Ketonal DUO - instructions for use, dose, side effects, contraindications

Excipients: microcrystalline cellulose 34.0 mg; lactose monohydrate 20.00 mg; Povidone 5.00 mg; croscarmellose sodium 10.00 mg; polysorbate 80 1.00 mg;

pellet shell¹: eudragit Rs 30 D (ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer [1: 2: 0.1]) 4.908 mg; eudragit RL 30 D (ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate copolymer [1: 2: 0.2]) 4.908 mg; triethyl citrate 0.880 mg; polysorbate 80 0.008 mg; talc² 1,760 mg; iron (III) oxide yellow (E 172) 0.080 mg; talc 0,200 mg; Silica colloidal dioxide² 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%.

¹In the capsule, only 40% of the pellets are coated.

²The amounts of talc (0.200 mg) and colloidal silica are not taken into account in the weight of the contents of the capsule.

Description:

Capsule № 1 with a transparent casing and a blue lid. The contents of the capsule are white and yellow pellets.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID)

ATX: & nbsp

M.02.A.A.10 Ketoprofen

Pharmacodynamics:

Ketoprofen is a non-steroidal anti-inflammatory drug. Ketoprofen has anti-inflammatory, analgesic and antipyretic effect.

Ketoprofen blocks the action of the enzyme cyclooxygenase 1 and 2 (COX₁ and COX₂) and, in part, lipoxygenase, which leads to suppression of the synthesis of prostaglandins (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 by the release of the active substance. Modified-release capsules contain two types of pellets: white (about 60% of the total) and yellow (40% of the total, coated). Ketoprofen quickly released from white pellets and slowly from yellow, which causes a combination of rapid and prolonged action of the drug.

The drug is well absorbed after ingestion.The bioavailability of both conventional capsules and modified-release capsules is the same, and is 90%.

Eating does not affect the overall bioavailability (AUC) of ketoprofen, but decreases the rate of absorption.

After ingestion of ketoprofen in the form of capsules with a modified release of 150 mg, the maximum plasma concentration (C_max) = 9036.64 ng / ml is achieved within 1.76 hours.

Distribution

Ketoprofen is 99% bound to blood plasma proteins, mainly with 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 equal to 30% of the plasma. Significant concentrations of ketoprofen in the synovial fluid are stable and persist up to 30 hours, resulting in long-term pain and joint stiffness.

Metabolism and excretion

Ketoprofen undergoes intensive metabolism by means of microsomal liver enzymes, half-life (T_1/2) of ketoprofen for 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 in a dosage of 100 mg or more, excretion by the kidneys can be difficult. In patients with severe renal insufficiency most of the drug is secreted through the intestine. When taking high doses, the liver clearance also increases. Up to 40% of the drug is excreted through the intestine.

In patients with hepatic impairment the plasma concentration of ketoprofen is doubled (probably due to hypoalbuminemia, and, as a result, a high level of unbound active ketoprofen); such patients need the administration of the drug in a minimal therapeutic dose.

Patients from renal insufficiency clearance of ketoprofen is reduced, which also requires a reduction in dosage.

In elderly patients metabolism and excretion of ketoprofen occur more slowly, but this is of clinical importance only for patients with decreased renal function.

Indications:

Symptomatic therapy of painful and inflammatory processes of various origin, including:

- inflammatory and degenerative diseases of the musculoskeletal system:

rheumatoid arthritis;
seronegative arthritis: ankiloziruyugtsy spondylitis -Diseases spondylitis, psoriatic arthritis, reactive arthritis (Reiter's syndrome);
gout, pseudogout;
osteoarthritis;

- pain syndrome:

headache;
tendonitis, bursitis, myalgia, neuralgia, sciatica;
post-traumatic and postoperative pain syndrome;
pain syndrome in cancer;
algodismenorea.

Contraindications:

- Hypersensitivity to ketoprofen or other components of the drug, as well as salicylates or other non-steroidal anti-inflammatory drugs;

- complete or incomplete combination of asthma, recurrent nasal polyposis mucous membrane and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) (including history);

- gastric ulcer or duodenal ulcer in the acute stage, ulcerative colitis, Crohn's disease in the acute phase inflammatory bowel disease in the acute stage;

- hemophilia and other disorders of blood coagulability;

- Children's age (up to 15 years);

severe hepatic impairment;

- severe renal failure (creatinine clearance (CK) less than 30 ml / min), progressive kidney disease;

Decompensated heart failure;

- Postoperative period after aortocoronary shunting;

- gastrointestinal, cerebrovascular and other bleeding (or suspicion of bleeding);

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

- chronic dyspepsia;

- III trimester of pregnancy;

lactation period.

Carefully:

A history of peptic ulcer disease, a history of bronchial asthma, clinically expressed cardiovascular, cerebrovascular diseases and peripheral arterial diseases, dyslipidemia, progressive liver disease, hyperbilirubinemia, alcoholic cirrhosis, renal failure (CK 30-60 ml / min), chronic heart failure , arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, smoking, concomitant therapies anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid), glucocorticosteroids for oral administration (for example, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), long-term use of NSAIDs, the presence of infection Helicobacter pylori, hepatic insufficiency, elderly age.

Pregnancy and lactation:

Inhibition of prostaglandin synthesis may have an adverse effect on the course of pregnancy and / or on embryonic development. Data from epidemiological studies using prostaglandin synthesis inhibitors in early pregnancy confirm the increased risk of spontaneous abortion and heart disease (1-1.5%).

Prescribe the drug to pregnant women in the I and II trimesters of pregnancy is possible only if the benefits for the mother justify the possible risk to the fetus.

