Active substanceKetorolacKetorolac
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  • Dosage form: & nbspsolution for intravenous and intramuscular administration
    Composition:

    In 1 ml of solution contains:

    active substance: ketorolac trometamol (ketorolac tromethamine) 30 mg;

    Excipients: ethanol (ethyl alcohol), sodium chloride, 1 M sodium hydroxide solution, 1 M hydrochloric acid solution, water for injection.

    Description:

    A clear solution of light yellow color.

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

    M.01.A.B.15   Ketorolac

    Pharmacodynamics:

    Ketorolac has a pronounced analgesic effect, it also has an anti-inflammatory and moderate antipyretic effect.

    The mechanism of action is associated with a non-selective inhibition of the activity of the enzyme cyclooxygenase 1 and 2, mainly in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins - modulators of pain sensitivity, thermoregulation and inflammation. Ketorolac is a racemic mixture [-]S and [+]R enantiomers, while the analgesic effect is due to [-]S form.

    By the strength of the analgesic effect comparable to morphine, it is much superior to other non-steroidal anti-inflammatory drugs.

    After intramuscular injection, the beginning of analgesic effect is observed after 0.5 h, the maximum effect is achieved in 1-2 hours.

    Pharmacokinetics:

    Bioavailability - 80-100%, absorption at intramuscular injection - complete and fast. After intramuscular injection of 30 mg ketorolac, the maximum concentration in the blood plasma (Cmax) is 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, the time to reach the maximum concentration is 15-73 min and 30-60 min, respectively; FROMmafter intravenous infusion 15 mg - 1.96-2.98 mcg / ml, 30 mg - 3.69-5.61 mcg / ml. Time to reach equilibrium concentrations (Css) with parenteral administration - 24 hours when administered 4 times a day, Css when administered intramuscularly, 15 mg of ketorolac is 0.65-1.13 μg / ml, 30 mg is 1.29-2.47 μg / ml, with intravenous infusion of 15 mg of ketorolac 0.79-1.39 μg / ml, 30 mg - 1.68-2.76 μg / ml.

    99% of the drug binds to blood plasma proteins, with hypoalbuminemia, the amount of free ketorolac in the blood plasma increases.

    The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the volume of ketorolac distribution may increase 2-fold, and the volume of distribution of ketorolac R-enantiomer by 20%.Poorly passes through the blood-brain barrier, penetrates the placenta (10%). In small quantities found in breast milk.

    More than 50% of the administered dose is metabolized in the liver with the formation of pharmacologically inactive metabolites. The main metabolites are glucuronides, which are excreted by the kidneys, and p-hydroxycetorolac.

    It is excreted on 91% by kidneys (40% in the form of metabolites), 6% - through the intestine.

    The half-life (T1/2) in patients with normal renal function averages 5.3 hours (3.5-9.2 hours after IM for 30 mg, 4-7.9 hours after IV injection 30 mg). T1/2 lengthens in elderly patients and is shortened in young patients. The function of the liver does not affect T1/2. In patients with impaired renal function with a creatinine concentration in the blood plasma of 19-50 mg / l (168-442 μmol / L) T1/2 is 10.3-10.8 hours, with more pronounced renal failure - more than 13.6 hours.

    The total clearance with the / m introduction of 30 mg ketorolac is 0.023 l / kg / h (0.019 l / kg / h in elderly patients), intravenous infusion of 30 mg - 0.03 l / kg / h; in patients with renal insufficiency with a creatinine concentration in the blood plasma of 19-50 mg / l with a / m injection of 30 mg - 0.015 l / kg / h.

    It is not excreted by hemodialysis.

    Indications:

    Pain syndrome of strong and moderate severity: trauma, toothache, pain in the postoperative period, oncological diseases, myalgia, arthralgia, neuralgia, sciatica, dislocations, sprains, rheumatic diseases.

    It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

    Contraindications:

    Hypersensitivity to ketorolac, complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including history), urticaria, rhinitis caused by taking non-steroidal anti-inflammatory drugs (in anamnesis) , dehydration.

    Intolerance to drugs pyrazolone, hypovolemia (regardless of the cause), bleeding or a high risk of their development, a condition after aortocoronary shunting, confirmed hyperkalemia, inflammatory bowel disease.

    Erosive-ulcerative lesions of the gastrointestinal tract in the stage of exacerbation, peptic ulcers, hypocoagulation (including hemophilia).

