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

    1 ml of the preparation contains:

    Active substance: ketorolac tromethamine 30.0 mg.

    Excipients: sodium chloride - 4.35 mg, disodium edetate - 0.5 mg, 1M sodium hydroxide solution or 1M hydrochloric acid solution to pH 6.9-7.9, water for injection - up to 1.0 ml.

    Description:Ptransparent, light yellow liquid.
    Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID)
    ATX: & nbsp

    M.01.A.B.15   Ketorolac

    Pharmacodynamics:

    Nonsteroidal anti-inflammatory drug (NSAID), has a pronounced analgesic effect, has anti-inflammatory and moderate antipyretic effect.

    The mechanism of action is associated with a non-selective inhibition of cyclooxygenase (COX) -COG-1 and COC-2 activity catalyzing the formation of prostaglandins from arachidonic acid, which play an important role in the pathogenesis of pain, inflammation and fever. 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 significantly exceeds other NSAIDs.

    The drug does not affect the opioid receptors, does not depress respiration, does not cause drug dependence, does not have sedative and anxiolytic effects.

    The beginning of analgesic effect is observed after 0.5 h, the maximum effect is achieved in 1-2 hours and lasts about 4-6 hours.

    Pharmacokinetics:

    Suction

    The pharmacokinetics of ketorolac after single and multiple intravenous and intramuscular administration is linear.

    With intramuscular injection, absorption is complete and rapid. The maximum concentration of the drug (Cmax) after intramuscular injection 30 mg - 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, time to reach the maximum concentration (TCmax) - 15-73 min and 30-60 min, respectively. FROMmax after intravenous administration of 15 mg - 1.96-2.98 μg / ml, 30 mg - 3.69-5.61 μg / ml, TSmax - 0.4-1.8 min and 1.1-4.7 min respectively.

    Distribution

    The connection with plasma proteins is 99%. Time to reach equilibrium concentrations of the drug (Css) with parenteral administration of 30 mg 4 times a day - 24 hours; when administered intramuscularly, 15 mg is 0.65-1.13 μg / ml, 30 mg is 1.29-2.47 μg / ml.

    Volume of distribution (Vg) with intramuscular injection - 0,136-0,214 l / kg, with intravenous - 0,166-0,254 l / kg. In patients with renal insufficiency, the volume of distribution of the drug can be doubled, and the volume of its distribution R-enantiomer by 20%.

    Penetrates into breast milk by taking 10 mg of ketorolac CmOh in milk is achieved in 2 hours after the first dose and is 7.3 ng / ml, 2 hours after the second dose of ketorolac (using the drug 4 times a day) - 7.9 ng / l. About 10% ketorolac passes through the placenta.

    Metabolism

    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 pharmacologically inactive p-hydroxycetorolac.

    Listed on 91% kidneys (40% in the form of metabolites), 6% - through the intestines.

    Excretion

    Half-life (T1/2) in patients with normal renal function - 3.5-9.2 hours after parenteral administration of 30 mg. T1/2 increases in elderly patients and is shortened in young people.

    Changes in liver function have no effect on T1/2.

    In patients with impaired renal function, at a plasma creatinine concentration of 19-50 mg / l (168-442 μmol / L), T1/2 - 10,3-10,8 h, with more severe renal failure - more than 13.6 hours.

    With the introduction of 30 mg ketorolac, intramuscular total clearance is 0.023 l / h / kg (0.019 l / h / kg in elderly patients); in patients with renal insufficiency (at a creatinine concentration in the plasma of 19-50 mg / l) - 0.015 l / h / kg.With the introduction of 30 mg ketorolac intravenously, the total clearance is 0.03 l / h / kg.

    It is not excreted by hemodialysis.

    Indications:

    Pain syndrome of strong and moderate severity of various origin with trauma, toothache, pain in the postoperative period, with oncological and rheumatic diseases, myalgia, arthralgia, neuralgia, sciatica.

