Is Ketorol a prescription drug or not? Ketorol - what helps? Indications for use of Ketorol, release forms, composition, dosage, instructions, analogues. Tablets and injections

NSAIDs have a pronounced analgesic effect, have anti-inflammatory and moderate antipyretic effects. The mechanism of action is associated with non-selective inhibition of COX activity (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. Ketorolac is a racemic mixture of [-]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 NSAIDs.

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

After oral administration, the analgesic effect develops within 1 hour.

Pharmacokinetics

Suction

When taken orally, ketorolac is well and quickly absorbed from the gastrointestinal tract. The bioavailability of ketorolac is 80-100%, Cmax after oral administration at a dose of 10 mg is 0.82-1.46 mcg/ml, Tmax is 10-78 minutes. Rich in fats food reduces the Cmax of the drug in the blood and delays its achievement by an hour.

Distribution

Plasma protein binding is 99%, Vd – 0.15-0.33 l/kg. The time to reach C ss when taken orally at a dose of 10 mg 4 times a day is 24 hours, C ss - 0.39-0.79 μg/ml.

Excreted in breast milk: when taking ketorolac at a dose of 10 mg, Cmax in breast milk is reached 2 hours after taking the first dose and is 7.3 ng/ml, 2 hours after taking the second dose of ketorolac (when using the drug 4 times a day) - 7.9 ng/l.

Metabolism

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.

Removal

Excreted mainly by the kidneys - 91%, through the intestines - 6%, glucuronides are excreted in the urine. Not excreted by hemodialysis.

T1/2 in patients with normal renal function averages 5.3 hours (2.4-9 hours after oral administration at a dose of 10 mg). When administered orally at a dose of 10 mg, the total clearance is 0.025 l/h/kg.

Pharmacokinetics in special groups of patients

T1/2 increases in elderly patients and shortens in young ones.

Impaired liver function does not affect T1/2.

In patients with renal failure, the Vd of the drug may increase by 2 times, and the Vd of its R-enantiomer by 20%. 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 severe renal failure - more than 13.6 hours. In patients with renal failure ( at a plasma creatinine concentration of 19-50 mg/l), the total clearance is 0.016 l/h/kg.

Release form

Green film-coated tablets, round, biconvex, embossed with the letter “S” on one side; cross-sectional view - the shell is green and the core is white or almost white.

Excipients: microcrystalline cellulose - 121 mg, lactose - 15 mg, corn starch - 20 mg, colloidal silicon dioxide - 4 mg, magnesium stearate - 2 mg, sodium carboxymethyl starch (type A) - 15 mg.

Compound film shell: hypromellose - 2.6 mg, propylene glycol - 0.97 mg, titanium dioxide - 0.33 mg, olive green (quinoline yellow dye 78%, brilliant blue dye 22%) - 0.1 mg.

10 pieces. - blisters (2) - cardboard packs.

Dosage

Take orally in a single dose of 10 mg.

With pronounced pain syndrome The drug is taken repeatedly at 10 mg up to 4 times a day, depending on the severity of pain. Maximum daily dose is 40 mg. The minimum effective dose should be used. When taken orally, the duration of treatment should not exceed 5 days.

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

Overdose

Symptoms: abdominal pain, nausea, vomiting, erosive and ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents ( Activated carbon) and conducting symptomatic therapy(maintenance vital important functions organism). Not eliminated sufficiently by dialysis.

Interaction

The simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium preparations, corticosteroids, ethanol, corticotropin can lead to ulcerative lesions of the gastrointestinal tract and the development of gastrointestinal bleeding.

When used simultaneously with other nephrotoxic drugs medicines(including with gold preparations) the risk of developing nephrotoxicity increases. Simultaneous administration with paracetamol increases nephrotoxicity, and with methotrexate - hepato- and nephrotoxicity. Co-administration of ketorolac and methotrexate is possible only when the latter is used in low doses (monitor the concentration of methotrexate in the blood plasma).

Probenecid reduces the plasma clearance and Vd of ketorolac, increases its concentration in the blood plasma and increases its T1/2. With the use of ketorolac, the clearance of methotrexate and lithium may decrease and the toxicity of these substances may increase.

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 ketorolac.

Ketorolac enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs (dose adjustment is necessary).

Simultaneous administration with valproic acid causes a violation of platelet aggregation. Increases the plasma concentration of verapamil and nifedipine.

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

Side effects

Frequency determination side effects: often (1-10%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%), including individual messages.

From the outside 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; sometimes – 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 and others), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

From the urinary system: rarely - acute renal failure, low 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 of renal origin.

From the senses: rarely - hearing loss, ringing in the ears, visual impairment (including blurred visual perception).

From the outside respiratory system: rarely - bronchospasm, shortness of breath, rhinitis, laryngeal edema.

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

From the outside of cardio-vascular system: sometimes – increased blood pressure; rarely – pulmonary edema, fainting.

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

From the side of hemostasis: rarely - bleeding from postoperative wound, nosebleeds, rectal bleeding.

From the outside skin: Sometimes - skin rash(including maculopapular rash), purpura; rarely - exfoliative dermatitis (fever with or without chills, redness, thickening or flaking of the skin, swelling and/or tenderness of the tonsils), urticaria, Stevens-Johnson syndrome, Lyell's syndrome.

Allergic reactions: rarely - anaphylaxis or anaphylactoid reactions (change in facial skin color, skin rash, urticaria, skin itching, tachypnea or dyspnea, swelling of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in chest, wheezing).

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

Indications

Pain syndrome of severe and moderate severity:

• injuries;
• toothache;
• pain in the postpartum and postoperative period;
• oncological diseases;
• myalgia;
• arthralgia;
• neuralgia, radiculitis;
• dislocations, sprains;
• rheumatic diseases.

Intended for symptomatic therapy, reducing the intensity of pain and inflammation at the time of use, does not affect the progression of the disease.

Contraindications

• complete or incomplete combination bronchial asthma, recurrent nasal or sinus polyposis and intolerance acetylsalicylic acid and other NSAIDs (including in history);
• erosive and ulcerative changes in the mucous membrane of the stomach and duodenum;
• active gastrointestinal bleeding;
• cerebrovascular or other bleeding;
• inflammatory bowel diseases (Crohn's disease, ulcerative colitis) in the acute phase;
• bleeding disorders, incl. hemophilia;
• decompensated heart failure;
• liver failure or active liver disease;
• severe renal failure (CK<30 мл/мин), прогрессирующие заболевания почек;
• confirmed hyperkalemia;
• period after coronary artery bypass surgery;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• pregnancy, childbirth;
• lactation period (breastfeeding);
• children and adolescents up to 16 years of age;
• hypersensitivity to ketorolac.

With caution: hypersensitivity to other NSAIDs; bronchial asthma; IHD; congestive heart failure; edema syndrome; arterial hypertension; cerebrovascular diseases; pathological dyslipidemia/hyperlipidemia; impaired renal function (creatinine clearance 30-60 ml/min); diabetes; cholestasis; active hepatitis; sepsis; SLE; peripheral arterial disease; smoking; simultaneous use with other NSAIDs; history of ulcerative lesions of the gastrointestinal tract; alcohol abuse; severe somatic diseases; concomitant therapy with the following drugs - anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), oral corticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline); elderly patients (over 65 years old).