    Severe hepatic and / or renal failure (creatinine clearance less than 30 ml / min) or active liver disease.

    Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, hematopoiesis.

    Pregnancy, childbirth and lactation.

    Children under 18 years.

    The drug is not used for anesthesia before and during surgery due to high risk of bleeding, as well as for the treatment of chronic pain.
    Carefully:

    Bronchial asthma; cholecystitis; chronic heart failure; arterial hypertension; impaired renal function (creatinine clearance 30-60 ml / min); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; old age (over 65 years); polyps of the nasal mucosa and nasopharynx, simultaneous reception with other non-steroidal anti-inflammatory drugs; presence of factors that increase gastrointestinal toxicity: alcoholism, tobacco smoking; postoperative period, edematous syndrome, ischemic heart disease, cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial diseases, history of gastrointestinal ulcers, infection Helicobacter pylori, Prolonged use of nonsteroidal anti-inflammatory drugs, heavy somatic diseases, concomitant use of oral corticosteroids (e.g., prednisone), anticoagulants (eg, warfarin), antiplatelet agents (e.g., clopidogrel), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline ).

    Dosing and Administration:

    Injected deep into the muscle or intravenously slowly for at least 15 seconds at the lowest effective doses selected in accordance with the intensity of the pain and the patient's response. If necessary, it is also possible to additionally prescribe opioid analgesics in reduced doses.

    Single doses for single intramuscular or intravenous administration:

    - adults from 18 to 65 years - 10-30 mg, depending on the severity of the pain syndrome,

    - adults over 65 years old or with impaired renal function - 10-15 mg.

    Doses with multiple parenteral administration:

    intramuscularly

    - adults 18 to 65 years 10-60 mg administered in the first administration, then - 10-30 mg every 6 hours (usually from 30 mg every 6 hours)

    - adults over 65 years of age or with impaired renal function - 10-15 mg every 4-6 hours;

    intravenously

    - adults between 18 and 65 years of age are injected 10-30 mg, then 10-30 mg every 6 hours, with continuous infusion with an infusomator, the initial dose is 30 mg, and then the infusion rate is 5 mg / h,

    - adults over 65 years of age or with impaired renal function injected 10-15 mg every 6 hours.

    The maximum daily dose for adults from 18 to 65 years should not exceed 90 mg, and for adults over 65 years or with impaired renal function - 60 mg for both intramuscular and intravenous routes of administration.

    Continuous intravenous infusion should not last more than 24 hours.

    For parenteral administration, the duration of treatment should not exceed 5 days.

    When switching from parenteral administration of the drug to its administration inside the total daily dose of both dosage forms on the day of transfer should not exceed 90 mg for adults from 18 to 65 years and 60 mg for adults over 65 years or with impaired renal function. In this case, the dose of the drug in tablets on the day of transition should not exceed 30 mg.

    Side effects:

    Often - more than 3%, less often - 3%, rarely - less than 1%.

    From the digestive system: often (especially in elderly patients, over 65 years of age, having a history of erosive and ulcerative lesions of the gastrointestinal tract) - gastralgia,diarrhea; less often - stomatitis, flatulence, constipation, vomiting, sensation of stomach overflow; rarely - decreased appetite, nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and / or bleeding - abdominal pain, spasm or burning in the epigastric region, blood in the feces or melena, vomiting with blood or by type "coffee grounds", nausea, heartburn, etc.), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

    From the urinary system: rarely acute renal failure, back pain with or without hematuria and / or azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased urine volume, nephritis, edema of renal genesis.

    From the sense organs: rarely - hearing loss, ringing in the ears, impaired vision (including blurred vision).

    From the respiratory system: rarely - bronchospasm or dyspnoea, rhinitis, pulmonary edema, laryngeal edema (shortness of breath, difficulty breathing).

    From the side of the central nervous system: often - headache, dizziness, drowsiness; rarely - aseptic meningitis (fever,severe headache, cramps, stiff neck and / or back muscles), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

    From the side of the cardiovascular system: less often - increased blood pressure; rarely - faint.

    On the part of the organs of hematopoiesis: rarely - anemia, eosinophilia, leukopenia.

    From the side of the hemostasis system: rarely bleeding from a postoperative wound, epistaxis, rectal bleeding.

