Vimovo Information
Vimovo () Cardiovascular Risk
• Non-Steroidal Anti-inflammatory Drugs (NSAIDs), a component of Vimovo () , may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk [see ].
• Vimovo () is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see and ].
• NSAIDs, including naproxen, a component of Vimovo () , cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events [].
Vimovo () 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.
Vimovo () Dosage And Administration
Carefully consider the potential benefits and risks of Vimovo () and other treatment options before deciding to use Vimovo () . Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. 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.
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 and ].
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
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 and
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.
Vimovo () Dosage Forms And Strengths
Oval, yellow, delayed release tablets for oral administration containing either:
• 375 mg enteric coated naproxen and 20 mg esomeprazole (as magnesium trihydrate) tablets printed with 375/20 in black, or
• 500 mg enteric coated naproxen and 20 mg esomeprazole (as magnesium trihydrate) tablets printed with 500/20 in black.
Vimovo () Contraindications
Vimovo () is contraindicated in patients with known hypersensitivity to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any of the excipients.
Vimovo () is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients [see ]. Hypersensitivity reactions, eg, angioedema and anaphylactic reaction/shock, have been reported with esomeprazole use.
Vimovo () is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see ].
Vimovo () is contraindicated in patients in the late stages of pregnancy [see and ].
Vimovo () Warnings And Precautions
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, myocardial infarction, and stroke, which can be fatal. All NSAIDS, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or 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.
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 [see ].
NSAIDs, including naproxen, a component of Vimovo () , can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. While Vimovo () has been shown to significantly decrease the occurrence of gastric ulcers compared to naproxen alone, ulceration and associated complications can still occur.
These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3–6 months, and in about 2–4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed.
Vimovo () should be prescribed with caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk of developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants or antiplatelets (including low-dose aspirin), longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients, and therefore special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID or NSAID-containing product, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Epidemiological studies of the case-control and cohort design have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of an NSAID, COX-2 inhibitor, or aspirin potentiated the risk of bleeding [see ]. Although these studies focused on upper gastrointestinal bleeding, bleeding at other sites cannot be ruled out.
NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.
Gastrointestinal symptomatic response to therapy with Vimovo () does not preclude the presence of gastric malignancy.
Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole, of which esomeprazole is an enantiomer and a component of Vimovo () .
Pregnancy Category C
In late pregnancy, as with other NSAIDs, naproxen, a component of Vimovo () , should be avoided because it may cause premature closure of the ductus arteriosus [see (4), and ].
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including naproxen, a component of Vimovo () . Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with Vimovo () .
If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), Vimovo () should be discontinued.
Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. It is prudent to use the lowest effective dose for the shortest possible duration of adequate treatment.
Vimovo () should be avoided in patients with severe hepatic impairment [see and ].
Anemia is sometimes seen in patients receiving NSAIDs. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Vimovo () who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants or antiplatelets, should be carefully monitored.
Vimovo () contains naproxen as one of its active ingredients. It should not be used with other naproxen-containing products since they all circulate in the plasma as the naproxen anion.
The concomitant use of Vimovo () with any dose of a non-aspirin NSAID should be avoided due to the potential for increased risk of adverse reactions.
Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines. [see and ].
Vimovo () (a combination PPI/NSAID) is approved for use twice a day and does not allow for administration of a lower daily dose of the PPI. [see ].
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Vimovo () should be discontinued.
Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically.
Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Providers should temporarily stop esomeprazole treatment before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see ].
Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. 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 ].
Drugs that induce CYP2C19 or CYP3A4 (such as St John’s Wort or rifampin) can substantially decrease esomeprazole concentrations. Avoid concomitant use of Vimovo () with St John’s Wort or rifampin [see Drug Interactions (7.15)].
Vimovo () Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The adverse reactions reported below are specific to the clinical trials with Vimovo () . See also the full prescribing information for naproxen and esomeprazole magnesium products.
