Drug Safety-related Labeling Changes (SrLC)

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VIMOVO (NDA-022511)

(ESOMEPRAZOLE MAGNESIUM; NAPROXEN)

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

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07/18/2023 (SUPPL-29)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Reproductive System and Breast: gynecomastia, erectile dysfunction

…

03/04/2022 (SUPPL-28)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.9 Serious Skin Reactions

NSAIDs, including naproxen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. PPIs can cause severe cutaneous adverse reactions, SJS, TEN, and acute generalized exanthematous pustulosis (AGEP) [see Adverse Reactions (6.2)]. These serious events may occur without warning. …

5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs and PPIs such as those contained in VIMOVO. Some of these events have been fatal or life-threatening. … If such signs or symptoms are present, discontinue VIMOVO and evaluate the patient immediately [see also Warnings and Precautions (5.9)].

Additions and/or revisions underlined:

5.24 Hypomagnesemia and Mineral Metabolism

… Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of VIMOVO and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism).

Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing VIMOVO.

6 Adverse Reactions

Additions and/or revisions to bulleted line listing:

• Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.24)]

• Additions and/or revisions underlined:

6.3 Postmarketing Experience

Esomeprazole Magnesium

Metabolism and Nutritional Disorders: hypomagnesemia, hypocalcemia, hypokalemia [see Warnings and Precautions (5.24)], hyponatremia

Skin and Subcutaneous Tissue: alopecia, erythema multiforme, photosensitivity, SJS, TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus

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

MEDICATION GUIDE

Additions and/or revisions underlined:

Before taking VIMOVO, tell your healthcare provider about all of your medical conditions, including if you:

• have low magnesium levels, low calcium levels and low potassium levels in your blood.

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

See “What is the most important information I should know about VIMOVO?”

Newly added information:

• Severe skin reactions. VIMOVO can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:

• Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).

• You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.

Stop taking VIMOVO and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Hypomagnesemia and Mineral Metabolism

Advise patients to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to their healthcare provider, if they have been receiving VIMOVO for at least 3 months [see Warnings and Precautions (5.24)].

04/28/2021 (SUPPL-26)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

New subsection added

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as VIMOVO. 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 VIMOVO and evaluate the patient immediately.

5.11 Fetal Toxicity

Additions underlined

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs, including VIMOVO, in pregnant women at about 30 weeks gestation and later. NSAIDs, including VIMOVO, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment:

Use of NSAIDs, including VIMOVO, 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 VIMOVO use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if VIMOVO treatment is needed in a pregnant woman. Discontinue VIMOVO if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].

6 Adverse Reactions

Addition of the following to the bulleted line listing:

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.10)]

• Fetal Toxicity [see Warnings and Precautions (5.11)]

8 Use in Specific Populations

8.1 Pregnancy

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

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PATIENT COUNSELING INFORMATION

Additions underlined

…

Serious Skin Reactions, Including DRESS

Advise patients to stop taking VIMOVO immediately if they develop any type of rash or fever and contact their health care provider as soon as possible [see Warnings and Precautions (5.9, 5.10)].

Fetal Toxicity

Inform pregnant women to avoid use of VIMOVO and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closure of the fetal ductus arteriosus. If treatment with VIMOVO 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 (5.11), Use in Specific Populations (8.1)].

…

MEDICATION GUIDE

Additions underlined

…

Before taking VIMOVO, tell your healthcare provider about all of your medical conditions, including if you:

• have liver, kidney, or heart problems.

• have high blood pressure.

• have asthma.

• have low magnesium levels in your blood.

• have ulcerative colitis or Crohn’s disease (inflammatory bowel disease or IBD).

• are pregnant or plan to become pregnant. Taking VIMOVO at about 20 weeks of pregnancy or later may harm your unborn baby. If you need to take VIMOVO for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take VIMOVO after about 30 weeks of pregnancy.

11/27/2020 (SUPPL-25)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined

VIMOVO is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. Hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.7, 5.8, 5.9, 5.17), Adverse Reactions (6.2)].

…

5 Warnings and Precautions

5.17 Acute Tubulointerstitial Nephritis

Additions and/or revisions underlined

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue VIMOVO and evaluate patients with suspected acute TIN [see Contraindications (4)].

6 Adverse Reactions

Additions and/or revisions underlined

…

• Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.17)]

…

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

MEDICATION GUIDE

Additions and/or revisions underlined

…

VIMOVO can cause serious side effects including:

…

• A type of kidney problem (acute tubulointerstitial nephritis). Some people who take proton pump inhibitor (PPI) medicines, including VIMOVO, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with VIMOVO. Call your healthcare provider right away if you have a decrease in the amount that you urinate or if you have blood in your urine.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined

…

Acute Tubulointerstitial Nephritis

Advise patients to report to their health care provider immediately if they experience a decrease in the amount they urinate or have blood in their urine [see Warnings and Precautions (5.17)].

