Ketonal Duo capsules 150mg, No. 30

Symptomatic therapy of painful and inflammatory processes of various origins, including:
- inflammatory and degenerative diseases of the musculoskeletal system:
Х rheumatoid arthritis;
Х seronegative arthritis: ankylosing spondylitis - ankylosing spondylitis, psoriatic arthritis, reactive arthritis (Reiter's syndrome);
Х gout, pseudogout;
Х osteoarthritis;
- pain syndrome:
Х headache;
Х tendinitis, bursitis, myalgia, neuralgia, sciatica;
Х post-traumatic and postoperative pain syndrome;
Х pain syndrome in cancer;
Х algodismenorrhea.

Inside.
The standard dose of KetonalЃ DUO for adults and children over 15 years old is 150 mg / day (1 modified-release capsule). Capsules should be taken during or after meals with water or milk (the volume of liquid must be at least 100 ml).
The maximum dose of ketoprofen is 200 mg / day.

1 capsule contains: pellet core: active ingredient: ketoprofen - 150.00 mg;

excipients: microcrystalline cellulose - 34.00 mg; lactose monohydrate - 20.00 mg; povidone - 5.00 mg; croscarmellose sodium - 10.00 mg; polysorbate 80 - 1.00 mg;

Х Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other non-steroidal anti-inflammatory drugs;
Х complete and incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) (including a history);
Х gastric ulcer or duodenal ulcer in the acute stage, ulcerative colitis, Crohn's disease in the acute phase, inflammatory bowel diseases in the acute phase;
Х hemophilia and other blood clotting disorders;
Х children's age (up to 15 years old);
Х severe liver failure;
Х severe renal failure (creatinine clearance (CC) less than 30 ml / min), progressive kidney disease;
Х decompensated heart failure;
Х postoperative period after coronary artery bypass grafting;
Х gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding);
Х lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
Х chronic dyspepsia;
Х III trimester of pregnancy;
Х lactation period.

Carefully: history of peptic ulcer disease, history of bronchial asthma, clinically severe cardiovascular, cerebrovascular and peripheral arterial diseases, dyslipidemia, progressive liver disease, hyperbilirubinemia, alcoholic liver cirrhosis, renal failure (CC 30-60 ml / min), chronic heart disease insufficiency, arterial hypertension, blood diseases, dehydration, diabetes mellitus, history of the development of ulcerative lesions of the gastrointestinal tract, smoking, concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid), glucocorticosteroids for oral administration (for example, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), long-term use of NSAIDs, the presence of infectionHelicobacter pylori, liver failure, old age.

Pharmacological properties

Pharmacodynamics
Ketoprofen is a non-steroidal anti-inflammatory drug.
Ketoprofen has anti-inflammatory, analgesic and antipyretic effects.
Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX1 and COX2) and, in part, lipoxygenase, which leads to suppression of prostaglandin synthesis (including in the central nervous system, most likely in the hypothalamus).
Stabilizes liposomal membranes in vitro and in vivo; at high concentrations in vitro, ketoprofen inhibits the synthesis of bradykinin and leukotrienes.
Ketoprofen does not adversely affect the condition of the articular cartilage.
Pharmacokinetics
Absorption
KetonalЃ DUO is a new dosage form that differs from conventional capsules in the way the active substance is released. Modified release capsules contain two types of pellets: white (about 60% of the total) and yellow (40% of the total, coated). Ketoprofen is quickly released from white pellets and slowly from yellow ones, which results in a combination of fast and prolonged action of the drug.
The drug is well absorbed after oral administration. The bioavailability of both conventional capsules and modified-release capsules is the same and amounts to 90%.
Food intake does not affect the overall bioavailability (AUC) of ketoprofen, but decreases the rate of absorption.
After oral administration of ketoprofen in the form of capsules with modified release of 150 mg, the maximum plasma concentration (Cmax) = 9036.64 ng / ml is achieved within 1.76 hours.
Distribution
Ketoprofen is 99% bound to plasma proteins, mainly to the albumin fraction.
The volume of distribution in tissues is 0.1-0.2 l / kg. The drug penetrates well into the synovial fluid and reaches a concentration equal to 30% of the plasma concentration there.
Significant concentrations of ketoprofen in the synovial fluid are stable and persist up to 30 hours, as a result of which pain and stiffness of the joints decreases for a long time.
Metabolism and excretion
Ketoprofen is extensively metabolized by liver microsomal enzymes, the half-life (T1 / 2) of ketoprofen is less than 2 hours. It binds to glucuronic acid and is excreted from the body as glucuronide. There are no active metabolites of ketoprofen.
Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly in the form of ketoprofen glucuronide. When using the drug in a dosage of 100 mg or more, excretion by the kidneys may be difficult. In patients with severe renal impairment, most of the drug is excreted through the intestines. When high doses are taken, hepatic clearance also increases. Up to 40% of the drug is excreted through the intestines.
In patients with hepatic insufficiency, the plasma concentration of ketoprofen is doubled (probably due to hypoalbuminemia, and, as a result, a high level of unbound active ketoprofen); such patients need to prescribe the drug in the minimum therapeutic dose.
In patients with renal insufficiency, the clearance of ketoprofen is reduced, which also requires a reduction in dosage.
In elderly patients, the metabolism and excretion of ketoprofen are slower, but this is of clinical importance only for patients with reduced renal function.

