Ketonal capsules 150 instructions for use. Ketonal duo modified release capsules. Special instructions for admission
Instruction
on the use of a medicinal product for medical use
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If you have any questions, please contact your doctor.
Registration number:
LSR-008841/08
Trade name of the drug:
Ketonal ® DUO.
International non-proprietary name:
ketoprofen.
Dosage form:
modified release capsules.
Composition:
1 capsule contains: pellet core: active substance: ketoprofen - 150.00 mg; Excipients: microcrystalline cellulose - 34.00 mg; lactose monohydrate - 20.00 mg; povidone - 5.00 mg; croscarmellose sodium - 10.00 mg; polysorbate 80 - 1.00 mg; shell pellet 1: eudragit RS 30 D (ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer) - 4.908 mg; Eudragit RL 30 D (ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer) - 4.908 mg; triethyl citrate - 0.880 mg; polysorbate 80 - 0.008 mg; talc - 1.760 mg; iron (III) oxide yellow (E 172) - 0.080 mg; talc 2 - 0.200 mg; colloidal silicon dioxide 2 - 0.200 mg; capsule: capsule 1 L 970/53.051: 1 pc; gelatin - up to 100%; indigo carmine (E 132) - 0.4%; titanium dioxide (E 171) - 0.9%.
1 in a capsule, only 40% of the pellets are coated.
2 quantities of talc (0.200 mg) and colloidal silicon dioxide are not taken into account by the mass of the contents of the capsule.
Description: #1 capsule with transparent body and blue cap. The contents of the capsule are white and yellow pellets.
Pharmacotherapeutic group:
non-steroidal anti-inflammatory drug (NSAID).
ATX code: M01AE03.
Pharmacological properties
Pharmacodynamics
Ketoprofen is a non-steroidal anti-inflammatory drug.
Ketoprofen has anti-inflammatory, analgesic and antipyretic effects.
Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX1 and COX2) and, in part, lipoxygenase, which leads to suppression of prostaglandin synthesis (including in the central nervous system, most likely in the hypothalamus).
Stabilizes in vitro And in vivo liposomal membranes, at high concentrations in vitro Ketoprofen inhibits the synthesis of bradykinin and leukotrienes.
Ketoprofen does not adversely affect the condition of the articular cartilage.
Pharmacokinetics
Suction
Ketonal ® DUO is a new dosage form that differs from conventional capsules in the way the active substance is released. Modified release capsules contain two types of pellets: white (about 60% of the total) and yellow (40% of the total, coated). Ketoprofen is rapidly released from white pellets and slowly from yellow ones, which leads to a combination of fast and prolonged action of the drug.
The drug is well absorbed after oral administration. The bioavailability of both conventional capsules and capsules with modified release is the same, and is 90%.
Food intake does not affect the overall bioavailability (AUC) of ketoprofen, but reduces the rate of absorption.
After oral administration of ketoprofen in the form of capsules with a modified release of 150 mg, the maximum plasma concentration (Cmax) = 9036.64 ng / ml is reached within 1.76 hours.
Distribution
Ketoprofen is 99% bound to plasma proteins, mainly to the albumin fraction.
The volume of distribution in tissues is 0.1-0.2 l / kg. The drug penetrates well into the synovial fluid and reaches a concentration there equal to 30% plasma.
Significant concentrations of ketoprofen in the synovial fluid are stable and persist for up to 30 hours, as a result of which pain and stiffness of the joints decrease for a long time.
Metabolism and excretion
Ketoprofen is extensively metabolized by microsomal liver enzymes, the half-life (T1 / 2) of ketoprofen is less than 2 hours. It binds to glucuronic acid and is excreted from the body in the form of glucuronide. There are no active metabolites of ketoprofen.
Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly in the form of ketoprofen glucuronide. When using the drug at a dosage of 100 mg or more, excretion by the kidneys may be difficult. In patients with severe renal failure most of the drug is excreted through the intestines. When taking high doses, hepatic clearance also increases. Up to 40% of the drug is excreted through the intestines.
In patients with liver failure the plasma concentration of ketoprofen is doubled (probably due to hypoalbuminemia, and as a result of this high level of unbound active ketoprofen); such patients require the appointment of the drug in the minimum therapeutic dose.
In patients with kidney failure the clearance of ketoprofen is reduced, which also requires a dosage reduction.
At elderly patients metabolism and excretion of ketoprofen are slower, but this is of clinical importance only for patients with reduced renal function.
Indications for use
Symptomatic therapy of painful and inflammatory processes of various origins, including:
- inflammatory and degenerative diseases of the musculoskeletal system:
rheumatoid arthritis;
seronegative arthritis: ankylosing spondylitis - Bechterew's disease, psoriatic arthritis, reactive arthritis (Reiter's syndrome);
gout, pseudogout;
osteoarthritis;
- pain syndrome:
headache;
tendinitis, bursitis, myalgia, neuralgia, sciatica;
post-traumatic and postoperative pain syndrome;
pain syndrome in oncological diseases;
algomenorrhea.
Contraindications
Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other non-steroidal anti-inflammatory drugs;
complete and incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) (including history);
peptic ulcer of the stomach or duodenum in the acute stage, ulcerative colitis, Crohn's disease in the acute phase, inflammatory bowel disease in the acute stage;
hemophilia and other bleeding disorders;
children's age (up to 15 years);
severe liver failure;
severe renal failure (creatinine clearance (CC) less than 30 ml / min), progressive kidney disease;
decompensated heart failure;
postoperative period after coronary artery bypass grafting;
gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding);
lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
chronic dyspepsia;
III trimester of pregnancy;
lactation period.
