08 Mar 2012

VIMOVO 500 (naproxen - esomeprazole magnesium trihydrate) - United Kingdom

Updated: 08 Mar 2012

VIMOVO 500 mg/20 mg modified-release tablets

Symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, in patients who are at risk for developing non-steroidal anti-inflammatory drug (NSAID)-associated gastric and/or duodenal ulcers and where treatment with lower doses of naproxen or of other NSAIDs is not considered sufficient.

VIMOVO 500 Description, Presentation and Dosage

VIMOVO 500 Description

VIMOVO 500 Drug Class Description

naproxen and esomeprazole - ATC code: M01AE52

VIMOVO 500 Drug Description

Each modified-release tablet contains 500 mg naproxen and 20 mg esomeprazole (as magnesium trihydrate). VIMOVO contains very low, non-preserving levels of 0.02 mg methyl parahydroxybenzoate and 0.01 mg propyl parahydroxybenzoate

VIMOVO 500 Generic Name

naproxen - esomeprazole magnesium trihydrate

VIMOVO 500 Presentation

VIMOVO 500 Presentation

Modified-release tablet containing enteric-coated (gastro-resistant) naproxen and film-coated esomeprazole. Oval, biconvex, yellow tablet marked '500/20' in black ink.

VIMOVO 500 Manufacturer

AstraZeneca UK Limited

Free Medical Education Resources

VIMOVO 500 Dosage

VIMOVO 500 Adult Dosage

Posology in adults

The dose is 1 tablet (500 mg/20 mg) twice daily.

Undesirable effects of naproxen may be minimised by using the lowest effective dose for the shortest duration possible. In patients not treated with a NSAID previously, a lower daily dose of naproxen or of another NSAID should be considered. When total daily dose of 1000 mg of naproxen is not considered appropriate, alternative therapeutic regimens should be utilized.

Treatment should be continued to achieve individual treatment goals, reviewed at regular intervals and discontinued if no benefit seen.

Due to the delayed release of naproxen from the enteric-coated formulation, VIMOVO is not intended for the treatment of acute pain conditions (such as dental pain or gout). However, flares of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis may be treated with VIMOVO.

Method of administration

VIMOVO must be swallowed whole with water, and not split, chewed or crushed.

It is recommended that VIMOVO is taken at least 30 minutes prior to food intake.

Special populations

Patients with renal impairment

In patients with mild to moderate renal impairment VIMOVO should be used cautiously and renal function should be monitored closely. A reduction in the total daily naproxen dose should be considered. When total daily dose of 1000 mg of naproxen is considered not appropriate, alternative therapeutic regimens should be utilized.

VIMOVO is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml/minute) because accumulation of naproxen metabolites has been seen in patients with severe renal failure and in those on dialysis.

Patients with hepatic impairment

In patients with mild to moderate hepatic impairment VIMOVO should be used cautiously and hepatic function should be monitored closely. A reduction in the total daily naproxen dose should be considered. When total daily dose of 1000 mg of naproxen is considered not appropriate, alternative therapeutic regimens should be utilized.

VIMOVO is contraindicated in patients with severe hepatic impairment.

VIMOVO 500 Child Dosage

Children (LESS-THAN OR EQUAL TO (8804)18 years)

VIMOVO is not recommended for use in children, due to lack of data on safety and efficacy.

VIMOVO 500 Elderly Dosage

Elderly (>65 years)

The elderly are at an increased risk of the serious consequences of adverse reactions (see sections 4.4 and 5.2). When total daily dose of 1000 mg of naproxen is considered not appropriate (e.g. in elderly with impaired renal function or low body weight), alternative therapeutic regimens should be utilized.

VIMOVO 500 Precautions, Reactions and Contraindications

VIMOVO 500 Special Precautions

VIMOVO 500 Special Precautions

General

The use of VIMOVO with other concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided. VIMOVO can be used with low dose aspirin.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptom.

When total daily dose of 1000 mg of naproxen is considered not appropriate, alternative therapeutic regimens should be utilized.

