Ketorolak

General characteristics. Structure:

Active ingredient: a ketorolaka трометамол (a ketorolaka трометамин) - 30 mg; 

excipients: dinatrium of an edetat a dihydrate (Trilonum of B), ethanol (alcohol) (in terms of anhydrous), propylene glycol, sodium chloride, sodium hydroxide of 1 M solution, water for injections.

Description: Transparent liquid of light yellow color.

Pharmacological properties:

Pharmacodynamics. NPVP 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 the cyclooxygenase 1 and cyclooxygenase 2 catalyzing formation of prostaglandins from arachidonic acid which play an important role in a pathogeny of pain, an inflammation and fever. On force of analgeziruyushchy effect it is comparable to morphine, considerably surpasses other NPVP.

After intramuscular introduction the beginning of analgeziruyushchy action is noted in 0.5 h, the maximum effect is reached in 1-2 h.

Pharmacokinetics. Absorption at intramuscular introduction full and bystry. The maximum concentration (Stakh) after intramuscular introduction of 30 mg - 2.4 mkg/ml, 60 mg - 4.5 mkg/ml, time of achievement of the maximum concentration from 15 to 73 min. Communication with proteins of plasma - 99 ° / the lake. Time of achievement of equilibrium concentration (Css) at parenteral administration - 24 h, at appointment 4 times a day (above subtherapeutic) also makes at intramuscular introduction 15 mg - 0.9 mkg/ml, 30 mg - 1.9 mkg/ml.

Distribution volume - 0.15-0.3 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 - for 20% Gets into breast milk. 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 - on average about the 5th p. T1/2 increases at elderly patients and is 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 plasma of 19-50 mg/l (168-442 µmol/l) of T 1/2 increases to 10 h, at more expressed renal failure - more than 13 h. The general clearance makes at intramuscular introduction 30 mg - 0.02 l/h/kg (elderly patients have 0.019 l/h/kg), at patients with a renal failure at concentration of creatinine in plasma of 19-50 mg/l at intramuscular introduction of 30 mg - 0.015 l/h/kg. It is not removed by a hemodialysis.

Indications to use:

Pain syndrome of strong and moderate expressiveness: injuries, a dentagra, pains in the puerperal and postoperative period, oncological diseases, a mialgiya, an arthralgia, neuralgia, radiculitis, dislocations, stretchings, rheumatic diseases. It is intended for symptomatic therapy, reduction of pain and an inflammation at the time of use, does not influence progressing of a disease.

Route of administration and doses:

Intramusculary. At parenteral use to patients from 16 to 64 years with the body weight exceeding 50 kg intramusculary for 1 introduction enter no more than 60 mg; usually on 30 mg each 6 h. To adult patients with body weight less than 50 kg or with a chronic renal failure for 1 introduction enter no more than 30 mg; usually - on 15 mg (no more than 20 doses for 5 days). The maximum daily doses for patients from 16 to 64 years with the body weight exceeding 50 kg - 90 mg/days; to adult patients with body weight less than 50 kg or with a chronic renal failure, and also to elderly patients (65 years are more senior) - 60 mg. Duration of treatment should not exceed 5 days.

Features of use:

Before purpose of drug it is necessary to find out a question of the previous allergy to drug or NPVP. Because of risk of development of allergic reactions introduction of the first dose is carried out under careful observation of the doctor. The hypovolemia increases risk of development of nephrotoxic side reactions. If necessary it is possible to appoint in a combination with narcotic analgetics. It is not recommended to apply as medicine to premedication, anesthesia maintenance. At joint reception with other NPVP the liquid delay, a decompensation of cordial activity, increase in arterial pressure can be observed. Influence on aggregation of thrombocytes stops in 24-48 h.

