Instructions Ketolong-Darnitsa solution for injection 30 mg/ml ampoule 1 ml No. 10
Composition
active ingredient: 1 ml of solution contains 30 mg of ketorolac tromethamine;
Excipients: sodium chloride, disodium edetate, sodium sulfite anhydrous (E 221), benzyl alcohol, povidone, propylene glycol, tromethamine, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent liquid of slightly yellowish or greenish-yellowish color.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATX code M01A B15.
Pharmacological properties
Pharmacodynamics
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID), a cyclooxygenase (COX) inhibitor, a derivative of pyrrolizinecarboxylic acid, which exhibits a pronounced analgesic effect. Due to the characteristics of the dosage form, the duration of the analgesic effect of the drug is 10-12 hours. It is able to relieve or reduce pain of low and moderate intensity.
Like other NSAIDs, it has antipyretic and anti-inflammatory effects. It is able to inhibit platelet aggregation.
Pharmacokinetics
With intramuscular administration, a depot is formed at the site of drug administration, from which ketorolac gradually enters the systemic bloodstream.
The time to reach the maximum concentration (Cmax = 3 mg/l) in blood plasma (Tmax) is 40-50 min. Binding to plasma proteins is over 99%. Up to 10% of the administered dose of the drug is metabolized in the liver, the rest in the kidneys. It is excreted from the body mainly with urine (up to 90%), 60% of the administered dose is unchanged. Up to 10% of the administered dose is excreted with feces. The half-life of the drug (T1/2) is 4-6 hours. In patients with impaired renal function and in the elderly, the rate of drug excretion decreases, and the half-life increases. Penetrates the placental barrier and into breast milk.
Indication
Short-term relief of moderate to severe postoperative pain.
Contraindication
Hypersensitivity to ketorolac or to any other component of the drug and to other NSAIDs.
Active peptic ulcer, recent gastrointestinal bleeding or perforation, or history of peptic ulcer or gastrointestinal bleeding.
Presence or suspicion of gastrointestinal bleeding or intracranial hemorrhage. Condition with high risk of bleeding or incomplete hemostasis, hemorrhagic diathesis.
Severe renal impairment (serum creatinine above 160 μmol/l).
Risk of kidney failure due to fluid depletion.
Blood clotting disorders.
Concomitant use of antiplatelet agents (acetylsalicylic acid), anticoagulants, including warfarin and low-dose heparin (2500-5000 IU every 12 hours).
Severe heart and liver failure.
Contraindicated in patients in whom other prostaglandin synthesis inhibitors cause allergic reactions such as asthma, rhinitis, angioedema, or urticaria.
Bronchial asthma, bronchospasm, nasal polyps, angioedema in history.
The drug is contraindicated during labor.
Concomitant treatment with other NSAIDs, including selective cyclooxygenase inhibitors, acetylsalicylic acid, warfarin, pentoxifylline, probenecid or lithium salts.
Hypersensitivity to acetylsalicylic acid or to other prostaglandin synthesis inhibitors (severe anaphylactic reactions have been observed in such patients).
Do not use as an analgesic before and during surgery.
Epidural or intrathecal administration of the drug is contraindicated.
Interaction with other medicinal products and other types of interactions
Ketolorac is extensively bound to plasma proteins (average 99.2%). Ketolorac tromethamine does not alter the pharmacokinetics of other agents through enzyme induction or inhibition.
Warfarin, Digoxin, Salicylates, and Heparin. Ketorolac tromethamine significantly reduced the plasma protein binding of warfarin in vitro and did not alter the plasma protein binding of digoxin. In vitro studies indicate that at therapeutic concentrations of salicylates (300 mcg/mL), ketorolac binding was reduced from approximately 99.2% to 97.5%, indicating a potential two-fold increase in unbound ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide do not alter the plasma protein binding of ketorolac tromethamine.
Acetylsalicylic acid. When used with acetylsalicylic acid, the binding of ketolorac to plasma proteins is reduced, although the clearance of free ketolorac is not changed. The clinical significance of this type of interaction is unknown, although, as with other NSAIDs, it is not recommended to prescribe ketolorac tromethamine and acetylsalicylic acid simultaneously due to the potential increase in the frequency of adverse events.
Probenecid: Concomitant use of ketorolac tromethamine and probenecid is contraindicated.
Zidovudine: Concomitant use of NSAIDs with zidovudine increases the risk of hematological toxicity. There is an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia treated concomitantly with zidovudine and ibuprofen.
Concomitant use with anticoagulants may increase bleeding. Concomitant use with anticoagulants (such as warfarin) is contraindicated.