Carefully: peptic ulcer in history, bronchial asthma in history, clinically significant cardiovascular, cerebrovascular and peripheral arterial diseases, dyslipidemia, progressive liver disease, hyperbilirubinemia, alcoholic cirrhosis of the liver, renal failure (CC 30-60 ml / min), chronic heart disease malnutrition, hypertension, blood disorders, dehydration, diabetes mellitus, history of gastrointestinal ulceration, smoking, concomitant therapy with anticoagulants (eg, warfarin), antiplatelet agents (eg, acetylsalicylic acid), oral glucocorticosteroids (eg, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), long-term use of NSAIDs, infection Helicobacter pylori, liver failure, old age.
Use during pregnancy and during breastfeeding
Inhibition of prostaglandin synthesis may have an undesirable effect on the course of pregnancy and/or embryonic development. Data obtained in the course of epidemiological studies with the use of prostaglandin synthesis inhibitors in early pregnancy confirm an increased risk of spontaneous abortion and the formation of heart defects (~ 1-1.5%).
It is possible to prescribe the drug to pregnant women in the I and II trimesters of pregnancy only if the benefits to the mother justify the possible risk to the fetus.
The use of ketoprofen in pregnant women during the third trimester of pregnancy is contraindicated due to the possibility of developing weakness of the labor activity of the uterus and / or premature closure of the ductus arteriosus, a possible increase in bleeding time, oligohydramnios and renal failure.
To date, there are no data on the release of ketoprofen into breast milk, therefore, if it is necessary to prescribe ketoprofen to a nursing mother, the issue of stopping breastfeeding should be resolved.
Dosage and administration
inside.
The standard dose of Ketonal ® DUO for adults and children over 15 years of age is 150 mg/day (1 modified-release capsule). Capsules should be taken during or after a meal with water or milk (the volume of liquid should be at least 100 ml).
The maximum dose of ketoprofen is 200 mg/day.
Side effect
According to the World Health Organization (WHO), adverse effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1/100,<1/10), нечасто (≥1/1000, <1/100), редко (≥1/10000, <1/1000) и очень редко (<1/10000); частота неизвестна (частоту возникновения явлений нельзя определить на основании имеющихся данных).
Hematopoietic and lymphatic system disorders
seldom: hemorrhagic anemia;
frequency unknown: agranulocytosis, thrombocytopenia, bone marrow dysfunction.
Immune System Disorders
frequency unknown: anaphylactic reactions (including anaphylactic shock).
Nervous System Disorders
infrequently: headache, dizziness, drowsiness;
seldom: paresthesia;
frequency unknown: convulsions, taste disturbance.
Mental disorders:
frequency unknown: emotional lability.
Sensory disturbances
seldom: blurred vision, tinnitus.
Cardiovascular disorders
frequency unknown: heart failure, increased blood pressure, vasodilation.
Respiratory system disorders
seldom: exacerbation of bronchial asthma;
frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.
Gastrointestinal disorders
often: nausea, vomiting, dyspepsia, abdominal pain;
infrequently: constipation, diarrhea, bloating, gastritis;
seldom: peptic ulcer, stomatitis;
very rarely: exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding, perforation.
Liver and biliary tract disorders
seldom: hepatitis, increased activity of "liver" transaminases, increased concentration of bilirubin.
Skin disorders
infrequently: skin rash, skin itching;
frequency unknown: photosensitivity, alopecia, urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.
Urinary system disorders
frequency unknown: acute renal failure, interstitial nephritis, nephritic syndrome, nephrotic syndrome, abnormal values of indicators of kidney function.
Other
infrequently: swelling;
seldom: weight gain;
frequency unknown: increased fatigue.
Overdose
As with other NSAIDs, overdose of ketoprofen may cause nausea, vomiting, abdominal pain, hematemesis, melena, impaired consciousness, respiratory depression, convulsions, impaired renal function and renal failure.
In case of overdose, gastric lavage and the use of activated charcoal are indicated.
Treatment- symptomatic; the effect of ketoprofen on the gastrointestinal tract (GIT) can be weakened with the help of H2-histamine receptor blockers, proton pump inhibitors and prostaglandins.
Interaction with other drugs
Ketoprofen may weaken the effect diuretics and antihypertensives and enhance action oral hypoglycemic agents and some anticonvulsants(phenytoin).
Simultaneous use with others NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of adverse events in the gastrointestinal tract.
Simultaneous use with anticoagulants(heparin, warfarin), thrombolytics, antiplatelet agents(ticlopidine, clopidogrel), pentoxifylline increases the risk of bleeding.
Simultaneous use with potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus, and trimethoprim increases the risk of developing hyperkalemia.
Increases plasma concentration cardiac glycosides, blockers of "slow" calcium channels, lithium preparations, cyclosporine, methotrexate and digoxin.
Increases toxicity methotrexate and nephrotoxicity cyclosporine.
Simultaneous use with probenecid significantly reduces the clearance of ketoprofen in plasma.
Combined reception with glucocorticosteroids and others NSAIDs (including selective COX2 inhibitors) increases the likelihood of side effects (in particular, from the gastrointestinal tract).
NSAIDs may decrease effectiveness mifepristone. NSAIDs should be started no earlier than 8-12 days after the abolition of mifepristone.
special instructions
Ketoprofen should not be combined with other NSAIDs and / or COX2 inhibitors. With long-term use of NSAIDs, it is necessary to periodically evaluate a clinical blood test, monitor kidney and liver function, especially in elderly patients (over 65 years), and conduct a fecal occult blood test.
Care must be taken and blood pressure monitored more often when using ketoprofen for the treatment of patients suffering from arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.
In the event of violations of the organs of vision, treatment should be stopped immediately.
