Ketorolak

General characteristics. Structure:

Active ingredient: 10 mg of a ketorolak трометамин.

 Excipients: cellulose microcrystallic, sugar milk (lactose), magnesium stearate.

The medicine having the expressed analgetic effect possesses also antiinflammatory and moderate febrifugal action.

Pharmacological properties:

Pharmacodynamics. Ketorolak has the expressed analgetic 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 is not vliit on 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 to Ketorolak-Verta it 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. The rich zhiramipishcha 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 a priyemapervy 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.

The elimination half-life (T1/2) at patients with normal function of kidneys averages 5,3 p. T1/2 is extended at elderly patients and shortened at young people. Function of a liver does not exert impact on T1/2. At patients with a renal failure at concentration of creatinine in a blood plasma of 19-50 mg/l (168-442 µmol/l) T1/2 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:

To Ketorolak-Verta apply to vnut 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 of number 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 appointment to Ketorolaka-Verta 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%, are less frequent — 1-3%, is 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 hemolitic uraemic 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 makulopa-pullezny rash), a purpura, it is rare — exfoliative dermatitis (fever with a fever and without, reddening, consolidation or a peeling of skin, swelling and/or morbidity of palatine tonsils), a small tortoiseshell, Stivenva-Johnson's syndrome, a Lyell's disease.

Local reactions: less often — burning or pain in an injection site.

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 nonsteroid protivospalitelny 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 — гепато — and nephrotoxicity. Joint purpose of a ketorolak and methotrexate is possible (to control only when using low doses of the last concentration of a methotrexate in a blood plasma).

Probenitsid 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, anti-агрегантами, tsefoperazony, tsefotetany and pentoksifilliny increases risk of developing of bleeding. Reduces effect of hypotensive and diuretic drugs (lowers synthesis of prostaglandins in kidneys). 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 drugs increases (recalculation of a dose is necessary). Joint appointment with Valproatum of sodium 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 are reduced by clearance of a ketorolak and increase its concentration in a blood plasma.

Contraindications:

Hypersensitivity to a ketorolak or other non-steroidal anti-inflammatory drugs, "aspirinovy" asthma, a bronchospasm, a Quincke's disease, a hypovolemia (irrespective of the reason which caused it), dehydration.

Digestive tract erosive cankers in aggravation stages, round ulcers, hypocoagulation (including hemophilia).

Liver and/or renal failure (creatinine of plasma is higher than 50 mg/l).

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

Pregnancy, childbirth and period of a lactation.

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

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; arterial hypertension; 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.

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 zhiznennovazhny functions of an organism). It is not removed sufficiently by means of dialysis.

Storage conditions:

List B. In dry, protected from light, at a temperature not over 25 ºС. To store in the place, unavailable to children! Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 10 mg. On 10 tablets in a blister strip packaging or on 20 tablets in bank of polymeric. 2 blister strip packagings or to one bank polymeric together with the application instruction in a pack from a cardboard.