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

    1 ml of the solution contains:

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

    Excipients: octoxynol 0.07 mg, disodium edetate 1 mg, sodium chloride 4.35 mg, ethanol 0.115 ml, propylene glycol 400 mg, sodium hydroxide 0.725 mg, water for injection up to 1 ml.

    Description:

    A clear, colorless or light yellow solution.

    Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug
    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 nonselective inhibition of activity cyclooxygenase (COX) - COX-1 and COX-2, which catalyzes 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 of [-] S and [+] R enantiomers, with an analgesic effect due to [-] S form.By the strength of the analgesic effect comparable to morphine, it significantly exceeds other NSAIDs.

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

    Pharmacokinetics:

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

    PBy 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. Cmax after intravenous administration of 15 mg - 1.96-2.98 μg / ml, 30 mg - 3.69-5.61 μg / ml, TCmax - 0.4-1.8 minutes and 1.1-4,7 minutes, respectively. The connection with plasma proteins is 99%. Time to reach the equilibrium concentration 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.

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

    Penetrates into breast milk: when taking the mother 10 mg ketorolac Cmax 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% of ketorolac passes through the placenta.

    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. It is excreted 91% by the kidneys, 6% by the intestine.

    The 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 do not affect 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:

    - Hypersensitivity to ketorolac;

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

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

    - hemophilia and other disorders of blood coagulability;

    Decompensated heart failure;

    - hepatic insufficiency or active course of liver diseases;

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

    - Postoperative period after aortocoronary shunting;

    -​ 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 period, lactation period;

    - 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, elderly age (over 65 years), anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, alcohol abuse, severe somatic diseases Bani,concomitant therapy with the following drugs: antiaggregants (eg, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).
    Dosing and Administration:Intravenous, intramuscular.

    Drug solution Ketorol® 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.

    For parenteral administration to patients aged 16 to 64 years with a body weight exceeding 50 kg, intramuscularly single administration of not 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 intake); 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). The maximum daily doses for intramuscular and intravenous administration are 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 with CRF,as well as elderly patients (over 65 years of age) - 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, 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, 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 cardiovascular system: less often - increased blood pressure; rarely - pulmonary edema, fainting.

    From the 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 anaphylaxis or anaphylactoid reactions (skin discoloration, skin rash, hives, itching of the skin, shortness of breath, eyelid swelling, periorbital edema, shortness of breath, chest pain, wheezing).

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

    Overdose:

    Symptoms: abdominal pain, nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

    Treatment: gastric lavage, administration of adsorbents (Activated carbon) and the conduct of symptomatic therapy (maintenance of vital body functions). It is not excreted sufficiently by dialysis.

    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 concurrently 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,drugs of the quinolone series, selective serotonin reuptake inhibitors, mifepristone.

    Special instructions:

    Ketorol® 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 or NSAIDs. 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 per ampoules of dark glass class I (USP). In the upper part of the ampoule, a ring and a point for the fault are marked. The label is attached to the ampoule.

    10 ampoules with instructions for use are placed in a PVC / aluminum blister.

    Storage conditions:

    In a dry, protected from light place at a temperature of no higher than 25 ° C.

    Do not freeze!

    Keep out of the reach of children!

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001365
    Date of registration:16.12.2011 / 22.03.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India
    Manufacturer: & nbsp
    Representation: & nbspDR REDDY'S LABORATORIS LTD. DR REDDY'S LABORATORIS LTD. India
    Information update date: & nbsp16.11.2017
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