Кетонал® DUO

General characteristics. Structure:

Capsules with the modified release 1 капс.
kernel of pellets  
active agent: ketoprofen of 150 mg
excipients: MKTs; lactoses monohydrate; povidone; sodium of a kroskarmelloz; polysorbate 80  
cover of pellets: eudragit RS30D (ethyl acrylate, methylmethacrylate and a trimetilammonioetilmetakrilat copolymer [1:2:0,1]); eudragit RL30D (ethyl acrylate, methylmethacrylate and a trimetilammonioetilmetakrilat copolymer [1:2:0,2]); triethyl citrate; polysorbate 80; talc; gland (III) oxide yellow (E172); silicon dioxide colloid  
capsule cover: gelatin; indigo carmine (E132); titanium dioxide (E171)  

Description of a dosage form

The capsule No. 1 with the transparent case and a blue cover. Contents of the capsule represent white and yellow pellets.

Pharmacological properties:

Pharmacodynamics. Ketoprofen — NPVP which has analgeziruyushchy, antiinflammatory and febrifugal effect.
At an inflammation ketoprofen inhibits synthesis of prostaglandins and leukotrienes, braking activity of TsOG and partially — lipoxygenases, also it inhibits synthesis of bradikinin and stabilizes lizosomalny membranes.
Has the central and peripheral analgesic effect and eliminates manifestations of symptoms of inflammatory and degenerative diseases of a musculoskeletal system.
At women ketoprofen reduces expressiveness of symptoms of primary dysmenorrhea owing to inhibition of synthesis of prostaglandins.

Pharmacokinetics. Absorption. At oral administration ketoprofen is quickly soaked up in a GIT. After oral administration of 100 mg of Cmax of ketoprofen in a blood plasma (10,4 mkg/ml) it is reached approximately in 1,5 h. Bioavailability of ketoprofen in peroral forms makes 90% and is directly proportional to the applied dose.
Capsules Ketonal Duo — a new dosage form which differs from ordinary capsules in way of release of active agent. Capsules contain two types of pellets: standard (white) and coated (yellow). Ketoprofen is quickly released from white pellets (60 from total quantity) and slowly — from yellow pellets (40% of total quantity) that causes the prolonged effect of drug.
Meal does not influence the general bioavailability of ketoprofen, but reduces absorption speed. Greasy food increases time of achievement of Cmax, but does not reduce bioavailability and Cmax of ketoprofen in a blood plasma. The concomitant use of drugs which reduce acidity of a gastric juice does not influence speed and volume of absorption of ketoprofen. After reception of capsules Ketonal Duo Cmax is reached during 1,76 h.
After rectal administration of 100 mg of Cmax ketoprofen in a blood plasma (10,4 mkg/ml) it is reached in 1,05–1,22 h. Bioavailability of ketoprofen after rectal administration — 71–96%.
Parenteral administration
Average concentration of ketoprofen in a blood plasma makes 26,4+5,4 mkg/ml in 4–5 min. after in/in infusions or introductions in oil. Bioavailability of ketoprofen makes 90%.
Distribution. Extent of linkng with proteins of a blood plasma — 99%. Distribution volume — 0,1–0,2 l/kg. Ketoprofen gets into synovial fluid. In 3 h after introduction of 100 mg of ketoprofen its concentration in a blood plasma makes about 3 mkg/ml, and concentration in synovial fluid — 1,5 mkg/ml. Though concentration of ketoprofen in synovial fluid is lower, than in a blood plasma, it is stabler (remains to 30 h; at parenteral administration in 9 h concentration of ketoprofen in a blood plasma — 0,3 mkg/ml, and in synovial fluid — 0,8 mkg/ml) therefore the pain syndrome and constraint of joints decrease by long time. Stable concentration of ketoprofen in a blood plasma is reached for 24 h. The pharmacokinetics of ketoprofen does not depend on age of the patient. For patients of advanced age stable concentration in a blood plasma is reached in 8,7 h and makes 6,3 mkg/ml. Cumulation of ketoprofen in fabrics is noted.
Metabolism and removal. Ketoprofen is intensively metabolized in a liver by means of microsomal enzymes. Out of an organism it is brought in the form of a conjugate with glucuronic acid. Т½ makes 2 h. To 80% of the entered dose of ketoprofen about 10% — with a stake are removed with urine, as a rule (more than 90%) in the form of a glucuronide.
Patients with a renal failure have a ketoprofen removal in a slowed-up way, Т½ increases by 1 h. At patients with a liver failure ketoprofen can collect in fabrics. Patients of more advanced age have a metabolism and removal of ketoprofen are slowed down, however it has clinical value only at a renal failure.

