Кетофрил®

General characteristics. Structure:

Active ingredient: 10 mg of a ketorolak of a trometamol (ketorolak of a trometamin).

Excipients (kernel): microcrystallic cellulose, lactose anhydrous, carboxymethylstarch of sodium, silicon dioxide colloid, magnesium stearate.

Excipients (cover): gipromelloza, talc, titanium dioxide, macrogoal, silicon dioxide colloid.

Pharmacological properties:

Pharmacodynamics. Ketorolak has the expressed analgeziruyushchy effect, possesses also antiinflammatory and moderate febrifugal action.

The mechanism of action is connected with non-selective oppression of activity of enzyme of cyclooxygenase 1 and 2, mainly in peripheral fabrics, braking of biosynthesis of prostaglandins - modulators of painful sensitivity, thermal control and an inflammation is a consequence of what. Ketorolak represents racemic mix |-] S and [+] R of enantiomer at the same time anesthetizing action is caused [-] S by a form.

Drug does not influence opioid receptors, does not oppress breath, does not cause medicinal dependence, does not possess sedative and anxiolytic action.

On force of analgeziruyushchy effect it is comparable to morphine, considerably surpasses other NPVP. After intake the beginning of the anesthetizing action is noted respectively, in 1 h, the maximum effect is reached in 1-2 h.

Pharmacokinetics. At intake Ketorolak is well soaked up in digestive tract - the maximum concentration (Cmax) in a blood plasma (0,7-1,1 mkg/ml) is reached in 40 min. after reception on an empty stomach of a dose of 10 mg. Food rich with fats reduces the maximum concentration of drug in blood and achievement for 1 hour detains her.

99% of drug contact proteins of a blood plasma and at a hypoalbuminemia the amount of free substance in blood increases.

Bioavailability - 80-100%. Time of achievement of equilibrium concentration (Css) at peroral introduction - 24 h at appointment 4 times a day (above subtherapeutic) also makes 10 mg - 0.39-0.79 mkg/ml after intake. The volume of distribution makes 0.15-0.33 l/kg. At patients with a renal failure the volume of distribution of drug can increase twice, and the volume of distribution of its R-enantiomera - by 20%.

Gets into breast milk: at reception by mother of 10 mg of a ketorolak of Cmax in milk it is reached in 2 h after reception of the first dose and makes 7.3 ng/ml, in 2 h after use of the second dose of a ketorolak (when using drug 4 times a day) - makes 7.9 ng/ml.

More than 50% of the entered dose are metabolized in a liver with formation pharmacological of inactive metabolites. The main metabolites are glucuronides which are removed by kidneys and r-gidroksiketorolak. 6% - through intestines are brought to 91% by kidneys.

Elimination half-life (T½ at patients with normal function of kidneys averages 5.3 h T½ it is extended at elderly patients and it is shortened at young people. Function of a liver does not exert impact on T½ U of patients with a renal failure at concentration of creatinine in a blood plasma of 19-50 mg/l (168-442 µmol/l) to T½ makes 10.3-10.8 h, at more expressed renal failure - more than 13.6 h. It is not removed during a hemodialysis.

Indications to use:

Pain syndrome of average and strong intensity of various genesis (including in the postoperative period, at oncological diseases, etc.)

Route of administration and doses:

Кетофрил® apply inside once or repeatedly depending on weight of a pain syndrome. The single dose - 10 mg, at repeated reception is recommended to accept on 10 mg to 4 times a day depending on expressiveness of pain; the maximum daily dose should not exceed 40 mg.

At intake duration of a course should not exceed 5 days.

Features of use:

Influence on aggregation of thrombocytes stops in 24-48 h.

The hypovolemia increases risk of development of side reactions from kidneys. If necessary it is possible to appoint in a combination with narcotic analgetics.

Not to use along with paracetamol more than 5 days. The patient with disturbance of a blood coagulation appoint drug only at constant control, numbers of thrombocytes, it is especially important in the post-operational period what demands careful control of a hemostasis.

As at a considerable part of patients at purpose of a ketorolak side effects from the central nervous system (drowsiness, dizziness, a headache) develop, it is recommended to avoid performance of work, the requiring special attention and bystry reaction (driving of motor transport, work with mechanisms and so forth).

Side effects:

Often - more than 3%, less often-1-3%, are rare - less than 1%.

From the alimentary system: often (especially at elderly patients, 65 years having digestive tract erosive cankers in the anamnesis are more senior) - a gastralgia, diarrhea; less often - stomatitis, a meteorism, a lock, vomiting, feeling of overflow of a stomach; seldom - nausea, digestive tract erosive cankers (including with perforation and/or bleeding - abdominal pain, a spasm or burning in epigastric area, a melena, vomiting as "a coffee thick", nausea, heartburn, etc.), cholestatic jaundice, hepatitis, a hepatomegalia, acute pancreatitis.

From an urinary system: seldom - an acute renal failure, a back pain with or without hamaturia and/or azotemias, a gemolitikouremichesky syndrome (hemolitic anemia, a renal failure, thrombocytopenia, a purpura), a frequent urination, increase or decrease in volume of urine, nephrite, hypostases of renal genesis.

From sense bodys: seldom: decrease in hearing, a ring in ears, a vision disorder (including an illegibility of visual perception).

From respiratory system: seldom: bronchospasm or диспноэ, rhinitis, throat hypostasis (asthma, breath difficulty).