Like other NSAIDs, ketoprofen may mask the symptoms of infectious and inflammatory diseases. In case of detection of signs of infection or deterioration of health during the use of the drug, you should immediately consult a doctor.
If there is a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer), long-term therapy and the use of high doses of ketoprofen, the patient should be under close medical supervision.
Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when administering ketoprofen to patients with heart or renal failure, as well as in the treatment of elderly patients taking diuretics and patients who, for whatever reason, have a decrease in circulating volume blood. The use of the drug should be discontinued before major surgery.
The use of ketoprofen can affect female fertility, so patients with infertility (including those undergoing examination) are not recommended to use the drug.
Influence on the ability to drive vehicles, mechanisms
There are no data on the negative effect of Ketonal ® DUO at recommended doses on the ability to drive a car or work with mechanisms. When driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, care must be taken, as the drug may cause dizziness and other side effects that may affect these abilities.
Release form
Modified release capsules 150 mg
10 capsules in aluminium/PVC/TEC/PVDC blister.
1, 2 or 3 blisters with instructions for use in a cardboard box.
Storage conditions
In a place protected from light at a temperature not exceeding 25 ° C.
In a place inaccessible to children.
Best before date
2 years.
Do not use the drug after the expiration date.
Holiday conditions
On prescription.
Manufacturer
RU holder: Lek d.d. Verovshkova 57, 1526 Ljubljana, Slovenia;
Produced: Lek d.d. Verovshkova 57, 1526 Ljubljana, Slovenia.
Send consumer claims to ZAO Sandoz:
125315, Moscow, Leningradsky prospect, 72, bldg. 3.
Excipients: microcrystalline cellulose - 34 mg, lactose monohydrate - 20 mg, povidone - 5 mg, croscarmellose sodium - 10 mg, polysorbate 80 - 1 mg.
The composition of the pellet shell1: Eudragit RS 30D (copolymer of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate) - 4.908 mg, Eudragit RL 30D (copolymer of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate) - 4.908 mg, triethyl citrate - 0.88 mg, polysorbate 80 - 0.008 mg, talc iron (III) oxide yellow (E172) - 0.08 mg, talc2 - 0.2 mg, colloidal silicon dioxide2 - 0.2 mg.
The composition of the capsule shell 1L970 / 53.051: gelatin - up to 100%, indigo carmine (E132) - 0.4%, titanium dioxide (E171) - 0.9%.
1 in the capsule only 40% of the pellets are coated;
2 the amount of talc (0.2 mg) of colloidal silicon dioxide is not taken into account by the mass of the contents of the capsule.
Modified release capsules, size #1, with clear body and blue cap. The contents of the capsules are white and yellow pellets.
Indications for use
Symptomatic therapy of painful and inflammatory processes of various origins, including:inflammatory and degenerative diseases of the musculoskeletal system:
- rheumatoid arthritis;
- seronegative arthritis (ankylosing spondylitis / Bechterew's disease /, psoriatic arthritis, reactive arthritis / Reiter's syndrome /);
- gout, pseudogout;
- osteoarthritis.
pain syndrome:
- headache;
- tendinitis, bursitis, myalgia, neuralgia, sciatica;
- post-traumatic and postoperative pain syndrome;
- pain syndrome in oncological diseases;
- algomenorrhea.
Mode of application
inside. The standard dose of Ketonal® Duo for adults and children over 15 years of age is 150 mg/day (1 modified-release capsule). Capsules should be taken during or after a meal with water or milk (the volume of liquid should be at least 100 ml).The maximum dose of ketoprofen is 200 mg/day.
Interaction
Weakens the effect of diuretics and antihypertensive drugs, enhances the effects of oral hypoglycemic and anticonvulsant drugs.Increases the concentration in the blood of methotrexate, lithium preparations, calcium channel blockers, cardiac glycosides, cyclosporine.
Adverse effects from the gastrointestinal tract are enhanced with simultaneous use with GCS, other NSAIDs.
The risk of bleeding occurs with the simultaneous appointment of anticoagulants, thrombolytics, antiplatelet agents.
When co-administered with diuretics and ACE inhibitors, there is a risk of impaired renal function.
NSAIDs reduce the effectiveness of estrogens (Mifepristone), so NSAIDs are prescribed 12 days after the end of the course of treatment with this drug.
Side effect
Definition of categories of frequency of undesirable effects (according to WHO): very often (? 1/10), often (? 1/100, From the side of the blood and lymphatic system:- rarely - hemorrhagic anemia, purpura;
frequency unknown - agranulocytosis, thrombocytopenia, impaired bone marrow hematopoiesis.
From the immune system: the frequency is unknown - anaphylactic reactions (including anaphylactic shock).
From the nervous system:
- infrequently - headache, dizziness, drowsiness;
- rarely - paresthesia;
frequency unknown - convulsions, impaired taste sensations, emotional lability.
From the senses: rarely - blurred vision, tinnitus.
Since the cardiovascular system: the frequency is unknown - heart failure, increased blood pressure, vasodilation.
From the respiratory system:
- rarely - exacerbation of bronchial asthma;
- the frequency is unknown - bronchospasm (especially in patients with established hypersensitivity to NSAIDs), rhinitis.
From the gastrointestinal tract:
- often - nausea, vomiting, dyspepsia, pain in the abdomen;
- infrequently - constipation, diarrhea, bloating, gastritis;
- rarely - peptic ulcer, stomatitis;
- very rarely - exacerbation of ulcerative colitis or Crohn's disease, gastrointestinal bleeding and perforation.
From the side of the liver and biliary tract: rarely - hepatitis, increased levels of hepatic transaminases and bilirubin.