Application during pregnancy and during breastfeeding

Inhibition of prostaglandin synthesis can have an undesirable effect on the course of pregnancy and / or on embryonic development. Data obtained in the course of epidemiological studies with the use of inhibitors of prostaglandin synthesis in early pregnancy confirm an increased risk of spontaneous abortion and the formation of heart defects (~ 1-1.5%).
It is possible to prescribe the drug to pregnant women in the I and II trimesters of pregnancy only if the benefits to the mother justify the possible risk to the fetus.
The use of ketoprofen in pregnant women during the third trimester of pregnancy is contraindicated due to the possibility of developing weakness of labor activity of the uterus and / or premature closure of the ductus arteriosus, a possible increase in bleeding time, oligohydramnios and renal failure.
To date, there are no data on the release of ketoprofen into breast milk, therefore, if it is necessary to prescribe ketoprofen to a nursing mother, the question of stopping breastfeeding should be decided.

Side effect

Violations of the hematopoietic and lymphatic system are
rare: hemorrhagic anemia;
frequency unknown: agranulocytosis, thrombocytopenia, bone marrow dysfunction.
Immune system disorders,
frequency unknown: anaphylactic reactions (including anaphylactic shock).
Nervous system disorders are
infrequent: headache, dizziness, drowsiness;
rarely: paresthesia;
frequency unknown: convulsions, impaired taste.
Mental disorders:
frequency unknown: emotional lability.
Sensory disorders are
rare: blurred vision, tinnitus.
Cardiovascular disorders
frequency unknown: heart failure, increased blood pressure, vasodilation.
Respiratory system disorders are
rare: exacerbation of bronchial asthma;
frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
Disturbances from the gastrointestinal tract
are often: nausea, vomiting, dyspepsia, abdominal pain;
infrequently: constipation, diarrhea, bloating, gastritis;
rarely: peptic ulcer, stomatitis;
very rare: exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding, perforation.
Violations of the liver and biliary tract are
rare: hepatitis, increased activity of 'hepatic' transaminases, increased concentration of bilirubin.
Skin disorders are
uncommon: skin rash, itching;
frequency unknown: photosensitivity, alopecia, urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.
Disturbances from the urinary system, the
frequency is unknown: acute renal failure, interstitial nephritis, nephritic syndrome, nephrotic syndrome, abnormal values ??of renal function indicators.
Other
infrequent: edema;
rarely: weight gain;
frequency unknown: increased fatigue.

Overdose

As with other NSAIDs, with an overdose of ketoprofen, nausea, vomiting, abdominal pain, vomiting of blood, melena, impaired consciousness, respiratory depression, seizures, impaired renal function and renal failure may occur.
In case of an overdose, gastric lavage and the use of activated carbon are indicated.
Treatment is symptomatic; The effects of ketoprofen on the gastrointestinal tract (GI tract) can be mitigated with H2-histamine receptor blockers, proton pump inhibitors, and prostaglandins.

Interaction with other medicinal products

Ketoprofen can weaken the effect of diuretics and antihypertensive drugs and enhance the effect of hypoglycemic drugs for oral administration and some anticonvulsants (phenytoin).
Simultaneous use with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of developing adverse events from the gastrointestinal tract.
Simultaneous use with anticoagulants (heparin, warfarin), thrombolytics, antiplatelet agents (ticlopidine, clopidogrel), pentoxifylline increases the risk of bleeding.
Concomitant use with potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia.
Increases the concentration in blood plasma of cardiac glycosides, blockers of 'slow' calcium channels, lithium preparations, cyclosporine, methotrexate and digoxin.
Increases the toxicity of methotrexate and the nephrotoxicity of cyclosporine.
Concomitant use with probenecid significantly reduces the plasma clearance of ketoprofen.
Combined use with glucocorticosteroids and other NSAIDs (including selective COX2 inhibitors) increases the likelihood of side effects (in particular, from the gastrointestinal tract).
NSAIDs can reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8-12 days after discontinuation of mifepristone.

special instructions

Do not combine ketoprofen with other NSAIDs and / or COX2 inhibitors. With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical blood test, monitor the function of the kidneys and liver, especially in elderly patients (over 65 years old), and conduct a fecal occult blood test.
Care must be taken and blood pressure should be monitored more often when using ketoprofen to treat patients with arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.
In the event of violations of the organs of vision, treatment should be stopped immediately.
Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. In case of detection of signs of infection or deterioration of health while using the drug, you should immediately consult a doctor.
If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high doses of ketoprofen, the patient should be under close medical supervision.
Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing ketoprofen to patients with heart or renal failure, as well as when treating elderly patients taking diuretics and patients who, for any reason, have a decrease in circulating volume. blood. The drug should be discontinued before major surgery.
The use of ketoprofen can affect female fertility, so patients with infertility (including those undergoing examination) are not recommended to use the drug.

Influence on the ability to drive vehicles, mechanisms

There are no data on the negative effect of KetonalЃ DUO in recommended doses on the ability to drive a car or work with mechanisms. When driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, care must be taken, since the drug can cause dizziness and other side effects that may affect these abilities.