The safety of Vimovo () was evaluated in clinical studies involving 2317 patients (aged 27 to 90 years) and ranging from 3-12 months. Patients received either 500 mg/20 mg of Vimovo () twice daily (n=1157), 500 mg of enteric-coated naproxen twice daily (n=426), or placebo (n=246). The average number of Vimovo () doses taken over 12 months was 69644.
The table below lists all adverse reactions, regardless of causality, occurring in >2% of patients receiving Vimovo () from two clinical studies (Study 1 and Study 2). Both of these studies were randomized, multi-center, double-blind, parallel studies. The majority of patients were female (67%), white (86%). The majority of patients were 50-69 years of age (83%). Approximately one quarter were on low-dose aspirin.
In Study 1 and Study 2, patients taking Vimovo () had fewer premature discontinuations due to adverse reactions compared to patients taking enteric-coated naproxen alone (7.9% vs. 12.5% respectively). The most common reasons for discontinuations due to adverse events in the Vimovo () treatment group were upper abdominal pain (1.2%, n=5), duodenal ulcer (0.7%, n=3) and erosive gastritis (0.7%, n=3). Among patients receiving enteric-coated naproxen, the most common reasons for discontinuations due to adverse events were duodenal ulcer 5.4% (n=23), dyspepsia 2.8% (n=12) and upper abdominal pain 1.2% (n=5). The proportion of patients discontinuing treatment due to any upper gastrointestinal adverse events (including duodenal ulcers) in patients treated with Vimovo () was 4% compared to 12% for patients taking enteric-coated naproxen.
The table below lists all adverse reactions, regardless of causality, occurring in >2% of patients from 2 clinical studies conducted in patients with osteoarthritis of the knee (Study 3 and Study 4).
The percentage of subjects who withdrew from the Vimovo () treatment group in these studies due to treatment-emergent adverse events was 7%. There were no preferred terms in which more than 1% of subjects withdrew from any treatment group.
The long-term safety of Vimovo () was evaluated in an open-label clinical trial of 239 patients, of which 135 patients received 500 mg/20 mg of Vimovo () for 12 months. There were no differences in frequency or types of adverse reactions seen in the long-term safety study compared to shorter-term treatment in the randomized controlled studies.
Naproxen
The following adverse reactions have been identified during post-approval use of naproxen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed below by body system:
Body as a Whole:
Cardiovascular:
Gastrointestinal:
Hepatobiliary:
Hemic and Lymphatic:
Metabolic and Nutritional:
Nervous System:
Respiratory:
Dermatologic:
Special Senses:
Urogenital:
Reproduction (female):
Esomeprazole
The following adverse reactions have been identified during post-approval use of esomeprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed below by body system:
Blood and Lymphatic:
Eye:
Gastrointestinal:
Hepatobiliary:
Immune System:
Infections and Infestations:
Metabolism and Nutritional Disorders:
Musculoskeletal and Connective Tissue:
Nervous System:
Psychiatric:
Renal and Urinary:
Reproductive System and Breast:
Respiratory, Thoracic, and Mediastinal:
Skin and Subcutaneous Tissue:
Vimovo () Drug Interactions
Several studies conducted with Vimovo () have shown no interaction between the two components, naproxen and esomeprazole.
Vimovo () can be administered with low-dose aspirin (≤325 mg/day) therapy. The concurrent use of aspirin and Vimovo () may increase the risk of serious adverse events [see and ].
When naproxen is administered with doses of aspirin (>1 gram/day), its protein binding is reduced. The clinical significance of this interaction is not known. However, as with other NSAIDs, concomitant administration of naproxen and aspirin is not generally recommended because of the potential of increased adverse effects.
Naproxen decreases platelet aggregation and may prolong bleeding time. In addition, because warfarin and NSAIDs are highly protein bound, the free fraction of warfarin and naproxen may increase substantially in some patients.
Concomitant use of Vimovo () and anticoagulants (such as warfarin, dicumarol and heparin) may result in increased risk of bleeding complications.
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Post-marketing reports of changes in prothrombin measures have been reported among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs such as sulphonylureas, hydantoins, and other NSAIDs. Patients simultaneously receiving Vimovo () and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.
Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers.
Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.
Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.
The administration of naproxen may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.
Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).
Concomitant use of atazanavir and nelfinavir with proton pump inhibitors such as esomeprazole is not recommended. Co-administration of atazanavir with proton pump inhibitors is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.
Omeprazole, the racemate of esomeprazole, has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19. For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole. Following multiple doses of nelfinavir (1250 mg, twice daily) and omeprazole (40 mg once a day), AUC was decreased by 36% and 92%, C by 37% and 89% and C by 39% and 75% respectively for nelfinavir and main oxidative metabolite, hydroxy--butylamide (M8). Following multiple doses of atazanavir (400 mg, once a day) and omeprazole (40 mg, once a day, 2 hr before atazanavir), AUC was decreased by 94%, C by 96%, and C by 95%. Concomitant administration with omeprazole and drugs such as atazanavir and nelfinavir is therefore not recommended. For other antiretroviral drugs, such as saquinavir, elevated serum levels have been reported with an increase in AUC by 82% in C by 75% and in C by 106% following multiple dosing of saquinavir/ritonavir (1000/100 mg) twice a day for 15 days with omeprazole 40 mg once a day co-administered on days 11 to 15. Therefore, clinical and laboratory monitoring for saquinavir toxicity is recommended during concurrent use with esomeprazole. Dose reduction of saquinavir should be considered from the safety perspective for individual patients. There are also some antiretroviral drugs of which unchanged serum levels have been reported when given with omeprazole.
Esomeprazole is extensively metabolized in the liver by CYP2C19 and CYP3A4.
However, post-marketing reports of changes in prothrombin measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Esomeprazole may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme. Co-administration of esomeprazole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of diazepam.
Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not normally required. Omeprazole acts as an inhibitor of CYP2C19. Omeprazole, given in doses of 40 mg daily for one week to 20 healthy subjects in cross-over study, increased C and AUC of cilostazol by 18% and 26% respectively. C and AUC of one of its active metabolites, 3,4-dihydrocilostazol, which has 4-7 times the activity of cilostazol, were increased by 29% and 69% respectively. Co-administration of cilostazol with esomeprazole is expected to increase concentrations of cilostazol and its above mentioned active metabolite. Therefore a dose reduction of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered.
Drugs known to induce CYP2C19 or CYP3A4 (such as rifampin) may lead to decreased esomeprazole serum levels. Omeprazole, of which esomeprazole is an enantiomer, has been reported to interact with St. John’s Wort, an inducer of CYP3A4. In a cross-over study in 12 healthy male subjects, St John’s Wort (300 mg three times daily for 14 days) significantly decreased the systemic exposure of omeprazole in CYP2C19 poor metabolizers (C and AUC decreased by 37.5% and 37.9%, respectively) and extensive metabolizers (C and AUC decreased by 49.6% and 43.9%, respectively). Avoid concomitant use of St. John’s Wort or rifampin with Vimovo () .
Vimovo () Use In Specific Populations
Teratogenic Effects:
Starting at 30 weeks gestation, Vimovo () , and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Vimovo () can cause fetal harm when administered to a pregnant woman starting at 30 weeks gestation. If this drug is used during this time period in pregnancy, the patient should be apprised of the potential hazard to a fetus. There are no adequate and well-controlled studies in pregnant women. Prior to 30 weeks gestation, Vimovo () should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Reproductive studies with naproxen have been performed in rats at 20 mg/kg/day (125 mg/m/day, 0.23 times the human systemic exposure), rabbits at 20 mg/kg/day (220 mg/m/day, 0.27 times the human systemic exposure), and mice at 170 mg/kg/day (510 mg/m/day, 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to the drug [see ]. However, animal reproduction studies are not always predictive of human response.
Reproductive studies in rats and rabbits with esomeprazole and multiple cohort studies in pregnant women with omeprazole use during the first trimester do not show an increased risk of congenital anomalies or adverse pregnancy outcomes. There are no adequate and well controlled studies of esomeprazole use in pregnancy. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Esomeprazole is the S-isomer of omeprazole. In four population-based cohort studies that included 1226 women exposed during the first trimester of pregnancy to omeprazole there was no increased risk of congenital anomalies.
