VimovoTM (VimovoTM)

Vimovo release form

According to the instructions, Vimovo is produced in the form of enteric film-coated yellow oval tablets, with the black inscription “500/20” on one side, in plastic bottles with a screw cap, with first opening control.

One Vimovo tablet contains 500 mg of naproxen and 22.3 mg of esomeprazole magnesium trihydrate, as well as:

• 50 mcg carnauba wax;
• 35 mg hypromellose 3 mPas77;
• 2.69 mg glycerol monostearate 40-55;
• 10.85 mg hypromellose 6 mPas;
• 680 mcg hypromellose 50 mPas;
• 580 mcg iron oxide yellow (E172);
• 22 mg croscarmellose sodium;
• 2.62 mg colloidal silicon dioxide;
• 1.38 mg magnesium stearate;
• 5.85 mg macrogol 8000;
• 20 μg methyl parahydroxybenzoate (E218);
• 4.55 mg polysorbate 80;
• 11 mg povidone K90;
• 6.3 mg polydextrose (E1200);
• 10 µg propyl parahydroxybenzoate (E216);
• 54.6 mg suspension 30%;
• 8.18 mg triethyl citrate;
• 13.26 mg titanium dioxide.

The tablet shell contains black ink - qs, which consists of 22% black iron oxide, 7% hypromellose 6 mPas, 10% propylene glycol, 12% isopropanol and 49% purified water.

Vimovo's analogs

There are no analogues of Vimovo tablets based on the active substance. Analogues of Vimovo according to the mechanism of action and belonging to the same pharmacological group include:

• Advil;
• Artrum;
• Algesir Ultra;
• ArthroCam;
• Bonifen;
• Bystrumcaps;
• Dexalgin 25;
• Ibuprofen;
• Ibufen;
• Ketoprofen;
• MIG 400;
• Naproxen-ICN;
• Nurofen active;
• Nurofen UltraCap;
• OKI;
• Rakstan-Sanovel;
• Teraflex Advance;
• Faspik;
• Flexen;
• Khairumath.

Contraindications

Vimovo tablets are contraindicated for:

• Severe uncontrolled heart failure;
• Severe liver failure or active liver disease;
• Confirmed hyperkalemia;
• History of urticaria, bronchial asthma and allergic reactions when taking non-steroidal anti-inflammatory drugs;
• Severe renal failure;
• Condition after coronary artery bypass surgery;
• Peptic ulcer of the duodenum or stomach in the acute phase;
• Inflammatory bowel diseases in the acute phase;
• Simultaneous use with Atazanavir and Nelfinavir;
• Hypersensitivity to the components of the drug;
• Gastrointestinal bleeding, cerebral hemorrhage or other bleeding;
• Hypersensitivity to other substituted benzimidazoles.

The drug is also contraindicated during the third trimester of pregnancy and lactation, as well as in childhood and adolescence under 18 years of age.

Vimovo

The drug contains naproxen and esomeprazole, so it is possible to develop the same undesirable effects that were observed when using these active substances separately. Undesirable effects from the gastrointestinal tract, such as dyspepsia, stomach pain, nausea and vomiting, most often develop with the use of naproxen. During the development of the drug, esomeprazole was included in its composition to reduce the incidence of gastrointestinal side effects of naproxen. It was shown that when taking the drug, the incidence of gastric ulcers and adverse events in the upper gastrointestinal tract associated with NSAIDs was significantly reduced compared with naproxen monotherapy.

In placebo-controlled studies, the most common adverse events with Vimovo (n=490) compared with placebo (n=246) included diarrhea, upper abdominal pain, constipation, dizziness and peripheral edema, which are all adverse drug reactions with use. active substances separately. No new safety data were obtained when using the drug in the general patient population (n=1157) compared to the well-known safety profiles of the active substances naproxen and esomeprazole.

There were no differences in the types of adverse reactions when using the drug for 12 months compared to short-term therapy. Patients taking the drug were significantly less likely to discontinue therapy early due to adverse reactions compared to patients taking enteric-coated naproxen alone (7.9% versus 12.5%, respectively). The proportion of patients who discontinued treatment due to any upper gastrointestinal adverse event (including duodenal ulcers) while using the drug was 4% compared to 12% of patients receiving enteric-coated naproxen alone.

