VIMOVO- naproxen and esomeprazole magnesium tablet, delayed release
Horizon Pharma Inc.
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Thrombotic Events
Non-Steroidal Anti-inflammatory Drugs (NSAIDs), a component of VIMOVO, 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 [see Warnings and Precautions (5.1)].
VIMOVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4), and Warnings and Precautions (5.1)].
Gastrointestinal Bleeding, Ulceration, and Perforation
NSAIDs, a component of VIMOVO 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
1 INDICATIONS AND USAGE
VIMOVO is a combination product that contains naproxen and esomeprazole. It is indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers. VIMOVO is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. Controlled studies do not extend beyond 6 months.
Limitations of Use:
VIMOVO is not interchangeable with the individual components of naproxen and esomeprazole magnesium.
2 DOSAGE AND ADMINISTRATION
Use the lowest dose for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5.1)]. Carefully consider the potential benefits and risks of VIMOVO and other treatment options before deciding to use VIMOVO. VIMOVO does not allow for administration of a lower daily dose of esomeprazole. If a dose of esomeprazole lower than a total daily dose of 40 mg is more appropriate, a different treatment should be considered.
Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
The dosage is one tablet twice daily of VIMOVO 375 mg naproxen and 20 mg of esomeprazole or 500 mg naproxen and 20 mg of esomeprazole.
The tablets are to be swallowed whole with liquid. Do not split, chew, crush or dissolve the tablet. VIMOVO is to be taken at least 30 minutes before meals.
Geriatric Patients
Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Use caution when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly use the lowest effective dose [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].
Patients with Moderate to Severe Renal Impairment
Naproxen-containing products are not recommended for use in patients with moderate to severe or severe renal impairment (creatinine clearance <30 mL/min) [see Warnings and Precautions (5.6) and Use in Specific Populations (8.7)].
Hepatic Insufficiency
Monitor patients with mild to moderate hepatic impairment closely and consider a possible dose reduction based on the naproxen component of VIMOVO.
VIMOVO should be avoided in patients with severe hepatic impairment [see Warnings and Precautions (5.3), Use in Specific Populations (8.6)].
Pediatric Patients
The safety and efficacy of VIMOVO in children younger than 18 years has not been established. VIMOVO is therefore not recommended for use in children.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
VIMOVO consists of an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5.
The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but inhibition of cyclooxygenase (COX-1 and COX-2).
VIMOVO has analgesic, anti-inflammatory, and antipyretic properties contributed by the naproxen component. Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because naproxen is an inhibitor of prostaglandin synthesis, its mode of action may be due to an increase of prostaglandins in peripheral tissues.
Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+ /K+ -ATPase in the gastric parietal cell. Esomeprazole is protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.