Reproductive studies with esomeprazole have been performed in rats at doses up to 57 times the human dose and in rabbits at doses up to 35 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus [see ].
Reproductive studies conducted with omeprazole on rats at oral doses up to 56 times the human dose and in rabbits at doses up to 56 times the human dose did not show any evidence of teratogenicity. In pregnant rabbits, omeprazole at doses about 5.5 to 56 times the human dose produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy loss. In rats treated with omeprazole at doses about 5.6 to 56 times the human dose, dose-related embryo/fetal toxicity and postnatal developmental toxicity occurred in offspring.
Vimovo () should not be used in nursing mothers due to the naproxen component.
Naproxen
The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers should be avoided.
Esomeprazole
The excretion of esomeprazole in milk has not been studied. It is not known whether this drug is excreted in human milk. However, omeprazole concentrations have been measured in breast milk of one woman taking omeprazole 20 mg per day. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for esomeprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Of the total number of patients who received Vimovo () (n=1157) in clinical trials, 387 were ≥65 years of age, of which 85 patients were 75 years and over. No meaningful differences in efficacy or safety were observed between these subjects and younger subjects [see ].
Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose [see and ].
Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of NSAIDs. Elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. Most spontaneous reports of fatal GI events are in the geriatric population [see ].
Naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of NSAIDs [see ].
Vimovo () Overdosage
There is no clinical data on overdosage with Vimovo () .
Significant naproxen overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation or vomiting. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactic reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. A few patients have experienced convulsions, but it is not clear whether or not these were drug-related. It is not known what dose of the drug would be life threatening. The oral LD of the drug is 543 mg/kg in rats, 1234 mg/kg in mice, 4110 mg/kg in hamsters, and greater than 1000 mg/kg in dogs.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. Activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine or hemoperfusion may not be useful due to high protein binding.
A single oral dose of esomeprazole at 510 mg/kg (about 103 times the human dose on a body surface area basis) was lethal to rats. The major signs of acute toxicity were reduced motor activity, changes in respiratory frequency, tremor, ataxia, and intermittent clonic convulsions.
The symptoms described in connection with deliberate esomeprazole overdose (limited experience of doses in excess of 240 mg/day) are transient. Single doses of 80 mg of esomeprazole were uneventful. Reports of overdosage with omeprazole in humans may also be relevant. Doses ranged up to 2,400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience (see omeprazole package insert - ). No specific antidote for esomeprazole is known. Since esomeprazole is extensively protein bound, it is not expected to be removed by dialysis. In the event of overdosage, treatment should be symptomatic and supportive.
If overexposure occurs, call the Poison Control Center at 1- 800-222-1222.
Vimovo () Description
The active ingredients of Vimovo () are naproxen which is a NSAID and esomeprazole magnesium which is a Proton Pump Inhibitor (PPI).
Vimovo () is available as an oval, yellow, multi-layer, delayed release tablet combining an enteric coated naproxen core and an immediate release esomeprazole magnesium layer surrounding the core. Each strength contains either 375 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) or 500 mg of naproxen and 20 mg of esomeprazole (present as 22.3 mg esomeprazole magnesium trihydrate) for oral administration. The inactive ingredients are carnauba wax, colloidal silicon dioxide, croscarmellose sodium, iron oxide yellow, glyceryl monostearate, hypromellose, iron oxide black, magnesium stearate, methacrylic acid copolymer dispersion, methylparaben, polysorbate 80, polydextrose, polyethylene glycol, povidone, propylene glycol, propylparaben, titanium dioxide, and triethyl citrate.
The chemical name for naproxen is (S)-6-methoxy-α-methyl- 2-naphthaleneacetic acid. Naproxen has the following structure:
Naproxen has a molecular weight of 230.26 and a molecular formula of CHO.
Naproxen is an odorless, white to off-white crystalline substance. It is lipid soluble, practically insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition coefficient of naproxen at pH 7.4 is 1.6 to 1.8.