When used simultaneously with other NSAIDs, additive side effects may develop.
Diuretics - the diuretic effect is reduced, resulting in increased nephrotoxic effects of ketorolac.
β-blockers, ACE inhibitors – the antihypertensive effect of β-blockers is reduced under the influence of ketorolac, which may result in the development of renal dysfunction.
Cyclosporine antibiotics – increases the nephrotoxicity of cyclosporines.
Glucocorticosteroids - due to the increased risk of gastrointestinal bleeding, the simultaneous use of ketorolac with glucocorticosteroids should be carried out with caution.
Quinolones - increased risk of seizures.
Mifepristone - ketorolac reduces the effectiveness of mifepristone, therefore the use of ketorolac is allowed only 8-12 days after the start of mifepristone.
Oxpentifylline – not recommended due to increased risk of bleeding.
Lithium salts – delay the elimination of lithium from the body.
Opioid analgesics – the effect of opioid analgesics is enhanced, which allows reducing the dose of the latter for pain relief.
Cardiac glycosides – NSAIDs may worsen heart failure, reduce glomerular filtration rate and increase plasma levels of cardiac glycosides. Methotrexate – co-administer with caution.
Anticonvulsants - isolated cases of seizures have been reported with the concomitant use of ketorolac tromethamine and anticonvulsants (phenytoin, carbamazepine).
Psychotropic drugs – with simultaneous use of ketorolac and psychotropic drugs (fluoxetine, thiotexene, alprazolam), hallucinations have been reported. Pentoxifylline – increases the risk of bleeding.
Preparations containing garlic, onions, and ginkgo biloba may enhance the effect of ketorolac and increase the risk of hemorrhagic complications.
Application features
It is recommended to use in a hospital setting.
The likelihood of side effects can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms.
Combined use of ketorolac tromethamine intramuscularly and orally in adult patients should not exceed 5 days.
It should be borne in mind that in some patients, anesthesia occurs only 30 minutes after intramuscular injection.
When treating patients with cardiac, renal or hepatic insufficiency who are taking diuretics, or after surgery with hypovolemia, careful monitoring of diuresis and renal function is necessary.
Impact on fertility.
Ketorolac tromethamine should be discontinued in women who are unable to become pregnant and are undergoing evaluation for this condition.
Effect on the digestive tract.
Ketorolac tromethamine can cause serious gastrointestinal adverse reactions at any stage of drug therapy with or without prodromal symptoms; such adverse reactions can be fatal. The risk of clinically serious gastrointestinal bleeding is dose-dependent. However, adverse reactions can occur even with short-term therapy. In addition to a history of peptic ulcer disease, predisposing factors include concomitant use of oral corticosteroids, anticoagulants, long-term therapy with nonsteroidal anti-inflammatory drugs, smoking, alcohol consumption, advanced age, and poor general health. Most spontaneous reports of gastrointestinal events have involved elderly or debilitated patients, so special attention should be paid to the treatment of such patients and ketorolac should be discontinued if suspected. Patients at risk should be prescribed an alternative type of therapy that does not include NSAIDs.
NSAIDs should be used with caution in patients with a history of Crohn's disease and ulcerative colitis due to the possibility of worsening of the disease.
Concomitant administration of ketorolac tromethamine may increase the risk of bleeding in patients receiving anticoagulant therapy. Detailed studies of the simultaneous use of ketorolac and prophylactic low-dose heparin (2500-5000 IU every 12 hours) have not been conducted, so this regimen may also increase the risk of bleeding. Patients already taking anticoagulants or who require low-dose heparin should not receive ketorolac tromethamine. Patients taking other drugs that negatively affect hemostasis should be closely monitored when ketorolac tromethamine is administered. Ketorolac inhibits platelet aggregation and prolongs bleeding time. In contrast to the prolonged effect after taking acetylsalicylic acid, platelet function returns to normal within 24-48 hours after ketorolac is discontinued. Ketorolac tromethamine should not be used in patients undergoing surgery with a high risk of bleeding or incomplete hemostasis. Ketorolac tromethamine does not have sedative or anxiolytic properties.
Use in patients with impaired renal function.
Like other NSAIDs, ketorolac inhibits prostaglandin synthesis and may have renal toxicity and should be used with caution in patients with impaired renal function or a history of renal disease. Risk groups include patients with impaired renal function, hypovolemia, heart failure, impaired liver function, patients taking diuretics, and elderly patients.