    From the skin: less often - skin rash (including maculopapular rash), purpura; rarely - exfoliative dermatitis (fever with chills or without, redness, densification or flaking of the skin, swelling and / or tenderness of the tonsils), hives, Stevens-Johnson syndrome, Lyell's syndrome.

    Local Reactions: less often - burning or pain at the injection site.

    Allergic reactions: rarely skin rash, anaphylaxis or anaphylactoid reactions (skin discoloration, skin itch, tachypnea, eyelid edema, periorbital edema, shortness of breath, shortness of breath, heaviness in the chest, wheezing).

    Other: often - swelling (face, legs, ankles, fingers, feet, weight gain); less frequent - increased sweating; rarely - swelling of the tongue, fever.

    Overdose:

    Symptoms (with a single administration): abdominal pain, nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

    Treatment: symptomatic (maintenance of vital body functions). Dialysis is ineffective.
    Interaction:

    Simultaneous use of ketorolac with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

    Co-administration with paracetamol increases nephrotoxicity, with methotrexate-hepato- and nephrotoxicity. Joint use of ketorolac and methotrexate is possible only with the use of low doses of the latter (it is necessary to monitor the concentration of methotrexate in the blood plasma).

    Against the background of the use of ketorolac, a decrease in the clearance of methotrexate and lithium is possible, and the toxicity of these substances is increased.

    Simultaneous application with indirect anticoagulants - derivatives of coumarin and indanedione, heparin, thrombolytics (alteplase, streptokinase, urokinase), antiplatelet agents, cephalosporins (cefoperazone, cefotetan), pentoxifylline, valproic acid and acetylsalicylic acid increases the risk of bleeding.

    Reduces the effect of hypotensive and diuretic drugs (by reducing the synthesis of prostaglandins in the kidneys).

    When combined with opioid analgesics, the doses of the latter can be significantly reduced, since their effect is enhanced.

    The hypoglycemic effect of insulin and oral hypoglycemic drugs is increased (dose recalculation is necessary).

    Joint application with valproic acid causes disruption of platelet aggregation.

    Increases the concentration in the blood plasma of verapamil and nifedipine.

    When used with other nephrotoxic drugs (including with gold preparations), the risk of developing nephrotoxicity increases.

    Probenecid and drugs that block tubular secretion, reduce the clearance of ketorolac and increase its concentration in the blood plasma.

    Solution for injection should not be mixed in one syringe with morphine, promethazine and hydroxyzine due to precipitation. Pharmaceutically it is not compatible with a solution of tramadol, lithium preparations.

    The solution for injection is compatible with 0.9% sodium chloride solution, 5% dextrose solution, Ringer's and Ringer's lactate solution, as well as with infusion solutions containing aminophylline, lidocaine, dopamine, human insulin (short-acting) and heparin sodium.

    Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

    Special instructions:

    When combined with other non-steroidal anti-inflammatory drugs, fluid retention, cardiac decompensation, and hypertension can occur.

    The effect on platelet aggregation stops after 24-48 hours.

    Hypovolemia increases the risk of adverse reactions from the kidneys.

    If necessary, you can prescribe in combination with narcotic analgesics. Ketorolac It is not recommended to be used as a means for premedication, supporting anesthesia and anesthesia in obstetric practice.

    Do not use simultaneously with paracetamol for more than 5 days.

    Patients with blood clotting disorder are prescribed a drug only with a constant control of the number of platelets, especially in the post-operation period.

    To reduce the risk of developing adverse events from the gastrointestinal tract, a minimum effective dose should be used with the minimum possible short course.

    Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speedpsychomotor reactions.
    Form release / dosage:

    Solution for intravenous and intramuscular injection 30 mg / ml.

    Packaging:

    1 ml per ampoule of light-protective glass.

    10 ampoules per carton box.

    5 or 10 ampoules in a contour cell box made of a polyvinylchloride film and aluminum foil or without foil.

    5 ampoules in a contour cell box from a polyethylene terephthalate film.

    1 or 2 contour packs in a pack of cardboard.

    In each box or bundle of instructions for use.

    Storage conditions:

    In the dark place at a temperature of 15 ° C to 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001721
    Date of registration:09.07.2010
    Expiration Date:Unlimited
    The owner of the registration certificate:PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspPHARMSTANDART-Ufa-VITA, JSCPHARMSTANDART-Ufa-VITA, JSC
    Information update date: & nbsp02.01.2018
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