Naproxen + Esomeprazole (Naproxenum + Aesomeprazolum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

NSAIDs - Propionic acid derivatives

Proton pump inhibitors

Included in the formulation
  • Vimovo TM
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    AstraZeneca UK Ltd     United Kingdom
    • АТХ:

    M.01.A.E.52   Naproxen and esomeprazole

    Pharmacodynamics:

    Naproxen: inhibition of COX-1 and COX-2, leading to a reduction in the synthesis of prostaglandins and thromboxane. Pharmacological effects: anti-inflammatory: develops in 1-2 weeks from the beginning of application, analgesic: the onset of action in 30 minutes, the duration is up to 8 hours, antipyretic, antidisguinogenic, weakening of headaches of vascular origin, antiaggregant: reversibly inhibits platelet aggregation. Functions of platelets are restored 1 day after discontinuation of admission.

    Esomeprazole: a prodrug protonated in the acid medium of a parietal cell esomeprazole causes irreversible inhibition of the proton pump (H+,TO+-ATPase) parietal cells of the gastric mucosa.

    Pharmacological effects: inhibition of basal and stimulated secretion of hydrochloric acid in the stomach. The onset of action is 1 hour, the duration of action is up to 72 hours, the total recovery of hydrochloric acid production is achieved in 4 days.

    Pharmacokinetics:

    Absorption naproxena full, fast; decreases when taken simultaneously with food, increases when sodium bicarbonate is taken from sodium. The connection with plasma proteins is 99%.Biotransformation occurs in the liver. The elimination half-life is 13 hours. Elimination by the kidney is 95%.

    Bioavailability of esomeprazole 50-64%, increases with repeated administration to approximately 68 and 89% for doses of 20 and 40 mg, respectively. Half-life 0.5-1 hour. The connection with plasma proteins is 97%. Biotransformation in the liver predominantly CYP2S19, to a lesser extent CYP34 with the formation of inactive metabolites. With repeated administration, the effect of primary passage through the liver, probably related to inhibition of CYP2C19 activity, decreases. The administration of equimolar doses of the S and R isomers results in a higher plasma concentration of the S-, rather than the R-isomer. Clearance - 500-600 ml / min. Elimination of the kidneys 70-80% (inactive metabolite), with faeces 20-30% (inactive metabolite).

    Indications:

    Inflammatory and degenerative diseases of the musculoskeletal system, including rheumatoid arthritis, osteoarthrosis, ankylosing spondylitis, articular syndrome with exacerbation of gout, juvenile rheumatoid arthritis; pain syndrome: neuralgia, myalgia, ossalgia, radiculitis, headache and toothache, tendonitis, pain in cancer, postoperative pain syndrome, accompanied by inflammation,injuries of the musculoskeletal system and soft tissues, adnexitis, primary dysmenorrhea; pain and febrile state with infectious-inflammatory diseases of the upper respiratory tract (as part of complex therapy).

    ICD-10

    XVIII.R00-R09.R07.4   Chest pain, unspecified

    XVIII.R00-R09.R07.2   Pain in the region of the heart

    XVIII.R00-R09.R07.1   Chest pain with breathing

    XVIII.R00-R09.R07.0   A sore throat

    XVIII.R00-R09.R07   Sore throat and chest

    XIII.M70-M79.M79.6   Pain in the limb

    XIII.M50-M54.M54.6   Pain in the thoracic spine

    XIII.M50-M54.M54.5   Lower back pain

    XIII.M20-M25.M25.5   Pain in the joint

    XIII.M05-M14.M13.9   Arthritis, unspecified

    XIII.M05-M14.M13.8   Other specified arthritis

    XIII.M05-M14.M13   Other arthritis

    XIII.M05-M14.M06.8   Other specified rheumatoid arthritis

    XIII.M00-M03.M01.5 *   Arthritis in other viral diseases classified elsewhere

    XIII.M00-M03.M00   Pyogenic arthritis

    XIII.M15-M19.M19.9   Osteoarthritis, unspecified

    XIII.M15-M19.M19.8   Other specified arthrosis

    XIII.M15-M19.M19.2   Secondary arthrosis of other joints

    XIII.M15-M19.M19.1   Post-traumatic arthrosis of other joints

    XIII.M15-M19.M19.0   Primary arthrosis of other joints

    XIII.M15-M19.M19   Other arthrosis

    XIII.M15-M19.M18.9   Osteoarthritis of first carpometacarpal joint, unspecified

    XIII.M15-M19.M18.5   Other secondary arthrosis of the first carpometacarpal joint