Adverse events are classified by frequency of development and organs and systems. The frequencies of undesirable effects were defined as: very common (> 1/10); frequent (>1/100 to 1/1000 to 1/10000 to

Naproxen

The following adverse events were observed in patients receiving naproxen during clinical trials and post-marketing:

Laboratory indicators: Infrequent/rare - increased liver enzyme activity, increased bleeding time, increased serum creatinine levels.

Cardiac disorders: often - palpitations; Infrequent/rare - arrhythmia, congestive heart failure, myocardial infarction, tachycardia.

Blood and lymphatic system disorders: Uncommon/rare - agranulocytosis, aplastic anemia, eosinophilia, granulocytopenia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia, thrombocytopenia.

Nervous system disorders: common - dizziness, drowsiness, headache, lightheadedness, vertigo; Uncommon/rare: cognitive dysfunction, coma, convulsions, decreased concentration, optic neuritis, paresthesia, syncope, tremor.

Violations of the organ of vision: frequent - visual impairment; Uncommon/rare: blurred vision, conjunctivitis, corneal opacities, papilledema.

Hearing disorders and labyrinthine disorders: frequent - tinnitus, hearing impairment; Infrequent/rare - hearing loss.

Disorders of the respiratory system, chest and mediastinal organs: often - shortness of breath; Uncommon/rare - bronchial asthma, bronchospasm, eosinophilic pneumonitis, pneumonia, pulmonary edema, respiratory depression.

Gastrointestinal disorders: common - dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, heartburn, peptic ulcers, stomatitis; Uncommon/rare - dry mouth, esophagitis, stomach ulcers, gastritis, glossitis, belching, flatulence, stomach and duodenal ulcers, gastrointestinal bleeding and perforation, melena, hematemesis, pancreatitis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis , Crohn's disease), non-peptic gastrointestinal ulcer, rectal bleeding, ulcerative stomatitis.

Renal and urinary tract disorders: Uncommon/rare - glomerulonephritis, hematuria, interstitial nephritis, nephrotic syndrome, oliguria/polyuria, proteinuria, renal failure, renal medullary necrosis, renal tubular necrosis.

Disorders of the skin and subcutaneous tissues: common - itching, bruising, purpura, skin rash; Uncommon/rare - alopecia, exanthema, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, persistent drug-induced erythema, lichen planus, systemic lupus erythematosus, Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including cases of rash like cutaneous porphyria tarda (pseudoporphyria), exfoliative dermatitis, angioedema.

Musculoskeletal and connective tissue disorders: Uncommon/rare - muscle weakness, myalgia.

Metabolic and nutritional disorders: Uncommon/rare - loss of appetite, fluid retention, hyperglycemia, hyperkalemia, hyperuricemia, hypoglycemia, changes in body weight (associated with edema/fluid retention).

Infections and infestations: often - diverticulitis; Infrequent/rare - aseptic meningitis, infection, sepsis.

Vascular disorders: Uncommon/rare - increased blood pressure, decreased blood pressure, vasculitis.

General disorders and reactions at the injection site: often - fatigue, swelling, sweating, thirst; Infrequent/rare - asthenia, malaise, fever.

Immune system disorders: Uncommon/rare - anaphylactic reactions, anaphylactoid reactions, hypersensitivity reactions.

Liver and biliary tract disorders: Uncommon/rare - cholestasis, hepatitis, jaundice, liver failure.

Disorders of the reproductive function and mammary glands: Infrequent/rare - infertility, menstrual irregularities.

Mental disorders: often - depression, insomnia; Infrequent/rare - agitation, anxiety, confusion, unusual dreams, hallucinations, nervousness.

Esomeprazole

The following adverse drug reactions were observed or suspected in patients receiving enteric-coated esomeprazole during clinical trials and/or post-marketing. None of these adverse reactions were dose dependent.

Disorders of the blood and lymphatic system: Rare - leukopenia, thrombocytopenia; Very rare - agranulocytosis, pancytopenia.

Nervous system disorders: often - headache; infrequently - dizziness, paresthesia, drowsiness; rarely - taste disorder.

Visual disturbances: rarely - blurred vision.

Hearing and labyrinthine disorders: uncommon - vertigo.

Disorders of the respiratory system, chest and mediastinal organs: rarely - bronchospasm.

Gastrointestinal disorders: often - abdominal pain, diarrhea, flatulence, nausea/vomiting, constipation; uncommon - dry mouth; rarely - stomatitis, gastrointestinal candidiasis; very rarely - microscopic colitis.

