Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID).
ATX code: M01AE03.
It has anti-inflammatory, analgesic and antipyretic effect. By inhibiting cyclooxygenase of types I and II, inhibits the synthesis of prostaglandins. It has anti-bradykinin activity, stabilizes lysosomal membranes and inhibits release of the enzymes from them, which contribute to destruction of tissues during chronic inflammation. It reduces release of cytokines, inhibits activity of neutrophils.
Limits morning stiffness and swelling of the joints and increases range of motion.
Ketoprofen lysine salt, unlike ketoprofen, is a rapidly soluble molecule with a neutral pH and causes almost no gastrointestinal (GI) irritation.
Ketoprofen is quickly and completely absorbed from the gastrointestinal tract when ingested, its bioavailability is about 80%. Maximal concentration in blood plasma when administered orally is observed after 0.5-2 hours and directly depends on the dose taken. Equilibrium concentration of ketoprofen is reached 24 hours after its regular use.
Up to 99% of adsorbed ketoprofen is bound to plasma proteins, mainly to 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 the synovial fluid and connective tissues. Although ketoprofen concentration in synovial fluid is slightly lower than in blood plasma, it is more stable (remains up to 30 h).
Ketoprofen is mainly metabolized in the liver, where it undergoes glucuronidation to form glucuronic acid esters.
The metabolites are excreted by the kidneys. The drug does not cumulate.
Inflammatory and degenerative diseases of the musculoskeletal system:
- rheumatoid arthritis;
- seronegative arthritis: Ankylosing spondylitis (Bechterew’s disease), psoriatic arthritis, reactive arthritis (Reiter’s disease;
- podagra, pseudopodagra;
- tendinitis, bursitis, myalgia, neuralgia, radiculitis.
Pain syndrome, including mild, moderate and severe:
- dental pain;
- posttraumatic and postoperative pain syndrome;
- pain syndrome in cancer;
In children (over 6 years): short-term symptomatic treatment of inflammatory processes accompanied by pain syndrome with or without fever in diseases of the musculoskeletal system, otitis media.
The drug is intended for symptomatic therapy, reduction of pain and inflammation at the time of use, does not affect the progression of the disease.
One two-volume sachet contains:
The active ingredient:
ketoprofen lysine salt – 80.0 mg (equivalent to 50.0 mg of ketoprofen);
Mannitol – 1822.0 mg,
Povidone K 30 – 40.0 mg,
Mint flavoring – 20.0 mg,
p> sodium chloride – 20.0 mg,
sodium saccharinate – 15.0 mg,
silicon dioxide colloid – 3.0 mg.
How to take, the dosage
The contents of one two-volume sachet (full dose) dissolve in half a cup of drinking water and take orally up to 3 times daily with meals.
In elderly patients, the dosage is determined by the doctor; it is advisable to reduce the dosage by half.
In children (6 to 14 years of age):
The contents of 1/2 of a two-volume sachet (half the dose) dissolve in half a glass of drinking water and take orally up to 3 times a day with meals.
Children (14 to 18 years of age):
The dosages of the drug are the same as those for adults.
To reduce the risk of adverse gastrointestinal reactions, the lowest effective dose should be used for as short a course as possible.
Combinations to avoid
Corticosteroids: increased risk of gastrointestinal mucosal ulceration and gastrointestinal bleeding.
Anticoagulants (parenteral heparin, warfarin), increased 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.
Antiaggregants (clopidogrel, ticlopidine) and selective serotonin reuptake inhibitors: the risk of bleeding caused by inhibition of platelet aggregation and GI mucosal damage increases. Patients should be monitored if co-administration cannot be avoided.
Other NSAIDs, including high-dose salicylates (>3 g/day): Concomitant administration of several NSAIDs may increase the risk of gastrointestinal mucosal ulceration and gastrointestinal bleeding due to synergistic effects.
