Ketorol for injection - instructions for use. Ketorol for injections - instructions for use From the side of the cardiovascular system

One tablet of the drug contains 10 mg ketorolac trometamol (ketorolac tromethamine ).

Auxiliary components: cellulose, lactose, calcium stearate, starch, Opadry II.

In 1 ml of solution for intravenous and intramuscular injection contains 30 mg ketorolac trometamol .

Excipients: disodium edetate dihydrate, ethanol, sodium chloride, sodium hydroxide, propylene glycol , water.

Release form

• Ketorolac tablets are white-coated, biconvex.
  10 such tablets in a contour pack; 1,2, 5 or 10 packs in a pack of paper.
  10 such tablets in a polymer jar; one such jar in a pack of paper.
  25 such tablets in a contour pack; 2 or 4 packs in a pack of paper.
• Ketorolac (in / in, in / m) in ampoules contains a clear solution of white-yellow color.
  1 or 2 ml of such a solution in an ampoule; 5 ampoules in a contour pack, 1 or 2 such packs in a carton box.
  1 or 2 ml of such a solution in an ampoule; 10 such ampoules in a cardboard box.

pharmachologic effect

Antipyretic, analgesic and anti-inflammatory .

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Renders strong analgesic action, moderate antipyretic and anti-inflammatory action.

They are associated with indiscriminate inhibition of the enzyme cyclooxygenases the first and second types in peripheral tissues, resulting in inhibition of synthesis - mediators of pain, inflammation and thermoregulation.

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

The strength of the analgesic effect is comparable to and superior to other drugs in its group.

After oral administration painkiller the action is fixed after one hour, the greatest effect - after one to two hours. After intramuscular injection painkiller action is fixed after 30 minutes, the greatest effect - after one to two hours.

Pharmacokinetics

When taken internally and when injected, it is actively absorbed from the intestines and tissues. The maximum concentration in the blood is recorded after 40-50 minutes, both after oral administration and after intramuscular injection. Eating does not affect absorption. Plasma protein binding is about 99%.

The half-life is close to 6 hours. 90% of the dose is excreted by the kidneys, in its original form - 60%; the remaining amount is excreted through the digestive tract.

Indications for use

moderate and strong pain syndrome :

• pain of traumatic etiology;
• pain in the postoperative and postpartum period;
• pain during oncological diseases ;
• dislocations , sprains ;
• arthralgia , myalgia , radiculitis ;

It is used for symptomatic therapy, relief of inflammation and pain at the time of use, does not affect the development of the disease.

Contraindications

• Combination (complete or incomplete), intolerance (or other drugs in this group) and recurrent polyposis of the paranasal sinuses and nose .
• hypovolemia .
• drugs pyrazolone series .
• Aggravation erosive and ulcerative diseases gastro- intestinal tract.
• Hypocoagulation , high risk of bleeding.
• Heavy renal or hepatic lesions , liver disease.
• Condition after coronary artery bypass grafting .
• Hyperkalemia .
• 3rd trimester of pregnancy, childbirth and lactation.
• Inflammatory bowel disease.
• Age less than 16 years.

Use with caution when: bronchial asthma , chronic heart failure, , postoperative period, edematous syndrome, kidney damage, active hepatitis, cholestasis, sepsis, ischemic disease heart, dyslipidemia , cerebrovascular disease, lesion peripheral arteries, , ulcerative lesions digestive tract in the past, infection H. pylori, prolonged use of other non-steroidal anti-inflammatory drugs, elderly age, 1st and 2nd trimesters of pregnancy.

Side effects

• Reactions from the circulatory system: pressure changes, bradycardiaI , , fainting.
• Reactions from the digestive system: abdominal pain, , flatulence, nausea, , vomiting, thirst, , stomatitis , erosive and ulcerative changes in the digestive tract, liver damage.
• Reactions from nervous system: , anxiety, , visual impairment, , movement disorders.
• Reactions from the respiratory system: asthma attacks.
• Reactions from the genitourinary system: oliguria , increased urination, polyuria, , hematuria, azotemia, .
• Reactions from the hematopoietic system: nosebleeds, anemia , eosinophilia, thrombocytopenia.
• Reactions from the side of metabolism:, hypokalemia , increasing content creatinine or urea in blood, hyponatremia.
• Allergic reactions: hemorrhagic rash, Stevens-Johnson syndrome , Lyell's syndrome , , bronchospasm, myalgia .
• Other reactions: .
• Local reactions: pain in the injection area.