From the skin and subcutaneous tissues:
- infrequently - skin rash, skin itching;
frequency unknown - photosensitivity, alopecia, urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the urinary system: very rarely - acute renal failure, interstitial nephritis, nephritic syndrome, nephrotic syndrome, abnormal values of renal function.
Other:
- infrequently - swelling, fatigue;
- rarely - weight gain;
- frequency unknown - increased fatigue.
Contraindications
- hypersensitivity to ketoprofen or other components of the drug, as well as salicylates, thiaprofenic acid or other NSAIDs;- complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history);
- erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;
- ulcerative colitis, Crohn's disease;
- hemophilia and other blood clotting disorders;
- severe liver failure;
- active liver disease;
- severe renal failure (CC less than 30 ml / min);
- progressive kidney disease;
- decompensated heart failure;
- postoperative period after coronary artery bypass grafting;
- gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding);
- diverticulitis;
- inflammatory bowel disease;
- confirmed hyperkalemia;
- chronic dyspepsia;
- children's age up to 15 years;
- III trimester of pregnancy;
- the period of breastfeeding;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
With caution, the drug should be prescribed for a history of peptic ulcer disease, a history of bronchial asthma, clinically significant cardiovascular, cerebrovascular and peripheral arterial diseases, dyslipidemia, progressive liver disease, liver failure, hyperbilirubinemia, alcoholic cirrhosis of the liver, renal failure (CC 30- 60 ml / min), chronic heart failure, arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnesis data on the development of gastrointestinal ulcers, the presence of Helicobacter pylori infection, with severe somatic diseases, smoking, concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (eg, acetylsalicylic acid), oral corticosteroids (eg, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), long-term use of NSAIDs, elderly patients (including those taking diuretics), patients with decreased ionic bcc.
Overdose
It is manifested by nausea, vomiting, vomiting with blood, abdominal pain, impaired consciousness, convulsions, impaired renal function.The gastric lavage and the use of sorbents are carried out. Treatment is symptomatic. The effect on the gastrointestinal tract can be reduced by the appointment of proton pump inhibitors.
In 1 capsule ketoprofen - 150 mg. MCC, lactose monohydrate, croscarmellose sodium, polysorbate, povidone - as excipients.
Release form
Capsules 150 mg № 30.
pharmachologic effect
Anti-inflammatory, analgesic.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Of all the representatives of NSAIDs, it has the strongest analgesic effect, comparable to that of . The powerful analgesic effect is explained by the peripheral and central mechanism. Inhibits the synthesis of prostaglandins, inhibiting the activity of cyclooxygenase, inhibits the synthesis of bradykinin.
The central action is realized due to the direct influence on the centers of pain in the thalamus. In terms of anti-inflammatory activity, it is comparable to classical NSAIDs. It is quickly excreted from the body, so it can be safely recommended to elderly patients. Capsules have two types of pellets (yellow and white). The drug is quickly released from white and slowly from yellow pellets, which gives a quick and prolonged effect (up to 24 hours).
Pharmacokinetics
Well absorbed. The bioavailability of the capsules is 90%, it is not affected by food intake. The maximum concentration is reached in 1.76 hours. It penetrates into the synovial fluid and significant concentrations remain in it for 30 hours, which ensures the elimination of pain for a long time. It is metabolized in the liver, there are no active metabolites. T 1/2 - 2 hours Mainly excreted by the kidneys and through the gastrointestinal tract. With liver failure, the concentration increases by 2 times, so the drug is prescribed in the minimum dose. With renal failure, clearance is reduced.
Indications for use
- , ;
- rheumatoid arthritis ;
- post-traumatic pain;
- headache;
- , tendinitis ;
- neuralgia , radiculitis ;
- postoperative pain;
- relief of pain in oncological practice;
- algomenorrhea .
Contraindications
- aspirin ;
- in the acute stage;
- bleeding from the gastrointestinal tract;
- exacerbation Crohn's disease , NUC and other inflammatory bowel diseases;
- hemophilia ;
- pronounced hepatic And kidney failure ;
- decompensated heart failure ;
- age up to 15 years;
- hypersensitivity to salicylates and other NSAIDs;
- pregnancy (III trimester).
Ketonal Duo should be used with caution in severe cardiovascular diseases, arterial hypertension , dyslipidemias , peripheral arterial disease, liver disease, alcoholism , .
Side effects
Common adverse reactions:
- nausea, or bloating, abdominal pain, vomiting, dry mouth;
- headache;
- irritability, fatigue, sleep disturbance, nightmares;
- decreased platelet aggregation;
- itch, .
Rarely seen:
- ulceration And perforation gastrointestinal mucosa, bleeding (with prolonged use of large doses);
- , polyneuropathy ;
- , speech disorder;
- tinnitus, blurred vision, change in taste, conjunctivitis ;
- , swelling, arterial hypertension ;
- anemia , ;
- interstitial nephritis , hematuria (with long-term use of NSAIDs in combination with diuretics), nephrotic syndrome;
- , , bronchospasm ;
- hemoptysis, metrorrhagia .
Tablets Ketonal Duo, instructions for use (Method and dosage)
There are various dosage forms of the drug: coated tablets (50 mg), forte tablets (100 mg), prolonged action - retard (150 mg), capsules Ketonal Duo (150 mg) and Ketonal Uno (200 mg).
Tablets 50 mg are taken one 3-4 times a day, prolonged action 1 time per day. The dose of Ketonal Duo and Ketonal Uno for adults is 1 capsule per day. It must be remembered that the maximum dose of 300 mg. For short-term use, it is permissible to take 1 capsule (150 mg) every 12 hours.
Instructions for use Ketonal Duo contains a warning that during treatment it is necessary to monitor the function of the kidneys and liver and the state of the blood. Some caution must be observed in hypertension, since NSAIDs lead to fluid retention.
