Instruction for use: Ibuprofen + Paracetamol (Ibuprophenum+ Paracetamolum)

Pharmacological group

NSAIDs - Propionic acid derivatives in combinations

Anilides in combinations

Nosological classification (ICD-10)

G43 Migraine

The pain of migraine, Migraine, hemiplegic migraine, Migraine headache, A migraine attack, Continuous headache, hemicranias

H92.0 Otalgia

Pain in the region of the external auditory canal, Ear pain, Ear pain with otitis

J06 Acute upper respiratory infections of multiple and unspecified

Frequent colds viral diseases, Infections of the upper respiratory tract, Acute respiratory disease influenza character, for colds Pain, Acute colds,Cold, respiratory infection,Seasonal colds, Pain in infectious and inflammatory diseases of the upper respiratory tract, Bacterial infections of the upper respiratory tract, Bacterial respiratory infections, Viral disease of the respiratory tract, Viral respiratory tract infections, Inflammatory disease of the upper respiratory tract, Inflammation of the upper respiratory tract disease, Inflammation of the upper respiratory tract illness with difficult sputum, Inflammatory airway disease, Secondary infections with colds, Shortness of sputum in acute and chronic respiratory diseases, Upper respiratory tract infection, Infections of the upper respiratory tract, Respiratory Tract Infections, Infections of the respiratory tract and lungs, Infectious-inflammatory diseases of the upper respiratory tract, Infectious-inflammatory diseases of the upper respiratory tract and ENT-organs, Infectious-inflammatory diseases of the upper respiratory tract in children and adults, Infectious-inflammatory diseases of the upper respiratory tract, Infectious inflammation of the airways,respiratory infection, Qatar upper respiratory tract, Catarrh of the upper respiratory tract, Catarrhal disease of the upper respiratory tract, Catarrhal symptoms of the upper respiratory tract, Coughing with a cold, SARS, ARI, ARI with rhinitis phenomena, Acute respiratory infection, Acute infectious and inflammatory disease of the upper respiratory tract, Acute respiratory disease, Sore throat or nose, Respiratory viral infections, Respiratory diseases, Respiratory infections, Recurrent respiratory infections, Secondary infection with influenza, cold in the chest, Feverish condition with flu usitis, acute sinusitis, genyantritis, purulent sinusitis

J11 Influenza, virus not identified

Flu, Influenza in the early stages of the disease, Flu in children, cold in the chest, Begins flu-like condition, Acute disease parainfluenza, parainfluenza, parainfluenza state, influenza epidemics, The pains of the flu, Influenza

K08.8.0 * Painful toothache

Dentinal pain, Dentinal pains, Pain pulpitis, Anesthesia in dentistry, Pain syndromes in dental practice, Pain after removal of tartar, Pain when extracting a tooth, Toothache, Pain after dental interventions

M25.5 Pain in the joint

Arthralgia, Pain syndrome in musculo-articular diseases, Pain syndrome in osteoarthritis, Pain syndrome in osteoarthritis, Pain syndrome in acute inflammatory diseases of the musculoskeletal system, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Pain in the joints, Soreness of the joints, Soreness of joints in severe physical exertion, Painful inflammatory joint damage, Painful conditions of the musculoskeletal system, Painful joint conditions, Painful traumatic affection of joints, Pain in the musculoskeletal system, Pain in Shoulder Joints, Pain in the joints, Joint pain, Joint pain with injuries, Musculoskeletal pain, Pain with osteoarthritis, Pain in the pathology of the joints, Pain in rheumatoid arthritis, Pain in chronic degenerative bone diseases, Pain in chronic degenerative joint diseases, Bone-joint pain, Joint pain, Arthritic pain of rheumatic origin, Articular pain syndrome, Joint pain, Rheumatic pain, Rheumatic pains

M54 Dorsalgia

Pain in the back area, Pain in the spine, Back pain, Pain in different parts of the spine, Backache, Painful pain syndrome in the spine, Pain in the musculoskeletal system

