied) or oral dosing syringe.
- Advise caregivers to inform their healthcare provider if the child’s weight changes in order to make sure that the child’s KALETRA dose is adjusted as needed.
- Inform patients and caregivers that KALETRA tablets may be taken with or without food but KALETRA oral solution should be taken with food to enhance absorption.
- Advise patients to remain under the care of a healthcare provider while using KALETRA and to take KALETRA 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 KALETRA 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 KALETRA 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 Kaletra is not a cure for HIV-1 infection and that they may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections.
…
Pancreatitis
Advise patients that pancreatitis has been observed in patients receiving KALETRA and to alert their healthcare provider if they experience symptoms such as nausea, vomiting or abdominal pain.
…
QT and PR Interval Prolongation
Advise patients that KALETRA 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.
…
Immune Reconstitution Syndrome
Advise patients that immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy, including KALETRA.
Lipid Disorders
Advise patients that treatment with KALETRA therapy can result in substantial increases in the concentration of total cholesterol and triglycerides.
…
Patients with Hemophilia
Advise patients with hemophilia that they may experience increased bleeding when treated with protease inhibitors such as KALETRA.
Pregnancy Exposure Registry
Inform patients that there is an antiretroviral pregnancy registry that monitors fetal outcomes of pregnant women exposed to KALETRA.
Lactation
Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk.
…
06/15/2017 (SUPPL-54)
4 Contraindications
Table 8. Drugs That are Contraindicated with KALETRA (The antianginal drug, ranolazine, has been added to the table; please refer to label)
5 Warnings and Precautions
5.2 Toxicity in Preterm Neonates(Additions and/or revisions are underlined)
KALETRA oral solution contains the excipients ethanol, approximately 42% (v/v) and propylene glycol, approximately 15% (w/v)…
… Total amounts of ethanol and propylene glycol from all medicines that are to be given to infants should be taken into account in order to avoid toxicity from these excipients.
7 Drug Interactions
7.3 Established and Other Potentially Significant Drug InteractionsTable 13. Established and Other Potentially Significant Drug Interactions (Information about the anticancer drug, venetoclax, and corticosteroids has been added/revised; please refer to label)
8 Use in Specific Populations
8.1 Pregnancy(Additions and/or revisions are underlined)
Clinical Considerations
…
Avoid use of KALETRA oral solution during pregnancy due to the ethanol content. KALETRA oral solution contains the excipients ethanol, approximately 42% (v/v and propylene glycol, approximately 15%.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(Additions and/or revisions are underlined)
Who should not take KALETRA?
Do not take KALETRA if you take any of the following medicines:
- ranolazine (Ranexa)
What should I tell my doctor before taking KALETRA?
Especially tell your doctor if you take:
- triamcinolone (Kenalog)
- venetoclax (Venclexta)
How should I take KALETRA?
- KALETRA oral solution contains propylene glycol and a large amount of ethanol.
- Contact your doctor if you are planning to take Kaletra Oral Solution through a feeding tube because some feeding tubes are not recommended for use with ethanol-containing products like KALETRA.
What are the possible side effects of KALETRA?
KALETRA can cause serious side effects, including:
- Babies taking KALETRA oral solution may have side effects. KALETRA oral solution contains ethanol and propylene glycol. Call your doctor right away if your baby appears too sleepy or their breathing has changed.
What are the ingredients in KALETRA?
Inactive ingredients:
KALETRA 100 mg lopinavir and 25 mg ritonavir tablets: copovidone, sorbitan monolaurate, colloidal silicon dioxide, and sodium stearyl fumarate. The film coating contains: polyvinylethanol, titanium dioxide, talc, polyethylene glycol 3350, and yellow ferric oxide E172.
KALETRA oral solution: acesulfame potassium, ethanol, artificial cotton candy flavor,…
KALETRA oral solution contains approximately 42% (v/v) ethanol and approximately 15% (w/v) propylene glycol.
11/22/2016 (SUPPL-52)
4 Contraindications
Section updated with the anti-arrhythmic drug, dronedarone, anti-gout drug, colchicine, and hepatitis C direct acting antiviral, elbasvir/grazoprevir. (please refer to label)
5 Warnings and Precautions
5.7 Diabetes Mellitus/Hyperglycemia (addition underlined)New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during post-marketing surveillance in HIV-1 infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.
Consider monitoring for hyperglycemia, new onset diabetes mellitus or an exacerbation of diabetes mellitus in patients treated with KALETRA.
7 Drug Interactions
7.3 Established and Other Potentially Significant Drug Interactions
Table 13. Established and Other Potentially Significant Drug Interactions (table updated; please refer to label).
7.4 Drugs with No Observed or Predicted Interactions with KALETRA (addition underlined)
Drug interaction or clinical studies reveal no clinically significant interaction between KALETRA and desipramine (CYP2D6 probe), etravirine, pitavastatin, pravastatin, stavudine, lamivudine, omeprazole, raltegravir, ranitidine, or rilpivirine.
Based on known metabolic profiles, clinically significant drug interactions are not expected between KALETRA and dapsone, trimethoprim/sulfamethoxazole, azithromycin, erythromycin, or fluconazole.
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 KALETRA. Thus, co-administration of KALETRA 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 13.
Additionally, KALETRA induces glucuronidation.
Published data suggest that lopinavir is an inhibitor of OATP1B1.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE (addition underlined)Who should not take KALETRA?
Do not take KALETRA if you take any of the following medicines:
• alfuzosin (Uroxatral®)
• cisapride (Propulsid®, Quicksolv®)
• colchicine (Colcrys®), if you have kidney and/or liver problems
• dronedarone (Multaq®)
• elbasvir/grazoprevir (Zepatier®)
• ergot containing medicines including
? ergotamine tartrate (Cafergot®, Migergot®, Ergomar®, Ergostat®, Medihaler®, Ergotamine, Wigraine®, Wigrettes®)
? dihydroergotamine mesylate (D.H.E. 45®, Migranal®)
? methylergonovine (Methergine®)
• lovastatin (Advicor®, Altoprev®, Mevacor®)
• midazolam oral syrup
• lurasidone (Latuda®), pimozide (Orap®)
• rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®)
• sildenafil (Revatio®), when used for the treatment of pulmonary arterial hypertension
• simvastatin (Zocor®, Vytorin®, Simcor®)
• St. John’s Wort (Hypericum perforatum)
• triazolam (Halcion®)
Serious problems can happen if you or your child take any of the medicines listed above with KALETRA.
• Do not take KALETRA if you are allergic to lopinavir, ritonavir or any of the ingredients in KALETRA. See the end of this Medication Guide for a complete list of ingredients in KALETRA.
Tell your doctor about all the medicines you take
• isavuconazonium (Cresemba®)
• ombitasvir/parataprevir/ritonavir and dasabuvir (Viekira Pak®)
09/15/2016 (SUPPL-53)
4 Contraindications
Table 8. Drugs That are Contraindicated with KALETRA (updated)
Drug Class
Antipsychotics- (added)
Lurasidone- Clinical Comments: Potential for serious and/or life- threatening reactions.
Pimozide - Clinical Comments: Potential for cardiac arrhythmias.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Who should not take KALETRA?
Do not take KALETRA if you take any of the following medicines:
• lurasidone (Latuda®) (added)