Risk-factors to develop NSAID related gastro-intestinal complications include high age, concomitant use of anticoagulants, corticosteroids, other NSAIDs including low-dose acetylsalicylic acid, debilitating cardiovascular disease, and a history of gastric and/or duodenal ulcers.

In patients with the following conditions, naproxen should only be used after a rigorous benefit-risk ratio:

• Inducible porphyries

• Systemic lupus erythematosis and mixed connective tissue disease. There may be an increased risk of aseptic meningitis in these patients.

Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.

VIMOVO contains very low levels of methyl- and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Elderly

Naproxen: The elderly have an increased frequency of adverse reactions especially gastro-intestinal bleeding, and perforation, which may be fatal. The esomeprazole component of VIMOVO decreased the incidence of ulcers in elderly.

Gastrointestinal effects:

Naproxen: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation with NSAIDs is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should begin treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk. The esomeprazole component of VIMOVO is a proton pump inhibitor.

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving NSAIDs with concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

Ulcer complications such as bleeding, perforation and obstruction were not studied in the VIMOVO trials.

When GI bleeding or ulceration occurs in patients receiving VIMOVO, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.

Esomeprazole: In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole magnesium may alleviate symptoms and delay diagnosis.

Dyspesia could still occur despite the addition of esomperazole to the combination tablet.

Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

Esomeprazole, as all acid-blocking medicines, might reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced body stores or risk factors of reduced vitamin B12 absorption on long-term therapy.

Cardiovascular and cerebrovascular effects

Naproxen: Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Although data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Renal effects

Naproxen: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Use in patients with impaired renal function

As naproxen and its metabolites is eliminated to a large extent (95%) by urinary excretion via glomerular filtration, it should be used with great caution in patients with impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. VIMOVO is contraindicated in patients having a baseline creatinine clearance of less than 30 ml/minute.

Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding.

Certain patients, specifically those whose renal blood flow is compromised, because of extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease, should have renal function assessed before and during VIMOVO therapy. Some elderly patients in whom impaired renal function may be expected, as well as patients using diuretics, may also fall within this category. A reduction in daily dosage should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients.

Hepatic effects

Borderline elevations of one or more liver tests may occur in patients taking NSAIDs. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. 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.

Hepatorenal syndrome

The use of NSAIDs may be associated with acute renal failure in patients with severe hepato-cirrhosis. These patients frequently also have concomitant coagulopathy related to inadequate synthesis of clotting factors. Antiplatelet effects associated with naproxen could further increase risk of severe bleeding in these patients.

Haematological effects

Naproxen: Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis should be carefully observed if naproxen-containing products are administered.

Patients at high risk of bleeding and those on full anti-coagulation therapy (e.g. dicoumarol derivates) may be at increased risk of bleeding if given naproxen-containing products concurrently.

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.

When active and clinically significant bleeding from any source occurs in patients receiving VIMOVO, the treatment should be withdrawn.

Eye effects

Naproxen: Because of adverse eye findings in animal studies with NSAIDs, it is recommended that an ophthalmic examination be carried out if any change or disturbance in vision occurs.

Dermatological effects

Naproxen: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring within the first month of treatment in the majority of cases. VIMOVO should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Anaphylactic (anaphylactoid) reactions

Naproxen: Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin, other NSAIDs or naproxen-containing products. They may also occur in individuals with a history of angio-oedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps.

Pre-existing asthma

Naproxen: The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, VIMOVO should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

Inflammation

Naproxen: The anti-pyretic and anti-inflammatory activities of naproxen may reduce fever and other signs of inflammation, thereby diminishing their utility as diagnostic signs.

Female fertility

The use of VIMOVO, as with any drug known to inhibit cyclooxygenase / prostaglandin synthesis, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of VIMOVO should be considered.

Combination with other medicinal products:

Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g. virus loading) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; esomeprazole 20 mg should not be exceeded and therefore VIMOVO must not be used concomitantly with atazanavir.

Esomeprazole is a CYP2C19 inhibitor. When starting or ending treatment with esomeprazole, the potential for interactions with drugs metabolised through CYP2C19 should be considered. An interaction is observed between clopidogrel and omeprazole. The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of esomeprazole and clopidogrel should be discouraged.