M79.1 Myalgia

Myofascial pain syndromes ,Pain syndrome in musculo-articular diseases, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Pain in the muscles, Tenderness of muscles, Muscular soreness in severe physical exertion, Painful conditions of the musculoskeletal system, Pain in the musculoskeletal system, Pain in the muscles, Pain at rest, Muscle aches, Muscle pain, Musculoskeletal pain, Myalgia, Muscle pain, Muscle pain at rest, Muscle pain, Muscular pain of non-rheumatic origin, Muscle pain of rheumatic origin, Acute muscle pain, Rheumatic pain, Rheumatic pains, Myofascial syndrome, Fibromyalgia

M79.2 Neurology and neuritis, unspecified

Pain syndrome with neuralgia, Brachialgia, Occipital and intercostal neuralgia, Neuralgia, Neuralgic pain, Neuralgia, Neuralgia of intercostal nerves,Neuralgia of the posterior tibial nerve, Neuritis, Neuritis traumatic, Neuritis, Neurological Pain Syndromes, Neurological contractures with spasms, Acute neuritis, Peripheral neuritis,Post-traumatic neuralgia,Severe pain of a neurogenic nature, Chronic neuritis, Essential neuralgia

M89.9 Disease of bone, unspecified

Local osteopathy, Disturbance of bone mineralization processes, Osteopenia, Pain syndrome in acute inflammatory diseases of the musculoskeletal system, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Pain in the musculoskeletal system, Infection of bones, Ossalgia, Pain in chronic degenerative bone diseases

M95.8 Other specified musculoskeletal deformities

Degenerative and dystrophic disease of the musculoskeletal system ,Degenerative disease of the musculoskeletal system, Obmenno-dystrophic diseases of the musculoskeletal system

M95.9 Acquired deformities of musculoskeletal system, unspecified

Age deformation of the musculoskeletal system

N94.6 Dysmenorrhea Unspecified

Pain during menstruation, Functional disorders of the menstrual cycle, Menstrual cramps, Emmeniopathy, Pain during menstruation, Painful menstrual irregularities, algomenorrhea, algomenoreya, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Disalgomenoreya, dysmenorrhea, Dysmenorrhea (essential) (Exfoliative), menstrual disorder, menstruation painful, metrorrhagia, Violation of the menstrual cycle, Menstrual irregularities, Prolaktinzavisimoe menstrual disorders, Prolaktinzavisimoe menstrual dysfunction, Pain spasm of smooth muscles of internal organs, Spasmodic dysmenorrhea, Primary disalgomenoreya

R07.0 Sore throat

A sharp pain in the throat, Sore throat

R50.0 Fever with chills

High fever, Heat, Chills, elevated temperature, hyperthermia, Prolonged fever, Feverish syndrome, Fervescence, Increased body temperature in infectious and inflammatory diseases, fever Symptoms, febrile syndrome, Febrile state, Fever, Fever in infectious and inflammatory diseases, Fever with SARS, Fever with cold, Fever for colds, febrility, Feverish condition with flu, Feverish state in infectious and inflammatory diseases , Feverish state of infectious diseases and in the postoperative period, Feverish condition for colds, Febrile of different genesis, Feverish syndrome on the background of infectious diseases, Feverish syndrome in infectious and inflammatory diseases, Feverish syndrome with colds, Feverish syndrome of different genesis, Increased temperature for colds, Increased temperature at catarrhal and infectious and inflammatory diseases, Increased body temperature in cold, etc., Increased body temperature in cold and other infectious and inflammatory diseases, Increased body temperature in cold and other infectious and inflammatory diseases, Fever during pregnancy, Fever with thrombocytopenia, Febrile reaction in blood transfusion

R51 Headache

Pain in the head, Cephalgia, Pain with sinusitis, Pain in the back of the head, Painful headache, Headache of vasomotor genesis, Headache of vasomotor origin, Headache with vasomotor disorders, Headache, Neurological headache, Serial headache

R52.0 Acute pain

Acute pain syndrome, Acute pain syndrome with osteoarthritis, Acute pain syndrome of traumatic origin, Severe pain of a neurogenic nature, Severe pain, Pain syndrome at delivery

