Artrosilene (Ketoprofen) capsules, ampoules, gel, aerosol

The composition and form of issue: 

Capsules. 1 capsule contains:

of a lysine salt of Ketoprofen 320 mg

auxiliary substances: diethylphthalate-2, 286 mg carboxypolymethylene-32, 857 mg magnesium stearate-15, 857 povidone-27, 857 polymers of acrylic and methacrylic acid-34, 143 talc-27 mg 

shell: body-titanium dioxide (E171), gelatin qsp cap-quinoline yellow (E104) indigotin (E132) titanium dioxide (E171) gelatin qsp 

in blister 10 PCs. in a pack of cardboard 1 blister.

Solution for intravenous and intramuscular administration. 1 m contains:

Ketoprofen lysine salt 80 mg

auxiliary substances: sodium hydroxide citric acid water for injection 

in sealed dark glass to 2 ml in the pan 6 PCs., the paper cartons 1 pallet.

Suppositories for rectal administration. 1 suppositorie contains:

of a lysine salt of Ketoprofen 160 mg

excipients: semi-synthetic glycerides 

in strip of 5 PCs. in cardboard pack 2 strip.

Gel for external use 5%. 1 g contains:

of a lysine salt of Ketoprofen 50 mg

excipients: carboxypolymethylene triethanolamine Polysorbate ethyl alcohol 95% methyl-p-hydroxybenzoate lavender/nerolin water 

in the aluminium tubes to 30 and 50 grams in a cardboard bundle 1 tuba.

Spray for external use 15%. 1 g of foam contains:

of a lysine salt of Ketoprofen 150 mg

auxiliary substances: Polysorbate 80, the polypropylene glycol PVP (povidone) lavender/nerolin benzyl alcohol purified water propellant — propane-butane 

in cylinders with a capacity of 25 ml with a nozzle-sprayer in a pack of cardboard 1 cylinder.

Description of dosage form:

Capsules: solid gelatin capsules oblong body-white, cover-dark green. The contents of the capsules — granules round shape from white to light yellow color.

Solution for intravenous and intramuscular injection: clear, colorless or slightly yellowish solution.

Suppositories rectal: homogeneous, from white to light yellow, torpedo-shaped.

Gel: a transparent, thick with the smell of lavender.

Aerosol: white homogeneous foam after gas release — transparent liquid of pale yellow color.

Pharmacokinetics:

Capsules

Suction. Appointed inside, Ketoprofen sufficiently absorbed from the digestive tract, and its bioavailability exceeds 80%. Cmax in plasma with capsules Artrosilene observed after 4-10 h after oral administration, its value depends directly on the dose is 3-9 mg/ml. T1/2 is 6, 5 hours the Maximum therapeutic effect is observed for from 4 to 24 h Food contributes lower values of Cmax and increased Tmax without changing AUC.

Distribution. Up to 99% of absorbed Ketoprofen binds to plasma proteins, mainly albumin. Vd — 0, 1-0, 2 l/kg. Easily permeates through gistogematicalkie barriers and relate to tissues and organs. Ketoprofen well penetrates into synovial fluid and connective tissue. Although the concentration of Ketoprofen in synovial fluid is slightly lower than in plasma, it is more stable (up to 30 h).

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

Breeding. Metabolites are excreted in the urine. Less than 1% is excreted with feces. The drug does not cumulate.

The solution for the on/in and/m introduction

Tmax parenteral 20-30 min. Effective concentration is maintained 24 hours Therapeutic concentrations in the synovial fluid is stored 18-20 h

Distribution. Up to 99% of absorbed Ketoprofen binds to plasma proteins, mainly albumin. Vd — 0, 1-0, 2 l/kg. Easily permeates through gistogematicalkie barriers and relate to tissues and organs. Ketoprofen well penetrates into synovial fluid and connective tissue. Although the concentration of Ketoprofen in synovial fluid is slightly lower than in plasma, it is more stable (up to 30 h).

Metabolized by microsomal liver enzymes. Excreted by the kidneys, 60-80% – in the form of glucuronide for 24 hours

Suppositories

Suction. Of a lysine salt of Ketoprofen is rapidly absorbed: Tmax after rectally — 45-60 min. Value of concentration in plasma is linearly dependent on the dose.

Distribution. Up to 99% of absorbed Ketoprofen binds to plasma proteins, mainly albumin. Vd — 0, 1-0, 2 l/kg. Easily permeates through gistogematicalkie barriers and relate to tissues and organs. Ketoprofen well penetrates into synovial fluid and connective tissue. Although the concentration of Ketoprofen in synovial fluid is slightly lower than in plasma, it is more stable (up to 30 h).