 

 

 

VIMOVO 500 Adverse Reactions

VIMOVO 500 Adverse Reactions

Summary of safety profile

Immediate release esomeprazole has been included in the tablet formulation to decrease the incidence of gastrointestinal side effects from naproxen. VIMOVO has been shown to significantly decrease the occurrence of gastric ulcers and NSAID associated upper gastrointestinal adverse events compared to naproxen alone.

No new safety findings were identified during VIMOVO treatment in the overall study population (n=1157) compared to the well-established safety profiles of the individual active substances naproxen and esomeprazole.

Tabulated summary of adverse reactions

Adverse reactions are classified according to frequency and System Organ Class. Frequency categories are defined according to the following convention: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data)

VIMOVO

The following adverse experiences have been reported in patients taking VIMOVO during clinical trials

 

Very Common

Common

Uncommon

Rare

Infections and infestations

   

infection

diverticulitis

Blood and lymphatic system disorders

     

eosinophilia, leucopenia

Immune system disorders

     

hypersensitivity reactions

Metabolism and nutrition disorders

   

appetite disorder

fluid retention, hyperkalemia, hyperuricemia

Psychiatric disorders

   

anxiety, depression, insomnia

confusion, dream abnormalities

Nervous system disorders

 

dizziness, headache, taste disturbance

paraesthesia, syncope

somnolence, tremor

Ear and labyrinth disorders

   

tinnitus, vertigo

 

Cardiac disorders

   

arrhythmia, palpitations

myocardial infarction, tachycardia

Vascular disorders

 

hypertension

   

Respiratory, thoracic and mediastinal disorders

   

asthma, bronchospasm, dyspnea

 

Gastrointestinal disorders

dyspepsia

abdominal pain, constipation, diarrhoea, esophagitis, flatulence, gastric/duodenal ulcers*, gastritis, nausea, vomiting

dry mouth, eructation, gastrointestinal bleeding, stomatitis

glossitis, hematemesis, rectal bleeding

Skin and subcutaneous tissue disorders

 

skin rashes

dermatitis, hyperhidrosis, pruritis, urticaria

alopecia, ecchymoses

Musculoskeletal and connective tissue disorders

 

arthralgia

myalgia

 

Renal and urinary disorders

     

proteinuria, renal failure

Reproductive system and breast disorders

     

menstrual disorder

General disorders and administration site disorders

 

oedema

asthenia, fatigue, pyrexia

 

Investigations

   

abnormal liver function tests, raised serum creatinine

 

*as detected by scheduled routine endoscopy

Naproxen

The following adverse experiences have been reported in patients taking naproxen during clinical trials and through postmarketing reports.

 

Common

Uncommon/Rare

Infections and infestations

diverticulitis

aseptic meningitis, infection, sepsis

Blood and lymphatic system disorders

 

agranulocytosis, aplastic anemia, eosinophilia, granulocytopenia, hemolytic anemia, leucopenia, lymphadenopathy, pancytopenia, thrombocytopenia

Immune system disorders

 

anaphylactic reactions, anaphylactoid reactions, hypersensitivity reactions

Metabolism and nutrition disorders

 

appetite disorder, fluid retention, hyperglycemia, hyperkalemia, hyperuricemia, hypoglycemia, weight changes

Psychiatric disorders

depression, insomnia

agitation, anxiety, confusion, dream abnormalities, hallucinations, nervousness

Nervous system disorders

dizziness, drowsiness, headache, lightheadedness, vertigo

cognitive dysfunction, coma, convulsions, inability to concentrate, optic neuritis, paresthesia, syncope, tremor

Eye disorders

visual disturbances

blurred vision, conjunctivitis, corneal opacity, papilloedema, papillitis

Ear and labyrinth disorders

tinnitus, hearing disturbances

hearing impairment

Cardiac disorders

palpitations

arrhythmia, congestive heart failure, myocardial infarction, tachycardia

Vascular disorders

 

hypertension, hypotension, vasculitis

Respiratory, thoracic and mediastinal disorders

dyspnea

asthma, bronchospasm, eosinophilic pneumonitis, pneumonia, pulmonary edema, respiratory depression

