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

    1 ml of the solution for intravenous and intramuscular administration contains:

    active substance: ketorolac tromethamine 30 mg;

    Excipients: sodium chloride, edetate disodium, propylene glycol, buffer solution (potassium dihydrogen phosphate, sodium hydroxide, water for injection), sodium hydroxide and hydrochloric acid - to adjust pH, water for injection.

    Description:A clear, colorless solution.
    Pharmacotherapeutic group:non-steroidal anti-inflammatory drug (NSAID)
    ATX: & nbsp

    M.01.A.B.15   Ketorolac

    Pharmacodynamics:

    NSAIDs. It has a pronounced analgesic effect, has also an anti-inflammatory and moderate antipyretic effect. The mechanism of action is associated with a nonselective inhibition of the activity of COX1 and COX2 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. After intramuscular (intramuscular) administration and oral administration, the onset of analgesic action is observed respectively after 0.5 and 1 hour, the maximum effect is achieved after 1-2 hours and 2-3 hours.

    Pharmacokinetics:

    Absorption at intake - fast, bioavailability - 80-100%; with the / m introduction - complete and fast. The maximum concentration (CmOh) after oral administration of 10 mg - 0.7-1.1 μg / ml, the time to reach the maximum concentration (TCmOh) - 10-78 min; after the / m introduction of 30 mg CmOh - 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, TSmOh - 15-73 min and 30-60 min respectively. After IV infusion, 15 mg CmOh - 1.96-2.98 μg / ml, 30 mg - 3.69-5.61 μg / ml. The connection with plasma proteins is 99%.

    The equilibrium concentration (Css) is achieved with parenteral and oral administration after 24 hours when administered 4 times a day (above the sub-therapeutic) and is 15 mg-0.65-1.13 μg / ml, 30 mg-1.29-2, 47 μg / ml; after oral administration of 10 mg - 0.39-0.79 μg / ml.

    The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the volume of distribution of the drug can be increased 2-fold, and the volume of its distribution R-enantiomer by 20%.

    Penetrates into breast milk: when the mother receives 10 mg of ketorolac CmOh in milk is achieved 2 hours after the first dose and is 7.3 ng / ml, 2 hours after the second dose of ketorolac (when the drug is used 4 times a day) -7.9 ng / l.

    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 91% by the kidneys, 6% by the intestine.

    The half-life period (T1 / 2) in patients with normal renal function was 5.3 hours on average (3.5-9.2 hours after IM / 30 mg and 2.4-9 hours after oral administration of 10 mg). T1 / 2 increases in elderly patients and is shortened in young patients. The liver function does not affect T1 / 2. In patients with impaired renal function with a creatinine concentration in the plasma of 19-50 mg / l (168-442 μmol / l) T1 / 2 - 10,3-10,8 h, with more pronounced renal failure - more than 13.6 hours.

    The total clearance is 30 mg to 0.023 l / h / kg (0.019 l / h / kg in elderly patients) with oral administration, oral administration of 10 mg to 0.025 l / h / kg; in patients with renal insufficiency with a plasma creatinine concentration of 19-50 mg / l with a / m 30 mg injection of 0.015 l / h / kg, with oral administration of 10 mg to 0.016 l / h / kg.

    It is not excreted by hemodialysis.

    Indications:

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

    Contraindications:

    Hypersensitivity, "aspirin" triad (combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance of acetylsalicylic acid and drugs of pyrazolone series), hypovolemia (regardless of the cause), erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, hypocoagulation (including hemophilia), bleeding or high risk of their development, severe renal failure (plasma creatinine above 50 mg / l), liver failure, childbirth period, lactation period and, children's age (up to 16 years - safety and efficacy not established).

    Carefully:

    Hypersensitivity to other NSAIDs, bronchial asthma, the presence of factors that increase toxicity in relation to the gastrointestinal tract: alcoholism, tobacco smoking and cholecystitis; postoperative period, chronic heart failure, edematous syndrome, hypertension,impaired renal function (plasma creatinine below 50 mg / l), cholestasis, active hepatitis, sepsis, systemic lupus erythematosus, simultaneous administration with other NSAIDs, advanced age (over 65 years), pregnancy.

    Pregnancy and lactation:

    It penetrates into breast milk in small amounts. Use during pregnancy and breast-feeding is contraindicated; in extreme situations, the benefit to the mother and the risk to the fetus or the child should be compared.

    Dosing and Administration:

    Intravenous, intramuscular.

    For parenteral administration to patients aged 16 to 64 years with a body weight exceeding 50 kg, no more than 60 mg (including oral dose) administered intramuscularly for 1 administration; Usually - 30 mg every 6 hours no more than 3 times a day, in / in - 30 mg (no more than 15 doses per 5 days).

    Intramuscularly adult patients with a body weight less than 50 kg or with chronic renal insufficiency for 1 administration are administered no more than 30 mg (including oral dose); usually - 15 mg (no more than 20 doses in 5 days).

    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 chronic renal failure,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 5 days.

    Side effects:

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

    From the digestive system: often - gastralgia, diarrhea; less often - stomatitis, flatulence, constipation, vomiting, sensation of stomach overflow; rare - loss of appetite, nausea, erosive and ulcerative lesions of the gastrointestinal tract (including perforation and / or bleeding - abdominal pain, cramping or burning sensation in the epigastric region, blood in the stool or melena, vomiting blood or type of "coffee grounds", nausea, heartburn, etc.), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

    From the urinary system: Rarely - acute renal failure, back pain, hematuria, azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia purpura), frequent urination, increased or decreased volume of urine, nephritis, edema, renal origin.

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

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

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

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

    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, hyperemia, densification or flaking of the skin, swelling and / or tenderness of the tonsils), urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (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, skin itch, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, shortness of breath, chest pain, wheezing).

    Other: often - swelling (face, legs, ankles, fingers, feet, weight gain); less often - 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:

    Co-administration with paracetamol increases the nephrotoxicity of ketorolac.

    Admission with other NSAIDs, glucocorticosteroids, ethanol, corticotropin, calcium preparations increases the risk of ulceration of the gastrointestinal mucosa and the development of gastrointestinal bleeding.

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

    Reduces the effect of antihypertensive and diuretic drugs (reduces the synthesis of prostaglandin in the kidneys).

    The appointment together with methotrexate increases hepato- and nephrotoxicity (their joint appointment is possible only with the use of low doses of the latter and control of its concentration in the plasma).

    At appointment with other nephrotoxic drugs (including with preparations of gold) the risk of development of nephrotoxicity increases.

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

    Increases the effect of narcotic analgesics.

    Myelotoxic drugs - increased hematotoxicity.

    Special instructions:

    Before prescribing the drug, it is necessary to clarify the question of the previous allergy 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 premedication, maintenance of anesthesia.

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

    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 40 mg / day.

    To reduce the risk of NSAID-gastropathy, antacid medicines 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 of the drug in ampoules of glass.

    10 ampoules placed in a paper grooved tray with partitions for each ampoule, in a pack of cardboard with instructions for use.

    Storage conditions:

    In dry and protected from light and out of reach of children at a temperature of 15-25 ° C.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:П N011254 / 01
    Date of registration:11.05.2010
    The owner of the registration certificate:Cadil Pharmaceuticals Co., Ltd.Cadil Pharmaceuticals Co., Ltd. India
    Manufacturer: & nbsp
    Representation: & nbspCADILA PHARMACEUTICALS LTD. CADILA PHARMACEUTICALS LTD. India
    Information update date: & nbsp06.11.2012
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