Overdose
It is manifested by nausea, vomiting, vomiting with blood, abdominal pain, impaired consciousness, convulsions, impaired renal function.
The gastric lavage and the use of sorbents are carried out. Treatment is symptomatic. The effect on the gastrointestinal tract can be reduced by prescribing proton pump inhibitors .
Interaction
Weakens action diuretics And antihypertensive drugs enhances the effects oral hypoglycemic And anticonvulsants .
Increases blood concentration , lithium preparations , calcium channel blockers , cardiac glycosides , .
Adverse events from the gastrointestinal tract are aggravated with simultaneous use with GKS , others NSAIDs .
The risk of bleeding occurs with the simultaneous appointment anticoagulants , thrombolytics , antiplatelet agents .
When co-appointed with diuretics And ACE inhibitors there is a risk of impaired renal function.
NSAIDs reduce the effectiveness of the action estrogen (), so NSAIDs are prescribed 12 days after the end of the course of treatment with this drug.
Terms of sale
Released by prescription.
Storage conditions
Storage temperature up to 25°C.
Best before date
Analogues
Coincidence in the ATX code of the 4th level:Tablets: Flamax Forte , Ketoprofen Forte , Ketonal Retard .
Lek d.d./Novartis Neva Ltd., Slovenia, Symptomatic therapy of painful and inflammatory processes of various origins, including: - inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid arthritis; seronegative arthritis: ankylosing spondylitis - Bechterew's disease, psoriatic arthritis, reactive arthritis (Reiter's syndrome); gout, pseudogout; osteoarthritis; - pain syndrome: headache; tendinitis, bursitis, myalgia, neuralgia, sciatica; post-traumatic and postoperative pain syndrome; pain syndrome in oncological diseases; algomenorrhea.
Symptomatic therapy of painful and inflammatory processes of various origins, including: inflammatory and degenerative diseases of the musculoskeletal system: - rheumatoid arthritis; - seronegative arthritis (ankylosing spondylitis / Bechterew's disease /, psoriatic arthritis, reactive arthritis / Reiter's syndrome /); - gout, pseudogout; - osteoarthritis. pain syndrome: - headache; - tendinitis, bursitis, myalgia, neuralgia, sciatica; - post-traumatic and postoperative pain syndrome; - pain syndrome in oncological diseases; - algomenorrhea.
inside. The standard dose of Ketonal-Duo for adults and children over 15 years of age is 150 mg / day (1 modified-release capsule). Capsules should be taken during or after a meal with water or milk (the volume of liquid should be at least 100 ml). The maximum dose of ketoprofen is 200 mg/day.
Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates, thiaprofenic acid or other NSAIDs; - complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history); - erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; - ulcerative colitis, Crohn's disease; - hemophilia and other blood clotting disorders; - severe liver failure; - active liver disease; - severe renal failure (CC less than 30 ml / min); - progressive kidney disease; - decompensated heart failure; - postoperative period after coronary artery bypass grafting; - gastrointestinal, cerebrovascular and other bleeding (or suspected bleeding); - diverticulitis; - inflammatory bowel disease; - confirmed hyperkalemia; - chronic dyspepsia; - children's age up to 15 years; - III trimester of pregnancy; - the period of breastfeeding; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome. With caution, the drug should be prescribed for a history of peptic ulcer disease, a history of bronchial asthma, clinically significant cardiovascular, cerebrovascular and peripheral arterial diseases, dyslipidemia, progressive liver disease, liver failure, hyperbilirubinemia, alcoholic cirrhosis of the liver, renal failure (CC 30- 60 ml / min), chronic heart failure, arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnesis data on the development of gastrointestinal ulcers, the presence of Helicobacter pylori infection, with severe somatic diseases, smoking, concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (eg, acetylsalicylic acid), oral corticosteroids (eg, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), long-term use of NSAIDs, elderly patients (including those taking diuretics), patients with decreased ionic bcc.
- Instructions for use Ketonal ® duo
- The composition of the drug Ketonal ® duo
- Indications for Ketonal ® duo
- Storage conditions of the drug Ketonal ® duo
- Shelf life of the drug Ketonal ® duo
Release form, composition and packaging
caps. with modified release 150 mg: 20 or 30 pcs.Reg. No: 9948/12 of 05/03/2012 - Valid
Modified release capsules with transparent body and blue cap.
| 1 caps. | |
| ketoprofen | 150 mg |
Excipients: microcrystalline cellulose, lactose monohydrate, povidone, croscarmellose sodium, polysorbate 80.
The composition of the pellet shell: Eudragit RS 30D (30% dispersion of aminomethacrylate copolymer (type B)), Eudragit RL 30D (30% dispersion of amminomethacrylate copolymer (type A)), triethyl citrate, talc, yellow iron oxide (E172), anhydrous colloidal silicon dioxide.
The composition of the capsule shell: gelatin, dye indigotine (E132), titanium dioxide (E171).
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
Description of the medicinal product KETONAL ® DUO based on the officially approved instructions for use of the drug and made in 2013. Date of update: 03/28/2013
NSAIDs, a derivative of propionic acid. It has analgesic, anti-inflammatory and antipyretic effects. Ketoprofen inhibits the synthesis of prostaglandins and leukotrienes by blocking the COX enzyme (COX-1 and COX-2), which catalyzes the synthesis of prostaglandins in the metabolism of arachidonic acid.
Ketoprofen stabilizes lysosomal membranes in vitro and in vivo, at high concentrations has an inhibitory effect on the synthesis of leukotrienes in vitro and has anti-bradykinin activity.
The mechanism of antipyretic action of ketoprofen is unknown. Perhaps ketoprofen inhibits the synthesis of prostaglandins in the central nervous system (most likely in the hypothalamus).
In some women, ketoprofen reduces the symptoms of primary dysmenorrhea, probably by suppressing the synthesis of prostaglandins and / or their effects.
Capsules Ketonal ® Duo are presented in a new pharmaceutical form, which differs from conventional capsules in a special release of the active substance. Capsules contain two types of granules:
- standard (white) and coated (yellow). Ketoprofen is rapidly released from white granules (60% of the contents of the capsule) and slowly from the coated granules (40% of the contents of the capsule), so the capsule has both an immediate and a delayed effect.
Suction
After ingestion of Ketonal ® Duo capsules, Ketoprofen is well absorbed from the gastrointestinal tract. The bioavailability of ketoprofen from conventional capsules, as well as from modified release capsules, is 90%.
When taking ketoprofen with food, its AUC does not change, but the rate of absorption slows down. Fatty food does not change plasma AUC and Cmax, but the time to reach them increases.
The simultaneous use of antacids or other drugs to increase the pH of the stomach does not affect the rate and extent of absorption of ketoprofen.
After oral administration of ketoprofen at a dose of 150 mg in the form of modified-release capsules, Cmax in plasma is 9036.64 ng / ml and is reached after 1.76 hours.
Distribution
The binding of ketoprofen to plasma proteins, mainly the albumin fraction, is 99%. Vd is 0.1 l/kg. Ketoprofen penetrates into the synovial fluid, where it reaches 30% of the plasma concentration.
Metabolism
Ketoprofen is largely metabolized in the liver. It binds to glucuronic acid, forming an unstable ketoprofen glucuronide metabolite, which serves as a reserve of unchanged active substance.
The active metabolites of ketoprofen are unknown. The hydroxyl metabolite is pharmacologically inactive. Plasma clearance of ketoprofen is about 0.08 l / kg / h.
breeding
Approximately 60-75% of ketoprofen is excreted in the urine, mainly as a glucuronide metabolite. Less than 10% of the dose is excreted unchanged in the feces.
Pharmacokinetics in special clinical situations
In patients with renal insufficiency, the clearance of ketoprofen is reduced (in severe renal insufficiency, a dose reduction is required). In these patients, the conjugate may accumulate in the serum and deconjugate back to the primary active.
It has been noted that conjugates appear in the plasma of healthy adults only in small amounts, but they are higher in the elderly (mainly due to reduced renal clearance).
In patients with hepatic insufficiency, probably due to hypoalbuminemia (biologically free active ketoprofen), the concentration of ketoprofen almost doubles (to ensure a therapeutic effect, the administration of ketoprofen in the minimum daily dose is sufficient).
In patients with renal insufficiency, the excretion of ketoprofen is slowed down, T 1/2 increases by 1 hour.
Pain syndrome:
- post-traumatic pain (for example, sports injuries, muscle or tendon strain or strain, sprains, sprains, and bruises);
- postoperative pain (eg, pain after surgery or orthopedic surgery);
- algomenorrhea;
- pain with bone metastases in cancer patients.
- rheumatoid arthritis;
- seronegative spondylitis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis);
- gout, pseudogout;
- osteoarthritis;
- extra-articular rheumatism (tendinitis, bursitis, capsulitis of the shoulder joint).
Symptomatic therapy of rheumatic, degenerative and metabolic diseases:
For oral administration.
For adults and adolescents over 15 years of age the recommended dose is 150 mg (1 capsule Ketonal ® Duo) 1 time / day.
To minimize unwanted side effects, it is necessary to prescribe the minimum effective dose of the drug for a short time, but sufficient to relieve the symptoms of the disease.
The maximum daily dose of ketoprofen is 200 mg.
Before starting treatment with Ketonal ® Duo, the benefit to the patient and the possible risk should be carefully weighed.
Ketonal ® Duo should be taken during or after meals with at least 100 ml of water or milk.
The patient can also take antacids at the same time, which reduce the likelihood of side effects of ketoprofen on the gastrointestinal tract.
At elderly patients there is an increased risk of severe side effects of NSAIDs. If NSAIDs are required, the drug should be used at the lowest effective dose and patients should be monitored for gastrointestinal bleeding within 4 weeks from the start of NSAID treatment.
For children the dose of the drug has not been established.
Minor side effects, which are often short-lived:
- - indigestion, dyspepsia, nausea, vomiting, constipation, diarrhea, heartburn, stomach discomfort;
- less common side effects from the nervous system- headache, dizziness, mild disorientation, drowsiness, swelling, mood changes and insomnia.
More severe side effects from the digestive system:
- rarely - ulcerative stomatitis, melena, vomiting of blood, peptic ulcers, gastrointestinal bleeding or perforation, gastritis, gastric and duodenal ulcers.
Less commonly described are more severe side effects involving other organs and systems.
If severe side effects occur, treatment should be discontinued.
Determination of the frequency of adverse reactions:
- very often (≥1/10);
- often (≥1/100,<1/10);
- infrequently (≥1/1000,<1/100);
- rarely (≥1/10,000,<1/1000);
- very rarely (<1/10 000), включая отдельные сообщения.
From the hematopoietic system: infrequently - anemia, hemolysis, purpura, thrombocytopenia, agranulocytosis. Ketoprofen in high doses is able to inhibit platelet aggregation, which increases bleeding time and is the cause of hemorrhages and bruising.
