VIMOVO (naproxen/esomeprazole magnesium)

There are 8 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Cerebrovascular accident
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
History of roux-en-Y gastric bypass
Post-operative from CABG surgery
Pregnancy
Renal transplant

There are 23 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Anemia
Chronic heart failure
Clostridioides difficile infection
Disease of liver
Edema
Esophageal dysmotility
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of kidney donation
Hypertension
Increased risk of bleeding
Interstitial nephritis
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Severe hepatic disease
Subacute cutaneous lupus erythematosus
Systemic lupus erythematosus
Systemic mastocytosis
Thrombotic disorder
Tobacco smoker

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
CYp2c19 poor metabolizer
Fracture
Hypomagnesemia
Increased risk of bleeding due to coagulation disorder
Osteoporosis
Vitamin b12 deficiency

There are 121 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Body fluid retention Skin rash Tinnitus Urticaria	Blurred vision Bruising Ecchymosis Hemorrhage Polydipsia Purpura Sinusitis Visual changes

Rare/Very Rare

Abnormal hepatic function tests Acute cognitive impairment Acute eruptions of skin Acute generalized exanthematous pustulosis Acute myocardial infarction Acute pancreatitis Aggressive behavior Agitation Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angioedema Aplastic anemia Arthralgia Atrial fibrillation Bacterial sepsis Benign fundic gland polyposis of stomach Biliary calculus Bloody vomit Blurred vision Bronchospastic pulmonary disease Bullous dermatitis Cardiac arrhythmia Cerebrovascular accident Chest tightness Chronic heart failure Clostridioides difficile infection Colitis Coma Corneal opacity Cystitis Depression DRESS syndrome Dyspnea Eosinophilia Eosinophilic pneumonia Erythema multiforme Exfoliative dermatitis Fever Fracture Gastric ulcer Gastritis Gastroenteritis Gastrointestinal candidiasis Gastrointestinal hemorrhage Gastrointestinal obstruction Gastrointestinal perforation Gastrointestinal ulcer Glomerulonephritis Goiter Hallucinations Heart failure Hematuria Hemolytic anemia Hepatic failure Hepatitis Herpes simplex infection Hyperglycemia Hyperkalemia Hypertension Hypocalcemia Hypoglycemic disorder Hypokalemia Hyponatremia Hypotension Increased alanine transaminase Increased aspartate transaminase Interstitial nephritis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Leukopenia Loffler syndrome Lupus-like syndrome Lymphadenopathy Muscle weakness Myalgia Nephrotic syndrome Non-infective meningitis Optic neuritis Pancreatitis Pancytopenia Peptic ulcer Pneumonia Polyuria Proteinuria Pruritus of skin Pulmonary edema Rectal bleeding Renal failure Renal papillary necrosis Renal tubular necrosis Respiratory depression Seizure disorder Skin inflammation Skin photosensitivity Stevens-johnson syndrome Stomatitis Subacute cutaneous lupus erythematosus Syncope Systemic lupus erythematosus Tachycardia Thrombocytopenic disorder Thrombotic disorder Toxic epidermal necrolysis Urticaria Vasculitis Wheezing

There are 91 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Constipation Diarrhea Dizziness Drowsy Edema Flatulence Headache disorder Heartburn Injection site sequelae Nausea Pruritus of skin Vertigo	Diarrhea Dyspepsia Dyspnea Hearing loss Hyperhidrosis Insomnia Palpitations Pharyngitis Symptoms of anxiety Upper abdominal pain Urinary tract infection Vertigo Vomiting Xerostomia

Rare/Very Rare

Abdominal distension Alopecia Anorexia Appetite changes Back pain Black tarry stools Blistering skin Bradycardia Chest pain Chills Colitis Concentration difficulty Conjunctivitis Dehydration Drowsy Dysgeusia Dysphagia Dysuria Edema Erectile dysfunction Eructation Erythema Erythema nodosum Esophagitis Facial edema Fatigue Fever Flu-like symptoms Flushing Gastritis General weakness Glossitis Gynecomastia Hallucinations Hyperhidrosis Hypomagnesemia Increased appetite Increased defecation frequency Increased urinary frequency Insomnia Lichen planus Malaise Menstrual disorder Muscle weakness Nervousness Oliguria Pain Palpitations Papilledema Paresthesia Peripheral edema Skin photosensitivity Skin rash Stomatitis Symptoms of anxiety Tachycardia Tenesmus Tremor Upper respiratory infection Vitamin b12 deficiency Vomiting Weight gain Weight loss Xerostomia

Category B. (See Users Guide.) Use of NSAIAs during pregnancy at about 30 weeks of gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks of gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks of gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks of gestation, the lowest effective dosage and shortest possible duration of treatment should be used.

Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice. Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks of gestation. Known effects of NSAIAs on the human fetus during the third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible (generally within 3-6 days) following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.

A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Deaths associated with neonatal renal failure have been reported.

Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as naproxen, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development.

In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses. Reproduction studies of naproxen in rats at 20 mg/kg daily (125 mg/m2, 0.23 times the human systemic exposure), rabbits at 20 mg/kg daily (220 mg/m2, 0.27 times the human systemic exposure), and mice at 170 mg/kg daily (510 mg/m2, 0.28 times the human systemic exposure) have not revealed evidence of harm to the fetus. Severe hypoxemia due to persistent pulmonary hypertension has occurred in infants whose mothers received naproxen to delay parturition.

Neonatal death also has been reported when the drug was used to prevent preterm labor; autopsy of a neonate showed brain hemorrhage, multiple gastric ulcers, extensive GI bleeding, and an adverse cardiovascular effect known to be associated with use of NSAIAs. In addition, severe hyponatremia, water retention, cerebral irritation, and paralytic ileus was reported in a neonate whose mother ingested 5 g of naproxen 8 hours before delivery; it has been suggested that naproxen adversely affected renal function. Renal dysfunction and abnormal prostaglandin E concentrations in premature infants also have been reported.

Effects of naproxen during labor or delivery have not been studied. In animal studies, NSAIAs, including naproxen, inhibited prostaglandin synthesis, delayed parturition, and increased the incidence of stillbirth.

It is unknown whether esomeprazole is distributed into milk. However, omeprazole is distributed into human milk; discontinue nursing or drug because of potential risk in nursing infants. Naproxen is distributed into milk at concentrations of approximately 1% of peak plasma concentrations of the drug. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for naproxen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.