Ketonal Activ Plus granules of oral solution 80mg sachets, 12pcs

Composition

One two-volume sachet contains:

Active ingredient:

ketoprofen lysine salt-80.0 mg (equivalent to 50.0 mg of ketoprofen);

Auxiliary substances:

mannitol-1822.0 mg,

povidone K 30-40.0 mg,

mint flavor-20.0 mg,

sodium chloride-20.0 mg,

sodium saccharinate-15.0 mg,

colloidal silicon dioxide-3.0 mg

Pharmacological action

Pharmacotherapy group: nonsteroidal anti-inflammatory drug (NSAID). ATX code: M 01 AE 03Pharmacological Properties Pharmacodynamics

It has anti-inflammatory, analgesic and antipyretic effects. Inhibiting cyclooxygenase type I and II, it inhibits prostaglandin synthesis. It has anti-radikinin activity, stabilizes lysosomal membranes and delays the release of enzymes from them that contribute to tissue destruction in chronic inflammation. Reduces the release of cytokines, inhibits the activity of neutrophils.

Reduces morning stiffness and swelling of the joints, increases the amount of movement.

Ketoprofen lysine salt, unlike ketoprofen, is a fast-soluble molecule with a neutral pH and almost does not cause irritation of the gastrointestinal tract (GIT).

Pharmacokinetics

Suction

Ketoprofen when taken orally is rapidly and fairly fully absorbed from the gastrointestinal tract, its bioavailability is about 80%. The maximum concentration in blood plasma when taken orally is noted after 0.5-2 hours and directly depends on the dose taken. The equilibrium concentration of ketoprofen is reached 24 hours after the start of its regular intake.

Distribution

Up to 99% of the adsorbed ketoprofen binds to plasma proteins, mainly albumin. The volume of distribution is 0.1-0.2 l / kg. It easily passes through histohematic barriers and is distributed in tissues and organs. Ketoprofen penetrates well into synovial fluid and connective tissues. Although the concentration of ketoprofen in synovial fluid is slightly lower than in blood plasma, it is more stable (persists for up to 30 hours).

Metabolism

Ketoprofen is mainly metabolized in the liver, where it undergoes glucuronidation to form esters with glucuronic acid.

Deduction

Metabolites are excreted by the kidneys. The drug does not accumulate.

Indications

Inflammatory and degenerative diseases of the musculoskeletal system:

• rheumatoid arthritis;
• seronegative arthritis: ankylosing spondylitis (Ankylosing spondylitis), psoriatic arthritis, reactive arthritis (Reiter’s disease;
• gout, pseudogout;
• osteoarthritis;
• tendinitis, bursitis, myalgia, neuralgia, sciatica.

Pain syndrome, including mild, moderate, and severe:

• headache;
• toothache;
• post-traumatic and postoperative pain syndrome;
• pain syndrome in cancer;
• algodismenorrhea.

Children (older than 6 years): short-term symptomatic treatment of inflammatory processes accompanied by pain in combination with or without fever in diseases of the musculoskeletal system, otitis media.

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

Use during pregnancy and lactation

In the third trimester of pregnancy, the use of ketoprofen is contraindicated. In the first and second trimesters of pregnancy, the drug can only be prescribed if the intended benefit to the mother exceeds the potential risk to the fetus. The drug should not be used during breastfeeding.

Contraindications

• Hypersensitivity to the Active ingredient and other components of the drug, as well as other NSAIDs;
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid or other NSAIDs (including in the anamnesis);
• erosive-ulcerative lesions of the stomach and duodenum in the acute phase;
• active gastrointestinal, cerebrovascular or other bleeding;
• inflammatory bowel disease (ulcerative colitis, Crohn’s disease) in the acute stage;
• hemophilia and other blood clotting disorder;
• decompensated heart failure;
• since the coronary artery bypass surgery;
• severe hepatic impairment or active liver disease;
• severe renal insufficiency (creatinine clearance (CC) <30 ml/min), progressive kidney disease;
• confirmed hyperkalemia;
• children age (to 6 years);
• pregnancy (III trimester) and lactation.

With caution

Peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn’s disease, liver diseases (in the anamnesis), hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, significant decrease in the volume of circulating blood (including after surgery), elderly patients (including those receiving diuretics, weakened patients and low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, diabetes mellitus peripheral arteries, smoking, presence of Helicobacter pylori infection, long-term use of NSAIDs, tuberculosis, severe osteoporosis, alcoholism, severe somatic diseases, pregnancy (I, II trimester).