Instructions for use Ketorolac (Method and dosage)

Ketorolac tablets instructions for use recommends taking them orally. Single dose - 10 mg. At the next application, you can take 10 mg up to four times a day; the largest daily dose should not exceed 40 mg. The duration of the course of treatment is up to 5 days.

Injections Ketorolac instructions for use recommends that when administered intramuscularly, adhere to a single dose of up to 30 mg every 4-6 hours. The highest dose is 90 mg (three ampoules) per day. The longest duration of use of the drug is up to 2 days.

Overdose

Symptoms: nausea, abdominal pain, vomiting, metabolic acidosis, kidney damage, erosive and ulcerative changes digestive organs.

Treatment: symptomatic.

Interaction

Use with other drugs from the same group (OKPD - non-steroidal anti-inflammatory drugs ), glucocorticosteroids, corticotropin, ethanol, calcium preparations increases the risk gastrointestinal tract and the appearance of bleeding from the stomach and intestines.

To reduce the risk of developing side effects the lowest effective dose should be used for the shortest possible course.

During treatment with the drug, you must be careful when driving a car.

Analogues

Analogues of Ketarolac: , Ketonort, Ketorolac-Credopharm and others.

children

It is forbidden to apply to persons under 16 years of age.

During pregnancy (and lactation)

3rd trimester, childbirth and are a strict contraindication for taking the drug. In the 1st and 2nd trimesters

Compound

1 ml ketorolac trometamol 30 mg. Excipients: lactose monohydrate, corn starch, pregelatinized starch, microcrystalline cellulose, povidone, magnesium stearate, sodium carboxymethyl starch.

Pharmacological effect

NSAIDs. Ketorolac trometamol has a pronounced analgesic effect, also has an anti-inflammatory and moderate antipyretic effect. The mechanism of action is associated with non-selective inhibition of the activity of 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. The strength of the analgesic effect is comparable to morphine, significantly superior to other NSAIDs. The onset of analgesic action is observed after 0.5 hours, respectively, the maximum effect is achieved after 1-2 hours.

Indications

Pain syndrome of strong and moderate severity: - injuries. - toothache. - pain in postoperative period. - oncological diseases. - myalgia, arthralgia. - neuralgia, sciatica. - dislocations, sprains. - rheumatic diseases. It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

Contraindications

Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history) - urticaria, rhinitis caused by taking NSAIDs (history) - intolerance medicines pyrazolone series - hypovolemia (regardless of the cause that caused it) - erosive and ulcerative lesions of the gastrointestinal tract in the acute phase - hypocoagulation (including hemophilia) - bleeding or a high risk of their development - kidney failure severe (CC less than 30 ml / min) - severe liver failure or active liver disease - condition after coronary artery bypass grafting - confirmed hyperkalemia - inflammatory diseases intestines - the period of childbirth - the period of lactation - children under 16 years of age (safety and effectiveness of use have not been established) - hypersensitivity to the components of the drug. With caution: bronchial asthma, the presence of factors that increase the toxic effect on the gastrointestinal tract (alcoholism, smoking and cholecystitis), the postoperative period, chronic heart failure, edematous syndrome, arterial hypertension, impaired renal function (serum creatinine less than 50 mg / l), cholestasis, sepsis, systemic lupus erythematosus, simultaneous use with other NSAIDs, coronary artery disease, cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes, peripheral arterial disease, chronic renal failure (CC 30-60 ml / min), a history of ulcerative lesions of the gastrointestinal tract, the presence of Helicobacter pylori infection, long-term use of NSAIDs, severe somatic diseases, simultaneous administration of oral corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), elderly patients (over 65 years of age).

Use during pregnancy and lactation

Use during pregnancy and lactation is contraindicated. At the time of treatment should stop breastfeeding.

