Artrum prolonged action tablets 150 mg

Artrum prolonged action tablets 150 mg

International nonproprietary name

Ketoprofen

Pharmacological group

Нестероидные противовоспалительные препараты

Composition

Active substance:
ketoprofen - 150 mg.
Excipients:
silicium dioxide colloidal (aerosil) - 2 mg;
hypromellose (hydroxypropylmethicellulose) - 45 mg;
calcium stearate monohydrate - 3 mg;
copovidone (kollidon VA 64) - 10.8 mg;
kollidon SR (polyvinyl acetate 80 %, povidone 19 %, - 30 mg sodium lauryl sulfate 0.8 %, silicon dioxide 0.2 %) lactose monohydrate (lactobiose) - 59.2 mg.
Weight of a tablet: - 300 mg.

Pharmacological action

Pharmacodynamics

Ketoprofen is non-steroidal anti-inflammatory drug (NSAID). The drug has anti-inflammatory analgetic and antipyretic effect.
Ketoprofen inhibits the action of cyclooxygenase 1 and 2 (COX1 and COX2) and partily lipoxygenase ferments resulting in inhibition of the prostaglandin synthesis (including in the central nervous system, most probably in the hypothalamus)
Stabilizes in vitro and in vivo liposomal membranes. Ketoprofen higher concentrations inhibit bradykinin and leukotrienes synthesis.
Ketoprofen has no adverse effect on the articular cartilage state.

Pharmacokinetics

Absorption

Ketoprofen is easily absorbed from the gastrointestinal tract, bioavailability is 90%. Binding with the plasma proteins - 99 %. After oral administration of 150 mg Ketoprofen the maximum plasma concentrations (10.4 µg/ml) are reached after 4-6 hours.
Distribution
99 % of ketoprofen are protein-bound, mainly with albumin fraction. Volume of distribution is 0.1 l/kg.
Ketoprofen penetrates into the synovial fluid and reaches there the concentration equal to 30% of the plasma concentration. Plasma clearance of ketoprofen is approximately 0.08 l/kg/h. Effective concentrations of ketoprofen are determined in the blood even in 24 hours after its administration.
Metabolism and excretion
Ketoprofen is metabolized intensively under the effect of microsomal liver enzymes, the half-life is less than 2 hours. Ketoprofen is bound with glucuronic acid and removed from the body in the form of glucoronide. Ketoprofen has now active metabolites. Up to 80% of ketoprofen are excreted by the kidneys during 24 hours mainly in the form of ketoprofen glucoronide.
After administration of the drug at dose 100 mg or more excretion by the kidneys can be difficult. In patients with severe renal failure, most of the drug is secreted by the intestine.
Administration of high doses increases the hepatic clearance. Up to 40% of the drug is excreted by the intestine.
In patients with hepatic failure, the plasma concentration of ketoprofen is doubled (probably due to hypoalbuminemia and, consequently, a high level of unbound active ketoprofen); such patients shall receive the drug in the minimum therapeutic dose.
In patients with renal failure, clearance of ketoprofen is reduced; however, dosage adjustment is required only in case of severe renal failure.
Ketoprofen metabolism and recovery proceed slower in elder patients and this is significant only for patients with renal failure.

Indications for Use

Symptomatic therapy of painful and inflammatory processes of various origin, including: inflammatory and degenerative diseases of the locomotor system: rheumatoid arthritis;

seronegative arthritis: ankylosing spondylitis (Bekhterev's disease), psoriatic arthritis, Reiter disease;
uratic arthritis, chondrocalcinosis;
osteoarthrosis;
tendinitis, bursitis, myodynia, neurodynia, radiculitis;
pain syndrome, including mild, moderate and severe: post traumatic and postsurgicalpain syndrome; pain syndrome associated with oncology diseases, etc.