Features of application

Use during pregnancy and breastfeeding

Use for liver dysfunction

Contraindicated in patients with liver failure or active liver disease.

Use for renal impairment

Use in children

Use in elderly patients

special instructions

Ketorol ® has two dosage forms (film-coated tablets and solution for intravenous and intramuscular administration). The choice of method of drug administration depends on the severity of the pain syndrome and the patient’s condition.

The risk of developing drug complications when taking the drug orally increases when the treatment period is extended beyond 5 days and the oral dose of the drug is increased to more than 40 mg/day.

The drug should not be used simultaneously with other NSAIDs. When used simultaneously with other NSAIDs, fluid retention, cardiac decompensation, and increased blood pressure may occur. The effect on platelet aggregation ceases after 24-48 hours.

For patients with bleeding disorders, the drug is prescribed only with constant monitoring of the platelet count, which is especially important for postoperative patients when careful monitoring of hemostasis is required.

The drug can change the properties of platelets, but does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

To reduce the risk of developing NSAID gastropathy, antacid medications, misoprostol, and omeprazole are prescribed.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

In this article you can read the instructions for use of the drug Ketorol. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Ketorol in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Ketorol in the presence of existing structural analogues. Use for the treatment of dental, headache and other types of pain, during menstruation in adults, children, as well as during pregnancy and lactation.

What kind of medicine is this

Ketorol is a drug most often used for pain relief in cases of severe pain arising for various reasons. It is used quite widely and for various pathologies.

Drug group

International nonproprietary name or INN: Ketorolac

Trade name: Ketorol

Latin name: Ketorolacum

Compound

Active ingredient: ketorolac trometamol - 0.03 g.

Additional substances: octoxynol - 0.00007 g.

Trilon B - 0.001 g.

sodium chloride - 0.00435 g.

ethanol - 0.115 ml.

propane-1,2-diol - 0.4 g.

caustic soda - 0.000725 g.

water for injection - the volume required to increase the contents of the ampoule to 1 ml.

Mechanism of action and properties

Characteristic

Non-steroidal anti-inflammatory drug or NSAID. Ketorolac in structure consists of two isoforms: S(−) and R(+), can be found in three microcrystalline variants, which have good solubility in water. The dissociation constant of Ketorolac acid is 3.5. Molecule mass: 376.41.

Pharmacodynamics (pharmacology)

Ketorol is an NSAID, acting on the body to suppress pain, inhibit inflammation, and also moderately reduce body temperature.

Mechanism of action

5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid non-selectively counteracts the activity of cyclooxygenase-1 and cyclooxygenase-2, which are catalysts for the synthesis of prostaglandins from arachidonic acid.

Prostaglandins are of great importance in the formation of pain, inflammatory reactions and an excessive increase in the patient’s body temperature.

Ketorol is a mixture of almost identical isomers S(-) and R(+), differing only in their mirror arrangement. It is the S form that causes the analgesic effect.

Ketorol, compared to morphine, shows the same strong analgesic effect, much greater than other NSAIDs.

Pharmacokinetics

The effectiveness of the drug and the speed of its action depend on the method of delivery of the active substance to the body.

When a solution of the drug is administered intramuscularly or into a vein, the effect occurs within 30 minutes and reaches its maximum after 60-120 minutes. Duration of action is from 4 to 6 hours. When administered enterally, the effect begins after 60 minutes, and the maximum effect occurs only after 120-180 minutes.

The bioavailability of the drug is rapid and fully manifested. When the contents of one ampoule are introduced into the muscle (1 ampoule - 30 mg), the highest concentration is from 0.00000174 to 0.0000031 g/ml, when two ampoules are administered - from 0.00000323 to 0.00000577 g/ml.

The time to reach the highest concentration is from 15 to 73 for 30 mg and from 30 to 60 minutes for 60 mg.

The share of interaction with blood plasma proteins is 99%.

The drug may pass into breast milk. 2 hours after administration, the concentration of the drug in milk becomes maximum (7.3 ng/ml).

About half the dose of the drug is converted in the liver into chemically inactive compounds: tetrahydroxy-2-oxanoic acids, which are eliminated by the kidneys, and p-hydroxyketorolac. Excreted by the kidneys (about 91%) and through the gastrointestinal tract (6%).

The half-life of Ketorol depends on the age of the patient: in the elderly it increases, in the young it decreases accordingly. In patients with renal pathologies, the half-life can range from 10 to 13 hours.

Hemodialysis does not affect the metabolism of the drug. The drug may affect the kidneys and liver.

Indications

What does it cure, what is it for and what is the benefit of it? The main use of the drug is pain relief, but it also helps reduce temperature and reduce the intensity of inflammation.

Why is Ketorol prescribed? Typically for symptomatic therapy.

Solutions are injected for severe and moderate pain:

• For injuries.
• During dental interventions.
• For tumors.
• To relieve pain after surgery.
• For pain in muscles and joints.
• With damage to peripheral nerves.
• For autoimmune diseases, for radiculopathy.

Drops are used for inflammation of the mucous membrane of the eye and after eye surgery.

The gel is used topically for injuries:

• For bruises.
• Sprains.
• For tendon inflammation.
• Inflammation of the synovial membranes.
• In inflammatory processes in the joint capsules.
• For pain in muscles and joints.
• When nerves remote from the center are affected.
• For autoimmune diseases.
• For radiculopathy.

Tablets are used at the same time as solutions.

Release forms

The drug is produced in the form of four dosage forms: a solution for infusions and injections (intramuscular or intravenous) in a 1 ml ampoule, in the form of tablets coated with a film on the outside, in the form of a gel for external use and in the form of eye drops.

What is better solution or tablets? Tablets are easier to use, but the solution is faster and more effective. The gel is used only externally, for example, for soft tissue bruises.

Instructions for use

When administered parenterally to patients from 16 to 64 years of age with a body weight of more than 50 kg, more than 60 mg cannot be injected into the muscle at a time (the dose of the drug taken orally must also be taken into account). Most often, 30 mg every 6 hours. 30 mg is administered intravenously, no more than 6 doses in 28 hours.

If the patient weighs less than 50 kg or has renal pathology, then no more than 30 mg is injected into the muscle at a time, usually 15 mg (no more than 8 times in 48 hours), and no more than 15 mg (less than 8 times) into the vein.

The maximum dose administered per day for patients from 16 to 64 years old and weighing more than 50 kg is 0.09 g (90 mg), for others - 0.06 g (60 mg). Duration of use - up to two days.

The drug must be injected into a vein or muscle slowly. The effect begins after 0.5 hours.

The gel must be spread in a thin layer over the disturbing surface.

The tablets must be taken with a sufficient amount of water.