Side effects

special instructions

Frequency of side effects: often (more than 3%), less often (1-3%), rarely (less than 1%). From the side digestive system: often - gastralgia, diarrhea. less often - stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach. rarely - loss of appetite, nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and / or bleeding - abdominal pain, spasm or burning in the epigastric region, blood in the feces or melena, vomiting with blood or coffee thick, nausea, heartburn), 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), increased urination, increased or decreased urine volume, nephritis, edema of renal origin. From the senses: rarely - hearing loss, tinnitus, visual impairment (including blurred vision). From the side respiratory system: rarely - bronchospasm or shortness of breath, rhinitis, pulmonary edema, laryngeal edema (difficulty breathing). From the nervous system: often - headache, dizziness, drowsiness. rarely - aseptic meningitis (fever, severe headache, convulsions, neck and / or back muscle stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis, fainting. From the side of cardio-vascular system: less often - increased blood pressure. On the part of the hematopoietic organs: rarely - anemia, eosinophilia, leukopenia. From the blood coagulation system: rarely - bleeding from a postoperative wound, epistaxis, rectal bleeding. From the side skin: less often - skin rash (including maculo-papular rash), purpura. rarely - exfoliative dermatitis (fever with or without chills, hyperemia, thickening or peeling of the skin, enlargement and / or soreness of the palatine tonsils), urticaria, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome). Allergic reactions: rarely - anaphylaxis or anaphylactoid reactions (discoloration of the skin of the face, skin rash, urticaria, itching of the skin, tachypnea, swelling of the eyelids, periorbital edema, heaviness in chest, wheezing). Local reactions: less often - burning or pain at the injection site. Other: often - swelling (of the face, legs, ankles, fingers, feet, weight gain). less often - increased sweating, rarely - swelling of the tongue, fever.

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) with a strong analgesic and moderate antipyretic effect. Its main purpose is to relieve pain. various genesis. Pain is a subjective sensation that serves as an indicator of tissue damage. To select the optimal analgesic, it is necessary to clearly understand its analgesic activity, selectivity for COX (cyclooxygenase 1 and 2), bioavailability, the presence of various routes of administration, the rate of onset therapeutic effect, security profile. Ketorolac is a non-selective (non-selective) NSAID, the mechanism of action of which is associated with the suppression of the activity of COX-1 and COX-2 in peripheral tissues, as a result of which the synthesis of prostaglandins, mediators of pain and inflammation, is inhibited. The drug does not interact with opioid receptors, does not affect respiratory function, does not cause addiction, does not have a sedative effect. The strength of the analgesic effect is similar to morphine and far superior to other NSAIDs. After oral administration, the analgesic effect develops after 1 hour, the peak of the drug's action occurs at the 2nd hour. In fact, ketorolac is the only NSAID used to relieve acute pain. The drug is devoid of most of the negative side effects inherent in opioids (sedation, respiratory depression, drug dependence). High analgesic activity ketorolac has been demonstrated in a number of clinical trials. Ketorolac is the drug of choice for acute pain, however, its short-term use is also possible in case of exacerbation of chronic pain (for example, with osteoarthritis, rheumatoid arthritis). So, with severe spinal pain, according to one of the studies, the effectiveness of ketorolac was comparable to that of meperidine and codeine, and side effects were much less pronounced.

At renal colic 30 mg ketorolac solution for intravenous administration had the same analgesic effect as 2.5 mg of metamizole in combination with antispasmodics with fewer negative adverse reactions. In accordance with experimental data, blocking prostaglandin synthesis in the kidneys with ketorolac inhibits peristalsis and reduces pressure in the urinary tract, relieves spasm and reduces the intensity of renal blood flow. The drug is rapidly absorbed in the intestine. Due to the high (80-100%) bioavailability, the analgesic effect develops quite quickly. The duration of the therapeutic effect of Ketorolac is up to 10 hours. The incidence of negative side effects in the treatment of ketorolac does not exceed 2.7%. The most characteristic in this regard is dyspeptic symptoms. Of particular interest is the study of the efficacy and safety of injectable forms of ketorolac in comparison with other NSAIDs: metamizole, diclofenac and lornoxicam. It was found that lornoxicam and ketorolac had the best analgesic efficacy, surpassing metamizole and diclofenac. These NSAIDs also differed in tolerability. It should be noted that a single administration of all study drugs was relatively safe. At the same time, the use of metamizole and diclofenac in some cases was associated with the occurrence of local reactions at the injection site. There was 1 case of tissue necrosis at the injection site after the administration of diclofenac and several cases of infiltrates after the administration of metamizole. The result of the study indicates the justification for the use of ketorolac for the treatment of acute pain, and this drug is more effective in injuries and musculoskeletal pain compared to other NSAIDs.

Pharmacology

Ketorolac has a pronounced analgesic effect, also has an anti-inflammatory and moderate antipyretic effect.

The mechanism of action is associated with non-selective inhibition of the activity of the enzyme cyclooxygenase 1 and 2, mainly. in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins - modulators pain sensitivity, thermoregulation and inflammation. Ketorolac is a racemic mixture of the [-] S and [+] R enantiomers, with the analgesic effect due to the [-] S form.