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency as follows: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥ 1 /1000, <1/100), rare (≥ 1/10,000, <1/1000) and very rare (

Disorders of the blood and lymphatic system:

• rare: hemorrhagic anemia;
• frequency unknown: thrombocytopenia, thrombocytopenic purpura, agranulocytosis, bone marrow dysfunction, leukocytopenia, leukocytosis, inflammation of the lymphatic vessels, vasculitis.

Immune system disorders: frequency unknown: anaphylactic reactions (including anaphylactic shock).

Disorders of the nervous system and sensory organs:

• infrequently: headache, dizziness, drowsiness;
• rarely: paresthesia, blurred vision, tinnitus;
• frequency unknown: convulsions, dysgeusia, mood changes, irritability, insomnia.

Cardiovascular disorders: frequency unknown: heart failure, tachycardia, palpitations, hypertension, hypotension, vasodilation.

Respiratory system disorders:

• rare: bronchial asthma;
• frequency unknown: bronchospasm (especially in patients with confirmed hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, shortness of breath, edema and laryngeal spasm.

Disorders of the gastrointestinal tract:

• common: nausea, vomiting, dyspepsia, abdominal pain;
• uncommon: constipation, diarrhea, bloating, gastritis;
• rare: stomatitis, stomach and duodenal ulcers;
• frequency unknown: exacerbation of ulcerative colitis or Crohn’s disease, gastrointestinal bleeding, perforation, heartburn.

Liver and biliary tract disorders: rare: hepatitis, increased activity of “hepatic” transaminases and increased concentration of bilirubin in the blood serum, caused by impaired liver function.

Skin and subcutaneous tissue disorders:

• infrequently: rash, pruritus;
• frequency unknown: photosensitization reactions, alopecia, urticaria, angioedema, bullous skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), erythema and exanthema, maculopapular rash, dermatitis.

Renal and urinary tract disorders: frequency unknown: acute renal failure, tubulointerstitial nephritis, nephritic syndrome, abnormal values of renal function indicators.

Other things:

• infrequently: edema, fatigue;
• frequency unknown: allergic and anaphylactoid reactions, oral mucosal edema, periorbital edema.

If any side effects occur, you should immediately stop taking the drug and consult a doctor.

Interaction

Combinations to avoid

Corticosteroids: increases the risk of ulceration of the gastrointestinal mucosa and gastrointestinal bleeding.

Anticoagulants (parenteral heparin, warfarin) increase the risk of bleeding caused by inhibition of platelet function and damage to the gastrointestinal mucosa. NSAIDs may increase the effects of anticoagulants such as warfarin.

Antiplatelet agents (clopidogrel, ticlopidine) and selective serotonin reuptake inhibitors: increased risk of bleeding caused by inhibition of platelet aggregation and damage to the gastrointestinal mucosa. Patients should be monitored if co-administration cannot be avoided.

Other NSAIDs, including high-dose salicylates (>3 g / day): concomitant use of several NSAIDs may increase the risk of ulceration of the gastrointestinal mucosa and gastrointestinal bleeding, due to a synergistic effect.

Lithium: NSAIDs increase the plasma level of lithium (reduced excretion of lithium in the kidneys), which can reach toxic levels. This parameter should be monitored at the beginning of treatment, during dose adjustment, and after discontinuation of ketoprofen treatment.

Methotrexate in high doses (more than 15 mg per week): the hematotoxicity of methotrexate increases, as its excretion by the kidneys decreases when taking anti-inflammatory drugs. When combined with methotrexate in low doses (less than 15 mg per week), a general blood test should be performed once a week during the first few weeks of treatment. It is mandatory to conduct more private monitoring of the patient’s clinical condition in the presence of even a slight deterioration in renal function, as well as in elderly patients.

Hydantoin and sulfamides: the toxic effects of these substances may increase.

Combinations that require precautions: Diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor antagonists: NSAIDs may reduce their effectiveness. In patients with impaired renal function (for example, patients with dehydration or elderly patients), concomitant use of ACE inhibitors or angiotensin II receptor antagonists with drugs that inhibit the cyclooxygenase system may cause additional renal dysfunction, including acute renal failure, usually reversible. Patients should be sufficiently hydrated before starting concomitant therapy, and renal function should be monitored after starting therapy.