Allergic reactions: infrequently - skin allergic reactions, increased reactivity of the respiratory tract, including bronchial asthma, complicated asthma, bronchospasm or dyspnea (especially in patients with hypersensitivity to acetylsalicylic acid and other NSAIDs);
From the side of the psyche: often - depression, irritability, nightmares, drowsiness;
From the nervous system: often - headache, asthenia, malaise, fatigue, weakness, dizziness, paresthesia;
From the sense organs: often - visual disturbances, ringing in the ears;
From the side of the cardiovascular system: often - swelling;
From the respiratory system: infrequently - hemoptysis, dyspnea, pharyngitis, rhinitis, bronchospasm, laryngeal edema (signs of an anaphylactic reaction);
From the digestive system: often - nausea, abdominal pain, diarrhea, constipation, stomatitis;
Hepatobiliary Disorders: very rarely - while taking NSAIDs, severe liver dysfunction is described in combination with jaundice and hepatitis.
From the side of the skin and subcutaneous tissue: often - skin rashes;
From the urinary system: very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, acute pyelonephritis.
From the reproductive system:
- infrequently - menometrorrhagia.
From the side of laboratory indicators: very often - a borderline increase in liver function tests;
- a history of bronchial asthma, urticaria or allergic reactions caused by ketoprofen or similar drugs, such as other NSAIDs, salicylates (including acetylsalicylic acid);
- severe heart failure;
- treatment of perioperative pain during coronary artery bypass surgery;
- chronic dyspepsia in history;
- peptic ulcer of the stomach or duodenum in the acute phase;
- history of gastrointestinal bleeding, ulceration or perforation;
- gastrointestinal, cerebrovascular bleeding;
- predisposition to bleeding;
- severe kidney disease;
- severe liver disease;
- bronchial asthma in combination with rhinitis;
- III trimester of pregnancy;
- children and adolescents up to 15 years;
- hypersensitivity to the components of the drug.
Use during pregnancy and lactation
The safety of ketoprofen during pregnancy has not been established. In the I and II trimesters of pregnancy, ketoprofen should be discontinued, unless the expected benefit of therapy for the mother outweighs the possible risk to the fetus.
Ketoprofen is contraindicated in the third trimester of pregnancy. The use of ketoprofen in the third trimester may interfere with the development of labor, cause premature fusion of the ductus botulinum with the development of pulmonary hypertension in the newborn.
The use of ketoprofen can reduce fertility, so it is not recommended for women planning a pregnancy. In women with difficulty in pregnancy or who are being examined for infertility, the use should be discontinued.
Ketonal ® Duo should not be used during lactation, because. the safety of using ketoprofen during breastfeeding has not been established.
The simultaneous use of Ketonal with NSAIDs, including selective COX-2 inhibitors, should be avoided.
Undesirable effects can be minimized by prescribing the drug at the lowest dose for the shortest period of time necessary to control symptoms.
In elderly patients, the incidence of side effects of NSAIDs is increased, especially gastrointestinal bleeding and perforation, which can be fatal.
Gastrointestinal bleeding, ulceration, or perforation with a risk of death has been reported for all NSAIDs at any stage of treatment, with or without warning symptoms, or a history of previous severe gastrointestinal disease.
Some epidemiological data suggest that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity compared to some other NSAIDs, especially at high doses.
In patients with a history of peptic ulcer disease, especially complicated by bleeding or perforation, and in elderly patients, the risk of gastrointestinal bleeding, ulceration or perforation increases with increasing dose of NSAIDs. In such patients, treatment should be initiated at the lowest effective dose.
For these patients, as well as for patients who require concomitant use of low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, concomitant administration of drugs that protect the gastrointestinal mucosa (for example, misoprostol or proton pump blockers) may be required.
Patients who have experienced gastrointestinal toxicity, especially elderly patients in the initial stages of treatment, should report any unusual symptoms in the abdomen. The risk of gastrointestinal bleeding should be kept in mind.
Caution is required when using the drug in patients receiving concomitant therapy with drugs that may increase the risk of ulcerative lesions or bleeding, for example, oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents, such as acetylsalicylic acid.
With the development of gastrointestinal bleeding or ulcerative lesions in patients receiving ketoprofen, treatment should be discontinued.
Care should be taken to prescribe NSAIDs to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), because. their exacerbation is possible.
Cardiovascular and cerebrovascular effects:
- Appropriate monitoring and consultation is required for patients with a history of hypertension and/or mild to moderate congestive heart failure manifested by fluid retention or edema associated with NSAID treatment.
Clinical experience and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with an increased risk of arterial thrombosis (eg, myocardial infarction or stroke). There are insufficient data to rule out such a risk for ketoprofen.
In patients with uncontrolled hypertension, congestive heart failure, established diagnosis of coronary artery disease, peripheral arterial disease and / or cerebrovascular disease, treatment with ketoprofen should be carried out only after a thorough assessment of the appropriateness of its use. Such an analysis should be done before starting long-term treatment in patients with risk factors for cardiovascular disease (eg, arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).
Patients suffering from bronchial asthma, in combination with chronic rhinitis, chronic sinusitis and / or nasal polyposis, are more likely to develop allergic reactions after taking acetylsalicylic acid and / or NSAIDs than in the general population. The use of this product may trigger an asthma attack.
Caution is also required in patients with impaired hemostasis, hemophilia, von Willebrand disease, severe thrombocytopenia and renal or hepatic insufficiency, as well as in those taking anticoagulants (coumarin and heparin derivatives, low molecular weight heparins).
In patients with liver damage receiving diuretics, after major surgical interventions with developed hypovolemia, and especially in elderly patients, urine output and the functional state of the kidneys should be carefully monitored.
Ketoprofen should be used with caution in patients with chronic alcoholism.
Very rarely, severe skin reactions (some of them fatal) such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis are observed in connection with the use of NSAIDs. Patients are most at risk of developing these reactions at the beginning of treatment, in most cases the onset of the reaction is noted during the first month of treatment. Ketonal ® should be canceled at the first manifestation of a skin rash, changes in the mucous membranes or other signs of hypersensitivity.