R52.2 Other constant pain

Pain syndrome, rheumatic origin, Pain at vertebral lesions, Pain in the chamber, Pain for burns, Pain syndrome weak or moderate, Perioperative pain,Moderate to severe pain, Moderately or weakly expressed pain syndrome, Moderate to severe pain, Ear pain of otitis, Neuropathic pain, neuropathic pain

R52.9 Unspecified Pain

Pain after cholecystectomy, Pain shooting, Non-malignant pain, Obstetric and gynecological pain, Pain syndrome, Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain of inflammatory genesis, Pain than cancer genesis, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after injuries, Pain after the removal of hemorrhoids, Pain at the non-rheumatic inflammation of nature, Pain in inflammatory lesions of the peripheral nervous system, Pain in diabetic neuropathy, Pain in acute inflammatory diseases of the musculoskeletal system, Pain when the tendon pathology, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs, Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Pain in trauma syndrome, Pain with injuries and after surgical interventions, Pain in chronic inflammatory diseases of the musculoskeletal system, Pain with duodenal ulcer, Pain syndrome in gastric ulcer, Pain syndrome in gastric ulcer and duodenal ulcer, pain, Pain during menstruation, pain syndromes, painful condition, Painful foot fatigue, Sore gums when wearing dentures, Soreness of the cranial nerves exit points, Painful menstrual irregularities, Painful dressings, Painful muscle spasm, Painful teeth growth, Melosalgia, Pain in the area of the surgical wound, Pain in the postoperative period, Pain in the body, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain after surgery, The pains of the flu, Pain in diabetic polyneuropathy, Pain for burns, Pain during sexual intercourse, Pain during diagnostic procedures, Pain during therapeutic procedures, for colds Pain, Pain in sinusitis, Pain in trauma, Pain traumatic, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, Pain after surgery, postoperative Pain, Pain postoperative and posttraumatic, posttraumatic pain, Pain when swallowing, Pain in infectious and inflammatory diseases of the upper respiratory tract, The pain of burns, The pain in traumatic muscle injury, Pain in trauma, The pain of tooth extraction, The pain of traumatic origin, Pain caused by spasm of smooth muscles, Expressed pain syndrome, Expressed pain syndrome, traumatic origin, Postoperative pain, Post-traumatic pain, Post-traumatic pain syndrome, Torpid pain, Traumatic pain, Traumatic pain, Mild pain, Moderately severe pain, Moderate pain, Polyarthralgia with polymyositis

R68.8.0 * Inflammatory syndrome

Painful syndrome of inflammatory genesis, Pain syndrome with inflammation of non-rheumatic nature, Pain syndrome with inflammatory lesions of the peripheral nervous system, Painful inflammation of the shoulder joint, Painful inflammation after trauma or surgery, Painful inflammation after surgery, Painful hemorrhoids, Inflammation of the tympanic membrane, Inflammation of the larynx, Inflammation of the gums, Inflammation of cellulose, Inflammation of lymph nodes, Tonsillitis, Inflammation of muscles, Inflammation of soft tissues, Inflammation of the mouth, Inflammation after surgery and trauma, Inflammation after orthopedic surgery, Inflammation after trauma, Inflammation in rheumatoid arthritis, Inflammation of the middle ear, Inflammatory gum disease, Inflammatory diseases of the eyelids, Inflammatory eye diseases, Inflammatory swelling of soft tissues, Inflammatory processes, Inflammatory processes after surgical interventions, Inflammatory process, Inflammatory Syndrome, Inflammatory syndrome of non-rheumatic origin, Inflammatory syndrome after surgery, Purulent infections, Infringements of function of a liver of an inflammatory etiology, Acute inflammation of the musculoskeletal tissue, Pre-inflammatory soft tissue inflammation