Pentoxifylline: increases the risk of bleeding. Be sure to conduct more frequent monitoring of the patient’s clinical condition and monitor the time of blood clotting.

Zidovudine: the risk of red blood cell toxicity is increased by affecting reticulocytes with the development of severe anemia one week after starting NSAID treatment. It is necessary to perform a general blood test and monitor the number of reticulocytes 1-2 times a week after starting NSAID treatment.

Sulfonylurea: NSAIDs may enhance the hypoglycemic effect of sulfonylurea by reducing its binding to plasma proteins.

Combinations to take into consideration Beta-blockers: NSAIDs may reduce the hypotensive effect of beta-blockers due to inhibition of prostaglandin synthesis.

Cyclosporine and tacrolimus: NSAIDs may increase nephrotoxicity due to effects associated with renal prostaglandins. When used together, it is necessary to monitor renal function.

Thrombolytics: increases the risk of bleeding.

Probenecid: the concentration of ketoprofen in the blood plasma may increase. This increase may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronoconjugation and requires adjustment of the ketoprofen dose.

How to take, course of use and dosage

For adults:

The contents of one two-volume sachet (full dose) should be dissolved in half a glass of drinking water and taken orally up to 3 times a day with meals.

For elderly patients, the dose is set by the doctor, it is advisable to reduce the dosage by 2 times.

Children (from 6 to 14 years old):

The contents of 1/2 two-volume sachet (half a dose) should be dissolved in half a glass of drinking water and taken orally up to 3 times a day with meals.

Children (14-18 years old):

Dosages of the drug correspond to those in adults.

To reduce the risk of developing adverse reactions from the gastrointestinal tract, the minimum effective dose should be used in the shortest possible course.

Overdose

Overdose cases have been reported when taking a dose of 2.5 g of ketoprofen. In most cases, symptoms were limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain.

Overdose management measures

The specific antidote is unknown. As symptomatic measures to ensure vital functions (stabilization of blood circulation, respiration, elimination of acidosis), drugs and procedures that reduce resorption and accelerate elimination (medical charcoal, forced diuresis) are indicated.

Special instructions

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

After 2 weeks of using the drug, monitoring of liver function indicators (transaminase levels) is necessary.

The use of ketoprofen in patients with asthma can lead to the development of an asthma attack.

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

The drug can change the properties of platelets, but it does not replace the preventive actions of acetylsalicylic acid in cardiovascular diseases.

Taking the drug may mask signs of infectious diseases. Elderly patients, patients with a history of gastric and duodenal ulcers, and patients taking low-dose acetylsalicylic acid or other medications that may increase the risk of gastrointestinal reactions should be treated with concomitant gastroprotective medications (misoprostol or proton pump inhibitors).

The use of the drug may negatively affect female fertility and is not recommended for women planning pregnancy. The use of the drug should be discontinued in women with fertility problems or undergoing a fertility study.

The drug does not affect low-calorie and controlled diets and can be used in patients with diabetes mellitus.

The drug does not contain gluten, so it can be used in patients with celiac disease.

The drug does not contain aspartame, so it can be used in patients with phenylketonuria.

Cardiovascular and cerebrovascular effectspatients with arterial hypertension and / or moderate heart failure, accompanied by fluid retention and edema (in the anamnesis) associated with the use of NSAIDs, should be carefully monitored and consult a doctor.

Clinical studies and epidemiological data indicate that the use of certain NSAIDs (especially at high doses for a long time) may be associated with a slight increase in the risk of arterial thrombotic events (for example, myocardial infarction or stroke). There are insufficient data to exclude the above risk for ketoprofen lysine salt.

Patients with uncontrolled hypertension, heart failure, established coronary artery disease, peripheral artery disease, and/or cerebrovascular diseases should only be treated with ketoprofen lysine salt after a thorough examination. Patients with risk factors for cardiovascular diseases (e. g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should also undergo the same screening before starting long-term treatment.

Influence on the ability to drive vehicles and mechanisms

The drug has a limited and moderate effect on the ability to drive vehicles or mechanisms due to the possible appearance of dizziness and drowsiness.

If drowsiness, dizziness or convulsions occur after using the drug, you should avoid driving vehicles and mechanisms, as well as other activities that require concentration of attention.

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use the product after the expiration date indicated on the package.

Active ingredient

Ketoprofen

Conditions of release from pharmacies

By prescription

Dosage form

granules