Contraindications

Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other NSAIDs;

 bronchial asthma, bronchospasm, rhinitis or urticaria fever in the past medical history, induced by administration of acetylsalicylic acid and other NSAIDs;
 ulcerative colitis, Crohn's disease; hemophilia and other blood-clotting disorders;
 pediatric use (age to 15 years old);
 severe hepatic failure;
 severe renal failure (creatine clearance less than 30 ml/min.),
decompensated heart failure; postsurgical period after coronary artery bypass graft surgery;
 active gastroduodenal ulcer;
 gastrointestinal, cerebrovascular and other haemorrhage (or suspected haemorrhage);
 chronic dyspepsia;
 III trimester of pregnancy;
 lactation period.
With care
Bronchial asthma in the past medical history; overt cardiovascular, cerebrovascular diseases and peripheral arterial diseases; chronic heart failure; arterial hypertension; blood diseases; dyslipidemia; advanced hepatic diseases; hepatic failure; hyperbilirubinemia; ging liver; renal failure (creatine clearance less than 30-60 ml/min.); elderly age; dehydration; diabetes mellitus; medical history data about development of ulcerative lesions of the gastrointestinal tract; infection Helicobacter pylori; smoking.
Concomitant treatment with anticoagulating agents (for example, Warfarin), antiplatelets (for example acetylsalicylic acid), glucocorticosteroids for oral administration (for example prednisolone), selective serotonin reuptake inhibitors (for example citalopram, sertraline), long-term administration of NSAIDs.
Administration during pregnancy and lactation period
Inhibition of the prostaglandin synthesis may have adverse effect on pregnancy and/or embryonal development. The data obtained during epidemiological studies of administration of the prostaglandin synthesis inhibitors during early pregnancy confirm increased risk of spontaneous miscarriage and development of valvular heart diseases ( ~ 1 - 1,5 %).
The drug can be administered in pregnant women during the I and II trimesters of pregnancy only when potential benefit to the mother outweighs any potential risk to the fetus.
Ketoprofen is condradicted in pregnant women during the III trimester of pregnancy due to possible development of weak uterine labor and / or premature closing of the ductus arteriosus, possible increase in bleeding time, hypamnion and renal failure.
At present data about ketoprofen secretion into the breast milk is not available, so if ketoprofen is prescribed to a nursing mother then breast-feeding stop shall be considered.

Cautions

Do not combine ketoprofen with other NSAIDs and/or COX2 inhibitors.

Long-term administration of NSAIDs requires regular assessment of clinical blood analysis as well as monitoring of kidney and liver functions especially in patients at the elderly age (more than 65 years old), faecal occult blood testing.
Administration of ketoprofen for treatment of patients with arterial hypertension, cardiovascular diseases causing water retention requires special precautions and more frequent monitoring of blood pressure.
Treatment shall be immediately stopped in case of visual organ disorders.
Ketoprofen like other NSAIDs can mask the symptoms of inflammatory infections. In case of identification of infection symptoms or feeling unwell after the drug administration consult the doctor immediately.
In case of any gastrointestinal contradictions in the past medical history (bleedings, perforation, ulcer disease), long-term therapy and administration of higher doses of ketoprofen the patient shall stay under careful supervision of the doctor.
Due to important role of prostaglandins supporting the renal blood flow special precautions shall be taken when prescribing ketoprofen to the patients with heart and renal failure as well as when treating elderly patients receiving diuretics and to patients with indicated depression in the circulating blood volume.
The drug shall be discontinued before a large surgical intervention.
Administration of ketoprofen may affect woman fertility so the patients with infertility (including undergoing screening) are not recommended to receive the drug.
Effects on ability to drive and use machines
Data on the negative effect of the drug Artrum at the recommended doses on the ability to drive or operate mechanisms is not available. At the same time, patients with somnolency, dizziness or other the nervous system discomfort, including visual impairment, shall avoid driving and operating mechanisms.

Dosing and Administration

Oral administration swallowing the whole tablet during or after a meal with water or milk (the volume of liquid shall be at least 100 ml).