Side effect

• Gastrointestinal dysfunction: diarrhea, nausea, vomiting, constipation, abdominal pain, peptic ulcer of the stomach or duodenum, bleeding in the stomach cavity, inflammatory diseases of the liver, Gospel disease caused by stagnation of bile, acute inflammation of the pancreas, enlarged liver, perforation of the stomach wall .
• Renal dysfunction: pain in the lumbar region, blood or increased nitrogen in the urine, hemolytic-uremic syndrome, pollakiuria, kidney inflammation, renal edema.
• Impaired visual perception, decreased hearing acuity.
• Convulsive contraction of bronchial smooth muscles, inflammation of the mucous layer of the nasal cavity, swelling of the larynx.
• Headache, aseptic inflammation of the meninges, increased body temperature, weakness of the neck or back muscles, muscle spasms, mental disturbances, increased activity, feelings of melancholy, hallucinations.
• Hypertension, acute pulmonary failure, loss of consciousness.
• Decreased levels of hemoglobin in the blood, increased levels of eosinophils and/or decreased levels of white blood cells.
• Bleeding from the nasal cavity, bleeding during operations.
• Urticaria, purpura, inflammatory skin inflammation, erythema effusion, bullous inflammation of the dermis.
• Burning when applied topically, pain along the vein when administered intravenously.
• Anaphylactic reactions, skin itching, shortness of breath, hyperemia, Quincke's edema.
• Increased sweating, weight gain, increased body temperature.

Contraindications

• Drug intolerance.
• Information about a history of hypersensitivity reactions when taking NSAIDs.
• Inflammatory diseases of the mucous layer of the nasal cavity.
• Bronchial asthma.
• Insufficient volume of circulating blood.
• Ulceration of the stomach or duodenum.
• Hemostasis disorders.
• Intestinal inflammation.
• Liver dysfunction.
• Renal dysfunction.
• Insufficient or excessive levels of potassium in the blood.
• Exacerbation of heart failure.
• Premedication in the preoperative and surgical period.
• Simultaneous use with drugs that affect blood clotting.
• Age up to 16 years.
• Dermatitis.
• Simultaneous use with probenecid and pentoxifylline.
• Pregnancy.
• Lactation.

Use in children

The drug is contraindicated for persons under 16 years of age.

Use during pregnancy and breastfeeding

The drug is prohibited during pregnancy and breastfeeding. It can reduce the contractile activity of the uterus and affect the formation of the fetal circulatory system. In infants, inhibition of prostaglandins may lead to adverse effects.

Use in the elderly

In pensioners, the risk of side effects is increased; the drug must be used with caution.

Driving a car and other mechanisms

Due to the high incidence of adverse reactions, activities that require increased attention are not recommended.

Do I need a prescription?

Ketorol is sold by prescription.

Compatibility with other drugs

In case of drug interactions with other drugs, Ketorol may have an adverse effect. Concomitant use with other NSAIDs, ethyl alcohol or alcohol, glucocorticosteroids, anticoagulants, calcium supplements can cause an ulcerogenic effect and bleeding.

Ketorol should not be prescribed with paracetamol for a period of more than 2 days, since when taken in parallel with paracetamol, toxicity to the kidneys increases, and with methotrexate - toxicity to both the kidneys and liver.

If narcotic analgesics are used together with Ketorol, their dosage may be reduced.

Due to a decrease in prostaglandins in the kidneys, the effectiveness of diuretics and blood pressure lowering drugs is reduced.

Antacids do not affect the absorption of the drug.

When used with glucose-lowering drugs, it increases their effect.

Increases the dose of verapamil and nifedipine in the blood.

Alcohol compatibility

When taken together with alcohol, it can cause inflammation of the mucous layer of the stomach and duodenum. Subsequently, ulcers may form in the gastrointestinal tract, so compatibility with alcohol is dangerous.

Analogues of the drug Ketorol

Structural analogues of the active substance:

• Adolor;
• Acular LS;
• Dolak;
• Dolomin;
• Ketalgin;
• Ketanov;
• Ketolac;
• Ketorolac;
• Ketofril;
• Toradol;
• Thorolak.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Arthrosis, osteochondrosis, trauma, tooth extraction, painful menstruation, inflammatory processes - all these diseases and pathological processes can be accompanied by acute pain, from which traditional analgesics usually do not save. However, Ketorol, a powerful pain reliever from the group of non-steroidal anti-inflammatory drugs, can often help in such cases. How effective is this drug, when should it be taken, what contraindications and side effects does it have?

Operating principle

The active component of Ketorol is ketorolac, which is a derivative of acetic acid. Ketorolac is a relatively new drug that appeared in the late 1980s. However, he quickly gained recognition throughout the world. Currently, ketorolac is used for the symptomatic treatment of various diseases and is widely used in gynecology, surgery, and ophthalmology.

The mechanism of action of ketorolac is a non-selective effect on a special enzyme - cyclooxygenase, which, in turn, is responsible for the synthesis of prostaglandins from arachidonic acid in the body. It is prostaglandins that are responsible for such phenomena as pain, inflammation and fever. Ketorol acts mainly in peripheral tissues.

Unlike many other non-steroidal anti-inflammatory drugs (NSAIDs), Ketorol mainly has only an analgesic effect, and its antipyretic and anti-inflammatory effect is relatively weak. The analgesic effect of ketorolac, however, is quite strong and is comparable to the analgesic effect of morphine, which is considered in medicine to be a kind of standard among painkillers. The analgesic effect of ketorolac exceeds that of all other NSAIDs and is second only to the effect of some narcotic analgesics.

Ketorol does not affect opioid receptors and the central nervous system, does not cause drug dependence, sedative and anxiolytic effects, does not depress respiration (unlike opioid analgesics), does not affect intestinal motility, does not lead to urinary retention, bradycardia, tachycardia or changes in blood pressure .

Ketorol, like almost all other NSAIDs, affects blood clotting and prolongs bleeding time, although these changes do not exceed dangerous limits. However, it is worth remembering this for people who have diseases that impair blood clotting or may cause severe internal bleeding (for example, hemophilia or stomach ulcers).

Release form

Ketorol can be purchased in pharmacies in three main forms. Firstly, these are tablets intended for oral administration. Ketorol tablets are round, biconvex, covered with a green coating, white inside. On one side there is the Latin letter S. Each Ketorol tablet contains 10 mg of active ingredient.

Secondly, this is a solution intended for parenteral (intravenous or intramuscular) administration. The solution is contained in ampoules, and 1 ml of solution contains 30 mg of the active substance.

In addition, there is a 30 g gel for external use. Each tube of gel contains 600 mg of ketorolac. The concentration of the active substance in the gel is 2% (20 mg per 1 g).

Excipients in the tablet:

• microcrystalline cellulose,
• lactose monohydrate,
• corn starch,
• silicon dioxide,
• magnesium stearate,
• hypromellose,
• titanium dioxide

Excipients in Ketorol solution:

• octoxynol,
• disodium edetate,
• sodium chloride,
• ethanol,
• sodium hydroxide,
• water.

The solution is produced in packs of 10 ampoules, tablets - in packs of 20 pcs. Ketorol is produced by the Indian pharmaceutical company Dr. Reddy's Laboratories.