…

07/22/2019 (SUPPL-24)

Approved Drug Label (PDF)

7 Drug Interactions

(information in table has been updated; please refer to labeling for complete information)

06/07/2018 (SUPPL-23)

Approved Drug Label (PDF)

5 Warnings and Precautions

Newly created subsection:

5.27 Fundic Gland Polyps

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use,

especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

6 Adverse Reactions

Addition of the following:

• Fundic Gland Polyps

6.2 Postmarketing Experience

Gastrointestinal:

Addition of: fundic gland polyps

07/06/2017 (SUPPL-19)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

• Proton pump inhibitors (PPIs), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products.

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions are underlined)

…

Clinical Trials Experience with Esomeprazole Magnesium

Additional adverse reactions that were reported as possibly or probably related to esomeprazole magnesium with an incidence of <1% are listed below by body system: …

 

The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to esomeprazole magnesium, were reported in ? 1% of patients: …

7 Drug Interactions

(Additions and/or revisions are underlined)

See Table 3 and Table 4 for clinically significant drug interactions and interactions with diagnostics with naproxen and esomeprazole magnesium.

Table 3: Clinically Significant Drug Interactions with Naproxen and Esomeprazole Magnesium – Affecting Drugs Co-Administered with VIMOVO and Interactions with Diagnostics (Table has been revised; please refer to label)

 

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium -- Affecting Co- Administered Drugs

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions are underlined)

Risk Summary

…

Esomeprazole

…When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.

 

Data

Animal Data

Esomeprazole

…

A follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age.

8.4 Pediatric Use

(Additions and/or revisions are underlined)

The safety and effectiveness of VIMOVO have been established in adolescent patients 12 years of age and older weighing at least 38 kg for the symptomatic relief of JIA and to decrease the risk of developing naproxen-associated gastric ulcers. Use of VIMOVO in this age group is based on extrapolation of adequate and well-controlled studies in adults and supported by a 6 month safety study including pharmacokinetic assessment of naproxen and esomeprazole magnesium in 36 adolescent patients with JIA. Based on the limited data, the plasma naproxen and plasma esomeprazole concentrations were found to be within the range to that observed to those found in healthy adults. The safety profile of VIMOVO in adolescent patients with JIA was similar to adults with RA.

The safety and effectiveness of VIMOVO in pediatric patients less than 12 years of age or less than 38 kg with JIA have not been established.

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Administration

• Patients should be instructed that if a dose is missed, it should be taken as soon as possible. However, if the next scheduled dose is due, the patient should not take the missed dose, and should be instructed to take the next dose on time. Patients should be instructed not to take 2 doses at one time to make up for a missed dose.

Medication Guide

(Additions and/or revisions are underlined)

What is the most important information I should know about VIMOVO?

You should take VIMOVO exactly as prescribed, at the lowest dose possible and for the shortest time needed.

…Talk with your healthcare provider.

VIMOVO contains naproxen, a nonsteroidal anti-inflammatory drug (NSAID) and esomeprazole magnesium, a proton pump inhibitor (PPI) medicine.

VIMOVO can cause serious side effects including:

• Increased risk of a heart attack or stroke that can lead to death…

Do not take VIMOVO right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

Avoid taking VIMOVO after a recent heart attack, unless your healthcare provider tells you to.

• Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines: …

Talk to your healthcare provider or pharmacist before using other medicines that contain NSAIDs, including low-dose aspirin, during treatment with VIMOVO. Some NSAIDs are sold in lower doses without a prescription (over-the-counter).

• Diarrhea caused by an infection (Clostridium difficile) in your intestines. Call your healthcare provider right away if you have watery stools or stomach pain that does not go away. You may or may not have a fever.

• Bone fractures (hip, wrist, or spine). Bone fractures in the hip, wrist, or spine may happen in people who take multiple daily doses of PPI medicines and for a long period of time (a year or longer). Tell your healthcare provider if you have a bone fracture, especially in the hip, wrist, or spine.

Talk to your healthcare provider about your risk of these serious side effects.

VIMOVO can have other serious side effects. See “What are the possible side effects of VIMOVO?”

What is VIMOVO?

VIMOVO is a prescription medicine used in adults and adolescents, 12 years of age and older who weigh at least 84 pounds (38 kg), who need to take naproxen for relief of symptoms of arthritis and who also need to decrease the risk of developing stomach ulcers caused by naproxen.

