Ketorolac solution 30mg/ml 1ml ampoules, 10pcs

Composition

>1 ml contains: Active ingredients: ketorolac trometamol-30 mg; Excipients: propylene glycol – 200 mg disodium phosphate dihydrate (Trilon B) 1 mg, ethanol 95% – 100 mg, sodium chloride – 4.35 mg,1 M solution of sodium hydroxide to pH 6.9-7.9, water d/and – up to 1 ml.

Pharmacological effect

of Pharmaco-therapeutic group: Nitrariaceae action

NSAIDs, has a pronounced analgesic (pain relieving) effect, also has anti-inflammatory and mild antipyretic action.

The mechanism of action is associated with non-selective inhibition of the activity of COX-1 and COX-2 enzymes, mainly in peripheral tissues, which results in inhibition of prostanglandin biosynthesis-modulators of pain sensitivity, inflammation, and thermoregulation. Ketorolac is a racemic mixture of R (+) and S(-)-enantiomers, while the analgesic (analgesic) effect is due to the S(-)-enantiomer.

Ketorolac 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 (analgesic) effect is comparable to morphine, significantly superior to other NSAIDs.

After oral use, the onset of analgesic (analgesic) action is noted, respectively, in 1 hour, the maximum effect is achieved in 2-3 hours.

After intravenous use, the onset of analgesic (analgesic) action is noted in 0.5 hours, the maximum effect is achieved in 1-2 hours

. Pharmacokinetics

When taken orally, ketorolac is well absorbed from the gastrointestinal tract. Bioavailability is 80-100%. _Cmax in blood plasma is 0.7-1.1 mcg / ml and is reached 40 minutes after taking the drug on an empty stomach at a dose of 10 mg. A fat-rich diet lowers the_cmax of the drug in the blood and delays its achievement by 1 hour.

When administered intravenously, absorption is complete and rapid. After intravenous use of the drug at a dose of 30 mg_{, cmax} in blood plasma is 1.74-3.1 mcg / ml, at a dose of 60 mg-3.23-5.77 mcg/ml. T_max is 15-73 min and 30-60 min, respectively.

After intravenous infusion of the drug at a dose of 15 mg, the_cmax is 1.96-2.98 mcg / ml, at a dose of 30 mg-3.69-5.61 mcg/ml.

Binding to plasma proteins is 99%. With hypoalbuminemia, the amount of free matter in the blood increases.

Vd is 0.15-0.33 l/kg.

The time to reach C_ss when taken orally is 24 hours when used 4 times/day (above subtherapeutic). C_ss after oral use at a dose of 10 mg is 0.39-0.79 mcg / ml.

C_ss for parenteral use is reached after 24 h when using 4 times/day (above subtherapeutic) and with the/m introduction in a dose of 15 mg is 0.65-1.13 µg/ml, with the/m introduction in a dose of 30 mg – 1.29-2.47 µg/ml; the on/in infusion at a dose of 15 mg – 0.79-1.39 µg/ml, if/V infusion at a dose of 30 mg – 1.68-2.76 µg/ml.

Poorly passes through the BBB, penetrates the placental barrier (10%).

It is excreted in breast milk: when the mother takes 10 mg of ketorolac orally_{, the maximum} in breast milk is reached 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 / day), the_maximum is 7.9 ng/ml.

When administered parenterally, it is excreted in breast milk in small amounts.

More than 50% of the administered dose is metabolized in the liver to form pharmacologically inactive metabolites. The main metabolites are glucuronides and p-hydroxyketorolac.

It is excreted in the urine – 91% (40% in the form of metabolites), with feces-6%. It is not excreted by hemodialysis.

After oral use, T_1/2 in patients with normal renal function is 2.4-9 hours (average 5.3 hours).

After intravenous use of 30 mg T_1/2 – 3.5-9.2 after intravenous use of 30 mg T_1/2 – 4-7.9 hours.

The total clearance for intravenous use of 30 mg is 0.023 l / kg / h, for intravenous infusion of 30 mg – 0.03 l/kg/h.

In patients with renal insufficiency, the Vd of the drug can increase by 2 times, andthe Vd of its R-enantiomer-by 20%. When the concentration of creatinine in the blood plasma is 19-50 mg / l with the intramuscular use of 30 mg of the drug, the total clearance is 0.015 l/kg/h.

In patients with impaired renal function at a plasma creatinine concentration of 19-50 mg / l (168-442 mmol/l) T_1/2 is 10.3-10.8 hours, with more severe renal insufficiency-more than 13.6 hours

. Liver function does not affect T_1/2.

In elderly patients, the total clearance with intravenous use at a dose of 30 mg is 0.019 l / kg / h. T_1/2 is prolonged in elderly patients and shortened in young ones.

Indications

Severe and moderate pain syndrome: injuries, toothache, pain in the 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, and does not affect the progression of the disease.

Use during pregnancy and lactation

It is contraindicated to use the drug during pregnancy, during childbirth and during breastfeeding.

Contraindications

Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis); urticaria, rhinitis caused by taking NSAIDs (in the anamnesis); intolerance to pyrazolone-type drugs; dehydration, hypovolemia (regardless of the cause); bleeding or a high risk of their development; condition after surgery coronary artery bypass grafting; confirmed hyperkalemia; inflammatory bowel diseases; erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers; hypocoagulation (including hemophilia); severe renal failure (creatinine clearance less than 30 ml/min); severe liver failure or active liver disease; hemorrhagic stroke (confirmed or suspected); hemorrhagic diathesis; hematopoiesis disorder; pregnancy; childbirth; lactation hypersensitivity to ketorolac and other NSAIDs (breast-feeding); children under 16 years of age (efficacy and safety have not been established); hypersensitivity to ketorolac and other NSAIDs.