Indications to use:

Diseases of joints: pseudorheumatism; serological negative spondylarthritis (ankylosing spondylarthritis, psoriasis arthritis, reactive arthritis); gout, pseudogout; osteoarthritis; extraarticular rheumatism (tendinitis, bursitis, capsulitis of a shoulder joint);
pain syndrome: lumbago, posttraumatic joint pain, muscles; postoperative pain; pain at metastasises of tumors in a bone; альгодисменорея.

Route of administration and doses:

Doses are selected individually, depending on a condition of the patient and his reaction to treatment.
The recommended dose for adults — on 1 capsule 3 times a day. The recommended dose at treatment of a pseudorheumatism and osteoarthritis — on 1 capsule each 6–8 h.
Duration of treatment depends on weight and the course of a disease, however side effects can be minimized at use of a minimal effective dose during whenever possible shortest time.
The maximum daily dose of ketoprofen makes 200 mg.
Capsules accept during food, washing down with water or milk.
For the purpose of prevention of negative effect of ketoprofen on mucous membranes of bodies of a GIT it is possible to accept inhibitors of a proton pomp at the same time.
Patients of advanced age. At patients of advanced age the risk of emergence of side reactions increases. In 4 weeks from an initiation of treatment it is necessary to carry out monitoring concerning displays of gastrointestinal bleedings.
Tablets Ketonal Forte. The recommended dose of 100-200 mg/days (on 1 tablet 1–2 times a day), depending on body weight and weight of symptoms of a disease.
Tablets Ketonal Forte can be applied in a combination with suppositories Ketonal according to such scheme: on 1 tablet in the morning and on 1 suppository (100 mg) in the evening. At the combined purpose of different forms of drug (the capsule, tablets, suppositories, solution for injections) the general daily dose should not exceed 200 mg.
Pill is taken during food, washing down with water or milk (not less than 100 ml).
Capsules Ketonal Duo. The standard dose for makes 1 capsule (150 mg) a day. Capsules accept during food, washing down with water or milk (not less than 100 ml).
Tablets of the prolonged action Ketonal Retard. The recommended dose for adults and children is more senior than 15 years — 1 tablet of 1 times a day.
Ketocash solution
For parenteral use.
The recommended doses for adults
Introduction in oil: 1–2 times a day apply 100 mg of ketoprofen.
If necessary introduction in oil can be added with purpose of peroral or rectal forms of Ketonal.
In/in infusion: infusions of ketoprofen carry out only in the conditions of a hospital. Infusion is performed for 0,5–1 h, the course of treatment at in introduction — is no more than 48 h.
Discontinuous in/in infusion: 100–200 mg of ketoprofen dissolve 0,9% of solution of sodium of chloride in 100 ml and enter for 0,5–1 h.
Continuous in/in infusion: 100–200 mg of ketoprofen dissolve in 500 ml of solution for infusions (0,9% chloride sodium solution, Ringer's solution with a lactate, a dextrose) and enter for 8 h.
Ketoprofen can be applied along with analgetics of the central action; it can be mixed with morphine rolled into one: 10–20 mg of morphine and 100–200 mg of ketoprofen dissolve in 500 ml of solution for infusions (0,9% solution of sodium of chloride or Ringer's solution with a lactate).
Caution: bottles with solution for infusion should be wrapped dark paper or aluminum foil as ketoprofen is sensitive to light influence.
Suppositories Ketonal apply rektalno.
The recommended dose — 1 suppository is entered into a rectum by 1–2 times a day.
Ketonal suppositories can be combined with peroral forms of Ketonal, for example, 1 capsule (50 mg) in the morning and in the afternoon and 1 suppository (100 mg) in the evening or 1 tablet of Ketonal Forte (100 mg) in the morning and 1 suppository (100 mg) in the evening.
At the combined purpose of different dosage forms of drug (the capsule, tablets, suppositories, solution for injections) the general daily dose should not exceed 200 mg.

Features of use:

Side effect (especially from a digestive tract and cardiovascular system) can be prevented, accepting a minimal effective dose during the shortest time.
With care patients should appoint ketoprofen with gastrointestinal diseases in the anamnesis. Bleeding and perforation can suddenly develop without preliminary symptoms.
The risk of gastrointestinal bleedings, than an ultseration or perforation is higher at increase in doses of NPVP, at patients with a round ulcer in the anamnesis, especially at complications of hemorrhagic type or perforation, and at elderly people. These patients have to begin treatment with the minimum dose.
Such patients, and also patients for whom the accompanying therapy by low doses of acetylsalicylic acid or other drugs which can increase risk of gastrointestinal bleedings is necessary should apply a combination therapy tire-tread drugs (for example mizoprostoly or inhibitors of the proton pump).
Patients with earlier noted side effect from a digestive tract, especially advanced age, have to report about any unusual abdominal symptoms (in particular, about gastrointestinal bleeding), especially in an initiation of treatment.
The patients using the accompanying drugs capable to increase risk of bleedings or ultseration, such as peroral GKS, anticoagulants (warfarin), selective serotonin reuptake inhibitors, antitrombotichesky drugs (acetylsalicylic acid) need to take drug with caution.
When developing bleeding or an ultseration at patients, against the background of treatment by Ketonal, therapy needs to be cancelled.
Drug should be taken with caution to patients with gastrointestinal diseases in the anamnesis (ulcer colitis, a disease Krone) as their current can become aggravated.
Careful control is necessary for patients with AG and/or chronic heart failure of weak or moderate degree in the anamnesis as at therapy of NPVP it was reported about a delay of liquid and hypostases.
Patients with uncontrollable AG, the chronic heart failure established to an ischemic heart disease, diseases of peripheral arteries and/or diseases of vessels of a brain have to accept ketoprofen only after careful monitoring. Before prolonged treatment patients with risk factors in the presence of a lipidemia, a diabetes mellitus or smokers have to undergo careful inspection also.
Patients OH in combination with chronic rhinitis, sinusitis and/or a nasal polipoz most often have allergic reactions after reception of acetylsalicylic acid and/or NPVP. Use of such medicines can become the reason OH.
Drug should be used with care at patients with disturbance of a hemostasis, hemophilia, van Villebrandt's disease, heavy thrombocytopenia, a renal or liver failure, and also the persons accepting anticoagulants (derivatives of coumarin and heparin, mainly, low-molecular heparins).
Careful control of a diuresis and function of kidneys at patients with a renal failure, at the patients receiving diuretics is necessary at a hypovolemia as a result of extensive surgical intervention, especially at patients of advanced age.
Ketoprofen with care is applied at persons with alcoholism.
In isolated cases at use of NPVP noted heavy skin reactions, including exfoliative dermatitis, Stephens's syndrome — Johnson and a toxic epidermal necrolysis. The high risk of such reactions exists at the beginning of therapy (in most cases such reactions arise in the first months of treatment). The ketocash needs to be cancelled at the first displays of skin rash, damage of mucous membranes or other signs of hypersensitivity.
At prolonged treatment by ketoprofen, especially patients of advanced age, it is necessary to control a blood count, and also function of a liver and kidneys. At clearance of creatinine <0,33 ml / with (20 ml/min.) it is necessary to korrigirovat a ketoprofen dose.
Ketoprofen can mask signs and symptoms of an infectious disease.
Use of ketoprofen can break female fertility and is not recommended to the women planning pregnancy.
Capsules Ketonal, Ketonal Duo and Ketonal forte contain lactose therefore they are not appointed to patients with a rare hereditary disease of intolerance of a galactose, deficit of lactase or a sprue of glucose galactose.
Use during pregnancy and feeding by a breast. Safety of use of ketoprofen during pregnancy was not defined therefore use of drug is possible only when the expected advantage for mother exceeds potential risk for a fruit.
Use of ketoprofen in the III trimester of pregnancy and during feeding by a breast contraindicated.
Children. Drug is not used at children aged up to 15 years.
Ability to influence speed of response at control of vehicles or work with other mechanisms. Before clarification of individual reaction to drug (there can be dizziness, drowsiness) it is recommended to adhere to care at control of vehicles or work with difficult mechanisms.

Side effects:

Side effects are classified on systems of bodies and the frequency of manifestations: very often (≥1/10), it is frequent (≥1/100, <1/10), infrequently (≥1/1000, <1/100), is rare (≥1/10 000, <1/1000), is very rare (<1/10 000), including separate messages.
Side effects usually have tranzitorny character.
From system of blood: seldom — anemia, hemolysis, a purpura, thrombocytopenia, an agranulocytosis.
High doses of ketoprofen can inhibit aggregation of thrombocytes, prolonging thereby a bleeding time and to serve as the reason of nasal bleeding and formation of hematomas.
From immune system: reactivity of respiratory system, including OH, its aggravation; a bronchospasm or an asthma (especially at patients with hypersensitivity to acetylsalicylic acid and other NPVP); very seldom — a Quincke's disease and an anaphylaxis.
Mental disturbances: often — a depression, nervousness, dreadful dreams, drowsiness; seldom — a delirium with visual and auditory hallucinations, a disorientation, a dyslalia (disturbance of the speech).
From TsNS: often — a headache, an adynamy, discomfort, increased fatigue, weakness, dizziness, paresthesias; very seldom — there were separate messages on brain psevdopukhola cases.
From an organ of sight: often — a vision disorder; very seldom — conjunctivitis.
From an acoustic organ: often — a sonitus.
From cardiovascular system: often — hypostases; seldom — heart failure, AG.
From respiratory system: infrequently — a pneumorrhagia, short wind, pharyngitis, rhinitis, a bronchospasm, throat hypostasis (signs of anaphylactic reaction); seldom — asthma attacks.
From a GIT: very often — dyspepsia; often — nausea, abdominal pain, diarrhea, a lock, a meteorism, anorexia, vomiting, stomatitis; seldom — gastritis; very seldom — colitis, perforation of intestines (as complications diverticulums), an exacerbation of ulcer colitis or disease Krone, an enteropathy with perforation, a stenosis. The enteropathy can be followed by weak bleeding with protein loss. There can be round ulcers, perforation or gastrointestinal bleedings, sometimes — fatal, especially at patients of advanced age.
Ultseration, the hemorrhage or perforation can develop at 1% of patients in 3–6 months of treatment or at 2–4% of patients in 1 year of treatment using NPVP.
From gepatobiliarny system: very seldom — heavy abnormal liver functions which are followed by jaundice and hepatitis.
From skin: often — skin rash; in isolated cases — an alopecia, eczema, purpuropodobny rash, the increased sweating, urticaria, exfoliative dermatitis; seldom — photosensitivity, a photodermatitis; very seldom — violent reactions, including Stephens's syndrome — Johnson and a toxic epidermal necrolysis.
From an urinary system: very seldom — OPN, intersticial nephrite, a nephrotic syndrome, acute pyelonephritis.
From reproductive system: very seldom — a menometrorrhagia.
Laboratory indicators: very often — an aberration of indicators of function of a liver; seldom — at treatment of NPVP indicators of ALAT and ASAT significantly raise.
Reactions in an injection site — for solution for infusions: a burning sensation and/or pain in an injection site; for suppositories — in an injection site (rectum) there can be such symptoms as irritation, an itch, burning, an inflammation, including rectal bleeding.
Ketoprofen reduces aggregation of thrombocytes, prolonging thereby a bleeding time.

Interaction with other medicines:

It is necessary to avoid simultaneous use of ketoprofen with NPVP, including the selection TsOG-2 inhibitors.
Ketoprofen contacts proteins; at simultaneous use with other drugs which contact proteins, for example, anticoagulants, sulfonamides, hydantoins, correction of doses can be necessary for prevention of increase in level of these drugs owing to the competition for linkng with proteins of a blood plasma.
Simultaneous use with GKS increases risk of a gastrointestinal yazvoobrazovaniye or bleeding.
NPVP can strengthen effects of anticoagulants, such as warfarin.
Use of ketoprofen is combined with antitrombotichesky agents and selective serotonin reuptake inhibitors increases risk of gastrointestinal bleedings.
Ketoprofen can reduce effects of anti-hypertensive means and diuretics.
Diuretics can increase risk of nephrotoxicity of NPVP.
The risk of renal disturbances increases at patients who accept diuretics or APF inhibitors along with nonsteroid antirheumatic means.
Potassium salts, kaliysberegayushchy diuretics, APF, NPVP inhibitors, heparins (low-molecular or unfractionated), cyclosporine, такролимус and Trimethoprimum can cause a hyperpotassemia.
Ketoprofen strengthens effects of peroral anti-diabetic and anti-epileptic means (Phenytoinum).
Simultaneous use of NPVP and cardiac glycosides can cause an exacerbation of heart failure, reduce the speed of glomerular filtering and increase the level of glycosides in a blood plasma.
At simultaneous use with drugs of lithium removal of salts of lithium decreases.
Simultaneous use with cyclosporine increases risk of nephrotoxicity.
After use of ketoprofen along with a methotrexate (generally in high doses), there was heavy, sometimes fatal, a toxicity. Toxicity is caused by increase and prolongation of concentration of a methotrexate in blood.
At simultaneous use with NPVP the effect of mifepristone can decrease. NPVP should be accepted in 8–12 days after mifepristone use.

Contraindications:

Hypersensitivity to ketoprofen or other components of medicine, salicylates and other NPVP; heavy heart failure; treatment of postoperative pain when carrying out operation of aortocoronary shunting; chronic dyspepsia; active round ulcer of a stomach or ульцерация / perforation; gastrointestinal, cerebrovascular or other bleedings, patients inclined to a hemorrhage; heavy abnormal liver functions or kidneys; OH, rhinitis; III trimester of pregnancy and period of feeding by a breast; children's age up to 15 years.

Overdose:

Symptoms: nausea, vomiting, pain in the field of an epigastrium, vomiting with blood impurity, a melena, consciousness disturbance, respiratory depression, spasms, depression of function of kidneys and a renal failure.
Treatment: therapy is symptomatic. To wash out a stomach, to apply absorbent carbon. Antagonists of H2 receptors, inhibitors of the proton pump and prostaglandins reduce dangerous influence of ketoprofen on a digestive tract.
The specific antidote is absent.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Drug Ketonal® period of validity
5 years.

Issue conditions:

According to the recipe

Packaging:

Capsules with the modified release, 150 mg. On 10 капс. in the blister; on 3 blisters in a cardboard pack.