Contraindicated in the use of ketoprofen in pregnant women during the third trimester of pregnancy because of the possibility of developing weakness in the uterine labor activity and / or premature closure of the arterial duct, a possible increase in bleeding time, lack of hydration and kidney failure.

To date, there is no data on the isolation of ketoprofen in breast milk, therefore, if it is necessary to prescribe ketoprofen to a nursing mother, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Inside.

The standard dose of Ketonap® for adults and children over 15 years is 150 mg / day (1 capsule with modified release).

Capsules should be taken during or after a meal, washed down with water or milk (the volume of the liquid should be at least 100 ml).

The maximum dose of ketoprofen is 200 mg / day.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

Disturbances from the hematopoiesis and lymphatic system

rarely: hemorrhagic anemia; frequency unknown: agranulocytosis, thrombocytopenia, impaired bone marrow function.

Immune system disorders

frequency unknown: anaphylactic reactions (including anaphylactic shock).

Disturbances from the nervous system

infrequently: headache, dizziness, drowsiness; rarely: paresthesia; the frequency is unknown: convulsions, a violation of taste.

Disorders of the psyche:

frequency unknown: emotional lability.

Impaired sensory organs

rarely: blurred vision, tinnitus.

Disorders from the cardiovascular system

frequency unknown: heart failure, increased blood pressure, vasodilation.

Disturbances from the respiratory system

rarely: exacerbation of bronchial asthma; frequency unknown: bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.

Disorders from the gastrointestinal tract

often: nausea, vomiting, indigestion, 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, perforation.

Disturbances from the liver and bile ducts

rarely: hepatitis, increased activity of "hepatic" transaminases, increased bilirubin concentration.

Disturbances from the skin

infrequently: skin rash, itchy skin; frequency unknown: photosensitivity, alopecia, urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the urinary system

frequency unknown: acute renal failure, interstitial nephritis, nephritic syndrome, nephrotic syndrome, abnormal values of renal function indicators.

Other

infrequently: swelling; rarely: weight gain; frequency unknown: increased fatigue.

Overdose:

As with other NSAIDs, with an overdose of ketoprofen, nausea, vomiting, abdominal pain, vomiting with blood, melena, impaired consciousness, respiratory depression, seizures, impaired renal function, and kidney failure may occur.

In case of overdosage, gastric lavage and the use of activated charcoal are indicated.

Treatment is symptomatic; the effect of ketoprofen on the gastrointestinal tract (GIT) can be weakened with the help of blockers H₂-histamine receptors, proton pump inhibitors and prostaglandins.

Interaction:

Ketoprofen can weaken the action diuretics and antihypertensive drugs and strengthen action hypoglycemic agents for oral administration and some anticonvulsants (phenytoin).

Simultaneous application with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of developing unwanted effects from the gastrointestinal tract.

Simultaneous application with anticoagulants (heparin, warfarin), thrombolytic agents, antiplatelet agents (ticlopidine, clopidogrel), pentoxifylline increases the risk of bleeding.

Simultaneous application with potassium salts, potassium-sparing diuretics, inhibitors of angiotensin-converting enzyme (ACE), NSAIDs, low molecular weight heparins, cyclosporin, tacrolimus and trimethoprim increases the risk of hyperkalemia.

Increases the concentration in the blood plasma cardiac glycosides, blockers of "slow" calcium channels, lithium preparations, cyclosporine, methotrexate and digoxin.

Increases toxicity methotrexate and nephrotoxicity cyclosporine. Simultaneous application with probenecid significantly reduces the clearance of ketoprofen in the blood plasma.

Combination with glucocorticosteroids and other NSAIDs (including selective COX inhibitors₂ increases the likelihood of side effects (in particular, from the gastrointestinal tract).

NSAIDs may decrease effectiveness mifepristone. Admission of NSAIDs should be started no earlier than 8-12 days after the withdrawal of mifepristone.

Special instructions:

Do not combine ketoprofen with other NSAIDs and / or COX inhibitors₂. With prolonged use of NSAIDs, it is necessary to periodically evaluate the clinical analysis of blood, monitor kidney and liver function, in particular, in elderly patients (over 65 years old), conduct fecal occult blood test.

It is necessary to be careful and to control blood pressure more often when using ketoprofen for the treatment of patients suffering from arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.

If abnormalities occur on the part of the visual organs, treatment should be stopped immediately.

Like other NSAIDs, ketoprofen can mask the symptoms of infectious and inflammatory diseases. In case of detection of signs of infection or deterioration of well-being on the background of 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 disease), prolonged therapy and high doses of ketoprofen, the patient should be carefully monitored by the doctor.

Because of the important role of prostaglandins in maintaining renal blood flow, caution should be exercised in prescribing ketoprofen to patients with cardiac or renal insufficiency, and also in the treatment of elderly patients taking diuretics and patients who, for whatever reason, blood. Use of the drug should be discontinued before a large surgical intervention.

The use of ketoprofen can affect women's fertility, so patients with infertility (including undergoing examination) are not recommended to use the drug.

Effect on the ability to drive transp. cf. and fur:

Data on the adverse effects of Ketonal® DIO at the recommended doses on the ability to drive or operate machinery are not.

When driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration and speed of psychomotor reactions, care must be taken since the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:Modified-Release Capsules 150 mg.

Packaging:

10 capsules per blister of aluminum / PVC / TE / PVDC.

For 1, 2 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

In a place inaccessible to children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008841/08

Date of registration:10.11.2008 / 05.07.2017

Expiration Date:Unlimited

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp05.01.2018

Illustrated instructions

Instructions

Ketonal® DUO (Ketonal® DUO)