Renal and urinary tract disorders: very rarely - interstitial

Drug interactions

Vimovo, according to the instructions, is not recommended to be combined with antiretroviral drugs; the drug should be used with caution with:

• Acetylsalicylic acid (in small doses);
• Diuretics;
• Selective serotonin reuptake inhibitors;
• Corticosteroids;
• ACE inhibitors;
• Lithium preparations;
• Methotrexate;
• Sulfonylurea and hydantoin derivatives;
• Warfarin;
• Beta-blockers;
• probenecid;
• Drugs whose absorption depends on gastric pH.

VimovoTM (VimovoTM)

Elderly patients

Naproxen

: In elderly patients, an increased incidence of adverse reactions has been observed with the use of NSAIDs, in particular gastrointestinal bleeding, ulceration and perforation of the gastrointestinal tract, which can lead to death of the patient. In clinical studies of Vimovo™ in elderly patients, there was no increased incidence of gastric and duodenal ulcers compared with patients younger than 60 years of age, and the reduction in ulcer risk was maintained in this elderly patient population. However, ulcer complications such as bleeding, perforation and gastrointestinal obstruction were not studied in these studies of Vimovo™.

Effect on the gastrointestinal tract

Naproxen

: Gastrointestinal bleeding, ulceration or perforation of the gastrointestinal tract, which can lead to death of the patient, has been observed with the use of all NSAIDs at any time during treatment, with or without the development of symptoms of the lesion, with or without a history of serious gastrointestinal diseases. Vimovo™ contains esomeprazole to reduce the incidence of gastrointestinal side effects of naproxen, including ulceration. Although Vimovo™ significantly reduces the incidence of gastric ulcers compared to naproxen alone, the development of ulcers and accompanying complications is still possible. The risk of developing gastrointestinal bleeding, ulceration and perforation of the gastrointestinal tract when using NSAIDs increases with increasing dosages in patients with a history of ulcers, especially if the ulcer is complicated by bleeding or perforation, and in elderly patients. Such patients should be prescribed therapy with the lowest dosage.

Patients with a history of gastrointestinal adverse events, especially elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) and especially at the beginning of treatment.

NSAIDs should be used with caution in patients already taking medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antithrombotic drugs such as acetylsalicylic acid.

If gastrointestinal bleeding or ulcers develop, use of Vimovo™ should be discontinued.

NSAIDs should be prescribed with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) due to a possible exacerbation of this disease.

Esomeprazole

: If any warning symptom develops (eg, significant, unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, or melena) and there is a suspicion or certainty of developing a gastric ulcer, malignancy must be excluded, as esomeprazole magnesium may relieve symptoms and delay presentation diagnosis.

Treatment with proton pump inhibitors may slightly increase the risk of gastrointestinal infection with microorganisms such as Salmonella

and
Campylobacter
.

Effect on the cardiovascular and cerebrovascular systems

Naproxen: As with any NSAID, it is necessary to monitor and advise patients with a history of arterial hypertension and/or chronic heart failure, since NSAID therapy is accompanied by fluid retention and the development of edema.

Patients with uncontrolled hypertension, chronic heart failure, coronary artery disease, peripheral arterial disease and/or cerebrovascular accident should be prescribed naproxen only after careful evaluation. The same examination should be performed before starting long-term therapy in patients with risk factors for cardiovascular disease (for example, hypertension, hyperlipidemia, diabetes mellitus, smoking).

Based on clinical and epidemiological studies, naproxen therapy (1000 mg daily) may be associated with a lower risk of arterial thrombosis than selective COX-2 inhibitors, but this small risk cannot be excluded. Overall, the data do not support a cardioprotective effect.

Effects on the kidneys

Naproxen

: Long-term use of NSAIDs has led to the development of medullary necrosis and other kidney damage.

Nephrotoxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. In these patients, the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin synthesis and, secondarily, a reduction in renal blood flow, which may precipitate the development of overt renal failure. The greatest risk of developing such a reaction is present in patients with impaired renal function, hypovolemia, heart failure, liver failure, with excessive excretion of sodium chloride from the body, in patients taking diuretics, ACE inhibitors or angiotensin II receptor antagonists, and in elderly patients. After discontinuation of NSAID therapy, the patient's condition usually returns to its original state.

Use in patients with renal failure

Since naproxen is largely (95%) eliminated by the kidneys via glomerular filtration, great caution should be used when administering it to patients with renal impairment, and monitoring of serum creatinine levels and/or creatinine clearance in these patients is recommended. It is not recommended to prescribe Vimovo™ to patients with an initial creatinine clearance of less than 30 ml/min.