Not to use more than 5 days along with paracetamol. The patient with disturbance of a blood coagulation appoint only at constant control of number of thrombocytes, it is especially important for the postoperative patients demanding careful control of a hemostasis. For decrease in risk of development of the NPVP-gastropathy antiacid medicines, мизопростол, омепразол are appointed. The risk of development of medicinal complications increases when lengthening treatment (at patients with chronic pains) and increase in a dose of drug more than 40 mg/days. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. For decrease in risk of development of the undesirable phenomena from digestive tract it is necessary to use a minimal effective dose minimum possible short course.

Side effects:

Often - more than 3%, are less frequent - 1-3%, is rare - less than 1%. From the alimentary system: often - a gastralgia, diarrhea; less often - stomatitis, a meteorism, a lock, vomiting, feeling of overflow of a stomach; seldom - a loss of appetite, nausea, digestive tract erosive cankers (including with perforation and/or bleeding - an abdominal pain, a spasm or burning in epigastric area, blood in Calais or a melena, vomiting with blood or 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, a hamaturia, an azotemia, a gemolitikouremichesky syndrome (hemolitic anemia, a renal failure, thrombocytopenia, a purpura), increase of an 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 - a bronchospasm or диспноэ, rhinitis, a fluid lungs, throat hypostasis (an asthma, breath difficulty).

From the central nervous system: 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, unconscious states.

From cardiovascular system: less often - increase in arterial pressure.

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 makulopapulezny rash), a purpura, it is rare - exfoliative dermatitis (fever with a fever or without, a hyperemia, consolidation or a peeling of skin, increase and/or morbidity of palatine tonsils), a small tortoiseshell, a malignant exudative erythema (Stephens's syndrome - Johnson), a toxic epidermal necrolysis (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). Other: often - hypostases (persons, shins, anklebones, fingers, a foot, increase in body weight); less often - the increased sweating, is rare - a paraglossa, fever.

Interaction with other medicines:

Reception with other NPVP, glucocorticosteroids, ethanol, corticotropin, drugs of calcium increases risk of an ulceration of a mucous membrane of digestive tract and development of gastrointestinal bleedings. Co-administration with anticoagulating medicines - derivatives of coumarin and an indandion, heparin, trombolitika (an alteplaza, Streptokinasa, an urokinase), antiagregantny medicines, cephalosporins, valproic acid and acetylsalicylic acid increases risk of development of bleedings.

Reduces effect of hypotensive and diuretic medicines (reduces synthesis of prostaglandins in kidneys). Appointment together with a methotrexate raises gepato-and nephrotoxicity (their joint appointment is possible only during the using of low doses of the last and control of its concentration in plasma). 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 increase its concentration in plasma. Increases effect of narcotic analgetics. Myelotoxic medicines strengthen manifestations of a gematotoksichnost of drug.

Contraindications:

Hypersensitivity, full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid or other NPVP (including in the anamnesis), the urticaria, rhinitis caused by reception of NPVP (in the anamnesis); intolerance of medicines of a pyrazolon row, a hypovolemia (irrespective of the reason which caused it), erozivnoyazvenny gastrointestinal tract diseases in an aggravation stage, hypocoagulation (including hemophilia), bleedings or high risk of their development, a heavy renal failure (clearance of creatinine less than 30 ml/min.), a heavy liver failure or an active disease of a liver, a state after performing aortocoronary shunting, the confirmed hyperpotassemia, pregnancy (the III trimester), inflammatory diseases of intestines, the period of childbirth, the lactation period, children's age up to 16 years (safety and efficiency of use are not established).

Overdose:

Symptoms. Abdominal pain, nausea, vomiting, digestive tract erosive canker, renal failure, metabolic acidosis.

Treatment: symptomatic (maintenance of the vital functions of an organism). Dialysis - is ineffective.

Storage conditions:

To store in the place protected from light at a temperature from 15 to 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for intramuscular introduction of 30 mg/ml. On 1 ml in ampoules from amber or light-protective glass. On 5 ampoules place in a blister strip packaging from a film polyvinyl chloride. On 1 or 2 planimetric packagings with the scarificator ampoule and the application instruction in a pack from a cardboard. When using ampoules with a point or a ring of a break the scarificator does not invest.