T14.0 Surface injury of unspecified body region

Abrasions, Scratch, Skin Wounds, Wounds of soft tissues, Hematoma, Hematoma of traumatic origin, Hematomas, Hematomas of muscles, Hematomas of soft tissues, Healing of the skin, Bruise, Bruising due to sprains and bruises, Microtrauma, External bruises, Small combing, Superficial hematoma, Superficial damage to the skin and mucous membranes, Subcutaneous hematoma, Post-traumatic hematoma, Post-traumatic disturbance of microcirculation, Skinness of the skin, Traumatic plexus lesions, Injury, Contusion of soft tissues, Joint bruise, Traumatic bruises, Traumatic injury, Primary treatment of surface contaminated wounds, Abrasion, Bruise

T14.2 Fracture in unspecified area of body

Internal fixation of bone fracture, Acute period after fractures of bones, Edema after interventions for fractures, Fracture, Fractures of bones, Reposition of bone fragments in fractures, Traumatic bone injuries, Traumatic bone injury,Injuries of the osteoarticular system, Injuries to bone tissue

T14.3 Dislocation, sprain and damage to the capsular-ligamentous apparatus of the joint of the unspecified area of the body

Painful stretching of muscles, Pain and inflammation in tension, Dislocation of dislocation, Degenerative changes in the ligamentous apparatus, Edema due to sprains and bruises, Edema after interventions for sprains, Damage and rupture of ligaments, The musculoskeletal system is damaged, Damage to ligaments, Damage to the joints, Ligament ruptures, Tendon tendons,Ruptures of the tendons of muscles,Stretching, Crick, Stretching of the muscle, Sprain, Tension of the tendons, Extensions,Stretch muscles, Sprains, Tension of the tendons, Injury of the musculoskeletal system, Injuries to the joints, Injuries of capsule-articular tissues, Injuries of the osteoarticular system, Injuries to ligamentsInjuries to the joints, Joint wounds, Stretching of the ligamentous apparatus, Habitual stretching and tearing

T14.6 Injury of muscles and tendons of unspecified body region

Pain syndrome in the pathology of tendons, Pain in tendons, Pre-inflammatory soft tissue inflammation, Muscle rupture, Rupture of muscles without compromising the integrity of the skin, Muscle ruptures, Soft tissue injuries, Injuries of muscle-tendon tissues, Muscle injuries, Soft tissue injuries, Injuries to tendons

T14.9 Injury unspecified

Pain syndrome after trauma, Pain syndrome with injuries, Pain syndrome with trauma and after surgery, Pain in case of injury, Pain of a traumatic nature, Joint pain with injuries, Postoperative and post-traumatic pain, Pain in case of injury, Pain of a traumatic origin, Severe pain syndrome of traumatic origin, Deep tissue damage, Deep scratches on the trunk, Closed injury, Minor Household Injuries, Minor skin damage, Violations of the integrity of soft tissues, Uncomplicated trauma, Extensive traumatic injury, Acute pain syndrome of traumatic origin, Edema with trauma, Postponed sports injuries, Post-traumatic pain, Soft tissue injuries, Joint wounds, Sports injuries, Injury, Traumatic pain, Traumatic pains, Traumatic infiltrate,Injuries to sports

T88.9 Complication of surgical and medical care, unspecified

Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after the removal of hemorrhoids, Pain in the application of excimer laser, Pain with injuries and after surgical interventions, Pain syndromes in the dental practice, Painful diagnostic intervention, Painful diagnostic manipulations, Painful instrumental diagnostic procedures, Painful instrumental manipulation, Painful treatments, Painful manipulations, Painful dressings, Painful therapeutic interventions, Pain in the area of the surgical wound, Pain in the postoperative period, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain during diagnostic procedures, Pain during therapeutic procedures, Pain in orthopedics, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, The pain after dental surgery, postoperative Pain, Pain postoperative and posttraumatic, The pain of tooth extraction, Inflammation after surgery or injury, Inflammation after orthopedic surgery, Inflammation after surgery, The inflammatory syndrome after surgery, Festering postoperative fistula, Operating wound, Complications after tooth extraction

Characteristics of substances Ibuprofen + Paracetamol

The combination of ibuprofen + paracetamol has anti-inflammatory, analgesic and antipyretic effects. Ibuprofen is characterized by a peripheral anti-inflammatory effect, while paracetamol also has a central analgesic effect.