The drug 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.

After oral administration, the onset of analgesic action is noted, respectively, after 1 hour, the maximum effect is achieved after 1-2 hours.

Pharmacokinetics

When taken orally, Ketorolac-Verte is well absorbed in the gastrointestinal tract, C max in blood plasma (0.7-1.1 μg / ml) is achieved 40 minutes after taking an empty stomach dose of 10 mg. Food rich in fats reduces Cmax of the drug in the blood and delays its achievement by 1 hour.

99% of the drug binds to plasma proteins and with hypoalbuminemia, the amount of free substance in the blood increases.

Bioavailability - 80-100%. Time to reach Css at oral administration- 24 hours when administered 4 times / day (above subtherapeutic) and after oral administration of 10 mg - 0.39-0.79 mcg / 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 increase by 2 times, and the volume of distribution of its R-enantiomer - by 20%. Penetrates into breast milk: when the mother takes 10 mg of ketorolac C max in milk is reached 2 hours after the first dose and is 7.3 ng / ml, 2 hours after the second dose of ketorolac (when using the drug 4 times / day) is 7.9 ng /ml

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-hydroxyketorolac. It is excreted by 91% by the kidneys, 6% - through the intestines.

T 1/2 in patients with normal renal function is, on average, 5.3 hours. T 1/2 is lengthened in elderly patients and shortened in young patients. Liver function does not affect T 1/2. In patients with impaired renal function, with a plasma creatinine concentration of 19-50 mg / l (168-442 μmol / l), T 1/2 is 10.3-10.8 hours, with more severe renal failure - more than 13.6 hours. Not excreted during hemodialysis.

Release form

10 pieces. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (2) - packs of cardboard.
10 pieces. - cellular contour packings (5) - packs of cardboard.
10 pieces. - cellular contour packings (10) - packs of cardboard.
25 pcs. - cellular contour packings (2) - packs of cardboard.
25 pcs. - cellular contour packings (4) - packs of cardboard.
10 pieces. - polymer cans (1) - packs of cardboard.

Dosage

Ketorolac-Verte is used orally once or repeatedly, depending on the severity of the pain syndrome. A single dose of 10 mg, with repeated administration, it is recommended to take 10 mg up to 4 times / day, depending on the severity of pain; the maximum daily dose should not exceed 40 mg.

When taken orally, the duration of the course should not exceed 5 days.

Overdose

Symptoms: abdominal pain, nausea, vomiting, peptic ulcers of the stomach or erosive gastritis, impaired renal function, metabolic acidosis.

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

Interaction

Simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

Co-administration with paracetamol increases nephrotoxicity, with methotrexate - hepato- and nephrotoxicity. The joint appointment of ketorolac and methotrexate is possible only when using low doses of the latter (to control the concentration of methotrexate in the blood plasma).

Probenicid 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. Simultaneous administration with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding. Reduces the effect of antihypertensive and diuretic drugs (the synthesis of prostaglandins in the kidneys decreases). When combined with opioid analgesics, the doses of the latter can be significantly reduced.

Antacids do not affect the complete absorption of the drug.

The hypoglycemic effect of insulin and oral hypoglycemic drugs increases (dose recalculation is necessary). Co-administration with sodium valproate causes a violation of platelet aggregation. Increases plasma concentration of verapamil and nifedipine.

When administered with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases. Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in blood plasma.

Side effects

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

From the digestive system: often (especially in elderly patients over 65 years of age with a history of erosive and ulcerative lesions of the gastrointestinal tract) - gastralgia, diarrhea; less often - stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach; rarely - nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and / or bleeding - abdominal pain, spasm or burning in the epigastric region, melena, vomiting like "coffee grounds", nausea, heartburn, etc.), 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, increase or decrease in urine volume, nephritis, edema renal genesis.

From the senses: rarely - hearing loss, tinnitus, visual impairment (including blurred vision).

From the respiratory system: rarely: bronchospasm or dyspnea, rhinitis, laryngeal edema (shortness of breath, shortness of breath).

From the side of the central nervous system: often - headache, dizziness, drowsiness, rarely - aseptic meningitis (fever, severe headache, convulsions, neck and / or back muscle 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 hematopoietic organs: rarely - anemia, eosiiophilia, leukopenia.

