Ketorolac-LF solution for intramuscular injection 30mg/ml in ampoules 1ml №5×2

Name:
Ketorolac-LF. Release form Solution for intramuscular injection. Dosage 1 ampoule of 1 ml, in a package of 10 pcs.
Description:
Transparent light yellow liquid. Composition One ampoule contains: Active substance: ketorolac tromethamine – 30.0 mg. Excipients: ethanol, sodium chloride, disodium edetate, 1M sodium hydroxide solution or 1M hydrochloric acid solution, water for injection. Pharmacotherapeutic groupNon-steroidal anti-inflammatory and antirheumatic drugs. ATH code. M01AB15. Pharmacodynamics Non-steroidal anti-inflammatory drug. It has a pronounced analgesic effect, also has an anti-inflammatory and moderate antipyretic effect. The mechanism of action is associated with selective inhibition of the activity of the cyclooxygenase enzyme (COX-1 and COX-2), mainly in peripheral tissues, resulting in inhibition of prostaglandin biosynthesis. Does not affect opioid receptors, does not depress breathing, does not cause drug dependence, does not have a sedative and anxiolytic effect. The strength of the analgesic effect is comparable to morphine, significantly superior to other NSAIDs. Ketorolac inhibits platelet aggregation and increases bleeding time. The functional state of platelets is restored 24-48 hours after drug withdrawal. Pharmacokinetics The bioavailability of ketorolac after intramuscular injection ranges from 80% to 100%. The pharmacokinetics of ketorolac under the conditions of prescribing medium therapeutic parenteral doses is a linear function. The equilibrium concentration of the drug in plasma is 50% higher than that determined after a single injection. More than 99% of the drug binds to plasma proteins, resulting in an apparent volume of distribution of less than 0.3 l/kg. More than 50% of the administered dose is metabolized in the liver with the formation of pharmacologically inactive metabolites. The main metabolites are glucuronides and p-hydroxyketorolac. Ketorolac passes into breast milk. It is excreted by the kidneys (91%) and through the intestines (6%). Glucuronides are excreted in the urine. The elimination half-life in patients with normal renal function averages 5 hours. The total clearance is 0.025 l / kg / h. In patients with renal insufficiency, the volume of distribution of ketorolac may increase by 2 times, and the volume of distribution of the R-enantiomer by 20%. The elimination half-life is prolonged in elderly patients and shortened in younger patients. Liver function does not affect the half-life. In patients with impaired renal function at a plasma creatinine concentration of 19-50 mg / l (168-442 μmol / l), the half-life is 10.3-10.8 hours, with more severe renal failure – more than 13.6 hours. The total clearance in patients with renal insufficiency at a plasma creatinine concentration is 0.016 l / kg / h. Ketorolac is not excreted by hemodialysis. Indications for use Short-term relief of moderate and severe acute pain in the postoperative period. Treatment should be started only in a hospital, the maximum duration of treatment is 2 days. Method of application and dosage Ketorolac-LF is intended for intramuscular administration, the drug should not be used for epidural or spinal administration. The solution is injected intramuscularly slowly deep into the muscle. The onset of the analgesic effect is about 30 minutes, the maximum severity is within 1-2 hours, the average duration of analgesia is 4-6 hours. The administration of the drug several times a day for more than 2 days is not recommended, since in most cases patients do not need longer pain relief therapy or can be transferred to oral Ketorolac-LF. In this case, the duration of the use of Ketorolac-LF parenterally and orally should not exceed a total of 5 days. To achieve the maximum analgesic effect in the early postoperative period, it is possible to use Ketorolac-LF and narcotic analgesics together, the daily dose of the latter in this case is reduced. Ketorolac-LF has no effect on addiction to opioids and does not increase the respiratory depression or sedation associated with them. Selection and dose adjustment should be made in accordance with the intensity of pain and the response to the administration of the drug. To minimize side effects, it is recommended to use the lowest effective dose for the shortest possible course of treatment. Adults: The generally recommended starting dose of Ketorolac-LF is 10 mg followed by 10 to 30 mg every 4 to 6 hours. In the early postoperative period, it is permissible to administer the drug every 2 hours, if necessary. The maximum daily dose is 90 mg / day, in patients weighing less than 50 kg – no more than 60 mg / day. Elderly patients (over 65 years of age): it is recommended to use the drug at the lowest effective dose, the total dose should not exceed 60 mg / day. Due to the higher risk of side effects in this group of patients, the minimum possible duration of treatment is recommended, as well as regular monitoring of the patient’s condition to exclude gastrointestinal bleeding. Children: The safety and efficacy of ketorolac in children have not been established. Ketorolac-LF