The chemical name for esomeprazole is bis(5-methoxy-2- [(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1-benzimidazole-1-yl) magnesium trihydrate. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R-isomers. Its molecular formula is (CHNOS)Mg x 3 HO with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. The structural formula is:
The magnesium salt is a white to slightly colored crystalline powder. It contains 3 moles of water of solvation and is slightly soluble in water.
The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C.
Vimovo () Clinical Pharmacology
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.
Naproxen is a NSAID with analgesic and antipyretic properties. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
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.
Antisecretory Activity
The effect of Vimovo () on intragastric pH was determined in 25 healthy volunteers in one study. Three Vimovo () combinations (naproxen 500 mg combined with either esomeprazole 10, 20, or 30 mg) were administered twice daily over 9 days. The results are shown in the following table:
Serum Gastrin Effects
The effect of esomeprazole on serum gastrin concentrations was evaluated in approximately 2,700 patients in clinical trials up to 8 weeks and in over 1,300 patients for up to 6-12 months. The mean fasting gastrin level increased in a dose-related manner. This increase reached a plateau within two to three months of therapy and returned to baseline levels within four weeks after discontinuation of therapy.
Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors.
Enterochromaffin-like (ECL) Cell Effects
In over 1,000 patients treated with esomeprazole (10, 20 or 40 mg/day) up to 6-12 months, the prevalence of ECL cell hyperplasia increased with time and dose. No patient developed ECL cell carcinoids, dysplasia, or neoplasia in the gastric mucosa.
Endocrine Effects
Esomeprazole had no effect on thyroid function when given in oral doses of 20 or 40 mg for 4 weeks. Other effects of esomeprazole on the endocrine system were assessed using omeprazole studies. Omeprazole given in oral doses of 30 or 40 mg for 2 to 4 weeks had no effect on carbohydrate metabolism, circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin.
Effects on Gastrointestinal Microbial Ecology
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as and and possibly in hospitalized patients.
Absorption
Naproxen
At steady state following administration of Vimovo () twice daily, peak plasma concentrations of naproxen are reached on average 3 hours following both the morning and the evening dose.
Bioequivalence between Vimovo () and enteric-coated naproxen, based on both area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C) of naproxen, has been demonstrated for both the 375 mg and 500 mg doses.
Naproxen is absorbed from the gastrointestinal tract with an bioavailability of 95%.
Steady-state levels of naproxen are reached in 4 to 5 days.
Esomeprazole
Following administration of Vimovo () twice daily, esomeprazole is rapidly absorbed with peak plasma concentration reached within on average, 0.43 to 1.2 hours, following the morning and evening dose on both the first day of administration and at steady state. The peak plasma concentrations of esomeprazole are higher at steady state compared to on first day of dosing of Vimovo () .
Figure 1 represents the pharmacokinetics of naproxen and esomeprazole following administration of Vimovo () 500 mg/20 mg.
Figure 1: Mean plasma concentrations of naproxen and esomeprazole following single dose administration of Vimovo () (500mg/20 mg)
Food effect
Administration of Vimovo () together with high-fat food in healthy volunteers does not affect the extent of absorption of naproxen but significantly prolongs t by 10 hours and decreases peak plasma concentration (C) by about 12%.
Administration of Vimovo () together with high-fat food in healthy volunteers delays t of esomeprazole by 1 hour and significantly reduces the extent of absorption, resulting in 52% and 75% reductions of area under the plasma concentration versus time curve (AUC) and peak plasma concentration (C), respectively.
Administration of Vimovo () 30 minutes before high-fat food intake in healthy volunteers does not affect the extent of absorption of naproxen but delays the absorption by about 4 hours and decreases peak plasma concentration (C) by about 17%, but has no significant effect on the rate or extent of esomeprazole absorption compared to administration under fasted conditions [see ].
Administration of Vimovo () 60 minutes before high-fat food intake in healthy volunteers has no effect on the rate and extent of naproxen absorption; however, increases the esomeprazole AUC by 25% and C by 50% compared to administration under fasted conditions. This increase in esomeprazole C does not raise a safety issue since the approved dosing regimen of esomeprazole at 40 mg QD would result in higher C [see ].