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

Breeding. Metabolites are excreted mainly in urine (up to 76% in 24 hours). The drug does not cumulate.

Gel, aerosol

When cutaneous application absorbed slowly dose of 50-150 mg every 5-8 h creates the level of concentration in plasma 0, 08-0, 15 µg/ml. Almost not koumouliruet in the body. Bioavailability is about 5%.

Description of the pharmacological action:

It has anti-inflammatory, analgesic and antipyretic effects. By inhibiting COX-1 and -2, inhibits the synthesis of GHGs. It has antibacterial activity, stabilizes lysosomal membranes and delays the release of enzymes from them, contributing 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 volume of movements.

Ketoprofen lysine salt, unlike Ketoprofen, is a rapidly soluble molecule with neutral pH and almost does not irritate the digestive tract.

When applied topically, it has a local anti-inflammatory, anti-exudative and analgesic effect. In the form of spray or gel provides a local therapeutic effect on the affected joints, tendons, ligaments, muscles. When the joint syndrome causes a weakening of pain in the joints at rest and when moving, reducing morning stiffness and swelling of the joints. A lysine salt of Ketoprofen has no catabolic effect on articular cartilage.

Indications:

Capsules, suppositories

• pain relief of mild to moderate intensity (including inflammatory pain, postoperative and post-traumatic).

Capsules, suppositories

• rheumatic disease:
• rheumatoid arthritis
• spondylitises
• osteoarthrosis
• gouty arthritis
• inflammatory lesion of the periarticular tissues.

The solution for the on/in and/m introduction

• short – term treatment of acute pain in diseases of the musculoskeletal system of various Genesis, postoperative pain, posttraumatic pain associated with inflammation.

Gel, aerosol:

• diseases of the musculoskeletal system (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis peripheral joints and spine, rheumatic lesions of soft tissues)
• muscle pain of rheumatic and non-rheumatic origin
• traumatic soft tissue injuries.

Contraindications:

All forms:

• hypersensitivity, incl. other NPVS
• aspirin asthma
• lactation
• peptic ulcer: gastric and duodenal ulcer disease in acute phase, peptic ulcer
• ulcerative colitis in the phase of deterioration, Crohn’s disease
• diverticulitis
• hemophilia and other blood clotting disorders
• chronic renal failure.

Capsules, solution for on/in and on/m introduction, suppositories

• children under 18 years of age.

Capsules, suppositories, gel, aerosol

• pregnancy (III trimester).

The solution for the on/in and/m introduction

• pregnancy.

For external use additionally:

• wet dermatoses
• eczema
• violation of the integrity of the skin
• children under 6 years old.

With caution:

All forms

• bronchial asthma
• chronic heart failure
• old age.

Capsules, suppositories, gel, aerosol

• pregnancy (I, II trimester).

Capsules, solution for on/in and on/m introduction, suppositories

• anemia
• alcoholism
• tobacco Smoking
• alcoholic cirrhosis
• hyperbilirubinemia
• liver failure
• diabetes
• dehydration
• sepsis
• edemas
• arterial hypertension
• blood disorders (including leukopenia)
• the deficit glukozo-6-fosfatdegidrogenaza
• stomatitis.

Gel, aerosol

• hepatic porphyria
• erosive-ulcerative lesions of the gastrointestinal tract
• severe violations of the liver and kidneys
• children under 12 years old.

Application during pregnancy and breast-feeding:

Capsules, solution for on/in and on/m introduction, suppositories

Like other NSAIDs, Artrosilene should not be applied in III trimester of pregnancy. The use of the drug in the I and II trimesters of pregnancy should be carefully monitored by your doctor. Breastfeeding with the use of the drug should be stopped.

Gel, aerosol

Can not be applied in III trimester of pregnancy.

Experience in the use of Artrosilene lactation is not available. Use in the I and II trimesters is possible only after consultation with the doctor.

Side effect:

Capsules, solution for on/in and on/m introduction, suppositories

On the part of the digestive tract: abdominal pain, diarrhea, stomatitis, esophagitis, gastritis, duodenitis, erosive and ulcerative lesions of the gastrointestinal tract, hematemesis, melena.

From the liver: increased bilirubin, increased activity of liver enzymes, hepatitis, liver failure, increased liver size

From the nervous system: dizziness, hyperkinesia, tremor, vertigo, mood swings, anxiety, hallucinations, irritability, General malaise.

From the sensory organs: conjunctivitis, impaired vision.

With the skin: urticaria, angioedema, erythematous rash, pruritus, maculopapular rash, increased sweating, erythema multiforme exudative (including Stevens-Johnson syndrome).

From the genitourinary system: painful urination, cystitis, edema, hematuria, menstrual disorders.

From the hematopoietic organs: leukocytopenia, leukocytosis, lymphangitis, a decrease in PV, thrombocytopenia, thrombocytopenic purpura, an increase in the size of the spleen, vasculitis.

From the respiratory system: bronchospasm, dyspnoea, feeling of laryngospasm, laryngospasm, swelling of the larynx, rhinitis.

From the side of cardiovascular system: hypertension, hypotension, tachycardia, chest pain, syncope, peripheral edema, pallor.

Allergic reactions: anaphylactoid reaction, swelling of the mucous membrane of the mouth, pharyngeal edema, periorbital edema.

Suppositories additionally

Local reactions: burning, itching, heaviness in the anorectal region, exacerbation of hemorrhoids.

Gel, aerosol

Allergic reactions, photosensitization.

In case of development of any undesirable phenomenon it is necessary to address to the doctor.

Drug interaction:

Inductors of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, flumecinol, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites.

Reduces the effectiveness of uricosuric drugs enhance the effects of anticoagulants, antiplatelet agents, fibrinolitikov, ethanol, side effects of mineralocorticoids, corticosteroids, estrogens, antihypertensive and diuretics.

Joint reception with other NSAIDs, GCS, ethanol, corticotropin can lead to ulcers and the development of gastrointestinal bleeding, to an increase in the risk of kidney disorders.

Co-administration with oral anticoagulants, heparin with thrombolytic drugs, antiplatelet agents, cefoperazone, cefamandole and cefotetan increases the risk of bleeding.

Increases hypoglycemic effect of insulin and oral hypoglycemic drugs (requires the recalculation of doses).

Joint appointment with sodium valproate causes a violation of platelet aggregation.

Increases plasma concentrations of verapamil and nifedipine, lithium, methotrexate.

Antacids and cholestyramine reduce the absorption.

Method of application and doses:

Orally, parenterally, rectally, topically.

Inside the drug is prescribed for 1 caps. per day during or after meals. The duration of treatment can be 3-4 months.

The/m or/in 1 amp. per day. The maximum daily dose is 1 amp. 2 times a day. On / in the introduction of the drug is allowed only in the hospital. The drug is used for short — term treatment-up to 3 days. If necessary, further use of the drug is recommended to proceed to the reception of oral dosage forms or suppositories. In elderly patients, use no more than 1 amp. per day.

Ampoules should be opened on a special line of fracture. After opening of the ampoule solution should be used immediately.

An aqueous solution of a lysine salt of Ketoprofen can be used in physiotherapeutic treatment (iontophoresis, mesotherapy) in the iontophoresis solution is applied on the negative pole.

At/in the application to increase the time of drug action it is recommended that a slow in/in infusion. The solution for infusion is prepared on the basis of 50 or 500 ml of the following aqueous solutions: 0, 9% sodium chloride solution, 10% aqueous solution of levulose, 5% aqueous dextrose solution, normal saline and ringer’s acetate, normal saline and ringer’s lactate (Hartman), a colloidal solution of dextran in 0 9% sodium chloride solution or 5% dextrose solution. When breeding Artrosilene in solutions of small volume (50 ml) the drug is injected in/in the bolus. In large volume solutions (500 ml), the duration of infusion is at least 30 minutes.

Rectally on 1 supp. 2-3 times a day. The maximum daily dose is 480 mg. in elderly patients, no more than 2 supp should be used. per day.

Outwardly. A single dose of gel is 3-5 g (volume of large cherries), aerosol — 1-2 g (volume of walnut). Depending on the size of the damaged area, the drug should be applied 2-3 times a day or according to the doctor’s instructions, gently rubbing until completely absorbed. In iontophoresis a drug is applied on the negative pole. The duration of treatment without medical advice should not exceed 10 days.

Overdose:

Currently, the cases of drug overdose Artrosilene was not reported.

Treatment: in case of overdose, monitoring of respiratory and cardiac activity is necessary. There is no specific antidote. If necessary, symptomatic therapy should be carried out. Hemodialysis is ineffective.

Special instruction:

Capsules, solution for on/in and on/m introduction, suppositories

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

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

Ketoprofen administration can mask the signs of an infectious disease.

At infringement of function of kidneys and liver should reduce the dose and closely monitored.

The use of Ketoprofen in patients suffering from bronchial asthma can lead to an attack of bronchial asthma.

Women planning pregnancy should refrain from using the drug, because it can reduce the likelihood of implantation of the egg.

Influence on the ability to drive vehicles and control mechanisms — during the use of the drug should refrain from potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Gel, aerosol

The drug should be applied only to intact skin. Avoid contact with eyes and mucous membranes. In order to avoid manifestations of hypersensitivity and photosensitivity, it is recommended to avoid exposure to sunlight during the course of treatment.