From TsNS: often - a headache, dizziness, drowsiness, it is rare - aseptic meningitis (fever, a severe headache, spasms, muscle tension of a neck and/or back), a hyperactivity (change of mood, concern), hallucinations, a depression, psychosis.

From cardiovascular system: less often - increase in the ABP, is rare - a fluid lungs, a syncope.

From bodies of a hemopoiesis: seldom - anemia, an eosinophilia, a leukopenia.

From system of a hemostasis: seldom - bleeding from a postoperative wound, nasal bleeding, rectal bleeding.

From integuments: less often - skin rash (including makulopapullezny rash), a purpura, it is rare - exfoliative dermatitis (fever with a fever or without, reddening, consolidation or a peeling of skin, swelling and/or morbidity of palatine tonsils) a small tortoiseshell, Stephens-Johnson's syndrome, a Lyell's disease.

Allergic reactions: seldom - an anaphylaxis or anaphylactoid reactions (face skin discoloration, skin rash, a small tortoiseshell, an itch of skin, a tachypnea or диспноэ, swell a century, periorbital hypostasis, an asthma, the complicated breath, weight in a thorax, goose breathing).

Others: often - hypostases (persons, shins, anklebones, fingers, a foot, increase in body weight); less often - the increased perspiration, it is rare - a paraglossa, fever.

Interaction with other medicines:

Simultaneous use of a ketorolak with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, calcium drugs, glucocorticosteroids, ethanol, corticotropin can lead to formation of ulcers of digestive tract and development of gastrointestinal bleedings.

Joint appointment with paracetamol increases nephrotoxicity, with a methotrexate - gepato-and nephrotoxicity. Joint purpose of a ketorolak. and a methotrexate perhaps only when using low doses of the last (to control concentration of a methotrexate in a blood plasma).

Probenetsid reduces plasma clearance and volume of distribution of a ketorolak, increases its concentration in a blood plasma and increases the period of its semi-removal.

Against the background of use of a ketorolak reduction of clearance of a methotrexate and lithium and strengthening of toxicity of these substances is possible.

Co-administration with indirect anticoagulants, heparin, trombolitika, antiagregant, tsefoperazony, tsefotetany and pentoksifilliny increases risk of developing of bleeding.

Reduces effect of hypotensive and diuretic drugs (synthesis of prostaglandins in kidneys goes down).

At a combination with opioid analgetics of a dose of the last can be significantly reduced.

Antiacid means do not influence completeness of absorption of medicine. Hypoglycemic effect of insulin and peroral hypoglycemic means increases (recalculation of a dose is necessary).

Joint appointment with valproic acid causes disturbance of aggregation of thrombocytes.

Increases concentration in a blood plasma of verapamil and nifedipine.

At appointment with other nefrotoksichny medicines (including with gold drugs) the risk of development of nephrotoxicity increases. The medicines blocking canalicular secretion reduce clearance of a ketorolak and raise it. concentration in a blood plasma.

Contraindications:

Hypersensitivity to active agent or auxiliary components; the anamnestic, given about an attack bronkhoobstruktion, rhinitis, a small tortoiseshell after reception of acetylsalicylic acid or other NPVP (the full or incomplete syndrome of intolerance of acetylsalicylic acid - rinosinusit, a small tortoiseshell, polyps mucous a nose, bronchial asthma); a Quincke's disease, a hypovolemia (irrespective of the reason which caused it), dehydration.

Erosive and ulcer changes mucous stomach or 12-perstny gut, active gastrointestinal bleeding; inflammatory diseases of intestines; hypocoagulation (including hemophilia).

The expressed liver failure or active disease of a liver; the expressed renal failure (creatinine of plasma is higher than 50 mg/l), the progressing diseases of kidneys; the confirmed hyperpotassemia.

The hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, a concomitant use with other NPVP, high risk of development or a recurrence a krovenschsniya (including after operations), hemopoiesis disturbance.

Pregnancy, childbirth and period of a lactation.

Children's age up to 16 years (efficiency and safety are not established).

The period after performing aortocoronary shunting; drug is not used for anesthesia before and during surgeries because of high risk of bleeding, and also for treatment of chronic pains.

With care - bronchial asthma; cholecystitis; chronic heart failure; coronary heart disease, cerebrovascular diseases, arterial hypertension; дислипидемия / a lipidemia, a diabetes mellitus, diseases of peripheral arteries, smoking, a renal failure (creatinine of plasma is lower than 50 mg/l); cholestasia; active hepatitis; sepsis; system lupus erythematosus; advanced age (65 years are more senior); polyps of a mucous membrane of a nose and nasopharynx.

Anamnestic data on development of a canker of a GIT, existence of an infection of Helicobacter pylori, long use of NPVP, frequent alcohol intake, heavy somatopathies, the accompanying therapy by the following drugs:

• anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), peroral glucocorticosteroids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).

For decrease in risk of development of the undesirable phenomena from a GIT it is necessary to use a minimal effective dose minimum possible short course.

Overdose:

Symptoms: abdominal pains, nausea, vomiting, emergence of round ulcers of a stomach or erosive gastritis, renal failure, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents (absorbent carbon) and performing symptomatic therapy (maintenance of the vital functions of an organism). It is not removed sufficiently by means of dialysis.

Storage conditions:

To store at a temperature not above 30 °C in the dry, protected from light place. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 10 mg. On 10 tablets in a strip from aluminum foil. 1 or 2 strips in a cardboard pack together with the application instruction.

Sample not for sale: on 10 tablets in a strip from aluminum foil. 1 strip together with the application instruction in a cardboard pack.