On the part of the hemostasis system: rarely - bleeding from a postoperative wound, epistaxis, rectal bleeding.

On the part of the skin: less often - skin rash (including maculopapular rash), purpura, rarely - exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swelling and / or soreness of the palatine tonsils), urticaria, Stevens syndrome; Johnson, Lyell's syndrome.

Local reactions: less often - burning or pain at the injection site.

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

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

Chronic pain.

With caution: bronchial asthma, cholecystitis, chronic heart failure, arterial hypertension, impaired renal function (plasma creatinine below 50 mg / l), cholestasis, active hepatitis, sepsis, systemic lupus erythematosus; old age (over 65 years); polyps of the nasal mucosa and nasopharynx.

Application features

Use during pregnancy and lactation

Application for violations of liver function

Application for violations of kidney function

Contraindicated in renal failure (plasma creatinine above 50 mg/l).

Use with caution in case of impaired renal function (plasma creatinine below 50 mg / l).

Use in children

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

special instructions

The effect on platelet aggregation stops after 24-48 hours. Hypovolemia increases the risk of developing adverse reactions from the kidneys. If necessary, it can be prescribed in combination with narcotic analgesics.

Do not use simultaneously with paracetamol for more than 5 days. Patients with impaired blood coagulation are prescribed the drug only with constant monitoring of the number of platelets, it is especially important in postoperative period which requires careful control of hemostasis.

Influence on the ability to drive vehicles and control mechanisms

Since a significant proportion of patients with the appointment of Ketorolac-Verte develop side effects from the central nervous system (drowsiness, dizziness, headache), it is recommended to avoid performing work that requires heightened attention and quick reaction (driving vehicles, working with mechanisms, etc.).

KETOROLAC

International non-proprietary name

Ketorolac

Dosage form

Solution for intravenous and intramuscular administration, 30 mg/ml

Compound

1 ml of solution contains

active substance - ketorolac trometamol 30 mg,

excipients: sodium chloride, disodium edetate, water for injection

Description

Clear yellowish liquid

Pharmacotherapeutic group

Anti-inflammatory and antirheumatic drugs. Non-steroidal anti-inflammatory drugs. Acetic acid derivatives.

Ketorolac

ATX code M01AB15

Pharmacological properties

Pharmacokinetics

Bioavailability - 80-100%, absorption with intramuscular injection - complete and fast. After intramuscular administration of 30 mg, the maximum concentration in blood plasma is (Cmax) 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, the time to reach the maximum concentration, respectively, is 15-73 minutes and 30-60 min; Cmax after intravenous infusion of 15 mg - 1.96-2.98 mcg / ml, 30 mg - 3.69-5.61 mcg / ml. The time to reach equilibrium concentrations (Css) when administered parenterally is 24 hours when administered 4 times a day (above subtherapeutic) and is 15 mg intramuscularly - 0.65-1.13 μg / ml, 30 mg - 1.29-2 47 mcg / ml, with intravenous infusion of 15 mg - 0.79-1.39 mcg / ml, 30 mg - 1.68-2.76 mcg / ml.

99% of the drug binds to plasma proteins and with hypoalbuminemia, the amount of free substance in the blood increases.

The volume of distribution is 0.15-0.33 l/kg. In patients with renal insufficiency, the volume of distribution of the drug can increase by 2 times, and the volume of distribution of its R-enantiomer - by 20%. Poorly passes through the blood-brain barrier, crosses the placenta (10%). Small amounts are found in breast milk.

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-hydroxyketorolac.

It is excreted by 91% by the kidneys (40% in the form of metabolites), 6% - through the intestines. The half-life (T1 / 2) in patients with normal renal function averages 5.3 hours (3.5-9.2 hours after intramuscular injection of 30 mg, 4-7.9 hours after intravenous administration of 30 mg). T1 / 2 lengthens in elderly patients and shortens in young ones. Liver function does not affect T1 / 2. In patients with impaired renal function, with a plasma creatinine concentration of 19-50 mg / l (168-442 μmol / l), T1 / 2 is 10.3-10.8 hours, with more severe renal failure - more than 13.6 hours .

The total clearance is with intramuscular injection of 30 mg - 0.023 l / kg / h (0.019 l / kg / h in elderly patients), intravenous infusion of 30 mg - 0.03 l / kg / h; in patients with renal insufficiency with a plasma creatinine concentration of 19-50 mg / l with intramuscular injection of 30 mg - 0.015 l / kg / h.