is not recommended for use in children under 16 years of age. Patients with impaired renal function: the use of ketorolac is contraindicated in patients with severe and moderate renal impairment. In the case of mild renal impairment, the use of Ketorolac-LF at a dose of not more than 60 mg / day is acceptable. If necessary, joint parenteral and oral administration, the total daily dose of Ketorolac-LF should not exceed 90 mg (60 mg in patients over 65 years of age, patients weighing less than 50 kg or impaired renal function), while the dose of the drug taken orally should not exceed 40 mg/day. It is recommended that the patient be switched to the oral form of the drug as soon as possible. Side effectsGastrointestinal tract: anorexia, discomfort in the abdomen, feeling of stomach fullness, nausea, dyspepsia, gastrointestinal pain, epigastric pain, diarrhea, flatulence, belching, vomiting, constipation, erosive and ulcerative changes, bleeding and perforation gastrointestinal tract (sometimes fatal), vomiting of blood, blood in the feces, gastritis, peptic ulcer, pancreatitis, ulcerative stomatitis, esophagitis, exacerbation of Crohn’s disease and colitis. From the side of the liver and biliary tract: abnormal liver function, liver failure, jaundice, hepatitis, hepatomegaly, increased activity of hepatic transaminases. From the nervous system: headache, dizziness, fainting, fatigue, weakness, irritability, feeling of dry mouth, increased thirst, mood changes, anxiety, impaired concentration, euphoria, nervousness, confusion, paresthesia, unusual dreams, depression, drowsiness, sleep disturbance, insomnia, hallucinations, agitation, hyperkinesia, convulsions, pathological thoughts, aseptic meningitis, neck stiffness, anxiety, vertigo, disorientation, thinking disorder. From the senses: a violation of taste sensations, blurred vision, optic neuritis, tinnitus, hearing loss and loss. From the musculoskeletal system: myalgia. From the urinary system: pain at the site of the projection of the kidneys, dysuria, frequent urination, oliguria, hematuria, proteinuria, increased levels of urea and creatinine in the blood serum, hyponatremia, hyperkalemia, urinary retention, renal failure, interstitial nephritis, papillary necrosis, nephrotic syndrome, hemolytic uremic syndrome. From the side of the cardiovascular system: pallor, hyperemia, chest pain, palpitations, bradycardia, heart failure, arterial hypertension, edema. Data from clinical and epidemiological studies suggest that the use of some NSAIDs, especially at high doses and for a long time, may be associated with an increased risk of developing arterial thromboembolic complications (myocardial infarction or stroke). On the part of the blood: purpura, leukopenia, eosinophilia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia, a decrease in the rate of blood clotting, the occurrence of hemorrhages under the skin, hematomas, nosebleeds, an increase in bleeding time, increased bleeding of postoperative wounds. On the part of the respiratory system: – shortness of breath, tachypnea, bronchospasm, complication of asthma, pulmonary edema. From the reproductive system: infertility (in women). From the skin: itching, urticaria, photosensitivity, Lyell’s syndrome, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, skin rashes, including maculopapular and weeping, discoloration of the skin of the face. Allergic reactions: anaphylactic and anaphylactoid reactions, urticaria, bronchospasm, laryngeal edema, angioedema, eyelid edema, periorbital edema, exfoliative dermatitis, bullous dermatosis. On the part of the body as a whole: general malaise, swelling, fever, excessive sweating, weight gain, pain, swelling and hyperemia at the injection site. To prevent possible side effects, one should strive to use the minimum effective doses of the drug, strictly observe the established dosages and administration regimens, take into account the patient’s condition (age, concomitant diseases, liver and kidney function, the state of water-electrolyte metabolism and the hemostasis system), as well as possible drug interactions. with combination therapy. Contraindications Bronchial asthma. Complete or partial syndrome of nasal polyps, bronchospasm, angioedema in history; Peptic ulcer of the stomach and duodenum during an exacerbation, as well as a history of ulcers or gastrointestinal bleeding, the presence or suspicion of gastrointestinal bleeding; History of blood clotting disorders, conditions with a high risk of bleeding, hemorrhagic diathesis, coagulopathy, hemorrhagic stroke, intracranial bleeding, simultaneous use with anticoagulants (including warfarin, low doses of heparin). Surgical interventions with a high risk of bleeding or the risk of its incomplete stop; Moderate and severe renal failure (plasma creatinine more than 50 mg / l), risk of renal failure, hypovolemia, dehydration; Pregnancy, childbirth and lactation; Hypersensitivity to ketorolac, aspirin, other NSAIDs or any component of the drug; Simultaneous use of other NSAIDs (risk of summation of side effects); Age up to 16 years; congestive heart failure; The drug is not used for pain relief before and