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

    Contraindications:

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

    - erosive and ulcerous changes in the mucous membrane of the stomach and duodenum, active gastrointestinal bleeding; cerebrovascular or other bleeding;

    - inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation;

    - hemophilia and other bleeding disorders;

    - Decompensated heart failure;

    - hepatic insufficiency or active course of liver diseases;

    - marked renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia;

    - Postoperative period after coronary artery bypass grafting;

    - simultaneous administration with probenecid, pentoxifylline, acetylsalicylic acid and other NSAIDs (including cyclooxygenase-2 inhibitors), lithium salts, anticoagulants (including warfarin and heparin);

    - the drug is not used for preventive analgesia before and during extensive surgery because of the high risk of bleeding;

    - pregnancy, childbirth, lactation;

    - children under 16 years of age (safety and efficacy not established).

    Carefully:

    Bronchial asthma, ischemic heart disease, congestive heart failure, edematous syndrome, arterial hypertension, cerebrovascular disease, pathological dyslipidemia or hyperlipidemia, impaired renal function (creatinine clearance 30-60 ml / l), diabetes mellitus, cholestasis, sepsis, systemic lupus erythematosus, diseases of peripheral arteries, smoking, old age (over 65 years),anamnesthetic data on the development of ulcerative lesions of the gastrointestinal tract, alcohol abuse, severe somatic diseases, concomitant therapy with the following drugs: antiplatelet agents (for example, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).

    Pregnancy and lactation:

    The drug is contraindicated in pregnancy.

    In childbirth and delivery, the use of the drug is contraindicated. inhibiting the synthesis of prostaglandins, ketorolac can adversely affect the blood circulation of the fetus and weaken the contractile activity of the uterus, which increases the risk of uterine bleeding.

    If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued, as the drug, by inhibiting the synthesis of prostaglandins, can cause adverse effects in newborns.

    Dosing and Administration:

    Intravenous, intramuscular.

    Solution of the drug Ketorolac are used in minimally effective doses, selected according to the intensity of the pain.If necessary, you can simultaneously prescribe narcotic analgesics in reduced doses.

    When parenteral application patients aged 16 to 64 years with a body weight exceeding 50 kg, intramuscularly once administered no more than 60 mg (taking into account oral administration). Usually - 30 mg every 6 hours; intravenously - 30 mg (no more than 6 doses per 2 days).

    Intramuscularly adult patients with a body weight of less than 50 kg or with chronic renal failure (CRF) once administered no more than 30 mg (taking into account oral reception); usually - 15 mg (no more than 8 doses per 2 days); intravenously - no more than 15 mg every 6 hours (no more than 8 doses per 2 days).

    Maximum daily doses for intramuscular and intravenous administration, for patients from 16 to 64 years with a body weight exceeding 50 kg, 90 mg / day; adult patients with a body weight of less than 50 kg or CRF, as well as elderly patients (over 64 years old) for intramuscular and intravenous administration of 60 mg. The duration of treatment should not exceed 2 days.

    When administered intravenously, the dose should be administered no less than 15 seconds.

    Intramuscular injection is carried out slowly, deep into the muscle. The beginning of an anesthetic action is observed after 30 minutes, the maximum anesthesia occurs in 1-2 hours.The analgesic effect lasts about 4-6 hours.

    Side effects:

    The frequency of side effects is classified according to the incidence of the case: often - (1-10%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01% ), including individual messages.

    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 - nausea, erosive and ulcerative lesions of the gastrointestinal tract (including abdominal pain, spasm or burning in the epigastric region, melena, vomiting like "coffee grounds", nausea, heartburn and others) with perforation and / or bleeding; Cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

    From the urinary system: rarely acute renal failure, back pain with or without hematuria and / or azotemia, haemolytic 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, visual impairment (including blurred vision).

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

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

    From the side of the cardiovascular system: less often - increased blood pressure, rarely - pulmonary edema, fainting.

    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, exacerbation of ulcerative colitis or Crohn's disease.

    From the skin: infrequent 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: infrequent - burning or pain at the injection site.