Not excreted by hemodialysis.

Pharmacodynamics

Ketorolac has a pronounced analgesic effect, also has an anti-inflammatory and moderate antipyretic effect. The mechanism of action is associated with non-selective inhibition of the activity of the enzyme cyclooxygenase 1 and 2, mainly in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins - modulators of pain sensitivity, thermoregulation and inflammation. Ketorolac is a racemic mixture of the [-] S and [+] R enantiomers, with the analgesic effect due to the [-] S form.

The strength of the analgesic effect is comparable to morphine, significantly superior to other non-steroidal anti-inflammatory drugs.

The drug does not affect opioid receptors, does not depress breathing, does not cause drug dependence, does not have a sedative and anxiolytic effect.

After intramuscular injection, the onset of analgesic action is noted after 0.5 hours, the maximum effect is achieved after 1-2 hours.

Indications for use

For short-term relief of pain syndrome of moderate and severe intensity, mainly in case of injuries, in the postoperative period, with radicular syndrome, muscle and joint pain

Dosage and administration

It is injected deep into the muscle, slowly (or intravenously by stream) for at least 15 seconds in the minimum effective doses, selected in accordance with the intensity of pain and the patient's response. If necessary, opioid analgesics in reduced doses can be additionally prescribed at the same time.

Single doses with a single intramuscular or intravenous injection:

Adults under 65 years old and children over 16 years old - 10-30 mg, depending on the severity of the pain syndrome;

Adults over 65 years of age or with impaired renal function - 10-15 mg.

Doses for repeated parenteral administration:

intramuscularly

Adults under 65 years of age and children over 16 years of age are administered 10-30 mg in the first injection, then 10-30 mg every 6 hours (usually 30 mg every 6 hours);

Adults over 65 years of age or with impaired renal function - 10-15 mg every 4-6 hours;

intravenously

Adults under 65 years of age and children over 16 years of age are injected with 10-30 mg, then 10-30 mg every 6 hours, with continuous infusion using an infusator, the initial dose is 30 mg, and then the infusion rate is 5 mg / h;

Adults over 65 years of age or with impaired renal function are injected with a bolus of 10-15 mg every 6 hours.

The maximum daily dose for adults under 65 years of age and children over 16 years of age should not exceed 90 mg, and for adults over 65 years of age or with impaired renal function - 60 mg, both intramuscularly and intravenously.

Continuous intravenous infusion should not last more than 24 hours. With parenteral administration, the duration of the course of treatment should not exceed 5 days.

When switching from parenteral administration of the drug to its oral administration, the total daily dose of both dosage forms on the day of transfer should not exceed 90 mg for adults under 65 years of age and children over 16 years of age and 60 mg for adults over 65 years of age or with impaired renal function. In this case, the dose of the drug in tablets on the day of the transition should not exceed 30 mg.

Side effects

Often - more than 3%, sometimes- 1-3 %, rarely- less than 1%

Often

Gastralgia, diarrhea (especially in elderly patients over 65 years of age with a history of erosive and ulcerative lesions of the gastrointestinal tract)

Headache, dizziness, drowsiness

Edema (face, shins, ankles, fingers, feet, weight gain)

Sometimes

Stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach

Increase in blood pressure

Skin rash (including maculopapular rash), purpura

Burning or pain at the injection site

excessive sweating

Rarely

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

- acute renal failure, back pain with or without hematuria and/or azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increase or decrease in urine volume, nephritis, renal edema

- hearing loss, tinnitus, visual impairment (including blurred vision)

- bronchospasm or dyspnea, rhinitis, pulmonary edema, laryngeal edema (shortness of breath, difficulty breathing)

- aseptic meningitis (fever, severe headache, seizures, neck and/or back stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis

- fainting

- anemia, eosinophilia, leukopenia

- bleeding from a postoperative wound, epistaxis, rectal bleeding

- exfoliative dermatitis (fever with or without chills, redness, induration or peeling of the skin, swelling and/or tenderness of the tonsils), urticaria, Stevens-Johnson syndrome, Lyell's syndrome

- anaphylaxis or anaphylactoid reactions (discoloration of the face, itching of the skin, tachypnea or dyspnea, swelling of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest, wheezing)

- swelling of the tongue, fever.