Gastrointestinal disorders

dyspepsia, abdominal pain, nausea, vomiting, diarrhoea, constipation, heartburn, peptic ulcers, stomatitis

dry mouth, esophagitis, gastric ulcers, gastritis, glossitis, eructation, flatulence, gastric/duodenal ulcers, gastrointestinal bleeding and/or perforation, melena, hematemesis, pancreatitis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease), nonpeptic gastrointestinal ulceration, rectal bleeding, ulcerative stomatitis

Hepatobiliary disorders

 

cholestasis, hepatitis, jaundice, liver failure

Skin and subcutaneous tissue disorders

pruritis, ecchymoses, purpura, skin rashes

alopecia, exanthema,urticaria, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, systemic lupus erythematoses, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria), exfoliative dermatitis, angioneurotic edema, pustular reaction

Musculoskeletal and connective tissue disorders

 

muscle weakness, myalgia

Renal and urinary disorders

 

glomerular nephritis, hematuria, interstitial nephritis, nephrotic syndrome, oliguria/polyuria, proteinuria, renal failure, renal papillary necrosis, tubular necrosis

Reproductive system and breast disorders

 

infertility, menstrual disorder

General disorders and administration site disorders

fatigue, oedema, sweating, thirst

asthenia, malaise, pyrexia

Investigations

 

abnormal liver function tests, increased bleeding time, raised serum creatinine

Esomeprazole:

The following adverse drug reactions have been identified or suspected in the clinical trials programme for enteric-coated esomeprazole and/or from post-marketing use. None were found to be dose-related.

 

Common

Uncommon

Rare

Very rare

Blood and lymphatic system disorders

   

leukopenia,

thrombocytopenia

agranulocytosis,

pancytopenia

Immune system disorders

   

hypersensitivity reactions e.g. fever, angioedema and anaphylactic reaction/shock

 

Metabolism and nutrition disorders

 

peripheral oedema

hyponatraemia

hypomagnesaemia

Psychiatric disorders

 

insomnia

agitation,

confusion,

depression

aggression,

hallucinations

Nervous system disorders

headache

dizziness,

paraesthesia,

somnolence

taste disturbance

 

Eye disorders

   

blurred vision

 

Ear and labyrinth disorders

 

vertigo

   

Respiratory, thoracic and mediastinal disorders

   

bronchospasm

 

Gastrointestinal disorders

abdominal pain,

diarrhoea,

flatulence,

nausea/vomiting,

constipation

dry mouth

stomatitis,

gastrointestinal candidiasis

 

Hepatobiliary disorders

 

increased liver enzymes

hepatitis with or without jaundice

hepatic failure,

hepatic encephalopathy in patients with pre-existing liver disease

Skin and subcutaneous tissue disorders

 

dermatitis,

pruritus,

urticaria,

rash

alopecia,

photosensitivity

erythema multiforme,

Stevens-Johnson syndrome,

toxic epidermal necrolysis (TEN)

Musculoskeletal and connective tissue disorders

   

arthralgia,

myalgia

muscular weakness

Renal and urinary disorders

     

Interstitial nephritis

Reproductive system and breast disorders

     

gynaecomastia

General disorders and administration site disorders

   

malaise,

increased sweating

 

Description of selected adverse reactions

Naproxen

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Although data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded.

Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed.

VIMOVO has been developed with esomeprazole to decrease the incidence of gastrointestinal side effects from naproxen and has been shown to significantly decrease the occurrence of gastric and/or duodenal ulcers and NSAID associated upper gastrointestinal adverse events compared to naproxen alone.

VIMOVO 500 Contraindications

VIMOVO 500 Contraindications

 

• Known hypersensitivity to naproxen, esomeprazole, substituted benzimidazoles, or to any of the excipients

• History of asthma, urticaria or allergic-type reactions induced by administration of aspirin or other NSAIDs

• Third trimester of pregnancy

• Severe hepatic impairment (e.g. Childs-Pugh C)

• Severe heart failure

• Severe renal impairment

• Active peptic ulceration

• Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders

• VIMOVO must not be used concomitantly with atazanavir and nelfinavir.

 

Related Drugs - Rheumatology

Back to top