The naproxen in VIMOVO is used for the relief of signs and symptoms of:

• osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis in adults

• juvenile idiopathic arthritis (JIA) in adolescents

  The esomeprazole magnesium in VIMOVO is used to:

• decrease the risk of developing stomach ulcers in people who are taking naproxen

  It is not known if VIMOVO is safe and effective in children less than 12 years of age or who weigh less than 84 pounds (38 kg). You should not take a naproxen tablet and an esomeprazole magnesium tablet together instead of taking VIMOVO, because they will not work the same way.

  Studies in people who take VIMOVO have not extended past 6 months.

Do not take VIMOVO:

• if you are allergic to naproxen, esomeprazole magnesium, omeprazole, any other PPI medicine, or any of the ingredients in VIMOVO. See the end of this Medication Guide for a complete list of ingredients in VIMOVO.

• if you are taking a medicine that contains rilpivirine (Edurant, Complera, Odefsey) used to treat HIV-1 (Human Immunodeficiency Virus).

Before taking VIMOVO, tell your healthcare provider about all of your medical conditions, including if you:

• have liver, kidney, or heart problems.

• have low magnesium levels in your blood.

• are pregnant or plan to become pregnant. Talk to your healthcare provider if you are considering taking VIMOVO during pregnancy. You should not take VIMOVO after 29 weeks of pregnancy.

• are breastfeeding or plan to breastfeed. The naproxen in VIMOVO can pass into your breast milk. It is not known if VIMOVO will harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take VIMOVO.

• are a female who can become pregnant. VIMOVO may be related to infertility in some women that is reversible when treatment with VIMOVO is stopped.

Especially tell your healthcare provider if you take:

• medicine used to reduce the risk of blood clots, such as warfarin (Coumadin, Jantoven)

• methotrexate (Otrexup, Rasuvo, Trexall, Xatmep)

How should I take VIMOVO?

• Take VIMOVO exactly as prescribed by your healthcare provider.

• Take 1 VIMOVO tablet 2 times each day.

If you take too much VIMOVO, call your healthcare provider or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.

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

• hiding (masking) symptoms of an infection, such as swelling and fever.

• Low vitamin B-12 levels in your body can happen in people who have taken VIMOVO for a long time (more than 3 years). Tell your healthcare provider if you have symptoms of low vitamin B-12 levels, including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, feeling tired, mood changes, and tingling or numbness in the arms or legs.

• Low magnesium levels in your body can happen in people who have taken VIMOVO for at least 3 months. Tell your healthcare provider if you have symptoms of low magnesium levels, including …

If you take too much VIMOVO, call your healthcare provider or get medical help right away…

How should I store VIMOVO?

• Keep the bottle of VIMOVO tightly closed to protect from moisture.

General information about the safe and effective use of VIMOVO.

…Do not give VIMOVO to other people, even if they have the same symptoms that you have. It may harm them…

10/24/2016 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Presence of Gastric Malignancy

In adults, response to gastric symptoms with VIMOVO does not preclude the presence of gastric malignancy. Consider additional gastrointestinal follow-up and diagnostic testing in adult patients who experience gastric symptoms during treatment with VIMOVO or have a symptomatic relapse after completing treatment. In older patients, also consider an endoscopy. (Additions and/or revisions underlined)

5.2 Cutaneous and Systemic Lupus Erythematosus (added subsection)

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE.

The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy inpatients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

SLE is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving VIMOVO, discontinue drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cutaneous and Systemic Lupus Erythematosus

6.2 Postmarketing Experience

Esomeprazole Magnesium

Immune System: anaphylactic reaction/shock, systemic lupus erythematosus

Skin and Subcutaneous Tissue: alopecia, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), cutaneous lupus erythematosus

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

PATIENT COUNSELING INFORMATION

Gastric Malignancy

To return to their healthcare provider if they have a gastric symptoms while taking VIMOVO or after completing treatment.

Cutaneous and Systemic Lupus Erythematosus

Advise patients to immediately call their healthcare provider any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus.

05/09/2016 (SUPPL-18)

Approved Drug Label (PDF)

Boxed Warning

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
• {Product} is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

• NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

5 Warnings and Precautions

Cardiovascular Thrombotic Events

• Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
• To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
• There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as meloxicam, increases the risk of serious gastrointestinal (GI) events.

     Status Post Coronary Artery Bypass Graft (CABG) Surgery

• Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG.

     Post-MI Patients

• Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
• Avoid the use of {Product} in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If {Product} is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Heart Failure and Edema

• The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
• Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of {Product} may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).
• Avoid the use of {Product} in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If {Product} is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

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

MG - Includes new safety information pertaining to the risks of Cardiovascular Thrombotic Events, Heart Failure and Edema.

 

PCI - Cardiovascular Thrombotic Events

• Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately.

PCI - Heart Failure and Edema

• Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.