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

active substance: ketoprofen - 50.0 mg; Excipients: lactose - 186.1 mg; magnesium stearate - 2.4 mg; silicon dioxide colloidal - 1.5 mg; shell capsules - titanium dioxide - 0.94 mg; dye blue patented - 0.17 mg; gelatin to 47 mg.

Description:

Capsules: opaque capsules No. 3 with a white casing and blue lid. Contents of capsules: crumbly or compacted white powder with a yellowish tinge.

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 (NSAID). 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 the central nervous system (CNS), 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:

Absorption

Ketoprofen is easily absorbed from the gastrointestinal tract, bioavailability is 90%. Connection with blood plasma proteins - 99%. When administered 100 mg of ketoprofen, the maximum concentrations (C_m_Oh) of the drug in the blood plasma (10.4 μg / ml) are achieved after 1 h 22 min.

Distribution

Ketoprofen is 99% bound to blood plasma proteins, mainly with the albumin fraction. The volume of distribution is 0.1 l / kg. Ketoprofen penetrates into the synovial fluid and reaches there a concentration equal to 30% of the concentration in the blood plasma. Plasma clearance of ketoprofen is approximately 0.08 l / kg / h.

Metabolism and excretion

Ketoprofen undergoes intensive metabolism under the action of microsomal liver enzymes, the half-life period (T1 / 2) is less than 2 hours. Ketoprofen 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 dose 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.

Have patients with hepatic insufficiency 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 to prescribe the drug in the minimum therapeutic dose.

Have patients with renal insufficiency clearance of ketoprofen is reduced, but correction of doses is required only in the case of severe renal failure.

In elderly patients metabolism and excretion of ketoprofen proceed more slowly, which is of clinical importance only for patients with severe renal insufficiency.

Indications:

Symptomatic therapy of painful and inflammatory processes of various origin, 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;

· tendonitis, bursitis, myalgia, neuralgia, sciatica;

- pain syndrome, including mild, moderate and severe:

· headache;

· toothache;

· post-traumatic and postoperative pain syndrome;

· pain syndrome in cancer;

· algodismenorea;

- symptomatic therapy of pain syndrome in inflammatory diseases of the pelvic organs in women.

Contraindications:

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

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);

- peptic ulcer of the stomach or duodenum in the stage of exacerbation;

- inflammatory bowel disease in the acute stage;

- ulcerative colitis; Crohn's disease;

- hemophilia and other bleeding disorders;

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

- severe hepatic impairment;

- marked renal failure (creatinine clearance (CK) less than 30 ml / min);

- Decompensated heart failure;

- Postoperative period after coronary artery bypass grafting;

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

- chronic dyspepsia;

- III trimester of pregnancy,

- the period of breastfeeding;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Peptic ulcer disease, history of bronchial asthma, clinically expressed cardiovascular, cerebrovascular diseases and peripheral arterial diseases, dyslipidemia, progressive liver diseases, hyperbilirubinemia, alcoholic liver cirrhosis, hepatic insufficiency, renal insufficiency (KK 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 ( Gastrointestinal), the presence of infection Helicobacter pylori, old age, smoking, concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid), glucocorticosteroids for oral administration (eg, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, sertraline), prolonged use of NSAIDs.

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 the formation of heart defects (~ 1-1.5%).

Applying the drug to pregnant women in I and II trimesters of pregnancy is only possible 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 apply ketoprofen to a nursing mother, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Inside.

Capsules Ketonal ® should be swallowed whole during or after meals, washed down with water or milk (the volume of the liquid should be at least 100 ml). Usually the drug is prescribed 1-2 capsules 2-3 times a day.

Ketonal ® preparations for oral administration can be combined with the use of rectal suppositories; for example, a patient can take 1 capsule Ketonal® (50 mg) in the morning and in the middle of the day and inject 1 suppository (100 mg) rectally in the evening.

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 and subcutaneous tissues

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

Disorders from the kidneys and urinary tract

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 can be weakened with the help of drugs that reduce the secretion of the glands of the stomach (for example, proton pump inhibitors) and prostaglandins.

Interaction:

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

Joint application with other NSAIDs, salicylates, glucocorticosteroids, ethanol increases the risk of development undesirable phenomena 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, ACE inhibitors, 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 you have a history of contraindications from the gastrointestinal tract (bleeding, perforation, peptic ulcer disease), prolonged therapy and the use of high doses of ketoprofen, the patient should be carefully monitored by the doctor.

Due to the importance of prostaglandins in maintaining renal blood flow should be particularly careful when using ketoprofen patients with cardiac or renal insufficiency as well as in the treatment of elderly patients taking diuretics, and patients who, for whatever reason, the decrease in the volume of circulating observed blood. The drug should be discontinued before a large surgical intervention.

Use of ketoprofen can affect female fertility, so patients with infertility (including passing examination) is not recommended to apply the preparation.

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

Data on the adverse effects of Ketonal ® in the recommended doses on the ability to drive or work with mechanisms are not present. At the same time, patients who are drowsy when the drug is used,dizziness or other unpleasant sensations on the part of the nervous system, including visual impairment, should refrain from driving motor vehicles and practicing potentially dangerous Activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Capsules 50 mg.

Packaging:

Primary packaging: 25 capsules per bottle of dark glass, sealed with a polymer lid with a safety ring.

Secondary packaging: 1 bottle is placed in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

Terms of leave from pharmacies:On prescription

Registration number:P N 013942/05

Date of registration:19.11.2007

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® (Ketonal®)