It is not used as a means for premedication, maintenance anesthesia, anesthesia before and during surgical operations (including in obstetric practice) due to the high risk of bleeding.

It is not indicated for the treatment of chronic pain.

Caution

bronchial asthma; cholecystitis; chronic heart failure; hypertension; impaired renal function (plasma creatinine below 50 mg/l); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; older age (over 65 years); the polyps of the nasal mucosa and nasopharynx, concomitant use with other NSAIDs, the presence of factors that increase the toxicity of the gastrointestinal tract: chronic alcoholism, tobacco Smoking; the postoperative period, edematous syndrome, coronary artery disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery disease, creatinine clearance less than 60 ml/min, ulcerative lesions of the gastrointestinal tract in history, the presence of infection Helicobacter pylori, long-term use of NSAIDs, severe somatic diseases, concomitant use of oral corticosteroids (e. g. prednisone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective inhibitors of serotonin reuptake (including citalopram, fluoxetine, paroxetine, and sertraline).

Side effects

From the digestive system:  often (especially in elderly patients over 65 years of age who have a history of erosive and ulcerative lesions of the gastrointestinal tract)-gastralgia, diarrhea; less often – stomatitis, flatulence, constipation, vomiting, a feeling of fullness of 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, melena, vomiting with blood or “coffee grounds”, nausea, heartburn), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

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

Nervous system disorders:  often-headache, dizziness, drowsiness; rarely-aseptic meningitis (including fever, severe headache, convulsions, neck and/or back stiffness), hyperactivity (including mood changes, anxiety), hallucinations, depression, psychosis.

From the cardiovascular system:  less often-increased blood pressure; rarely-fainting.

Respiratory system disorders:  rarely-bronchospasm, dyspnoea, rhinitis, pulmonary edema, laryngeal edema (including shortness of breath, difficulty breathing).

From the side of the senses:  rarely – hearing loss, ringing in the ears, visual impairment (including blurred vision).

From the hematopoietic system:  rarely-anemia, eosinophilia, leukopenia.

From the side of the blood coagulation system:  rarely-bleeding from a postoperative wound, nosebleeds, rectal bleeding.

From the side of the skin:  less often-skin rash (including maculopapular), purpura; rarely-exfoliative dermatitis (includingfever with or without chills, redness, tightness or flaking of the skin, swelling and / or soreness of the palatine tonsils), urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

Allergic reactions: rarely – anaphylaxis or anaphylactoid reactions (including discoloration of the skin of the face, skin rash, urticaria, itchy skin, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest, wheezing).

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

Other services: often – edema (including face, shins, ankles, fingers, feet), increased body weight; less often – increased sweating; rarely – swelling of the tongue, fever.

Interaction

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

Co-use with paracetamol increases nephrotoxicity, with methotrexate-hepatotoxicity and nephrotoxicity.

Co-use of ketorolac and methotrexate is possible only when using low doses of the latter (monitor the concentration of methotrexate in blood plasma).

When using ketorolac, it is possible to reduce the clearance of methotrexate and lithium and increase the toxicity of these substances.

Concomitant use with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetan, and pentoxifylline increases the risk of bleeding.

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

When used concomitantly with opioid analgesics, the doses of the latter can be significantly reduced, since their effect increases.

When used concomitantly, it enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs (dose recalculation is necessary).

Co-use with valproic acid causes a violation of platelet aggregation.

Increases plasma concentrations of verapamil and nifedipine.

When prescribed 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.

Myelotoxic drugs increase the manifestations of hematotoxicity of the drug.

Pharmacologically incompatible with tramadol solution, lithium preparations.

How to take, course of use and dosage

Ketorolac should be administered orally once or repeatedly, depending on the severity of the pain syndrome. A single dose is 10 mg, with repeated use 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.

With intravenous or intravenous use, depending on the patient’s age and the severity of pain, a single dose can vary from 10 mg to 60 mg. The frequency and duration of use are set individually.

The maximum daily dose for intravenous and intravenous use for adults under 65 years of age and children over 16 years of age is 90 mg; for elderly patients over 65 years of age or with impaired renal function-60 mg.

Continuous IV infusion should not last more than 24 hours.

With parenteral use, the duration of the course of treatment should not exceed 5 days.

When switching from parenteral use to oral use, the total daily dose of ketorolac in 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 elderly patients over 65 years of age or with impaired renal function. In this case, the dose of ketorolac for oral use on the day of transition should not exceed 30 mg.

Special instructions

When combined with other NSAIDs, fluid retention, decompensation of cardiac activity, and arterial hypertension may occur.

To reduce the risk of developing NSAID gastropathies, antacids, misoprostol, omeprazole are prescribed.

The effect on platelet aggregation persists for 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys.

If necessary, it can be prescribed in combination with opioid analgesics.

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

In patients with impaired blood clotting, it is used only when the number of platelets is constantly monitored, especially in the postoperative period, which requires careful monitoring of hemostasis.

Influence on the ability to drive vehicles and mechanisms

Since a significant part of patients with ketorolac develop side effects from the central nervous system (drowsiness, dizziness, headache), it is recommended to avoid performing work that requires increased attention and rapid reaction (driving vehicles, working with mechanisms).

Active ingredient

Ketorolac

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection