Drug Safety-related Labeling Changes (SrLC)

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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.

SOLIQUA 100/33 (BLA-208673)

(INSULIN GLARGINE; LIXISENATIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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11/01/2024 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.12 Pulmonary Aspiration During General Anesthesia or Deep Sedation

Newly added subsection

SOLIQUA 100/33 delays gastric emptying [see Clinical Pharmacology (12.1)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking SOLIQUA 100/33, including whether modifying preoperative fasting recommendations or temporarily discontinuing SOLIQUA 100/33 could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SOLIQUA 100/33.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.12)]

6.3 Postmarketing Experience

Newly added information:

Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Newly added information:

Pulmonary Aspiration During General Anesthesia or Deep Sedation

Inform patients that SOLIQUA 100/33 may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SOLIQUA 100/33 [see Warnings and Precautions (5.12)].

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Before using SOLIQUA 100/33, tell your healthcare provider about all your medical conditions including if you:

…

are scheduled to have surgery or other procedures that use general anesthesia or deep sleepiness (deep sedation).

…

What are the possible side effects of SOLIQUA 100/33?

SOLIQUA 100/33 can cause serious side effects including:

...

Food or liquid getting into the lungs during surgery or other procedures that use general anesthesia or deep sleepiness (deep sedation). SOLIQUA 100/33 may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking SOLIQUA 100/33 before you are scheduled to have surgery or other procedures.

09/28/2023 (SUPPL-13)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Gastrointestinal: ileus

Nervous system: dysgeusia

06/10/2022 (SUPPL-12)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.11 Acute Gallbladder Disease

Newly added subsection:
Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a cardiovascular outcomes trial, cholelithiasis occurred in 0.4% of lixisenatide-treated patients versus 0.2% in placebo-treated patients and acute cholecystitis in 0.3% of lixisenatide-treated patients versus 0.2% in placebo- treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow- up are indicated.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Acute Gallbladder Disease [see Warnings and Precautions (5.11)]

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…
Acute Gallbladder Disease
In a cardiovascular outcomes trial, cholelithiasis occurred in 0.4% of lixisenatide-treated patients versus 0.2% in placebo-treated patients and acute cholecystitis in 0.3% of lixisenatide-treated patients versus 0.2% in placebo-treated patients.

…

6.3 Postmarketing Experience

Additions and/or revisions underlined:
The following additional adverse reactions have been identified during post approval use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
…
Hepatobiliary: Cholecystitis, cholelithiasis requiring cholecystectomy

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Gallbladder problems. Gallbladder problems have happened in some people who take SOLIQUA 100/33. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:

pain in your upper stomach (abdomen)
yellowing of skin or eyes (jaundice)
fever
clay-colored stools

...

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…
Acute Gallbladder Disease
Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up [see Warnings and Precautions (5.11)].

…

07/28/2021 (SUPPL-11)

Approved Drug Label (PDF)

4 Contraindications

Additions underlined

…

In patients with serious hypersensitivity to insulin glargine, lixisenatide, or any of the excipients in SOLIQUA 100/33. Hypersensitivity reactions including anaphylaxis have occurred with both lixisenatide and insulin glargine [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

5 Warnings and Precautions

5.1 Anaphylaxis and Serious Hypersensitivity Reactions

Additions underlined

… There have been postmarketing reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33 [see Adverse Reactions (6.1)].

Inform and closely monitor patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist for allergic reactions, because it is unknown whether such patients will be predisposed to anaphylaxis with SOLIQUA 100/33. SOLIQUA 100/33 is contraindicated in patients with known serious hypersensitivity to lixisenatide or insulin glargine [see Contraindications (4)].

If a hypersensitivity reaction occurs, the patient should discontinue SOLIQUA 100/33 and promptly seek medical attention.

6 Adverse Reactions

6.3 Postmarketing Experience

Additions underlined

…

Renal: Acute kidney injury

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions underlined

…

How should I use SOLIQUA 100/33?