Lithium: NSAIDs increase plasma levels of lithium (decrease renal excretion of lithium), which may 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): hematotoxicity of methotrexate is increased because its excretion by kidneys when taking anti-inflammatory drugs is reduced. When concomitant use with methotrexate in low doses (less than 15 mg weekly) it is necessary to perform a general blood test once a week during the first few weeks of treatment. More frequent monitoring of the patient’s clinical condition is obligatory in case of even a slight worsening of renal function, as well as in elderly patients.
Hydantoin and sulfamides: the toxic effects of these agents may increase.
Combinations that require precautions
Diuretics, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists: NSAIDs may decrease their effectiveness. In patients with impaired renal function (e.g., dehydrated 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 adequately hydrated before starting concomitant therapy, and renal function should be monitored after initiation of therapy.
Pentoxifylline: increased risk of bleeding. More frequent monitoring of the patient’s clinical condition and monitoring of clotting time are mandatory.
Zidovudine: Increased risk of erythrocyte toxicity through effects on reticulocytes with development of severe anemia one week after initiation of NSAID treatment. A complete blood count and reticulocyte counts should be monitored 1-2 times per week after initiation of NSAID treatment.
Sulfonylurea: NSAIDs may increase the hypoglycemic effect of sulfonylurea by reducing its binding to plasma proteins.
Combinations to consider
Beta-adrenoblockers: NSAIDs may decrease the hypotensive effect of beta-adrenoblockers due to inhibition of prostaglandin synthesis.
Cyclosporine and tacrolimus: NSAIDs may increase nephrotoxicity due to effects related to renal prostaglandins. Renal function should be monitored when used together.
Trombolytics: increased risk of bleeding.
Probenecid: the concentration of ketoprofen in 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.
At the beginning of treatment it is necessary to control peripheral blood count and functional status of the liver and kidneys.
After 2 weeks of the drug use it is necessary to monitor the liver function parameters (transaminases level).
The use of ketoprofen in patients with bronchial asthma may lead to the development of an attack of bronchial asthma.
If it is necessary to determine 17-ketosteroids, the drug should be withdrawn 48 hours before the study.
The drug may alter platelet properties, but it does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular disease.
The drug may mask signs of infectious diseases. In elderly patients, patients with a history of peptic ulcer disease, and patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal reactions, co-administration of gastroprotective drugs (misoprostol or proton pump inhibitors) is indicated.
The use of the drug may adversely affect female fertility and is not recommended for women planning to become pregnant. The use of the drug should be discontinued in women with fertility problems or who are undergoing fertility studies.
The drug does not affect low-calorie and controlled diets and can be used in patients with diabetes.
The drug is gluten-free, so it can be used in patients with celiac disease.
The product is aspartame-free, so it can be used in patients with phenylketonuria.
Cardiovascular and cerebrovascular effects
Patients with arterial hypertension and/or with moderate heart failure accompanied by fluid retention and edema (history) associated with NSAID use require close monitoring and medical consultation.
Clinical studies and epidemiologic data indicate that use of some NSAIDs (especially in high doses over a long period of time) may be associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to rule out the above risk for ketoprofen lysine salt.
Patients with uncontrolled arterial hypertension, heart failure, established coronary heart disease, peripheral artery disease and/or cerebrovascular disease should use ketoprofen lysine salt only after a thorough evaluation. Patients with risk factors for cardiovascular disease (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should undergo the same evaluation before starting long-term treatment.
Influence on driving and operating machinery
The drug has limited and moderate effect on driving and operating machinery due to possible dizziness and somnolence.
If drowsiness, dizziness or seizures are noted after using the drug, driving, operating machinery and other activities requiring concentration should be avoided.