Contraindications

Hypersensitivity to ketorolac, complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including history), urticaria, rhinitis caused by taking non-steroidal anti-inflammatory drugs (history ), dehydration

Intolerance to pyrazolone drugs, hypovolemia (regardless of the cause), bleeding or high risk of its development, condition after coronary artery bypass grafting, confirmed hyperkalemia, inflammatory bowel disease

Erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, hypocoagulation (including hemophilia)

Severe renal and / or liver failure (creatinine clearance less than 30 ml / min)

Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, hematopoietic disorder

Pregnancy, childbirth and lactation

Childhood up to 16 years old.

Pain relief before and during surgery due to high risk of bleeding, chronic pain

Drug Interactions

Simultaneous use of ketorolac with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to the formation of ulcers of the gastrointestinal tract and the development of gastrointestinal bleeding.

Co-administration with paracetamol increases nephrotoxicity, with methotrexate - hepato- and nephrotoxicity. The joint appointment of ketorolac and methotrexate is possible only when using low doses of the latter (to control the concentration of methotrexate in the blood plasma).

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. Co-administration with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding. Reduces the effect of antihypertensive and diuretic drugs (the synthesis of prostaglandins in the kidneys decreases). When combined with opioid analgesics, the doses of the latter can be significantly reduced, as their effect is enhanced.

The hypoglycemic effect of insulin and oral hypoglycemic drugs increases (dose recalculation is necessary). Co-administration with valproic acid causes a violation of platelet aggregation. Increases plasma concentration of verapamil and nifedipine.

When administered with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases.

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

Solution for injection should not be mixed in the same syringe with morphine sulfate, promethazine and hydroxyzine due to precipitation. Pharmaceutically incompatible with tramadol solution, lithium preparations.

The solution for injection is compatible with 0.9% sodium chloride solution, dextrose solution, Ringer's and Ringer's lactate solution, Plasmalit solution, as well as infusion solutions containing aminophylline, lidocaine hydrochloride, dopamine hydrochloride, short-acting human insulin and heparin sodium salt.

special instructions

Carefully: bronchial asthma; cholecystitis; chronic heart failure; arterial hypertension; impaired renal function (plasma creatinine below 50 mg / l); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; old age (over 65 years); polyps of the nasal mucosa and nasopharynx, concomitant use with other non-steroidal anti-inflammatory drugs; the presence of factors that increase the toxicity of the gastrointestinal tract: alcoholism, smoking; postoperative period, edematous syndrome, ischemic heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial disease, creatinine clearance less than 60 ml/min, history of ulcerative lesions of the gastrointestinal tract, presence of H. pylori infection, long-term use of non-steroidal anti-inflammatory drugs, severe somatic diseases, simultaneous administration of oral glucocorticosteroids (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

When combined with other non-steroidal anti-inflammatory drugs, fluid retention, cardiac decompensation, and arterial hypertension may occur. The effect on platelet aggregation stops after 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys. If necessary, it can be prescribed in combination with narcotic analgesics.

Do not use simultaneously with paracetamol for more than 5 days. Patients with impaired blood coagulation are prescribed the drug only with constant monitoring of the number of platelets, it is especially important in the postoperative period, requiring careful monitoring of hemostasis.

Features of the effect of the drug on the ability to drive vehicle or potentially dangerous mechanisms

Overdose

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

Country of origin

Product group

Non-steroidal anti-inflammatory drug (NSAID)

Release forms

• 10 tablets in a blister pack. 20 or 100 tablets in a glass or polymer jar. 1, 2, 3, 4, 5 or 10 blister packs 1 ml - dark glass ampoules (5) - blister packs (1) - cardboard packs. 1 ml - dark glass ampoules (5) - blister packs (2) - cardboard packs. 1 ml - dark glass ampoules (5) - blister packs (2) - cardboard packs. 1.0 ml - ampoules (5) - plastic trays (2) - packs of cardboard 10 - blister packs (2) - packs of cardboard 10 ampoules of 1 ml in a package of 10 tablets in a blister pack of PVC film and aluminum foil printed lacquered . 10 pieces. - cellular contour packings (2) - packs of cardboard. 20 tabs per pack Solution for intravenous and intramuscular injection 30 mg / ml, 1 ml in ampoules - 10 pcs per pack. Film-coated tablets, 10 mg: 10 tablets in a blister pack. 20 or 100 tablets in a glass or polymer jar. 1, 2, 3, 4, 5 or 10 blisters pack 10 1ml ampoules pack 20 tablets