…

Change (rotate) your injection site within the area you choose with each dose to reduce your risk of getting pits in skin or thickened skin (lipodystrophy) and skin with lumps (localized cutaneous amyloidosis) at the injection sites.
…
What are the possible side effects of SOLIQUA 100/33?
SOLIQUA 100/33 can cause serious side effects including:
…

Severe allergic reactions. Severe allergic reactions can happen with SOLIQUA 100/33. Stop taking SOLIQUA 100/33 and get medical help right away if you have any symptoms of a severe allergic reaction. See “Who should not use SOLIQUA 100/33?”
…
What are the ingredients in SOLIQUA 100/33?
…
Inactive ingredients: glycerol (20 mg), metacresol (2.7 mg), methionine (3 mg), zinc (30 mcg) and Water for Injection, USP. Hydrochloric acid and sodium hydroxide are added as needed to adjust the pH.

…

11/15/2019 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

(Additions and/or revisions are underlined)

Changes in insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia.

Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant oral antidiabetic treatment may be needed. When converting from basal insulin therapy or a GLP-1 receptor agonist to SOLIQUA 100/33 follow dosing recommendations.

6 Adverse Reactions

6.3 Postmarketing Experience

(Newly added subsection)

The following additional adverse reactions have been identified during postapproval use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Localized cutaneous amyloidosis at the injection site has occurred with insulins. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

(Extensive changes; please refer to labeling)

PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Hypersensitivity Reactions

Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in clinical trials of SOLIQUA 100/33 and during postmarketing use of other GLP-1 receptor agonists. If symptoms of hypersensitivity reactions occur, instruct patients to stop taking SOLIQUA 100/33 and seek medical advice promptly.

Risk of Pancreatitis

Inform patients that persistent severe abdominal pain that may radiate to the back and which may or may not be accompanied by vomiting is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue SOLIQUA 100/33 and contact their physician if persistent severe abdominal pain occurs.

Never Share a SOLIQUA 100/33 Pen

Advise patients that they must never share a SOLIQUA 100/33 prefilled pen with another person, even if the needle is changed because doing so carries a risk for transmission of blood- borne pathogens.

Hyperglycemia or Hypoglycemia

Inform patients that hypoglycemia is the most common adverse reaction with insulin-containing products. Inform patients of the symptoms of hypoglycemia. Inform patients that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.

Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision.

Dehydration and Renal Failure

Advise patients treated with SOLIQUA 100/33 of the potential risk of dehydration due to gastrointestinal adverse reactions and to take precautions to avoid fluid depletion. Inform patients of the potential risk for worsening renal function, which in some cases may require dialysis.

Overdose due to Medication Errors

Inform patients that SOLIQUA 100/33 contains two drugs: insulin glargine and lixisenatide. Accidental mix-ups between insulin products have been reported. To avoid medication errors between SOLIQUA 100/33 and other insulin products, instruct patients to always check the label before each injection. Advise patients that the administration of more than 60 units of SOLIQUA 100/33 daily can result in overdose of the lixisenatide component. Instruct patients not to administer concurrently with other glucagon-like peptide-1 receptor agonists.

Use in Pregnancy

Advise patients to inform their physicians if they are pregnant or intend to become pregnant.

02/27/2019 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen

Additions and/or revisions underlined:

… When converting from basal insulin therapy or a GLP-1 receptor agonist to SOLIQUA 100/33 follow dosing recommendations.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

… The studies, Study A and B, had the following characteristics: mean age …

Gastrointestinal Adverse Reactions

Gastrointestinal adverse reactions are the most commonly observed adverse reaction in patients using lixisenatide. Gastrointestinal adverse reactions occur more frequently …

In Study A, vomiting was 6.4% in the lixisenatide-treated patients vs 3.2% in the SOLIQUA 100/33–treated patients and 1.5% in the insulin glargine-treated patients; nausea was 24% in the lixisenatide-treated patients vs 9.6% in the SOLIQUA 100/33–treated patients and 3.6% in the insulin glargine-treated patients.

7 Drug Interactions

7.2 Effects of Delayed Gastric Emptying on Oral Medications

Additions and/or revisions underlined:

Lixisenatide containing products, including SOLIQUA 100/33, delays …

08/29/2017 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Hypoglycemia

Addition of the following:

No clinically important differences in risk of severe hypoglycemia between SOLIQUA 100/33 and comparators were observed in clinical trials.