As with any long-term treatment with non-steroidal antirheumatic drugs, ketoprofen therapy requires monitoring of blood cells, as well as liver and kidney function, especially in elderly patients. With QC< 20 мл/мин необходима коррекция дозы кетопрофена.
Like other NSAIDs, ketoprofen masks the signs and symptoms of infectious diseases.
Ketonal ® Duo should be discontinued before major surgery.
Ketonal ® Duo contains lactose. Therefore, the drug should not be administered to patients with rare hereditary problems of galactose intolerance, lactase deficiency or malabsorption of glucose or galactose.
Influence on the ability to drive vehicles and control mechanisms
Patients should be warned about the possible occurrence of drowsiness, dizziness or convulsions while taking the drug. In the event of a risk of developing such reactions, patients should refrain from driving vehicles and working with mechanisms.
Results of preclinical studies on safety
Acute toxicity. After oral administration, the LD 50 of ketoprofen was 360 mg/kg in mice, 160 mg/kg in rats, and 1300 mg/kg in guinea pigs. The LD 50 of ketoprofen is several times higher than that of indomethacin.
chronic toxicity. Ketoprofen was administered orally to rats for 4 weeks at doses of 2, 6 or 18 mg/kg. 10% of the animals treated with ketoprofen at a dose of 18 mg/kg died on the 6-30th day, some had ulcerations of the intestinal mucosa. In dogs receiving the same dose, only intestinal ulceration has been described, while no animal has died. Among the animals treated with indomethacin at a dose of 6 mg/kg of body weight, half died; all animals treated with 18 mg/kg body weight died.
In a 6-month study, rats were administered oral ketoprofen at doses of 3, 6, or 9 mg/kg. After 8 weeks, 53% of male rats treated with 6 mg/kg and 67% of male and 20% of female rats treated with 9 mg/kg died. In animals that received 9 mg/kg, plasma concentrations of all proteins decreased and spleen and liver weight increased. Histopathological studies of tissues of surviving animals did not reveal significant pathological changes.
Carcinogenicity, mutagenicity and effects on fertility. Long-term toxicity studies in mice administered orally with ketoprofen up to 32 mg/kg/day did not reveal carcinogenic effects of this drug. The Ames test showed no mutagenic properties. Ketoprofen did not affect the fertility of male rats given orally up to 9 mg/kg/day. In female rats receiving 6 or 9 mg/kg/day, the number of implantations decreased. Spermatogenesis was found to be inhibited in male rats and dogs. In dogs and male monkeys treated with high doses of ketoprofen, a decrease in testicular weight was observed.
Teratogenicity. Neither teratogenic effects nor effects on the fetus were shown in mice treated with ketoprofen up to 12 mg/kg/day and in rats treated with up to 9 mg/kg/day. In rabbits, maternally toxic doses of ketoprofen were embryotoxic but teratogenic.
The safety of Ketoprofen has been proven by long-term clinical practice.
Symptoms: as with other NSAIDs, nausea, vomiting, epigastric pain, hematemesis, black feces, impaired consciousness, respiratory depression, convulsions, impaired renal function and renal failure are possible.
Treatment: in case of an overdose of oral forms, gastric lavage and activated charcoal are prescribed. Conduct symptomatic and supportive therapy;
Ketoprofen is characterized by high plasma protein binding, therefore, when used simultaneously with other drugs that bind to proteins, such as anticoagulants, sulfonamides, hydantoins, a dose change may be required to avoid an increase in plasma concentrations of these drugs due to competition for protein binding.
Ketoprofen should not be used simultaneously with other NSAIDs and salicylates.
With simultaneous use with corticosteroids, the risk of erosive and ulcerative lesions or bleeding from the gastrointestinal tract increases.
NSAIDs can enhance the effects of anticoagulants such as warfarin.
Antiplatelet agents and selective serotonin reuptake inhibitors increase the risk of gastrointestinal bleeding.
Ketoprofen reduces the effects of antihypertensive drugs.
Ketoprofen reduces the effect of diuretics.
Diuretics may increase the risk of NSAID nephrotoxicity.
The risk of kidney damage is higher in patients receiving diuretics or ACE inhibitors concomitantly with non-steroidal antirheumatic drugs.
A number of substances or therapeutic classes have the potential to cause hyperkalemia:
- potassium salts, potassium-sparing diuretics, ACE inhibitors, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, trimethoprim.
Ketoprofen increases the effects of oral hypoglycemic and some antiepileptic drugs (phenytoin).
NSAIDs can worsen heart failure, reduce glomerular filtration rate and increase plasma concentrations of cardiac glycosides.
Ketoprofen reduces the renal excretion of lithium, which can lead to an increase in the concentration of lithium in the blood plasma to toxic levels. In patients receiving lithium preparations, the concentration of lithium in plasma should be monitored when prescribing, changing the dose or canceling ketoprofen. With this combination, possible symptoms of lithium intoxication should be monitored.
With simultaneous use with cyclosporine, the risk of nephrotoxicity increases.
Severe, sometimes fatal, toxicity was observed with the appointment of NSAIDs, incl. and ketoprofen, along with methotrexate (especially in high dose therapy). Toxicity has been associated with elevated and long-lasting methotrexate concentrations in the blood.
With simultaneous use with non-steroidal antirheumatic drugs, the effectiveness of mifepristone may decrease. Non-steroidal antirheumatic drugs should not be administered within 8-12 days after the withdrawal of mifepristone.
SANDOZ PHARMACEUTICALS d.d., representative office, (Slovenia)
Representative office of JSC "Sandoz Pharmaceuticals d.d." (Slovenia) in the Republic of Belarus