    XIII.M15-M19.M18.4   Other secondary arthrosis of the first carpometacarpal joint is bilateral

    XIII.M15-M19.M18.3   Other posttraumatic arthrosis of the first carpometacarpal joint

    XIII.M15-M19.M18   Osteoarthritis of the first carpometacarpal joint

    XIII.M15-M19.M15.4   Erosive (osteo) arthrosis

    XIII.M15-M19.M15.3   Secondary multiple arthrosis

    XIII.M15-M19.M15.0   Primary generalized (osteo) arthrosis

    XIII.M15-M19   Osteoarthritis

    XIII.M70-M79.M79.1   Myalgia

    I.B25-B34.B33.0   Epidemic myalgia

    XIV.N70-N77.N70.9   Salpingitis and oophoritis, unspecified

    XIV.N70-N77.N70.1   Chronic salpingitis and oophoritis

    XIV.N70-N77.N70.0   Acute salpingitis and oophoritis

    XIV.N70-N77.N70   Salpingitis and oophoritis

    Contraindications:

    Hypersensitivity, "aspirin" asthma, "aspirin" triad (combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance of acetylsalicylic acid and preparations of pyrazolone series), erosive and ulcerative lesions of the gastrointestinal tract in the phase of exacerbation, hematopoiesis, hepatic and / or renal insufficiency , children under 1 year.

    Carefully:

    Severe heart failure, adolescence (up to 16 years).

    Pregnancy and lactation:

    Category FDA AT.

    Teratogenic effects. In studies of reproduction in animals with the administration of naproxen in doses of 20 mg / kg per day (125 mg / m2 per day), which is approximately equivalent to 0.23 MPHP,Rabbits - 20 mg / kg per day (220 mg / m2 per day), or 0.27 MPD, mice - 170 mg / kg / day (510 mg / m2 per day), or 0.28 MPHP, there was no violation fertility or harm to the fetus.

    However, reproductive studies in animals do not always predict effects in humans. Adequate and strictly controlled studies in pregnant women have not been conducted. Use in pregnancy is possible if the expected effect of therapy exceeds the potential risk to the fetus.

    Nonteratogenic effects. Since it is known that prostaglandin synthesis inhibiting agents are used to delay premature delivery, the risk of neonatal complications such as necrotizing enterocolitis, open arterial duct, intracranial hemorrhage increases. The use of naproxen in the late period of pregnancy can lead to a delay in labor, persistent pulmonary hypertension, renal dysfunction, an abnormal level of prostaglandin E in prematurely born children. Since the effects of substances of this class on the fetal cardiovascular system are known (closure of the botulinum duct), use in the III trimester is excluded.

    It is not recommended to use in the III trimester of pregnancy due to the potential risk of premature closure of the open ductus arteriosus.

    Because of potential carcinogenicity and the likelihood of serious side effects in infants, a decision should be made to discontinue therapy with the drug during lactation or stop lactation, the time of treatment with the drug, depending on the importance of therapy for the mother.

    Dosing and Administration:

    Inside, the average dose for adults is 250-500 mg 2 times a day, the maximum single dose is 500 mg, the maximum daily intake is 1750 mg in 2 divided doses (morning and night).

    The average daily dose for children from 1 to 5 years is 2.5-10 mg / kg body weight in 1-3 doses, children over 5 years - 10 mg / kg per day in 2 divided doses, the usual duration of treatment is 2 weeks ( the preferred dosage form for children is a suspension); with juvenile arthritis in children older than 5 years, the daily dose is 10 mg / kg.

    Side effects:

    The side effects most commonly encountered in clinical trials (possibly related to the use of naproxen)

    On the part of the intestine: 3-9% - heartburn, abdominal pain,nausea, constipation; > 1% - diarrhea, indigestion, stomatitis; <1% - flatulence, bleeding / perforation, gastrointestinal ulcers (gastroduodenal), vomiting, increased activity of hepatic transaminases.