    Allergic reactions: rarely anaphylaxis or anaphylactoid reactions (discoloration of the face, itching of the skin, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, shortness of breath, heaviness in the chest, wheezing.

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

    Overdose:

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

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

    Interaction:

    Simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, including cyclooxygenase-2 inhibitors, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to gastrointestinal ulceration and the development of gastrointestinal bleeding.

    Do not use the drug concomitantly with other NSAIDs (including cyclooxygenase-2 inhibitors), as well as simultaneously with probenecid, pentoxifylline,Acetylsalicylic acid, lithium salts, anticoagulants (including warfarin and heparin).

    Do not use with paracetamol for more than 2 days. Co-administration with paracetamol increases nephrotoxicity, with methotrexate-hepato- and nephrotoxicity.

    Co-administration of ketorolac and methotrexate is possible only with the use of low doses of ketorolac (control the concentration of methotrexate in the blood plasma).

    Probenecid reduces plasma clearance and the volume of ketorolac distribution, increases its concentration in blood plasma and increases its half-life.

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

    Simultaneous administration with indirect anticoagulants (for example, warfarin), heparin, thrombolytic agents, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

    Reduces the effect of antihypertensive and diuretic drugs (decreases the synthesis of prostaglandins in the kidneys).

    When combined with narcotic analgesics, the doses of the latter can be significantly reduced.

    Antacids do not affect the full absorption of the drug.

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

    Co-administration with valproic acid causes disruption of platelet aggregation.

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

    At appointment with other nefrotoksicnymi medical products (including with preparations of gold) the risk of development nefrotoksichnosti raises.

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

    It is necessary to take into account possible interactions with the simultaneous administration of ketorolac with cyclosporine, zidovudine, digoxin, tacrolimus, quinolone drugs, selective serotonin reuptake inhibitors, mifepristone.

    Special instructions:

    Ketorolac has two dosage forms (film-coated tablets and a solution for intravenous and intramuscular administration). The choice of the method of administration depends on the severity of the pain syndrome and the patient's condition.

    Before prescribing the drug, it is necessary to clarify the question of the previous allergic reaction to the drug orNSAIDs. Because of the risk of developing allergic reactions, the first dose is administered under close supervision of the doctor.

    Hypovolemia increases the risk of developing nephrotoxic adverse reactions.

    If necessary, you can prescribe in combination with narcotic analgesics.

    It is not recommended to be used as a medicine for preventive analgesia, before and during extensive surgical interventions due to high risk of bleeding. Do not use the drug with NSAIDs (including cyclooxygenase-2 inhibitors), because when combined with other NSAIDs, fluid retention, cardiac decompensation, and increased blood pressure may occur. The effect on platelet aggregation stops after 24-48 hours.

    The drug can change the properties of platelets.

    Patients with blood clotting disorder are appointed only with a constant control of the number of platelets, it is especially important for postoperative patients requiring careful control of hemostasis.

    The risk of developing drug complications increases with prolonged treatment (in patients with chronic pain) and an increase in the dose of the drug more than 90 mg / day.

    To reduce the risk of adverse events, a minimally effective dose should be applied with the minimum possible short course.

    To reduce the risk of developing NSAIDs, gastropathies are prescribed misoprostol, omeprazole.

    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 that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:Solution for intravenous and intramuscular injection, 30 mg / ml.
    Packaging:

    1 ml or 2 ml in the ampoules of a neutral light-protective glass.

    5 ampoules per contour cell pack of polyvinyl chloride film.

    1 or 2 contour mesh packages are placed in a pack of cardboard,

    10 ampoules are placed in a box of cardboard.

    In each pack or box, put the instructions for use and the ampoule scaler.

    When using ampoules with an incision, a ring of fracture or a break point, the ampoule scaper is not inserted.

    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003941
    Date of registration:07.11.2016 / 25.10.2017
    Expiration Date:07.11.2021
    The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia
    Manufacturer: & nbsp
    Representation: & nbspPROMO-MED LLC PROMO-MED LLC Russia
    Information update date: & nbsp07.01.2018
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