Therefore, Vimovo () should be taken at least 30 minutes before the meal.
Distribution
Naproxen
Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough C 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of naproxen, respectively). The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma [see ].
Esomeprazole
The apparent volume of distribution at steady state in healthy subjects is approximately 16L. Esomeprazole is 97% plasma protein bound.
Metabolism
Naproxen
Naproxen is extensively metabolized in the liver by the cytochrome P450 system (CYP), CYP2C9 and CYP1A2, to 6-0-desmethyl naproxen. Neither the parent drug nor the metabolites induce metabolizing enzymes. Both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites. Consistent with the half-life of naproxen, the area under the plasma concentration time curve increases with repeated dosing of Vimovo () twice daily.
Esomeprazole
Esomeprazole is extensively metabolized in the liver by the CYP enzyme system. The major part of the metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation of the hydroxyl- and desmethyl metabolites of esomeprazole. The remaining part is dependent on another specific isoform CYP3A4, responsible for the formation of esomeprazole sulphone, the main metabolite in plasma. The major metabolites of esomeprazole have no effect on gastric acid secretion.
The area under the plasma esomeprazole concentration-time curve increases with repeated administration of Vimovo () . This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated administration. An increased absorption of esomeprazole with repeated administration of Vimovo () probably also contributes to the time-and dose-dependency.
Excretion
Naproxen
Following administration of Vimovo () twice daily, the mean elimination half-life for naproxen is approximately 15 hours following the evening dose, with no change with repeated dosing.
The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen from any dose is excreted in the urine, primarily as naproxen (
Esomeprazole
Following administration of Vimovo () twice daily, the mean elimination half-life of esomeprazole is approximately 1 hour following both the morning and evening dose on day 1, with a slightly longer elimination half-life at steady state (1.2-1.5 hours).
Almost 80% of an oral dose of esomeprazole is excreted as metabolites in the urine, the remainder in the feces. Less than 1% of the parent drug is found in the urine.
Special Populations
There is no specific data on the pharmacokinetics of Vimovo () in patients over age 65.
Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly, although the unbound fraction is
The AUC and C values of esomeprazole were slightly higher (25% and 18%, respectively) in the elderly as compared to younger subjects at steady state. Dosage adjustment for the esomeprazole component based on age is not necessary.
Pharmacokinetic differences due to race have not been studied for naproxen.
Approximately 3% of Caucasians and 15 to 20% of Asians lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers).
The pharmacokinetics of Vimovo () or naproxen have not been determined in subjects with hepatic impairment.
In patients with severe hepatic impairment, Vimovo () should be avoided due to increase of risk of NSAID associated bleeding and/or renal failure associated with naproxen.
Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for the naproxen component of Vimovo () dosing is unknown but it is prudent to use the lowest effective dose.
The AUCs of esomeprazole in patients with severe hepatic insufficiency (Child Pugh Class C) have been shown to be 2-3 times higher than in patients with normal liver function. For this reason, it has been recommended that esomeprazole doses not exceed 20 mg daily in patients with severe hepatic impairment. However, there is no dose adjustment necessary for patients with Child Pugh Class A and B for the esomeprazole component of Vimovo () . There is no Vimovo () dosage form that contains less than 20 mg esomeprazole for twice daily dosing [see and ].
The pharmacokinetics of Vimovo () or naproxen have not been determined in subjects with renal impairment.
Given that naproxen, its metabolites and conjugates are primarily excreted by the kidney, the potential exists for naproxen metabolites to accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment. Naproxen-containing products, including Vimovo () , is not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance
No studies have been performed with esomeprazole in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
The AUC and C values of esomeprazole were slightly higher (13%) in females than in males at steady state. Dosage adjustment for the esomeprazole component based on gender is not necessary.
Vimovo () Nonclinical Toxicology
Naproxen
A 2-year study was performed in rats to evaluate the carcinogenic potential of naproxen at rat doses of 8, 16, and 24 mg/kg/day (50, 100, and 150 mg/m). The maximum dose used was 0.28 times the highest recommended human dose. No evidence of tumorigenicity was found.