1 tablet (150 mg) once per day.
The maximum dose of ketoprofen is 200 mg/day.

Side effect

According to the World Health Organization (WHO) the adverse effects are classified based on their frequency as follows:

- very common (1/10),
- common (frequent)(100, < 1/10),
- uncommon (infrequent) (1/1000, < 1/100),
- rare (1/10000, < 1/1000),
- very rare (1/10000),
- unknown frequency (frequency of adverse events cannot be determined based on the current data).
Adverse hematopoietic and lymphoid system effects:
rare: hemorrhagic anemia;
unknown frequency: agranulocytosis, thrombocytopenia, bone marrow dysfunction.
Adverse immune system effects:
unknown frequency: anaphylactic reactions (including anaphylactic shock).
Adverse nervous system effects:
uncommon (infrequent): headache, dizziness, somnolency;
rare: paresthesia
unknown frequency: convulsions, taste disturbance;
Mental disorders:
unknown frequency: emotional instability.
Adverse sense organ effects:
rare: blurred vision, tympanophony.
Adverse cardiovascular effects:
unknown frequency: heart failure, blood pressure increase, vasodilation.
Adverse respiratory system effects:
rare: exacerbation of bronchial asthma;
unknown frequency: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
Adverse gastrointestinal effects:
common (frequent): nausea, vomiting, dyspepsia, abdominal pain;
uncommon (infrequent): constipation, diarrhea, abdominal distention, gastritis;
rare: peptic ulcer, stomatitis;
very rare: exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding, perforation.
Adverse liver and biliary tract effects:
rare: hepatitis, increased activity of liver transaminases, increased bilirubin concentration.
Adverse skin and subdermal tissue effects:
uncommon (infrequent): exanthema, skin itching;
unknown frequency: photosensitization, baldness, urticaria fever, angioneurotic edema, erythema, bullous eruption, including Steve-Johnson syndrome,  toxic epidermal necrolysis.
Adverse kidney and urinary tract effects:
very rare: acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of renal function indicators;
Other:
rare: edema;
rare: body weight gain;
unknown frequency: increased fatigability.
Overdose
As for other NSAIDs Ketoprofen overdose symptoms can include headache, nausea, vomiting, abdominal pain, vomiting with blood, melaena, impairment of consciousness, respiratory depression, convulsions, renal disorders and renal failure.
In case of overdose stomach lavage and administration of activated carbon shall be applied. Treatment is expectant ; the effect of ketoprofen on the gastrointestinal tract can be weakened with the help of drugs reducing secretion of the stomach glands (for example, proton pump inhibitors or H2-histamine receptor blockers) and prostaglandins.

Interaction with other medicines

Ketoprofen can reduce the effect of diuretics and antihypertensive agents and increase the effect of hypoglycemic drugs for oral administration and some anti-seizure medications (phenytoin).
Combined administration with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of adverse gastrointestinal tract events.
Simultaneous administration with anticoagulating agents (heparine, warfarin), thrombolytics, antiaggregants (ticlopidine, clopidogrel) and pentoxifylline increase the risk of bleeding.
Simultaneous administration with potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, NSAIDs, low molecular heparines, cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia.
The drug increases the plasma concentration of cardiac glycosides, calcium channel blocking agents, potassium  agents, cyclosporine, methotrexate and digoxin.
Ketoprofen increases toxicity of methotrexate and nephrotoxicity of cyclosporine.
Simultaneous administration with probenecid reduces significantly ketoprofen clearance  in the plasma.
Combination with glucocorticosteroids and other NSAIDs (including selective inhibitors of COX2) increases the risk of adverse effects (in particular, in the gastrointestinal tract).
NSAIDs can decrease the efficacy of mifepristone. Administration of NSAIDs shall be started not earlier than 8-12 days after withdrawal of mifepristone.

 

Form release

Storage conditions

In a dry and dark place at temperature maximum 25 °С.

Expiration date

2 years