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.

ONGLYZA (NDA-022350)

(SAXAGLIPTIN HYDROCHLORIDE)

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

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10/11/2024 (SUPPL-26)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

ONGLYZA is contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin or any of the ingredients in ONGLYZA. Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported with ONGLYZA [see Warnings and Precautions (5.4) and Adverse Reactions (6.2)].

5 Warnings and Precautions

5.3 Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues

Additions and/or revisions underlined:

When ONGLYZA was used in combination with insulin or an insulin secretagogue, the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with insulin or an insulin secretagogue [see Adverse Reactions (6.1)]. Therefore, a lower dosage of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycemia when used in combination with ONGLYZA [see Drug Interactions (7.2)]. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

7 Drug Interactions

7.2 Insulin or Insulin Secretagogues

Newly added subsection:

Insulin and insulin secretagogues are known to cause hypoglycemia. Concomitant use of ONGLYZA with insulin or an insulin secretagogue may require lower dosages of insulin or the insulin secretagogue to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3)].

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of ONGLYZA as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus have not been established in pediatric patients.

Effectiveness of ONGLYZA was not demonstrated in a 26-week, placebo-controlled, double-blind randomized clinical trial with a 26-week safety extension (NCT03199053) in 164 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues

Inform patients that hypoglycemia can occur, particularly when insulin or an insulin secretagogue is used in combination with ONGLYZA. Educate patients about the risks, symptoms and appropriate management of hypoglycemia [see Warnings and Precautions (5.3)].

…

Missed Dose

If a dose is missed, advise patients to take ONGLYZA as soon as they remember unless it is time for their next dose. Instruct patients not to take two doses of ONGLYZA at the same time.

Administration Instructions

Advise patients not to cut, crush, or chew ONGLYZA tablets.

…

MEDICATION GUIDE

Extensive additions and/or revisions, please refer to label for complete information.

07/01/2019 (SUPPL-23)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(additions underlined)

…

Rhabdomyolysis

02/27/2017 (SUPPL-18)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion, as below:

Risk Summary

Limited data with ONGLYZA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriages. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.

No adverse developmental effects independent of maternal toxicity were observed when saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis and in pregnant and lactating rats during the pre- and postnatal period.

The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an HbA1c greater than 7 and has been reported to be as high as 20 to 25% in women with an HbA1c greater than 10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Data

Animal Data

In embryo-fetal development studies, saxagliptin was administered to pregnant rats and rabbits during the period of organogenesis, corresponding to the first trimester of human pregnancy. No adverse developmental effects were observed in either species at exposures 1503- and 152-times the 5 mg clinical dose in rats and rabbits, respectively, based on AUC. Saxagliptin crosses the placenta into the fetus following dosing in pregnant rats.

In a prenatal and postnatal development study, no adverse developmental effects were observed in maternal rats administered saxagliptin from gestation day 6 through lactation day 21 at exposures up to 470-times the 5 mg clinical dose, based on AUC.

8.2 Lactation

PLLR conversion, as below:

Risk Summary

There is no information regarding the presence of ONGLYZA in human milk, the effects on the breastfed infant, or the effects on milk production.

Saxagliptin is present in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ONGLYZA and any potential adverse effects on the breastfed infant from ONGLYZA or from the underlying maternal condition.

Data

Saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations.

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

MEDICATION GUIDE

What is the most important information I should know about ONGLYZA? Serious side effects can happen to people taking ONGLYZA, including:

2) Heart failure. Heart failure means your heart does not pump blood well enough.

Before you start taking ONGLYZA:

Tell your healthcare provider if you

Contact your healthcare provider right away if you have any of the following symptoms:

swelling or fluid retention, especially in the feet, ankles or legs
unusual tiredness

01/18/2017 (SUPPL-19)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.6 Bullous Pemphigoid

(Newly added subsection)

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving ONGLYZA. If bullous pemphigoid is suspected, ONGLYZA should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.

6 Adverse Reactions

(Additions and/or revisions are underlined)

Severe and disabling arthralgia
Bullous pemphigoid

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

Bullous pemphigoid

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Bullous Pemphigoid

Inform patients that bullous pemphigoid may occur with this class of drugs. Instruct patients to seek medical advice if blisters or erosions occur.

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What are the possible side effects of ONGLYZA? ONGLYZA can cause serious side effects, including:

Skin reaction. Some people who take medicines called DPP-4 inhibitors, like ONGLYZA, may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your healthcare provider right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your healthcare provider may tell you to stop taking ONGLYZA.

04/05/2016 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

Pancreatitis

There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. In a cardiovascular outcomes trial enrolling participants with established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial), cases of definite acute pancreatitis were confirmed in 17 of 8240 (0.2%) patients receiving ONGLYZA compared to 9 of 8173 (0.1%) receiving placebo. Preexisting risk factors for pancreatitis were identified in 88% (15/17) of those patients receiving ONGLYZA and in 100% (9/9) of those patients receiving placebo. After initiation of ONGLYZA, observe patients for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue ONGLYZA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA.

Heart Failure

In a cardiovascular outcomes trial enrolling participants with established ASCVD or multiple risk factors for ASCVD (SAVOR trial), more patients randomized to ONGLYZA (289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to placebo (228/8212, 2.8%). In a time-to-first-event analysis the risk of hospitalization for heart failure was higher in the ONGLYZA group (estimated Hazard Ratio: 1.27; 95% CI: 1.07, 1.51). Subjects with a prior history of heart failure and subjects with renal impairment had a higher risk for hospitalization for heart failure, irrespective of treatment assignment. Consider the risks and benefits of ONGLYZA prior to initiating treatment in patients at a higher risk for heart failure. Observe patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of ONGLYZA.