    From the nervous system and sensory organs: 3-9% - headache, drowsiness, dizziness, tinnitus, visual impairment, hearing impairment; > 1% - vertigo.

    From the cardiovascular system and blood (hematopoiesis, hemostasis):> 1% - palpitation; <1% - anemia, increased bleeding time.

    On the part of the respiratory system: 3-9% - dyspnea.

    From the skin: 3-9% - ecchymosis.

    From the genitourinary system: <1% - renal dysfunction.

    Allergic reactions: 3-9% - itching, skin rashes, anaphylactoid reactions.

    Other: 3-9% - edema; > 1% - increased sweating, purpura, thirst.

    Side effects that occurred with a frequency of <1% in clinical trials and in post-marketing studies (possibly related to the use of naproxen)

    On the part of the intestine: colitis, hematemesis, jaundice, pancreatitis, melena.

    From the genitourinary system: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal failure, renal papillary necrosis.

    From the cardiovascular system and blood (hematopoiesis, hemostasis): agranulocytosis, eosinophilia, granulocytopenia, leukopenia, thrombocytopenia.

    From the nervous system and sensory organs: depression, unusual dreams, inability to concentrate, insomnia, malaise, myalgia, muscle weakness.

    Side effects occurred with a frequency of <1% (causal connection with application of naproxen not established):

    From the cardiovascular system and blood (hematopoiesis, hemostasis): aplastic anemia, hemolytic anemia.

    From the nervous system and sensory organs: aseptic meningitis, cognitive dysfunction.

    On the part of the digestive tract: non-peptic ulceration of the gastrointestinal tract, ulcerative stomatitis.

    Allergic reactions: epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, urticaria; photosensitivity reactions similar to bullous porphyric epidermolysis.

    Others: vasculitis, hyperglycemia, hypoglycemia, alopecia, photodermatitis.

    Overdose:

    Symptoms: drowsiness, lethargy, dizziness, epigastric pain, abdominal discomfort, heartburn, dyspepsia, nausea, transient liver dysfunction,hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation, vomiting; possibly bleeding from the gastrointestinal tract; rarely - hypertension, acute renal failure, respiratory depression, coma.

    Treatment: gastric lavage, induction of vomiting and / or administration of activated charcoal (60-100 g for adults, 1-2 g / kg for children) and / or osmotic laxatives, symptomatic and supportive therapy. A specific antidote was not found. Forced diuresis, alkalization of urine or hemodialysis are not effective due to high binding to proteins.

    Interaction:

    When used simultaneously with antacids containing magnesium and aluminum, sodium hydrogen carbonate, decreases the absorption of naproxen.

    With simultaneous use with indirect anticoagulants, cases of slight enhancement of the effect of anticoagulants are described.

    With simultaneous use with amoxicillin, a case of developing a nephrotic syndrome is described; with acetylsalicylic acid - it is possible to reduce the concentration of naproxen in the blood plasma.

    With simultaneous application, it is possible to change the pharmacokinetic parameters of diazepam; with caffeine - the effect of naproxen is enhanced; with lithium carbonate -it is possible to increase the concentration of lithium in blood plasma; with methotrexate - may increase the toxicity of methotrexate.

    There are reports of the development of myoclonus when used simultaneously with morphine.

    With simultaneous use with prednisolone, a significant increase in the concentration of prednisolone in the blood plasma is possible; with probenecid - a decrease in the concentration of naproxen in the blood plasma; with salicylamide - increases the effect of salicylamide.

    With simultaneous application with furosemide, a decrease in the diuretic effect of furosemide is possible.

    Special instructions:

    With caution apply for liver and kidney disease, gastrointestinal diseases in history, with dyspeptic symptoms, with arterial hypertension, heart failure, immediately after serious surgical interventions.

    In the process of treatment, systematic monitoring of liver and kidney function, a picture of peripheral blood is necessary.

    If it is necessary to determine the concentration of 17-ketosteroids naproxen should be canceled 48 hours before the test.

    Impact on the ability to drive vehicles and manage mechanisms

    During the period of application, it is necessary to refrain from potentially dangerous activities related to the need for concentration of attention and increased speed of psychomotor reactions.

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