The shelf life of tablets and solution is 3 years, gel – 2 years. Tablets and solution for parenteral administration are available with a prescription; a prescription is not required for the gel.

Analogs

Structural analogues of the drug, that is, medicines containing ketorolac as an active substance, are:

• Ketanov,
• Adolor,
• Dolak,
• Dolomin,
• Ketalgin,
• Ketolak,
• Ketofril,
• Ketokam,
• Ketonal (gel only).

You can also find other NSAIDs in pharmacies, but it should be remembered that most of them differ significantly from Ketorol in their principle of action and indications.

Pharmacokinetics

Ketorol is quickly absorbed into the blood when taken orally. Fat-rich foods reduce the maximum concentration of the drug in the blood and slow down its onset. Ketorol is able to pass into breast milk, partially (approximately 10% of the drug) penetrates the placental barrier. Moreover, the bioavailability of the drug is about 100%, regardless of the dosage form. When administered parenterally, Ketorol begins to act faster than when taking tablets. The maximum concentration of the drug in the blood when taking tablets is observed after 1 hour, and the maximum therapeutic effect occurs a little later and lasts 4-6 hours. When administered parenterally, the maximum concentration depends on the route of administration (intramuscular or intravenous), as well as on the dose.

The highest concentration in the blood and the time of the highest concentration after intramuscular administration:

Maximum concentration in the blood and time of maximum concentration after intravenous administration:

Ketorol is metabolized 50% in the liver. Excreted from the body mainly by the kidneys (91%) and intestines (6%).

The half-life in patients with unimpaired renal function is on average 5.3 hours. This value is slightly higher for young patients and lower for elderly patients. In patients with impaired renal function (creatinine clearance 19-50 ml/min), the half-life rate increases to 10.3-10.8 hours. With even lower creatinine clearance, the time is extended to 13.6 hours. Liver function does not affect the half-life.

Indications

Indications for use of tablets and solution are almost the same. The choice of a particular dosage form is dictated by considerations such as speed of action and the patient's condition. The solution is indicated for use where the fastest effect is needed. In addition, sometimes the patient for some reason cannot take the pills (unconsciousness, vomiting, stomach ulcers, problems with swallowing). In this case, it is also worth using injections. In all other cases, tablets are indicated for use.

Ketorol is indicated for use, first of all, if it is necessary to get rid of pain of various origins:

• toothache;
• injuries;
• dislocations and muscle strains;
• bruises and inflammation of soft tissues;
• ligament damage;
• pain with bursitis, tendonitis, epicondylitis, synovitis;
• myalgia;
• neuralgia;
• radiculitis;
• arthrosis;
• oncological diseases;
• headache;
• pain due to various inflammatory processes;
• postoperative pain;
• postpartum pain;
• wounds;
• joint and bone pain;
• pain due to rheumatism.

Ketorol is more suitable for relieving pain of severe and moderate severity. For relatively mild pain, other drugs are indicated for use. In addition, Ketorol should not be used for a long time, more than 5 days. This means that for chronic pain it is also necessary to use other drugs.

Reviews

Reviews about the drug are mostly positive. Patients and doctors note the high effectiveness of the product and its reasonable price. However, there are also patients in whom the drug caused adverse reactions, and doctors point out that the drug is not intended for long-term use and cannot be used during pregnancy.

Contraindications

Ketorol has a number of contraindications. First of all, this is hypersensitivity to the components of the drug. In addition, it should not be given to children under 16 years of age (in tablet or injection form). This is due to the fact that when children take the drug, there is a high probability of developing side effects, such as nephritis, depression, hearing impairment, and pulmonary edema.

Therefore, for parents who want to relieve their children from the unpleasant symptoms of acute respiratory infections, flu and colds, Ketorol is not suitable. It is better to use ibuprofen and paracetamol, which are more effective and safe in this case. Adolescents over 16 years of age can use the drug for the same indications as adults.

Ketorol gel can be used from 12 years of age. In addition, Ketorol is prohibited in the form of tablets and injections for pregnant women. In the form of a gel, Ketorol is approved for pregnant women during the 1st and 2nd trimesters. In the third trimester, Ketorol should not be used even in the form of a gel, as this can lead to post-term pregnancy or complications of labor. Ketorol during lactation is prohibited in all forms.

Other contraindications when taken in the form of tablets and injections:

• • history of bronchospasms and angioedema;
  • dehydration;
  • ulcers and erosions of the gastrointestinal tract;
  • decreased blood clotting;
  • insufficiency of liver functions;
  • hemorrhagic diathesis;
  • history or current cerebral hemorrhage;
  • hematopoietic disorders;
  • risk of major bleeding;
  • decompensated heart failure;
  • high concentration of potassium in the blood.

recent coronary artery bypass surgery;

• milk sugar intolerance;
• acute phases of Crohn's disease, ulcerative colitis.

Ketorol is taken with caution when:

• bronchial asthma;
• hypersensitivity to NSAIDs;
• congestive heart failure;
• damage to peripheral arteries;
• systemic lupus erythematosus;
• coronary heart disease;
• arterial hypertension;
• stagnation of bile;
• hepatitis;
• sepsis;
• history of gastrointestinal ulcers;
• simultaneous use of anticoagulants and antiplatelet agents, NSAIDs, selective serotonin reuptake inhibitors, corticosteroids;
• in old age (over 65 years old);
• alcoholism;
• polyps of the nasal and nasopharyngeal mucosa;
• renal failure (creatinine clearance less than 60 ml/min);
• other severe somatic diseases.

Contraindications for use in gel form are:

• weeping dermatoses,
• eczema,
• wounds and abrasions at the site of application,
• "aspirin" bronchial asthma,
• third trimester of pregnancy.

The gel is prescribed with caution in old age (over 65 years), in childhood (under 16 years), with bronchial asthma, during the 1st and 2nd trimester of pregnancy.

Also, the drug should not be used if the patient suffers from intolerance to other NSAIDs or renal failure (creatinine clearance less than 30 ml/min). If creatinine clearance is less than 60 ml/min, the dose should be reduced.

Ketorol should not be used for preventive pain relief before operations, as well as in obstetric practice due to possible blood clotting disorders.

Side effects

When taking Ketorol orally, a number of side effects may occur. However, most of them are not life-threatening.

The most common side effects are abdominal pain and diarrhea (in more than 3% of cases). These side effects are usually observed in older people who have gastrointestinal ulcers. Also, a number of patients experience swelling (of the face, legs, ankles, fingers, feet), dizziness, and headaches. Less commonly (in 1-3% of cases), side effects such as increased blood pressure, stomatitis, flatulence, vomiting, constipation, and skin reactions may occur.

Ketorol may also cause other types of rare side effects:

Sometimes there may be an increase in temperature and increased sweating.

Skin reactions are more common when using the drug in gel form. However, when applying the drug to a significant surface of the body, systemic side effects cannot be excluded:

• ulcerative pathologies of the gastrointestinal tract,
• heartburn,
• diarrhea,
• stomach pain,
• hematuria,
• vomit,
• nausea,
• fluid retention,
• anemia,
• agranulocytosis,
• leukopenia,
• thrombopenia.