during surgical operations; The drug is not used for epidural and intrathecal injections; severe liver failure; Joint use with lithium preparations, pentoxifylline, probenecid. Overdose Ketorolac overdose with a single or repeated use is usually manifested by pain in the abdomen, the occurrence of peptic ulcers of the stomach or erosive gastritis, impaired renal function, hyperventilation, metabolic acidosis, these symptoms are cured after discontinuation of the drug. In these cases, gastric lavage, the introduction of adsorbents (activated charcoal) and symptomatic therapy are recommended. Ketorolac is not sufficiently eliminated by dialysis. Precautions Application features. Ketorolac-LF should be used with caution in patients with impaired liver function. While taking Ketorolac-LF, an increase in the level of liver enzymes is possible. In the presence of functional abnormalities in the liver while taking ketorolac, a more severe pathology may develop. If signs of liver pathology are detected, treatment should be discontinued. In patients with renal insufficiency or a history of kidney disease, Ketorolac-LF is prescribed with caution. Elderly patients: since patients in this age group are more likely to develop adverse reactions, the minimum effective dose should be used (daily therapeutic dose of not more than 60 mg for patients over 65 years of age). Children: there is insufficient data on the safety and efficacy of Ketorolac-LF in children, and therefore the drug is not recommended for use in children under 16 years of age. Impact on laboratory tests: an increase in bleeding time is possible when examining coagulation parameters. Ketorolac can cause severe adverse reactions from the digestive tract at any stage of drug therapy with or without warning symptoms, such adverse reactions can be fatal. The risk of serious gastrointestinal bleeding is dose dependent, but side effects may occur even with short therapy. In addition to a history of peptic ulcer, provoking factors are the simultaneous use of oral corticosteroids, anticoagulants, long-term therapy with non-steroidal anti-inflammatory drugs, smoking, drinking alcohol, and old age. If you suspect the development of adverse reactions from the gastrointestinal tract, ketorolac should be canceled. NSAIDs should be used with caution in patients with Crohn’s disease and a history of ulcerative colitis due to the possibility of worsening the course of the disease. Ketorolac inhibits platelet aggregation and prolongs bleeding time, platelet function returns to normal within 24-48 hours after discontinuation of the drug. In patients receiving anticoagulant therapy, the use of ketorolac may increase the risk of bleeding. Patients who are already taking anticoagulants, or patients requiring low-dose heparin, should not receive ketorolac. In patients taking other drugs that affect hemostasis, ketorolac should be used with caution. In patients who underwent surgery with a high risk of bleeding or incomplete hemostasis, ketorolac should not be used. Like other NSAIDs, ketorolac inhibits prostaglandin synthesis and may have a toxic effect on the kidneys, so it should be used with caution in patients with impaired renal function or a history of kidney disease. The risk group includes patients with impaired renal function, hypovolemia, heart failure, impaired liver function, patients who use diuretics, and elderly patients. Fluid retention, sodium chloride, hypertension, oliguria and peripheral edema have been observed in some patients taking NSAIDs, including ketorolac, so it should be used with caution in patients with hypertension, heart failure. Before the administration of the drug, disturbances in the water and electrolyte balance should be corrected. Clinical studies and epidemiological data suggest that the use of some NSAIDs, especially at high doses and for a long time, may be associated with an increased risk of arterial thrombotic complications such as myocardial infarction or stroke. It is impossible to exclude such a risk for Ketorolac. To minimize the potential risk of developing adverse cardiovascular events in patients using NSAIDs, the lowest effective dose should be used for the shortest possible period of time. Ketorolac should only be administered to patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial and/or cerebrovascular disease after a thorough assessment of all the advantages and disadvantages of such treatment. Ketorolac should be used with caution in patients with impaired liver function or a history of liver disease. Significant increases (more than three times normal) in serum ALT and AST were observed in controlled clinical trials in less than 1% of patients. In addition, isolated cases of severe hepatic reactions have been reported, including jaundice, fulminant hepatitis, hepatic necrosis and liver failure, in some cases fatal. If signs of impaired liver function appear, ketorolac should be discontinued. The use of the drug in patients with systemic lupus erythematosus or connective tissue diseases may be associated with an increased risk of developing aseptic meningitis. There have been reports of serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The highest risk of developing these reactions exists at the beginning of treatment. It was reported about the development of serious anaphylactic and anaphylactoid reactions, such as bronchospasm, laryngeal edema, angioedema, anaphylactic shock. Ketorolac should not be used in patients with bronchial asthma, nasal polyp syndrome, bronchospasm, angioedema in history. If a rash or other manifestations of hypersensitivity appear, treatment with the drug should be discontinued. LS Ketorolac-LF contains a small amount of ethanol (100 mg per 1 ml). Interaction with other drugs Ketorolac slightly reduces the degree of binding to warfarin proteins. In vitro studies have shown the effect of therapeutic doses of salicylates on the degree of binding of ketorolac to plasma proteins downward from 99.2% to 97.5%. When combined with furosemide, its diuretic effect may be reduced by approximately 20%. Probenecid reduces plasma clearance and volume of distribution of ketorolac 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 an increase in the toxicity of these substances are possible. A possible interaction of ketorolac and non-depolarizing muscle relaxants, leading to the development of apnea, was noted. It is possible that concomitant use with ACE inhibitors may increase the risk of impaired renal function. Rare cases of the development of convulsive seizures have been described when Ketorolac is combined with anticonvulsants (phenytoin, carbamazepine). Perhaps the occurrence of hallucinations against the background of the simultaneous administration of ketorolac and psychostimulant drugs (fluoxetine, thiothixene, alprazolam). The concomitant use of ketorolac and NSAIDs, including selective COX-2 inhibitors, should be avoided due to an increased risk of serious adverse events. Ketorolac inhibits platelet aggregation, reduces the concentration of thromboxane and prolongs bleeding time. Platelet function returns to normal within 24-28 hours after discontinuation of ketorolac. The simultaneous use of ketorolac and therapeutic doses of warfarin, prophylactic doses of heparin (2500-5000 units for 12 hours) and dextrans may be associated with an increased risk of bleeding. NSAIDs should not be used within 8-12 days after mifepristone administration, due to a possible decrease in the effectiveness of mifepristone. Simultaneous administration of ketorolac and pentoxifylline increases the risk of bleeding. Caution should be exercised when co-administered with corticosteroids due to an increased risk of gastrointestinal ulceration or bleeding. Ketorolac reduces the need for opioid analgesics when used to relieve postoperative pain. Ketorolac may increase the risk of seizures in patients who are taking quinolines at the same time. The simultaneous use of NSAIDs and zidovudine increases the risk of hematological toxicity. With the combined use of ketorolac with tacrolimus or cyclosporine, the risk of nephrotoxicity increases. NSAIDs can worsen heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides when used together. Incompatibility. Ketorolac-LF solution for intramuscular injection should not be mixed in small containers (for example, in one syringe) with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride, as ketorolac may precipitate. Ketorolac-LF is pharmaceutically incompatible with tramadol and lithium preparations. Use during pregnancy and lactation The safety and efficacy of Ketorolac-LF during pregnancy has not been established. Drugs that affect the synthesis of prostanlandins, including ketorolac, can cause a decrease in fertility, and therefore are not recommended for use by women planning pregnancy. The safety of the drug in pregnant women has not been studied. In a study on rats and rabbits at toxic doses, no teratogenic effect was detected. In rats, prolongation of the gestation period and delayed delivery were noted. Due to the known negative effect of NSAIDs on the fetal cardiovascular system (risk of occlusion of the ductus arteriosus), ketorolac is contraindicated in pregnant women. The use of ketorolac during childbirth is not recommended due to the increased risk of bleeding in the mother and child. Ketorolac passes into milk, therefore Ketorolac-LF is not recommended during breastfeeding. Influence on the ability to drive vehicles and control mechanisms Since a significant part of patients with the appointment of ketorolac develop side effects from the central nervous system (drowsiness, dizziness, headache), it is recommended to avoid performing work that requires increased attention and quick response. Storage conditions Store in a place protected from light at a temperature not exceeding 25 ºС. Keep out of the reach of children. Shelf life 3 years. Do not use after the expiry date stated on the package. Packing: 1 ml solution for intramuscular injection in dark glass ampoules with a break ring. 5 ampoules in a blister pack. 1 or 2 blister packs together with instructions for medical use in a cardboard box injections of 30mg/ml in 1ml ampoules No. 5×2 Instructions for use for Ketorolac-LF solution for intramuscular injection 30mg/ml in 1ml ampoules No. 5×2