Pharmacology

Pharmacological action - anti-inflammatory, antipyretic, analgesic.

Pharmacodynamics

Ibuprofen

The mechanism of action of ibuprofen, a derivative of propionic acid from the NSAID group, is due to inhibition of the synthesis of PG (prostaglandins) - mediators of pain, inflammation and hyperthermia. Non-selectively blocks COX (cyclooxygenase) -1 and COX-2, which inhibits the synthesis of PG. Has a fast directing analgesic, antipyretic and anti-inflammatory effect. Ibuprofen reversibly inhibits platelet aggregation.

Paracetamol

Non-selectively blocks COX, mainly in the central nervous system (CNS), affecting the centers of pain and thermoregulation. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on COX, which explains the almost complete absence of significant anti-inflammatory effect. The absence of influence on the synthesis of PG in peripheral tissues causes the absence of a negative effect on water-salt metabolism and gastrointestinal mucosa (gastrointestinal tract).

Pharmacokinetics

Ibuprofen

Quickly absorbed from the digestive tract after oral administration. Tmax after oral administration - about 1-2 hours T1 / 2 - (2 ± 0.5) h. Ibuprofen is characterized by active binding to plasma proteins (90-99%). Slowly penetrates into the joint cavity, accumulates in the synovial fluid, creating higher concentrations in it than in the blood plasma. After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into an active S-form. Metabolism of ibuprofen is carried out in the liver with the formation of two inactive metabolites (hydroxylated and carboxylated compounds). More than 90% is excreted by the kidneys (in an unchanged form not more than 1%) and to a lesser extent with bile - in the form of metabolites and their conjugates.

Paracetamol

Quickly absorbed from the digestive tract, Tmax - 10-60 min. Cmax is 5-20 μg / ml. The connection with plasma proteins is <10% and slightly increases with an overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations. It is evenly distributed in the liquid medium of the body. Penetrates through the BBB.

About 90-95% of paracetamol is metabolized in the liver with the formation of inactive conjugates with glucuronic acid (60%), taurine (35%) and cysteine (3%), as well as a small amount of hydroxylated and deacetylated metabolites. A small part of paracetamol is hydroxylated by microsomal enzymes to form highly active N-acetyl-n-benzoquinonimine, which is rendered harmless by binding to the sulfhydryl groups of glutathione in the liver. After an overdose of paracetamol, N-acetyl-n-benzoquinonimine can accumulate and lead to liver damage.

T1 / 2 is 2-3 hours. In patients with cirrhosis of the liver, T1 / 2 slightly increases. In elderly patients paracetamol clearance decreases and T1 / 2 increases. It is excreted by the kidneys, mainly in the form of glucuronide and sulfate conjugates (<5% in unchanged form). Breast milk penetrates <1% of the accepted dose of paracetamol. In children, the ability to form conjugates with glucuronic acid is lower than in adults.

Application of Ibuprofen + Paracetamol

Adults. Symptomatic therapy of infectious and inflammatory diseases (cold, flu), accompanied by fever, chills, headache, pain in the muscles and joints, sore throat; myalgia; neuralgia; backache; pain syndrome with inflammatory and degenerative diseases of the musculoskeletal system; pain with bruises, sprains, dislocations, fractures; post-traumatic and postoperative syndrome; toothache; algodismenorea (painful menstruation).

Children from 2 years. As an antipyretic drug for acute respiratory infections, influenza, childhood infections, post-vaccination reactions and other infectious and inflammatory diseases accompanied by fever; pain syndrome of mild or moderate intensity, incl. headache and toothache, migraine, neuralgia, pain in the ears and throat, stretch pain and other types of pain.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications

Hypersensitivity to the components of the combination ibuprofen + paracetamol, complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis); hepatic and / or renal insufficiency with Cl creatinine <30 ml / min; progressive kidney disease; active liver disease; severe heart failure (NYHA class III-IV functional class); ulcer of the stomach and duodenum (in the phase of exacerbation); bleeding or perforation of a gastrointestinal ulcer in an anamnesis, provoked by NSAID application; hemophilia and other disorders of blood clotting (including hypocoagulation), hemorrhagic diathesis; bleeding of any etiology; intracranial hemorrhage; hypersensitivity reactions (bronchospasm, angioedema, asthma, rhinitis, urticaria) associated with acetylsalicylic acid or other NSAIDs; period after aortocoronary shunting; inflammatory bowel disease; confirmed hyperkalemia; diseases of the optic nerve; pregnancy, lactation; children under 2 years; simultaneous intake of other drugs containing NSAIDs, including selective inhibitors of COX-2 and acetylsalicylic acid in doses exceeding 75 mg per day; simultaneous reception of other drugs containing paracetamol, in connection with an increased risk of serious adverse reactions.

Restrictions for use

Elderly age; chronic heart failure (I-II functional class according to NYHA classification); cardiac ischemia; arterial hypertension; cerebrovascular diseases; diseases of peripheral arteries; dyslipidemia / hyperlipidemia; cirrhosis of the liver with portal hypertension; viral hepatitis; nephrotic syndrome; renal failure with Cl creatinine <60 mL / min; benign hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson and Rotor syndrome); systemic lupus erythematosus and other systemic connective tissue diseases; a stomach ulcer or duodenal ulcer (in anamnesis); gastritis, enteritis, colitis; Helicobacter pylori infection; blood diseases of unclear etiology (leukopenia, anemia); bronchial asthma; diabetes; long-term use of NSAIDs; smoking; alcoholism; severe physical illness; simultaneous reception of oral GCS (including prednisolone); simultaneous reception of anticoagulants (including warfarin); simultaneous administration of antiaggregants (including clopidogrel); simultaneous reception of serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

pregnancy and lactation

The combination of ibuprofen + paracetamol is contraindicated in pregnancy.

If breastfeeding is necessary, breastfeeding should be discontinued.

In experimental studies, embryotoxic, teratogenic and mutagenic effects of the components of ibuprofen + paracetamol combination have not been established.

Side effects of Ibuprofen + Paracetamol

To reduce the risk of adverse reactions, use the lowest effective dose as little as possible with a short course.

To assess the frequency of side effects, the following criteria were used: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1000); very rarely (<1/10000); the frequency is unknown (the incidence of side effects can not be estimated).

From the central and peripheral nervous system: infrequently - headache, dizziness; very rarely - paresthesia, optic neuritis, drowsiness; frequency unknown - insomnia, anxiety, nervousness and irritability, psychomotor agitation, aseptic meningitis (more often in patients with autoimmune diseases), stroke.

Mental disorders: very rarely - confusion, depression, hallucinations.

From the CCC: very rarely - edema, increased blood pressure, heart failure; frequency unknown - tachycardia, angina pectoris, myocardial infarction, peripheral edema.

From the respiratory system, chest and mediastinum: very rarely - asthma, exacerbation of asthma, dyspnea, bronchospasm.

From the gastrointestinal tract: often - NSAID-gastropathy (abdominal pain, nausea, vomiting, heartburn, decreased appetite, diarrhea); infrequently - flatulence, constipation, ulceration of the gastrointestinal mucosa, which in some cases is complicated by perforation and bleeding; frequency unknown - irritation or dryness of the oral mucosa, mouth pain, ulceration of the gingival mucosa, aphthous stomatitis, gastritis, melena, pancreatitis, Crohn's disease, exacerbation of colitis.

From the hepatobiliary system: very rarely - hepatitis, jaundice, liver necrosis, liver dysfunction, leading to the development of hepatic insufficiency, hepatic encephalopathy.

From the side of the kidneys and urinary tract: very rarely - nephrotic syndrome; frequency unknown - acute renal failure, polyuria, cystitis, acute tubular necrosis, medullary nephronecrosis, interstitial nephritis.

From the side of the organ of hearing: very rarely - ringing or noise in the ears; frequency unknown - hearing impairment, hearing loss.