If any side effects occur, you should interrupt treatment with the drug and seek medical advice.

Overdose

When using the gel, an overdose is impossible. Although sometimes the gel can get into the oral cavity, for example, from the lips. In this case, the oral cavity must be rinsed, and if the gel gets into the stomach, enterosorbents should be taken. An overdose when taking tablets orally can manifest itself in symptoms such as stomach pain, nausea, vomiting, urinary retention, renal dysfunction, and acidosis. The formation of ulcerative lesions in the stomach may also occur.

If an overdose occurs, it is recommended to do the standard gastric lavage procedures for such cases, take sorbents, and carry out symptomatic therapy, that is, therapy aimed at maintaining the performance of the main body systems. Hemodialysis in case of an overdose of the drug is usually not carried out, since it is ineffective.

Instructions for use

When using Ketorol in tablet form, they should be taken as needed, but no more than 4 tablets per day. The maximum dose is 40 mg per day. The course of treatment is 5 days, unless otherwise prescribed by the attending physician. The tablets must be swallowed without chewing and washed down with enough water. The effectiveness of Ketorol is not associated with food intake, however, when taking the drug immediately after a meal, the substance is absorbed into the blood more slowly and the analgesic effect appears later in this case. On the other hand, taking Ketorol before meals increases irritation of the gastric mucosa. Therefore, the most optimal time to take is 2 hours after meals.

Ketorol injections

Injections are preferable if the fastest possible analgesic effect is required, or the patient cannot take pills for any reason.

The solution is injected deep into the muscle. The injection site should be the outer upper third of the thigh, shoulder, buttock, or other area of ​​the body where the muscles come close to the skin. Small disposable syringes with a capacity of 0.5-1 ml are suitable for injections. Single dosage – 10-30 mg (0.3-1 ml). The largest single dose for intramuscular administration is 2 ml. A second injection can be given after 4-6 hours. No more than 90 mg of ketorolac (3 ml of solution) can be administered per day.

For people over 65 years of age, or weighing less than 50 kg, or having impaired renal function, the maximum single dose should not exceed 15 mg (0.5 ml). The maximum daily dose in this case is 60 mg. The solution must be administered slowly - this reduces the risk of developing negative reactions. The time for intravenous jet administration of the solution should not be less than 15 s.

The duration of treatment for parenteral administration should not exceed 5 days. When administered intravenously, the total dose for the entire course of treatment should not exceed 15 ml. For patients with reduced renal function, elderly people (over 65 years of age) or patients weighing less than 50 kg, this value is 10 ml.

If necessary, you can switch from the parenteral form of administration to taking tablets within 1 day. In this case, the maximum daily dose of both forms of the drug should not exceed 90 mg, and the dose of the drug in tablet form should not exceed 30 mg.

Instructions for intramuscular injections

The syringe and needle should be removed from the package immediately before injection. Use a syringe to draw the required amount of solution from the ampoule. Then the syringe should be raised with the needle up and tapped in the direction from the piston to the needle. This is necessary so that the air bubbles separate from the walls and rise up. To remove air, you need to lightly press the piston so that a drop appears on the needle. After this, the syringe is put aside and the injection site is treated with an antiseptic. The needle is inserted into the injection site perpendicularly and over its entire length, and then the contents of the syringe are squeezed out slowly and carefully. After the injection, the injection site is again treated with an antiseptic.

Ketorol infusions

Ketorol from an ampoule can be added to a dropper and used together with other saline solutions. Ketorol is compatible with the following solutions:

Physiological
dextrose 5%
lidocaine
dopamine
Ringer
Ringer-Locke
Plasma-lit
aminophylline
short-acting human insulin
heparin

Instructions for applying the gel (ointment)

The gel should be applied to an intact skin surface free of wounds, burns and abrasions. You should also avoid getting the gel in the eyes, mucous membranes of the mouth and nose.
Before applying the gel, the skin should be washed and dried.

From a 30 g tube of gel, squeeze out 1-2 cm of gel and apply it evenly to the surface of the skin. If the surface area to be treated is large, the amount of gel can be increased. The ointment must be rubbed into the skin several times in a circular motion until the composition is completely absorbed. The surface of the skin on which the gel was applied can be covered with a cotton or gauze bandage. However, it should not be tightly closed and should allow some air to pass through.

Do not apply the gel to the skin too often. It is enough to do this 4 times a day. In this case, the intervals between episodes of using the gel should not be less than 4 hours. The course of treatment with gel is no more than 10 days. If the desired improvement does not occur or if longer use of the drug is necessary, you should consult your doctor.

Interaction with other drugs

Interactions with other drugs that compete for binding to blood proteins cannot be ruled out.

When used with drugs that have a toxic effect on the kidneys (for example, gold preparations), Ketorol enhances their negative effect. The combination of Ketorol with some antihypertensive drugs may reduce their effect due to a decrease in the production of prostaglandins in the kidneys. When using Ketorol simultaneously with other NSAIDs or steroidal anti-inflammatory drugs, ethyl alcohol, the risk of gastric bleeding increases. Use with NSAIDs can lead to fluid retention in the body and increased blood pressure.

You should not use Ketorol simultaneously with paracetamol for more than 5 days, as this increases the risk of developing kidney pathologies. The same can be said about the simultaneous use of the drug with ACE inhibitors - in such a case, a negative effect on the kidneys is also manifested. Since the drug does not affect the effect of narcotic analgesics when used simultaneously with them, the dosage of the latter can be reduced to reduce the number of negative effects. Antacids do not affect the absorption of the drug from the gastrointestinal tract. Caution must be exercised when used with cyclosporine and lithium preparations.

Ketorol in the form of a solution cannot be mixed in the same syringe with certain medications due to drug incompatibility, for example, with morphine and tramadol.

Ketorol increases the effect of insulin and other hypoglycemic drugs, but at the same time reduces the effectiveness of antihypertensive drugs and furosemide, anti-epileptic drugs. Thrombolytic drugs and anticoagulants may promote bleeding.

Use with antidepressants may lead to the development of hallucinations.

If you use the drug simultaneously with all of the above drugs, you should consult your doctor.

special instructions

Ketorolac affects blood clotting, but this effect is limited in time and lasts no more than 1-2 hours. Ketorol is not able to replace the preventive effect of acetylsalicylic acid on platelet aggregation. Therefore, patients taking acetylsalicylic acid drugs in moderate doses as anticoagulants should not refuse them. If there is a risk of gastropathy, proton pump inhibitor drugs and antacids are simultaneously prescribed. While using the drug, it is necessary to monitor hemostasis parameters once a week. Elderly people have a higher risk of developing side effects, so they should use Ketorol in minimal doses. Patients with renal failure with regular use of the drug should monitor kidney function parameters by taking urine tests. For liver diseases, Ketorol should be used with caution and in short courses.

Due to the risk of adverse reactions, the first dose of the drug should be administered under close medical supervision.