- Hypersensitivity to the active substance and other components of the drug, as well as to other NSAIDs;
- complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other NSAIDs (including anamnesis);
- erosive-ulcerative lesions of the stomach and duodenum in the acute stage;
- active gastrointestinal, cerebrovascular or other bleeding;
- inflammatory bowel disease (ulcerative colitis, Crohn’s disease) in the acute stage;
- hemophilia and other clotting disorders;
- decompensated heart failure;
- period after coronary artery bypass surgery;
- severe liver failure or active liver disease;
- severe renal insufficiency (creatinine clearance (CK) <30 ml/min), advanced renal disease;
- childhood (under 6 years);
- pregnancy (3rd trimester) and breastfeeding period.
Gastric and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease (history), hepatic porphyria, chronic renal failure (CK 30-60 ml/min), chronic heart failure, arterial hypertension, significant reduction in circulating blood volume (including after surgery), elderly patients (including those receiving diuretics, weakened patients and those with low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes, peripheral artery disease, smoking, Helicobacter pylori infection, long-term use of NSAIDs, tuberculosis, severe osteoporosis, alcoholism, severe medical conditions, pregnancy (I, II trimester).
According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: Very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1 /1000, <1/100), rare (≥1 /10000, <1/1000), and very rare (<1 /10000); frequency unknown (frequency of events cannot be determined from available data).
Blood and lymphatic system disorders:
- rarely: hemorrhagic anemia;
- frequency unknown: thrombocytopenia, thrombocytopenic purpura, agranulocytosis, bone marrow dysfunction, leukocytopenia, leukocytosis, lymphatic inflammation, vasculitis.
Immune system disorders: frequency unknown: anaphylactic reactions (including anaphylactic shock).
Nervous system and sensory system disorders:
- infrequent: headache, dizziness, somnolence;
- frequent: paresthesias, blurred vision, tinnitus;
- frequent unknown: seizures, dysgeusia, mood changes, irritability, insomnia.
Cardiovascular system disorders: frequency unknown: heart failure, tachycardia, palpitations, hypertension, hypotension, vasodilation.
Respiratory system disorders:
- rarely: bronchial asthma;
- frequency unknown: bronchospasm (especially in patients with confirmed hypersensitivity to acetylsalicylic acid and other NSAIDs), rhinitis, shortness of breath, laryngeal edema and spasm.
- often: nausea, vomiting, dyspepsia, abdominal pain;
- frequently: constipation, diarrhea, bloating, gastritis;
- frequently: Stomatitis, gastric and duodenal ulcer;
- frequent unknown: exacerbation of ulcerative colitis or Crohn’s disease, gastrointestinal bleeding, perforation, heartburn.
Hepatic and biliary tract disorders: rare: hepatitis, increased “hepatic” transaminase activity and increased serum bilirubin concentration caused by liver dysfunction.
Skin and subcutaneous tissue disorders:
- infrequent: rash, itching;
- frequency unknown: Photosensitization reactions, alopecia, urticaria, angioneurotic edema, bullous skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell 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 parameters.
- infrequent: edema, fatigue;
- frequency unknown: allergic and anaphylactoid reactions, oral mucosal edema, periorbital edema.
In case of any side effect, immediately stop taking the drug and consult a physician.
Cases of overdose have been reported with a dose of 2.5 g of ketoprofen. In most cases the symptoms were limited to lethargy, drowsiness, nausea, vomiting and epigastric pain.
Any treatment for overdose
A specific antidote is not known. As symptomatic measures in providing vital functions (stabilization of circulation, respiration, elimination of acidosis) drugs and procedures that reduce resorption and accelerate elimination (medical charcoal, forced diuresis) are indicated.
The use of ketoprofen is contraindicated in the third trimester of pregnancy. In the first and second trimesters of pregnancy the drug may be administered only if the estimated benefit to the mother is greater than the potential risk to the fetus.
The drug should not be used during breastfeeding.
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2 years. Do not use the drug after the expiration date stated on the package.
|Conditions of storage|
Store at a temperature not exceeding 25 ° C. Keep out of reach of children.
Fine Foods & Pharmaceuticals N.T.M. S.P.A., Italy
granules for preparation of oral solution
Fine Foods & Pharmaceuticals N.T.M. S.P.A.
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