Dosing and uses of Vimovo (esomeprazole-naproxen)
Adult dosage forms and strengths
esomeprazole/naproxen
tablet
- 20mg/375mg
- 20mg/500mg
Rheumatoid Arthritis
1 tablet PO twice daily at least 30 min before meaL
Osteoarthritis
1 tablet PO twice daily at least 30 min before meaL
Ankylosing Spondylitis
1 tablet PO twice daily at least 30 min before meaL
Renal Impairment
CrCl <30 mL/min: Use not recommended
Dose Modification
If a dose of omeprazole needs to be < 40 mg/day consider alternate treatment
Administration
Tablet consists of immediate-release esomeprazole layer and enteric-coated naproxen core; swallow whole, do not chew, crush, dissolve, or split
Pediatric dosage forms and strengths
Safety and efficacy not established
Vimovo (esomeprazole-naproxen) adverse (side) effects
>10%
Gastric erosion (19%); compared with 38% for equal naproxen dose without PPI
Dyspepsia (18%); compared with 27% for equal naproxen dose without PPI
Gastritis (17%)
1-10%
Diarrhea (6%)
Abdominal pain (6%)
Nausea (5%)
Hiatal hernia (4%)
Abdominal distension (4%)
Flatulence (4%)
Esophagitis (4%)
Constipation (3%)
Headache (3%)
Dysgeusia (2%)
Erosive duodenitis (2%)
Hemorrhagic gastritis (1%)
<1%
GERd
Duodenal ulcer
Erosive esophagitis
Postmarketing reports
Gait disturbance
Abdominal distension
Gastroesophageal reflux
Hematochezia
Contusion
FalL
Joint swelling
Muscle spasms
Renal tubular necrosis
Naproxen
- Body as a Whole: Angioneurotic edema, menstrual disorders
- Cardiovascular: Congestive heart failure, vasculitis, pulmonary edema
- Gastrointestinal: Inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, and obstruction of the upper or lower gastrointestinal tract, esophagitis, stomatitis, hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
- Hepatobiliary: Hepatitis (some cases have been fatal)
- Hemic and Lymphatic: Eosinophilia, hemolytic anemia, aplastic anemia
- Metabolic and Nutritional: Hyperglycemia, hypoglycemia
- Nervous System: Depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions
- Respiratory: Eosinophilic pneumonitis
- Dermatologic: Alopecia, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa.
- Special Senses: Hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema
- Urogenital: Glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine
- Reproduction (female): Infertility
Esomeprazole
- Blood and Lymphatic: Agranulocytosis
- Eye: Blurred vision
- Gastrointestinal: Pancreatitis, microscopic colitis
- Hepatobiliary: Hepatic failure, hepatitis with or without jaundice
- Immune System: Anaphylactic reaction/shock
- Infections and Infestations: GI candidiasis, Clostridium difficile associated diarrhea
- Metabolism and Nutritional Disorders: Hypomagnesemia, with or without hypocalcemia and/or hypokalemia
- Musculoskeletal and Connective Tissue: Muscular weakness, myalgia, bone fracture
- Nervous System: Hepatic encephalopathy
- Psychiatric: Aggression, agitation, hallucination
- Renal and Urinary: Interstitial nephritis
- Reproductive System and Breast: Gynecomastia
- Respiratory, Thoracic, and Mediastinal: Bronchospasm
- Skin and Subcutaneous Tissue: Alopecia, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal)
Warnings
Black box warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI and stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Hypersensitivity, including angioedema and anaphylactic reaction/shock has been reported with esomeprazole
Asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
NSAIDs are contraindicated in late stage pregnancy (risk for closure of ductus arteriosus)
NSAIDs are contraindicated for perioperative pain in setting of CABG surgery
Perioperative pain in the setting of coronary artery bypass graft surgery
Cautions
NSAIDs increase risk for thrombotic events (eg, MI, stroke); consistent evidence does not exist that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events
NSAIDs increase risk for hypertension (or worsening hypertension), CHF, and edema
NSAIDs increase risk of GI ulceration, bleeding, and perforation
Caution with history of inflammatory bowel disease or GI bleeding
Long-term NSAID use may cause renal papillary necrosis or other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
Caution with pre-existing asthma
Inhibits platelet aggregation
PPIs may increase risk of osteoporosis-related fractures
Hypomagnesemia may occur with prolonged use (ie, >1 year); adverse effects may result and include tetany, arrhythmias, or seizures; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued
PPIs possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs with diarrhea that does not improve
PPIs decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels
Acute interstitial nephritis reported in patients taking PPIs; may occur at any point during PPI therapy and is generally attributed to idiopathic hypersensitivity reaction; discontinue VIMOVO if acute interstitial nephritis develops
Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo-or achlorhydria; rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy reported
Patients with advanced renal disease should be adequately hydrated
If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, discontinue treatment and monitor patient
Pregnancy and lactation
Pregnancy category: C <30 wk gestation; D ≥30 wk gestation
Lactation: Naproxen is distributed in breast milk, not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Vimovo (esomeprazole-naproxen)
Mechanism of action
Naproxen: NSAID that inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis; has antipyretic and analgesic effects
Esomeprazole: S-isomer of omeprazole, a proton pump inhibitor; inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells
Naproxen
Half-Life: 13-15 hr
Bioavailability: 95%
Duration: 4-7 hr
Onset: 1 hr
Distribution: 0.16 L/kg
Peak Serum Time: 1.5-3 hr; high fat meal prolongs Tmax by 10 hr
Peak Plasma Concentration: 62-96 mcg/mL Vd: 0.16 L/kg
Protein Bound: >99% albumin
Metabolism: hepatic via CYP2C9, CYP1A2; also undergoes hepatic conjugation
Clearance: 0.13 L/min/kg
Excretion: feces < 3%, urine 95%
Esomeprazole
Half-Life: 1.2-1.5 hr
Bioavailability: 90%, food decreases AUC by 33-53%
Duration: 17 hr gastric acid inhibition at steady state
Onset: 1-2 hr
Peak Plasma Time: 1-1.6 hr
Vd: 16 L
Protein Bound: 97%
Clearance: 9-16 L/hr
Excretion: Feces 20%, urine 80%
Metabolism
- Extensively by hepatic P450 enzyme: major metabolic pathway is via CYP2C19, the rest is via CYP3A4
- Slow metabolizers (3% of Caucasians and African-Americans) are deficient in CPY2C19 enzyme system, plasma concentration can be higher than those with the enzyme present
- CYP2C19 inhibitor