Patients with less severe renal impairment should receive lower doses of ketorolac (not to exceed 60 mg/day, intramuscularly). The renal status of such patients should be closely monitored. Patients should be well hydrated before starting treatment. In patients undergoing hemodialysis, ketorolac clearance was reduced to approximately half the normal rate and the terminal half-life was increased by almost threefold.
Effects on the cardiovascular system and cerebral vessels.
Patients with hypertension and/or a history of mild to moderate heart failure should be closely monitored.
To minimize the potential risk of adverse cardiovascular events in patients taking NSAIDs, the lowest effective dose should be used for the shortest possible duration. Ketorolac tromethamine should be prescribed to patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease only after careful consideration of the benefits and risks. Ketorolac should also be considered before initiating long-term treatment in patients at risk for cardiovascular disease (e.g., those with hypertension, hyperlipidemia, diabetes mellitus, or smokers).
Clinical trials and epidemiological data suggest that the use of some NSAIDs, particularly at high doses and over long periods, may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. Such a risk cannot be excluded for ketorolac.
Use in patients with impaired liver function.
Ketorolac tromethamine should be administered with caution to patients with impaired hepatic function or a history of liver disease. Significant elevations (greater than three times the upper limit of normal) in serum ALT and AST were observed in less than 1% of patients in controlled clinical trials.
In addition, there have been isolated reports of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, hepatic necrosis and hepatic failure, in some cases fatal. Ketorolac should be discontinued if clinical symptoms of liver disease or systemic manifestations (e.g. eosinophilia, rash) occur.
Respiratory system.
The patient's condition should be monitored due to the high likelihood of developing bronchospasm.
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.
Serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported. The risk of these reactions is highest at the beginning of treatment, with the first symptoms occurring in most cases within the first month of treatment. Patients should discontinue treatment at the first appearance of rash, mucosal lesions, or other signs of hypersensitivity.
Use during pregnancy or breastfeeding
The use of ketorolac tromethamine is contraindicated during pregnancy, labor, and delivery due to the known effects of NSAIDs on the fetal cardiovascular system.
Do not use during breastfeeding due to the possible negative effects of prostaglandin synthesis inhibitors on infants.
Ability to influence reaction speed when driving vehicles or other mechanisms
Some patients may experience dizziness, drowsiness, visual disturbances, headache, vertigo, insomnia, or depression while taking ketorolac tromethamine. If these or other similar side effects occur, you should not drive or operate machinery.
Method of administration and doses
It is recommended to use in a hospital setting. After intramuscular administration, the analgesic effect is observed after approximately 30 minutes, and maximum analgesia occurs after 1-2 hours. In general, the average duration of analgesia is 8-12 hours. The dose should be adjusted depending on the severity of the pain syndrome and the patient's response to treatment.
Continuous intramuscular administration of multiple daily doses of ketorolac should not last more than 2 days, as the risk of adverse reactions increases with prolonged use. Experience with long-term use is limited, as the vast majority of patients were transferred to oral administration or after a period of intramuscular administration, patients no longer required analgesic therapy.
The likelihood of side effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. The drug should not be administered epidurally or intraspinally.
Adults.
The recommended initial dose of ketorolac tromethamine, solution for intramuscular injection, is 10 mg, followed by 10-30 mg every 4-6 hours as needed. In the initial postoperative period, ketorolac tromethamine can be administered every 2 hours if needed. The minimum effective dose should be prescribed. The total daily dose should not exceed 90 mg for young patients, 60 mg for elderly patients, patients with renal insufficiency and body weight less than 50 kg. The maximum duration of treatment should not exceed 2 days. In patients weighing less than 50 kg, the dose should be reduced. Concomitant use of opioid analgesics (morphine, pethidine) is possible. Ketorolac does not adversely affect opioid receptor binding and does not increase the respiratory depression or sedative effects of opioid drugs. For patients receiving parenteral Ketolong-Darnitsa® solution and who are transferred to oral Ketolong-Darnitsa® tablets, the total combined daily dose should not exceed 90 mg (60 mg for elderly patients, patients with renal impairment and with a body weight less than 50 kg), and on the day of changing the dosage form, the dose of the oral component should not exceed 40 mg. Patients should be transferred to the oral form as soon as possible.
Elderly patients.
For patients aged 65 years and over, it is recommended to use the lower end of the dosage range. The total daily dose should not exceed 60 mg.
Patients with renal impairment.
Ketorolac is contraindicated in moderate to severe renal impairment. In less severe impairment, the dosage should be reduced (not higher than 60 mg/day intramuscularly).
Children
The drug is contraindicated in children under 16 years of age.