From the side of the organ of vision: very rarely - a vision disorder; frequency unknown - blurred vision or dilation, scotoma, dry and irritated eyes, conjunctival edema and eyelids (allergic origin).

Allergic reactions: infrequent - Quincke's edema; frequency unknown - anaphylaxis, afilaktoidnye reactions, anaphylactic shock, fever, multiple exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), eosinophilia, allergic rhinitis.

From the skin and subcutaneous tissues: infrequently - skin rash (usually erythematous or urticaria), maculopapular rash, itchy skin; very rarely - hyperhidrosis, purpura, photosensitivity; frequency unknown - exfoliative dermatitis.

From the hemopoiesis: very rarely - anemia (including hemolytic, aplastic), thrombocytopenia and thrombocytopenic purpura, agranulocytosis, and leukopenia.

The risk of ulceration of the gastrointestinal mucosa, bleeding (gastrointestinal, gingival, uterine, hemorrhoidal), visual impairment (impaired color vision, scotoma, optic nerve damage) increases with prolonged use of a combination of ibuprofen + paracetamol in large doses.

Laboratory indicators: often - an increase in the activity of hepatic transaminases, an increase in serum creatinine and urea concentration; frequency unknown - prolongation of bleeding time, decrease in serum glucose concentration, decrease in hematocrit, decrease in Hb concentration, pancytopenia.

Interaction

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which allows the development of severe intoxication in overdose.

Inhibitors of microsomal oxidation (including cimetidine) reduce the risk of hepatotoxic effects.

With the simultaneous use of ibuprofen reduces the effectiveness of uricosuric drugs.

The efficacy of furosemide and thiazide diuretics can be reduced because of sodium retention associated with inhibition of GHG synthesis in the kidneys.

Ibuprofen enhances the effect of direct (heparin) and indirect (coumarin and indanedione derivatives) anticoagulants, thrombolytic drugs (alteplase, anestreplase, streptokinase, urokinase), antiaggregants, colchicine - increases the risk of hemorrhagic complications.

Simultaneous administration of ibuprofen with SSRIs (citalopram, fluoxetine, paroxetine, sertraline) increases the risk of serious bleeding in the digestive tract.

With simultaneous use with acetylsalicylic acid, ibuprofen reduces its antiaggregant effect (possibly increasing the incidence of acute coronary insufficiency in patients receiving low-dose acetylsalicylic acid as antiplatelet drugs).

Ibuprofen may reduce the effectiveness of antihypertensive drugs.

Ibuprofen increases the concentration in the blood plasma of digoxin, phenytoin and lithium.

Ibuprofen (like other NSAIDs) should be used with caution in combination with acetylsalicylic acid or other NSAIDs and SCS due to an increased risk of adverse effects of this drug on the gastrointestinal tract.

Like other NSAIDs, ibuprofen, when used simultaneously with cardiac glycosides, can lead to an increase in the content of cardiac glycosides.

NSAIDs should not be used within 8-12 days after administration of mifepristone; the effect of mifepristone decreases.

With simultaneous use of ibuprofen (as well as other NSAIDs) and tacrolimus, the risk of nephrotoxicity of ibuprofen increases.

Ibuprofen may increase the concentration of methotrexate in the plasma.

With the simultaneous use of lithium-containing drugs and ibuprofen, lithium release decreases.

Caffeine increases the analgesic effect of ibuprofen.

Combined treatment with zidovudine and ibuprofen may increase the risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia.

Ibuprofen enhances the hypoglycemic effect of oral hypoglycemic agents and insulin; it may be necessary to adjust the dose.

Long-term combined use with cyclosporine, gold-containing drugs increases the risk of developing nephrotoxic effects. Cefamandol, cefaperazone, cefotetan, valproic acid, plikamycin increase the frequency of hypoprothrombinemia.

With prolonged treatment with carbamazepine and paracetamol, the risk of developing acute tubular nephronecrosis is increased.

The combination of paracetamol with ethanol, GCS, corticotropin increases the risk of erosive and ulcerative lesions of the digestive tract.

With prolonged use of paracetamol, the anticoagulant effect of warfarin and other coumarins increases, which leads to an increased risk of bleeding.