Description of the dosage form

• clear liquid light yellow with a slight odour. coated tablets, white color, with a biconvex surface. Clear colorless or slightly colored liquid. Clear, colorless to yellowish solution. Solution for intravenous and intramuscular administration Solution for intravenous and intramuscular administration is transparent, yellowish in color. The solution for intravenous and intramuscular administration is clear, light yellow in color. Solution for intramuscular injection light yellow, clear solution for intramuscular injection. tablets Coated tablets Coated tablets Coated tablets are white, rough, round, biconvex.

pharmachologic effect

Pharmacokinetics

Special conditions

Compound

• 1 ml of ketorolac trometamol (ketorolac tromethamine) 30 mg one tablet contains: active ingredient - ketorolac tromethamine - 10 mg; excipients: lactose monohydrate, potato starch, microcrystalline cellulose, calcium stearate, opadry II 1 ml ketorolac trometamol (ketorolac tromethamine) 30 mg 1 M or hydrochloric acid solution 1 M - up to pH 6.9-7.9, water for injection - up to 1 ml. 1 tab. ketorolac tromethamine 10 mg Excipients: microcrystalline cellulose 120 mg, lactose monohydrate (tabletose 80 mesh) 69 mg, magnesium stearate 1 mg. 1 ml of solution contains - active substance: ketorolac tromethamine - 30 mg; excipients: sodium chloride, disodium salt of ethylenediaminetetraacetic acid, rectified ethyl alcohol, tromethamine, water for injection. ketorolac tromethamine 10 mg; Excipients: lactose, potato starch, low molecular weight medical polyvinylpyrrolidone (povidone), magnesium stearate, talc, collidone CL-M. ketorolac tromethamine 10 mg; Excipients: MCC, lactose, sodium croscarmellose, magnesium stearate ketorolac tromethamine 30 mg -7.5, water for injections - up to 1 ml. ketorolac tromethamine -10 mg Excipients: milk sugar (lactose), potato starch, low molecular weight polyvinylpyrrolidone (povidone), magnesium stearate, talc, collidone CL M; shell: hydroxypropyl methylcellulose or hydroxypropyl methylcellulose (hypromellose), talc, titanium dioxide, polyethylene glycol 4000, propylene glycol. ketorolac tromethamine 30 mg Excipients: sodium chloride, disodium salt of ethylenediaminetetraacetic acid (Trilon B), water for injection. ketorolac tromethamine 30 mg Excipients: disodium edetate dihydrate (trilon B), ethanol (ethyl alcohol in terms of anhydrous), propylene glycol, sodium chloride, sodium hydroxide (1M solution), water for injection. One tablet contains: Active substance: ketorolac tromethamine -10 mg Excipients: milk sugar (lactose), potato starch, low molecular weight polyvinylpyrrolidone (povidone), magnesium stearate, talc, collidone CL M; shell: hydroxypropyl methylcellulose or hydroxypropyl methylcellulose (hypromellose), talc, titanium dioxide, polyethylene glycol 4000, propylene glycol

Ketorolac indications for use

• Pain syndrome of strong and moderate severity: injuries, toothache, pain in the postpartum and postoperative period, cancer, myalgia, arthralgia, neuralgia, sciatica, dislocations, sprains, rheumatic diseases. It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

Ketorolac contraindications

• Hypersensitivity to ketorolac or other non-steroidal anti-inflammatory drugs, "aspirin" asthma, bronchospasm, angioedema, hypovolemia (regardless of the cause that caused it), dehydration. Erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, hypocoagulation (including hemophilia). Hepatic and / or renal insufficiency (plasma creatinine above 50 mg / l). Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, concomitant use with other NSAIDs, a high risk of developing or recurrent bleeding (including after surgery), impaired hematopoiesis. Pregnancy, childbirth and lactation. Children under 16 years of age (efficacy and safety have not been established). The drug is not used for pain relief before and during surgical operations due to the high risk of bleeding, as well as for the treatment chronic pain. With caution - bronchial asthma; cholecystitis; chronic heart failure

Ketorolac dosage

• 10 mg 10 mg 30 mg/ml 30 mg/ml 30 mg/ml

Ketorolac side effects

• According to the World Health Organization (WHO), adverse events are classified according to their frequency of development as follows: very common (> 10%), frequent (> 1% and 0.1% and 0.01% and

drug interaction

Overdose

Storage conditions

• store in a dry place
• keep away from children
• store in a place protected from light

Synonyms

• Dolac, Ketalgin, Ketanov, Ketorol, Ketorolac,