Active ingredient - ketorolac tromethamine - 10 mg; excipients - microcrystalline cellulose, pregelatinized starch, corn starch, colloidal anhydrous silicon dioxide, magnesium stearate (E170). Shell: opadry 03K51148 green (hypromellose 6cP, titanium dioxide (E171), triacetin/glycerol triacetate, iron dioxide yellow (E172), varnish FD&C blue/diamond blue FCF (E133)).

Pharmacotherapeutic group

Non-steroidal anti-inflammatory drugs. ATX code: M01 AB15.

Pharmacologicalproperties

Pharmacodynamics: ketorolac, being a non-steroidal anti-inflammatory drug, has an analgesic, antipyretic and anti-inflammatory effect. The mechanism of action at the biochemical level is inhibition of the cyclooxygenase enzyme, 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 [-]S and [-]P enantiomers, and the analgesic effect is due to the [-]S form. The drug does not affect opioid receptors, does not depress respiration, does not inhibit intestinal motility, does not have a sedative or anxiolytic effect, does not cause drug dependence, and does not affect the progression of the disease. Ketorolac inhibits platelet aggregation and increases bleeding time. The functional state of platelets is restored 24-48 hours after discontinuation of the drug.

Pharmacokinetics: the bioavailability of ketorolac after oral administration ranges from 80% to 100%. Maximum plasma concentration is achieved within 30-60 minutes. The pharmacokinetics of ketorolac under conditions of mid-therapeutic doses is a linear function. The equilibrium concentration of the drug in plasma is 50% higher than that determined after a single dose. More than 99% of the drug is bound to plasma proteins, resulting in an apparent volume of distribution of less than 0.3 l/kg.

Ketorolac is metabolized primarily to form conjugated forms of glucuronic acid, which are excreted through the kidneys. Metabolites do not have analgesic activity. The half-life of the drug averages 5 hours.

Indications for use

Ketorol film-coated tablets 10 mg are used for short-term treatment of acute pain (including postoperative pain) of moderate intensity, only as a continuation of previous parenteral (intramuscular or intravenous) therapy in a hospital setting, if necessary. The total duration of parenteral and oral therapy with ketorolac should not exceed 5 days due to the possibility of increasing the frequency and severity of adverse reactions.

Before taking Ketorol, consider the potential benefits and risks and options for using another drug.

Use the lowest effective dose for the shortest possible time. Patients should be switched to alternative treatment as quickly as possible.

Dosage regimen and method of administration

The duration of the course of use of ketorolac should not exceed 5 days; long-term use, as well as oral administration at a dose of more than 40 mg per day, is not recommended. To reduce the risk of side effects, it is recommended to use the minimum effective dose for the minimum time required to relieve pain.

Adults: 10 mg every 4 or 6 hours as needed. The total daily dose when switching from parenteral administration of the drug to oral administration should not exceed 90 mg (60 mg for elderly patients, patients with renal failure, patients weighing less than 50 kg), and part of the dose prescribed orally for combined administration should not exceed 40 mg per day by changing the form of administration.

Adults weighing less than 50 kg or with impaired renal function: the frequency of use of the drug is reduced to 1-2 times a day.

Side effect

The most common gastrointestinal disorders occur, among which more than 10% of patients experience nausea, pain in the stomach and intestines, and dyspepsia; Diarrhea often occurs (7%). The central nervous system is characterized by disturbances in the form of headache (17%), drowsiness (6%), dizziness (7%). In 4% of cases, edema develops.

Somewhat less frequently, but more than 1% of patients develop hypertension, itching, rash, stomatitis, vomiting, constipation, flatulence, a feeling of heaviness in the abdomen, sweating and hemorrhagic rash. In less than 1% of patients, weight loss, fever, and asthenia are possible; palpitations, pale skin, fainting; skin rash; gastritis, bleeding from the rectum, loss or increase in appetite, belching; nosebleeds, anemia, eosinophilia, tremor, sleep disturbances, hallucinations, euphoria, extrapyramidal syndromes, paresthesia, depression, nervousness, thirst, dry mouth, visual impairment, impaired attention, hyperkinesis, stupor; shortness of breath, pulmonary edema, rhinitis, cough; hematuria, proteinuria, oliguria, urinary retention, polyuria, increased urination.

There have been cases of hypersensitivity reactions (in the form of anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema); hypotension and flushing of the skin; Lyell's syndrome, Stevens-Johnson syndrome, exfoliative dermatitis, maculopapular rash, urticaria; formation of ulcers in the gastric mucosa, gastrointestinal bleeding, perforation of the walls of the gastrointestinal tract, melena, acute pancreatitis; postoperative wound bleeding, thrombocytopenia, leukopenia; hepatitis, liver failure, cholestatic jaundice; convulsions, psychoses, aseptic meningitis; bronchospasm, acute renal failure, pain in the kidney area, hematuria and azotemia, hyponatremia, hyperkalemia, hemolytic uremic syndrome.

To prevent possible side effects, one should strive to use the minimum effective doses of the drug, strictly adhere to the established dosages and administration regimens, take into account the patient’s condition (age, renal function, state of the gastrointestinal tract, water-electrolyte metabolism and hemostatic 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 the period of exacerbation, as well as a history of ulcers or gastrointestinal bleeding, the presence or suspicion of gastrointestinal or intracranial bleeding.

History of coagulation disorders, conditions with a high risk of bleeding, bleeding diathesis, coagulopathies, hemorrhagic stroke, low-dose heparin therapy. Surgical interventions with a high risk of bleeding or the risk of incomplete stopping of bleeding.

Moderate and severe renal failure (plasma creatinine more than 50 mg/l), risk of renal failure, hypovolemia, dehydration.

Pregnancy, childbirth and breastfeeding.

Hypersensitivity to ketorolac, aspirin, other NSAIDs or any component of the drug.

Concomitant use of other NSAIDs (risk of additive side effects).

Age up to 16 years.

Congestive heart failure.

The drug is not used for pain relief before and during surgery. Ketorolac is not used for epidural and intrathecal injections.

Features of application

Prescription for patients with impaired function liver: prescribed with caution. While taking ketorolac, liver enzyme levels may increase. If there are functional abnormalities in the liver while taking ketorolac, a more severe pathology may develop. If signs of liver pathology are detected, treatment should be stopped.

Patients with renal failure or a history of kidney disease: ketorolac is prescribed with caution.

Purpose 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 no more than 60 mg for patients over 65 years of age).

Pregnancy and lactation

Efficacy and safety have not been established. Drugs that affect the synthesis of prostaglandins, including ketorolac, can cause a decrease in fertility, and therefore are not recommended for use by women planning to become pregnant.

Food: reduces the rate, but does not affect the volume of absorption of ketorolac.

Impact on laboratory test indicators: it is possible to increase bleeding time when studying coagulation parameters.

Since a significant proportion of patients who are prescribed 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 reaction.

Applyeducation in pediatric practice

Risk during childbirth: may adversely affect fetal circulation and suppress uterine contractions.