Esomeprazole
The carcinogenic potential of esomeprazole was assessed using omeprazole studies. In two 24-month oral carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44 and 140.8 mg/kg/day (about 0.7 to 57 times the human dose of 20 mg/day expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 5.6 times the human dose on a body surface area basis) for 1 year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of 1 year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for 2 years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive.
Esomeprazole was negative in the Ames mutation test, in the rat bone marrow cell chromosome aberration test, and the mouse micronucleus test. Esomeprazole, however, was positive in the human lymphocyte chromosome aberration test. Omeprazole was positive in the human lymphocyte chromosome aberration test, the mouse bone marrow cell chromosome aberration test, and the mouse micronucleus test.
The potential effects of esomeprazole on fertility and reproductive performance were assessed using omeprazole studies. Omeprazole at oral doses up to 138 mg/kg/day in rats (about 56 times the human dose on a body surface area basis) was found to have no effect on reproductive performance of parental animals.
Naproxen
Reproductive studies have been performed in rats at 20 mg/kg/day (125 mg/m/day, 0.23 times the maximum recommended human dose), rabbits at 20 mg/kg/day (220 mg/m/day, 0.27 times the maximum recommended human dose), and mice at 170 mg/kg/day (510 mg/m/day, 0.28 times the maximum recommended human dose) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response.
Esomeprazole
Reproductive studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole.
Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 56 times the human dose on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 56 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 5.5 to 56 times the human dose on a body surface area basis) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 5.6 to 56 times the human doses on a body surface area basis).
Vimovo () Clinical Studies
Two randomized, multi-center, double-blind trials (Study 1 and Study 2) compared the incidence of gastric ulcer formation in 428 patients taking Vimovo () and 426 patients taking enteric-coated naproxen. Subjects were at least 18 years of age with a medical condition expected to require daily NSAID therapy for at least 6 months, and, if less than 50 years old, with a documented history of gastric or duodenal ulcer within the past 5 years. The majority of patients were female (67%), white (86%). The majority of patients were 50-69 years of age (83%). Approximately one quarter were on low-dose aspirin.
Studies 1 and 2 showed that Vimovo () given as 500 mg/20 mg twice daily statistically significantly reduced the 6-month cumulative incidence of gastric ulcers compared to enteric-coated naproxen 500 mg twice daily (see Table 4).
Approximately a quarter of the patients in Studies 1 and 2 were taking concurrent low-dose aspirin (≤ 325 mg daily). The results for this subgroup analysis in patients who used aspirin were consistent with the overall findings of the study.
The results at one month, three months, and six months are presented in Table 4.
In these trials, patients receiving Vimovo () had a mean duration of therapy of 152 days compared to 124 days in patients receiving enteric-coated naproxen alone. A higher proportion of patients taking EC-naproxen (12%) discontinued the study due to upper GI adverse events (including duodenal ulcers) compared to Vimovo () (4%) in both trials [see ].
The efficacy of Vimovo () in treating the signs and symptoms of osteoarthritis was established in two 12-week randomized, double-blind, placebo-controlled trials in patients with osteoarthritis (OA) of the knee. In these two trials, patients were allowed to remain on low-dose aspirin for cardioprophylaxis. Vimovo () was given as 500 mg/20 mg twice daily. In each trial, patients receiving Vimovo () had significantly better results compared to patients receiving placebo as measured by change from baseline of the WOMAC pain subscale and the WOMAC physical function subscale and a Patient Global Assessment Score.
Based on studies with enteric-coated naproxen, improvement in patients treated for rheumatoid arthritis was demonstrated by a reduction in joint swelling, a reduction in duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and patient, and by increased mobility as demonstrated by a reduction in walking time. In patients with osteoarthritis, the therapeutic action of naproxen has been shown by a reduction in joint pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a reduction in walking time, and improvement in capacity to perform activities of daily living impaired by the disease. In patients with ankylosing spondylitis, naproxen has been shown to decrease night pain, morning stiffness and pain at rest.