Antacids and colostiramie reduce the absorption of the combination ibuprofen + paracetamol.

Myelotoxic drugs promote the manifestation of hematotoxicity of the ibuprofen + paracetamol combination.

With the simultaneous administration of chloramphenicol and paracetamol, the concentration of chloramphenicol in the blood plasma increases.

Absorption of paracetamol increases with simultaneous administration with metoclopramide and domperidone. Nevertheless, there is no need to avoid concurrent administration of paracetamol with metoclopramide and domperidone.

Paracetamol increases the effect of MAO inhibitors with simultaneous application. When using paracetamol during treatment with MAO inhibitors and for 2 weeks after the end, there is a risk of developing arousal and fever.

Overdose

Symptoms: gastrointestinal disorders (diarrhea, nausea, vomiting, anorexia, epigastric pain), retardation, drowsiness, depression, headache, ear tinnitus, impaired consciousness, convulsions, heart rhythm disturbance, decreased blood pressure, acute pancreatitis, bleeding through 12-48 h (vomiting of blood, hematuria), hypoglycemia and anomalies of glucose metabolism, increase in PV and MHO. Overdose of paracetamol leads to toxic kidney damage with the development of nephronecrosis, acute renal failure and impaired liver function, sometimes leading to liver necrosis, with the possible development of hepatic insufficiency, encephalopathy, cerebral edema. Hepatotoxic effect in adults is manifested by taking 10 g of paracetamol and more. An overdose of ibuprofen leads to violations of the CNS - drowsiness, sometimes excitation, convulsions, disorientation or coma. If you suspect an overdose, seek medical help immediately.

Treatment: gastric lavage (only for an hour after ingestion), reception of activated charcoal, alkaline drink, forced diuresis, administration of SH-group donors and glutathione-methionine synthesis precursors 8-9 hours after an overdose and N-acetylcysteine by mouth or intravenously - after 12 hours, the appointment of antacid drugs, hemodialysis, symptomatic therapy (correction of KHS, AD). The need for additional therapeutic measures (further introduction of methionine, intravenous injection of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration. With frequent or prolonged cramps caused by an overdose of ibuprofen, iv administration of diazepam or lorazepam is indicated.

Precautions for Ibuprofen + Paracetamol

If there are signs of bleeding from the gastrointestinal tract, the combination should be canceled.

At simultaneous application of anticoagulants of indirect action it is necessary to supervise parameters of a coagulating system of blood.

With simultaneous use with SSRIs, the risk of developing gastrointestinal bleeding increases. Care should be taken when simultaneous use of ibuprofen with SSRIs is required.

The combination may mask objective and subjective signs of infection, so ibuprofen therapy in patients with infection should be administered with caution.

Clinical and epidemiological studies show that the use of ibuprofen, especially at high doses (2,400 mg / day) for a long time, may be associated with a slight increase in the risk of arterial thrombotic events (myocardial infarction or stroke).

To reduce the risk of developing adverse reactions, the minimum effective dose should be used as short a course as possible. With prolonged use of analgesics, there is a risk of developing analgesic nephropathy.

Anorexia and malnutrition increase the risk of side effects of paracetamol.

Due to the fact that ibuprofen can affect the PG-dependent processes of egg maturation, its administration is not recommended for women during pregnancy planning.

Patients who report visual impairment with ibuprofen therapy should stop treatment and undergo ophthalmic examination.

During treatment, it is necessary to monitor the picture of peripheral blood and the functional state of the liver and kidneys.

When symptoms of gastropathy appear, careful monitoring including esophagogastroduodenoscopy, a blood test with the determination of Hb, a hematocrit, a fecal occult blood test are shown.

To prevent the development of NSAID-gastropathy is recommended to combine with drugs containing PGE (misoprostol).

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the test.

Combination of ibuprofen + paracetamol with other NSAIDs should be avoided.

During the period of treatment, ethanol is not recommended.

Influence on the ability to drive vehicles, mechanisms. Patients should refrain from all activities requiring increased attention, rapid mental and motor reaction.