Hemodialysis does not reduce plasma concentrations of naproxen due to high binding to plasma proteins. Certain patients, especially those with impaired renal blood flow due to depletion of interstitial fluid volume, cirrhosis of the liver, limited salt intake, chronic heart failure and pre-existing kidney disease, should have their renal function assessed before and while taking Vimovo™. Some elderly patients with suspected renal impairment, as well as patients taking diuretics, ACE inhibitors, or angiotensin II receptor antagonists, also fall into this category. To prevent possible excessive accumulation of naproxen metabolites in these patients, the daily dose of the drug should be reduced.

Effect on the hematopoietic system

Naproxen

: It is necessary to prescribe drugs containing naproxen with caution to patients with coagulation disorders or receiving therapy that affects hemostasis.

The risk of bleeding in patients at high risk of bleeding or receiving full anticoagulation therapy (for example, dicumarol derivatives) increases with concomitant use of drugs containing naproxen. Naproxen reduces platelet aggregation and prolongs bleeding time. This should be kept in mind when determining bleeding time.

If active or clinically significant bleeding develops in any area in patients taking Vimovo™, therapy should be discontinued.

Dermatological effects

Naproxen

: Very rarely, serious skin reactions have occurred with the use of NSAIDs, some of which have resulted in death, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The greatest risk of developing such reactions exists at the beginning of therapy, and in most cases the onset of such reactions occurs in the first month of treatment. At the first sign of skin rash, lesions of the mucous membranes or other symptoms of hypersensitivity, you should stop taking Vimovo™.

Effect on visual function

If visual disturbances occur while taking Vimovo™, consultation with an ophthalmologist is recommended.

Anaphylactic (anaphylactoid) reactions

Naproxen

: Hypersensitivity reactions may occur in susceptible patients. Anaphylactic (anaphylactoid) reactions may occur in patients with or without a history of hypersensitivity, or with or without hypersensitivity to acetylsalicylic acid, other NSAIDs, or naproxen-containing drugs. These reactions may develop in patients with a history of angioedema, bronchospasm (eg, bronchial asthma), rhinitis and polypous rhinosinusopathy.

Patients with bronchial asthma

Naproxen

: The use of acetylsalicylic acid in patients with aspirin-induced asthma was accompanied by the development of severe bronchospasm, which could lead to the death of the patient. Since cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs has been observed in patients with hypersensitivity to acetylsalicylic acid, it is not recommended to prescribe Vimovo™ to patients with such hypersensitivity to acetylsalicylic acid and use caution in patients with bronchial asthma.

Inflammation

Naproxen

: The antipyretic and anti-inflammatory properties of naproxen may reduce fever and other signs of inflammation, thereby reducing their usefulness as diagnostic factors.

Combinations with other drugs

It is not recommended to use Vimovo™ concomitantly with NSAIDs (other than acetylsalicylic acid), including selective COX-2 inhibitors, due to the cumulative risks of developing serious adverse events associated with NSAIDs.

According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and esomeprazole (40 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel by an average of 40% and reducing the maximum inhibition of ADP-induced platelet aggregation by an average of 14%. Therefore, the simultaneous use of esomeprazole and clopidogrel should be avoided (see section “Interaction with other drugs and other types of drug interactions”).

Fertility in women

Naproxen

: There is some evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may reduce fertility in women by affecting ovulation. This effect is reversible after discontinuation of therapy. In this regard, women who have problems conceiving or are undergoing examination for infertility should consider discontinuing Vimovo™ (see section “Use during pregnancy and breastfeeding”).

Are common

If the daily dose of naproxen 1000 mg is not acceptable, alternative treatment regimens should be used.

Patients receiving long-term therapy (especially more than 1 year) must be constantly monitored. Individual observational studies indicate that proton pump inhibitor therapy may modestly increase the risk of osteoporosis-related fractures, but other similar studies have not reported an increased risk.

Randomized, double-blind, controlled clinical trials of omeprazole and esomeprazole, including two open-label studies of long-term therapy (more than 12 years), did not confirm the association of osteoporotic fractures with the use of proton pump inhibitors.

Although a causal relationship between the use of omeprazole/esomeprazole and osteoporotic fractures has not been established, patients at risk of developing osteoporosis or osteoporotic fractures should be under appropriate clinical supervision.