Overdose
Symptoms: lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression and coma. Anaphylactoid reactions have been reported, which may also occur with overdose.
Treatment. Symptomatic and supportive therapy. There is no specific antidote. Patients with symptoms of overdose or after a large overdose (when taking an oral dose 5-10 times higher than the usual dose) should induce vomiting, take activated charcoal (60-100 g for adults) and/or take an osmotic laxative no later than 4 hours after taking the drug.
Forced diuresis, urine alkylation, hemodialysis, or blood transfusion are ineffective due to the high level of drug binding to plasma proteins. Single overdoses of ketorolac at various times have resulted in abdominal pain, nausea, vomiting, hyperventilation, peptic ulcers and/or erosive gastritis, and renal dysfunction, which resolved after drug withdrawal.
Adverse reactions
.
On the part of the gastrointestinal tract: anorexia, feeling of discomfort in the abdomen, feeling of fullness of the stomach, nausea, dyspepsia, gastrointestinal pain, epigastric pain, diarrhea, less often - flatulence, belching, vomiting, constipation, erosive-ulcerative changes, including bleeding and perforation of the gastrointestinal tract, sometimes fatal (especially in the elderly), vomiting blood, gastritis, peptic ulcer, pancreatitis, melena, rectal bleeding, ulcerative stomatitis, esophagitis, exacerbation of Crohn's disease and colitis.
From the side of the central and peripheral nervous systems: headache, dizziness, fainting, increased fatigue, weakness, irritability, dry mouth, increased thirst, hyperactivity (mood swings, restlessness), nervousness, confusion, paresthesia, functional disorders, unusual dreams, depression, drowsiness, sleep disorders, insomnia, impaired concentration, euphoria, hallucinations, agitation, hyperkinesia, seizures, psychotic reactions, pathological thoughts, aseptic meningitis (with corresponding symptoms), rigidity of the muscles of the back of the head, feeling of anxiety, vertigo, disorientation, thinking disorders.
From the sensory organs: taste disturbance, blurred vision, optic neuritis, retrobulbar neuritis, tinnitus, hearing loss.
Musculoskeletal system: myalgia.
From the urinary system: severe pain in the area of the kidney projection, dysuria, frequent urination, oliguria, hyponatremia, hyperkalemia, hematuria, proteinuria, increased levels of urea and creatinine in the blood serum, azotemia, urinary retention, acute renal failure, renal failure, interstitial nephritis, papillary necrosis, nephrotic syndrome, hemolytic uremic syndrome, flank pain (with/without hematuria).
Cardiovascular: pallor, flushing, chest pain, palpitations, bradycardia, heart failure, hypertension, palpitations, edema. Clinical and epidemiological data suggest that the use of some NSAIDs, especially in high doses and for a long time, may be associated with an increased risk of arterial thromboembolic complications (myocardial infarction or stroke).
On the part of the blood system: purpura, leukopenia, eosinophilia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, which may result in hemorrhages under the skin, hematomas, nosebleeds, decreased blood clotting rate, prolonged bleeding time, and increased postoperative wound bleeding.
Respiratory: shortness of breath, tachypnea or dyspnea, chest tightness, wheezing, asthma, asthma complications, pulmonary edema.
From the reproductive system (in women): infertility.
Skin: itching, urticaria, photosensitivity reactions, Lyell's syndrome, bullous reactions, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, skin rashes, including maculopapular and weeping, facial skin discoloration.
Allergic reactions: anaphylactic and anaphylactoid reactions, urticaria, airway reactivity, asthma, worsening of asthma, bronchospasm, laryngeal edema, angioedema, eyelid edema, periorbital edema, edema of the face, lower legs, fingers, feet, tongue edema, dyspnea, hypotension, flushing, exfoliative dermatitis, bullous dermatosis. Such reactions may occur in patients with or without known hypersensitivity to ketorolac or other NSAIDs. They may also occur in individuals with a history of angioedema, bronchospastic reactivity. Anaphylactoid reactions, such as anaphylaxis, may be fatal.
On the part of the body as a whole: asthenic syndrome, malaise, edema, fever with or without chills, increased sweating, weight gain; pain, swelling and hyperemia at the injection site.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C. Do not freeze. Keep out of the reach of children.
Incompatibility.
Ketorolac solution for injection should not be mixed in small containers (e.g., in the same syringe) with morphine sulfate, pethidine hydrochloride, promethazine, or hydroxyzine, as ketorolac may precipitate.
Packaging
1 ml in an ampoule; 5 ampoules in a contour blister pack, 2 contour blister packs in a pack; 10 ampoules in a contour blister pack, 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
