Drug Safety-related Labeling Changes (SrLC)
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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.
YOSPRALA (NDA-205103)
(ASPIRIN; OMEPRAZOLE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/18/2023 (SUPPL-9)
03/04/2022 (SUPPL-8)
04/28/2021 (SUPPL-7)
5 Warnings and Precautions
5.18 Fetal ToxicityAdditions underlined
Premature Closure of Fetal Ductus Arteriosus:
Avoid use of NSAIDs, including YOSPRALA, in pregnant women starting at about
30 weeks of gestation and later. NSAIDs, including YOSPRALA, increase
the risk of premature closure of the fetal ductus arteriosus at approximately
this gestational age.
Oligohydramnios/Neonatal Renal Impairment:
Use of NSAIDs, including YOSPRALA, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit YOSPRALA use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if YOSPRALA treatment is needed for a pregnant woman. Discontinue YOSPRALA if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].
New subsection added
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as YOSPRALA. Some of these events have been fatal or life- threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue YOSPRALA and evaluate the patient immediately.
6 Adverse Reactions
Addition of the following bulleted line listing:
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Coagulation Abnormalities [see Warnings and Precautions (5.1)]
Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2)]
Bleeding Risk with Use of Alcohol [see Warnings and Precautions (5.3)]
Interaction with Clopidogrel [see Warnings and Precautions (5.4)]
Interaction with Ticagrelor [see Warnings and Precautions (5.5)]
Renal Failure [see Warnings and Precautions (5.6)]
Presence of Gastric Malignancy [see Warnings and Precautions (5.7)]
Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.8)]
Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.9)]
Bone Fracture [see Warnings and Precautions (5.10)]
Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.11)]
Hepatic Impairment [see Warnings and Precautions (5.12)]
Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.13)]
Hypomagnesemia [see Warnings and Precautions (5.14)]
Reduced Effect of Omeprazole with St. John’s Wort or Rifampin [see Warnings and Precautions (5.15)]
Interactions with Diagnostic Investigations for Neuroendocrine Tumors [see Warnings and Precautions (5.16)]
Interaction with Methotrexate [see Warnings and Precautions (5.17)]
Fetal Toxicity [see Warnings and Precautions (5.18)]
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.19)]
Abnormal Laboratory Tests [see Warnings and Precautions (5.20)]
Fundic Gland Polyps [see Warning and Precautions (5.21)]
8 Use in Specific Populations
8.1 PregnancyExtensive additions and revisions, please refer to label for complete information.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions underlined
…
Fetal Toxicity
Inform pregnant women to avoid use of YOSPRALA and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closure of the fetal ductus arteriosus. If treatment with YOSPRALA is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios [see Warnings and Precautions (5.19) and Use in Specific Populations (8.1)].
…
DRESS
Advise patients to stop taking YOSPRALA immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.19)].
…
MEDICATION GUIDE
Additions underlined
…
Before taking YOSPRALA, tell your doctor about all of your medical conditions, including if you:
See “What is the most important information I should know about YOSPRALA?”
have any bleeding problems.
drink 3 or more drinks that contain alcohol every day.
have kidney or liver problems.
have been told that you have low magnesium levels in your blood.
are of Asian descent and have been told that your body’s ability to break down (metabolize) omeprazole is poor or if your genotype called CYP2C19 is not known.
are pregnant or plan to become pregnant. Taking NSAID-containing products like YOSPRALA at about 20 weeks of pregnancy or later may harm your unborn baby. If you need to take YOSPRALA when you are between 20 and 30 weeks of pregnancy, your doctor may need to monitor the amount of fluid in your womb around your baby. You should not take YOSPRALA after about 30 weeks of pregnancy.
…