Vimovo () How Supplied/storage And Handling
Vimovo () 375 mg/20 mg tablets are oval, yellow film-coated tablets printed with 375/20 in black ink, supplied as:
NDC 0186-0510-60 Bottles of 60 tablets
Vimovo () 500 mg/20 mg tablets are oval, yellow film-coated tablets printed with 500/20 in black ink, supplied as:
NDC 0186-0520-60 Bottles of 60 tablets
NDC 0186-0520-39 Unit Dose Blisters, package of 100 tablets
Vimovo () Patient Counseling Information
[See Medication Guide]
Patients should be informed of the following before initiating therapy with Vimovo () and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
1. Vimovo () , like other NSAID-containing products, may cause serious cardiovascular side effects, such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up [see ].
2. Vimovo () has been developed with esomeprazole to decrease incidence of ulceration from naproxen. NSAIDs, including naproxen, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up [see ].
3. Vimovo () , like other NSAID-containing products, can cause serious skin side effects such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible [see ].
4. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy [see and ].
6. Patients should be informed of the signs of an anaphylactic reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help [see ].
7. In late pregnancy, as with other NSAIDs, Vimovo () should be avoided because it may cause premature closure of the ductus arteriosus [see and ].
8. Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with Vimovo () .
9. Patients should be instructed to tell their physicians if they have a history of asthma or aspirin-sensitive asthma because the use of NSAIDs in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Patients with this form of aspirin sensitivity should be instructed not to take Vimovo () . Patients with preexisting asthma should be instructed to seek immediate medical attention if their asthma worsens after taking Vimovo () [see ].
10. Antacids may be used while taking Vimovo () .
11. Vimovo () tablets should be swallowed whole with liquid. Tablets should not be split, chewed, crushed or dissolved. Vimovo () tablets should be taken at least 30 minutes before meals [see ].
12. Advise patients to immediately report and seek care for any cardiovascular or neurological symptoms including palpitations, dizziness, seizures, and tetany as these may be signs of hypomagnesemia [see Warnings and Precautions (5.19)].
Vimovo () is a trademark of the AstraZeneca group of companies. Other trademarks are the property of their respective companies.
Distributed by: AstraZeneca LP, Wilmington, DE 19850
©AstraZeneca 2011
Vimovo () Medication Guide
Read this Medication Guide before you start taking Vimovo () and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
These are not all of the possible side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Vimovo () contains 2 medicines: naproxen, a non-steroidal anti-inflammatory drug (NSAID) and esomeprazole magnesium, a proton pump inhibitor (PPI).
Vimovo () is a prescription medicine used to:
It is not known if Vimovo () is safe or effective in children under the age of 18.
Especially tell your healthcare provider if you take:
Ask your healthcare provider if you are not sure if your medicine is one that is listed above.
Using Vimovo () with other medicines can cause serious side effects. Vimovo () may affect the way other medicines work, and other medicines may affect how Vimovo () works.
If you take more Vimovo () than your healthcare provider recommends, call your Poison Control Center at 1-800-222-1222.
Vimovo () can cause drowsiness, dizziness, or depression. You should not drive or do other activities that require you to be alert until you know how Vimovo () affects you.
See “What is the most important information I should know about Vimovo () ?”
Tell your doctor right away if you have any of these symptoms:
Your doctor may check the level of magnesium in your body before you start taking Vimovo () , during treatment, or if you will be taking Vimovo () for a long period of time.
The most common side effects of Vimovo () include
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Vimovo () . For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for purposes other than those listed in this Medication Guide. Do not use Vimovo () for a condition for which it was not prescribed. Do not give Vimovo () to other people, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about Vimovo () . If you would like more information, ask your healthcare provider. You can ask your healthcare provider or pharmacist for information that is written for healthcare professionals.
For more information, call 1-800-236-9933 or go to www.Vimovo () .com
Distributed by: AstraZeneca LP, Wilmington, DE 19850
Issued November 2011
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Vimovo () is a trademark of the AstraZeneca group of companies.
Other trademarks are the property of their respective companies.