Impact on the ability to drive vehiclessports and working with machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Warnings and Precautions

The course of treatment with Ketorol should not exceed 5 days.

Taking Ketorol can lead to peptic ulcers and gastrointestinal bleeding, which can be fatal.

The use of NSAIDs can lead to the development of cardiovascular diseases, myocardial infarction and stroke.

Ketorol is contraindicated for use in the postoperative period during coronary artery replacement.

Before administering ketorolac, hypovolemia and hypoproteinemia should be eliminated, as well as water and electrolyte balance should be restored.

Retention of fluid, sodium chloride, oliguria, increased concentrations of urea nitrogen and creatinine in plasma were observed during clinical studies, and therefore ketorolac should be prescribed with caution to patients with heart failure, arterial hypertension or pathological conditions with similar manifestations.

Since ketorolac affects platelet aggregation, use in patients with pathologies of the blood coagulation system should be carefully monitored. Ketorolac is prescribed with extreme caution simultaneously with anticoagulants.

Patients over 65 years of age are more likely to experience adverse reactions characteristic of NSAIDs, so this category of patients is recommended to prescribe doses that are at the lower limit of the therapeutic range.

Drug interactions

Ketorolac slightly reduces the degree of protein binding of warfarin.

In research in vitro the effect of therapeutic doses of salicylates on the degree of binding of ketorolac to plasma proteins is shown, downward from 99.2% to 97.5%.

When combined with furosemide, its diuretic effect may be weakened by approximately 20%.

Probenecid reduces the plasma clearance and volume of distribution of ketorolac, increases its concentration in the blood plasma and increases its half-life. With the use of ketorolac, the clearance of methotrexate and lithium may decrease and the toxicity of these substances may increase.

A possible interaction between ketorolac and non-depolarizing muscle relaxants has been noted, leading to the development of apnea.

It is possible that simultaneous use with ACE inhibitors may increase the risk of renal dysfunction.

Rare cases of the development of convulsive attacks have been described when ketorolac is combined with anticonvulsants (phenytoin, carbamazepine).

Hallucinations may occur during simultaneous use of ketorolac and psychostimulant drugs (fluoxetine, thiothixene, alprazolam).

Overdose

An overdose of ketorolac with 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, and metabolic acidosis. These symptoms are cured after stopping the drug. In these cases, gastric lavage, administration of adsorbents (activated carbon) and symptomatic therapy are recommended. Ketorolac is not sufficiently eliminated by dialysis.

Dosage form

Film-coated tablets, 10 mg

Compound

One tablet contains

active substance – ketorolac tromethamine 10 mg

Excipients:

microcrystalline cellulose (type 102), pregelatinized corn starch, corn starch, colloidal anhydrous silica, magnesium stearate

shell composition: Opadry 03K51148 green (hypromethylcellulose (6срs), titanium dioxide E171, triacetin/glycerin, iron (III) oxide yellow E172, dye FD&C No. 1 (diamond blue FCF, aluminum varnish 11-13%)

Description

Round, biconvex, olive green film-coated tablets, engraved with "S" on one side and smooth on the other side, with a diameter of (8.20 ± 0.20) mm and a thickness of (3.50 ± 0.20) mm.

Pharmacotherapeutic group

Anti-inflammatory and antirheumatic drugs. Non-steroidal anti-inflammatory drugs. Derivatives of acetic acid. Ketorolac

ATX code М01АВ15

Pharmacological properties

Pharmacokinetics

Ketorolac tromethamine is a racemic mixture of the enantiometric forms [-]S- and [+]R- with the S form, which has an analgesic effect.

When taken orally, ketorolac is well absorbed from the gastrointestinal tract. The maximum concentration in blood plasma (0.7 - 1.1 mcg/ml) is achieved 40 minutes after taking a dose of 10 mg on an empty stomach. Fat-rich foods reduce Cmax and delay its achievement by 1 hour.

Ketorol® is almost completely bound to plasma proteins (> 99%) due to its small volume of distribution (<0.3 л/кг).

The time to reach equilibrium concentration after oral administration is 24 hours when administered 4 times a day. When taken orally 10 mg it is 0.39 - 0.79 mcg/ml.

Almost all of the substance circulating in the blood plasma is ketorolac (96%) or its pharmacologically inactive metabolite p-hydroxyketorolac.

Ketorolac is primarily excreted through the kidneys by excretion of ketoralac and its metabolites. Up to 92% of the administered dose of the drug is found in the urine, 40% - in the form of metabolites, 60% - in the form of unchanged substance, 6% of the administered dose - through feces. The drug passes through the placental barrier by 10%. Found in low concentrations in breast milk. It does not pass through the blood-brain barrier well. The S-enantiomer is excreted twice as fast, 2.5 hours (SD ±0.4), than the R-enantiomer - 5 hours (SD ±1.7) and clearance does not depend on the route of administration of the drug, it follows that the ratio of plasma concentrations of S/R decreases with time after each doses. Metabolites do not have significant analgesic activity.

In elderly patients (over 65 years), the half-life of the terminal phase, compared with that in young people, increases to 7 hours (from 4.3 to 8.6 hours). Total plasma clearance, compared with young people, can be reduced to an average of 0.019 l/hour/kg.

Kidney failure

When renal function is impaired, the elimination of ketorolac slows down, as evidenced by a prolongation of the half-life, which ranges between 6 and 19 hours (depending on the degree of impairment) and leads to a decrease in total plasma clearance compared to young healthy volunteers.

There is a poor relationship between creatinine clearance and total clearance of ketorolac tromethamine in the elderly and in populations with renal impairment (r=0.5).

In patients with kidney disease, the area under the curve of each enantiomer increased by approximately 100% compared to healthy volunteers. The volume of distribution doubles for the S-enantiomer and increases by 1/5 for the R-enantiomer. An increase in the volume of distribution of ketorolac tromethamine means an increase in the unbound fraction.

The rate of elimination decreases approximately in proportion to the degree of renal impairment, except in patients with severe renal impairment. In such patients, plasma clearance of ketorolac becomes slightly higher than expected for a given degree of kidney damage.

Liver failure

There is no significant difference in the calculations of half-life and area under the curve.

Pharmacodynamics

Ketorol® is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory effects. The main mechanism of action of ketorol, like other NSAIDs, is manifested in its pharmacological effect - inhibition of prostaglandin synthesis. NSAIDs are most active in the periphery.

Ketorol® does not have a sedative or anxiolytic effect. The biological activity of ketorolac tromethamine is associated with the S form. The peak analgesic effect of Ketorol occurs after 2-3 hours.

Indications for use

Short-term relief of acute pain of moderate and severe severity, as well as with the necessary analgesia with opioid analgesics in the postoperative period.

Directions for use and doses

The potential benefits and risks of Ketorol should be carefully considered before deciding to use it.

The total duration of treatment with Ketorol injections and Ketorol tablets should not exceed 5 days due to the risk of increasing the frequency and severity of adverse reactions.

For patients from 18 to 64 years old

Ketorol tablets are taken as a single dose of 20 mg (2 tablets), followed by 10 mg (1 tablet) after 4 to 6 hours 4 times a day, no more than 40 mg/day.

For patients ≥ 65 years of age with renal impairment and/or weight< 50 кг:

Ketorol tablets 10 mg once (1 tablet), followed by 10 mg every 4-6 hours four times a day, not more than 40 mg/day.

The minimum effective dose must be used.

Do not reduce the dosing interval from 4 to 6 hours.

Side effects

As the dose of the drug increases, the risk of increased frequency and severity of adverse reactions increases. Patients should be warned about serious adverse reactions of the drug, such as ulceration of the gastrointestinal mucosa, bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, liver failure.

In patients taking Ketorol or other non-steroidal anti-inflammatory drugs (NSAIDs), the most common (approximately 1% to 10% of patients) observed:

From the gastrointestinal tract: abdominal pain*, constipation/diarrhea, dyspepsia*, flatulence, peptic ulcer of the gastrointestinal tract (stomach/duodenum), gastrointestinal bleeding/perforation, heartburn, nausea*, stomatitis, vomiting.

From other systems: impaired renal function, anemia, dizziness, drowsiness, edema, increased levels of liver enzymes,

headaches*, hypertension, prolonged bleeding time, itching, skin rashes, tinnitus, sweating.

* Incidence greater than 10%

Additionally, the following adverse events were reported:

General reactions: fever, infections, sepsis

Cardiovascular system: heart failure, tachycardia (rapid heartbeat), pallor, fainting.

Skin reactions: alopecia, photosensitivity, urticaria.

Gastrointestinal tract: anorexia, dry mouth, belching, esophagitis, thirst, gastritis, glossitis, hepatitis, increased appetite, jaundice, rectal bleeding.

Blood and lymphatic system: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia.

Metabolic disorders: weight changes.

Nervous system: confusion, anxiety, asthenia, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesia, inability to concentrate, insomnia, nervousness, paresthesia, drowsiness, stupor, tremor, dizziness, malaise.

Reproductive system (women): infertility.

Respiratory system: asthma, cough, shortness of breath, pulmonary edema, runny nose.

Organs of touch: changes in taste, visual impairment, hearing loss.

Urogenital tract: cystitis, dysuria, hematuria, increased frequency of urination, interstitial, nephritis, oliguria / polyuria, proteinuria, renal failure, urinary retention.

Rarely observed adverse reactions are:

Common reactions: Quincke's edema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reactions, laryngeal edema, tongue edema, myalgia

Cardiovascular system: arrhythmia, bradycardia, chest pain, redness, hypotension, myocardial infarction, vasculitis.

Skin reactions: exfoliative dermatitis, erythema multiforme, Lyell's syndrome, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Gastrointestinal system: acute pancreatitis, liver failure, nonspecific ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease).

Blood and lymphatic system: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative bleeding.

Metabolic disorders: hyperglycemia, hyperkalemia, hyponatremia.

Nervous system: aseptic meningitis, convulsions, coma, psychosis.

Respiratory system: bronchospasm, respiratory depression, pneumonia

Organs of touch: conjunctivitis

Urogenital tract: flank pain with hematuria and/or azotemia, or without hemolytic uremic syndrome.

Contraindications

Hypersensitivity to ketorolac or other non-steroidal anti-inflammatory drugs

Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including a history)

Urticaria, rhinitis caused by taking NSAIDs (history)

Intolerance to pyrazolone drugs

Hypovolemia (regardless of the cause)

Confirmed hyperkalemia

Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, gastrointestinal bleeding, including a history

Inflammatory bowel diseases

Hypocoagulation (including hemophilia)

Hematopoietic disorders

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

Severe liver failure or active liver disease

Concomitant use with other non-steroidal anti-inflammatory drugs

Concomitant use with probenecid

Concomitant use with pentoxifylline

High risk of bleeding (including after surgery

Suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis,

Persons with hereditary fructose intolerance, deficiency of the enzyme lapp-lactase, glucose-galactose malabsorption

Pregnancy, childbirth and lactation

Children and adolescents under 18 years of age (efficacy and safety have not been established)

As a prophylactic analgesic before any major surgery.

For the treatment of postoperative pain during coronary artery bypass grafting.

Ketorolac is not indicated for the treatment of chronic pain.

Drug interactions

Ketorolac exhibits a strong degree of binding to human plasma proteins (on average 99.2%), and the binding is independent of concentration.

Ketorolac should not be used with other ASA-based drugs (acetylsalicylic acid, aspirin) or with other NSAIDs (non-steroidal anti-inflammatory drugs), including selective cyclooxygenase-2 inhibitors, as there may be an increased risk of inducing serious adverse events associated with the effect of NSAIDs (see contraindications section).

Ketorolac inhibits platelet aggregation, reduces the concentration of thromboxane and increases the duration of bleeding. In contrast to the prolonged effects of aspirin, platelet function returns to normal within 24-48 hours after discontinuation of ketorolac.

The use of ketorolac in combination with anticoagulants such as warfarin is contraindicated, since the combined use of NSAIDs and anticoagulants may increase the anticoagulant effect (see contraindications section).

Although studies do not indicate a significant degree of interaction between ketorolac and warfarin or heparin, with simultaneous use of ketorolac and therapeutic drugs affecting hemostasis, including therapeutic doses of anticoagulants (warfarin), prophylactic low doses of heparin (2500-5000 units every 12 hours ) and dextrans may be associated with an increased risk of bleeding.

The use of certain drugs that inhibit prostaglandin synthesis has been reported to inhibit the renal clearance of lithium, leading to increased plasma lithium concentrations. Cases of elevated plasma lithium concentrations have been reported during therapy with ketorolac.

Probenecid should not be used concomitantly with ketorolac due to an increase in the plasma concentration of ketorolac and its half-life.

NSAIDs should not be used for eight to twelve days after using mifepristone because NSAIDs may reduce the effects of mifepristone.

When ketorolac is used concomitantly with oxpentiphylline, there is an increased tendency to bleeding.

Ketorol should be used concomitantly with other medications with caution:

As with all NSAIDs, caution should be exercised when co-administering the drug with corticosteroids due to the increased risk of ulceration or bleeding in the gastrointestinal tract (see section Special instructions).

There is an increased risk of gastrointestinal bleeding (see Precautions) when antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.

According to the literature, some drugs that inhibit prostaglandin synthesis reduce the clearance of methotrexate, and thus possibly increase its toxicity.

Ketorolac tromethamine does not affect the binding of digoxin to blood proteins. In vitro studies have shown that at therapeutic concentrations of salicylate (300 mcg/mL), ketorolac binding was reduced from approximately 99.2% to 97.5%, representing an estimated twofold increase in unbound ketorolac plasma concentration. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen (paracetamol), phenytoin and tolbutamide do not affect the protein binding of ketorolac.

Concomitant use with diuretics may lead to a decrease in the diuretic effect and an increased risk of developing NSAID nephrotoxicity.

As with all NSAIDs, the drug should be used with caution during concurrent use of cyclosporine due to the increased risk of nephrotoxicity.

There is a risk of nephrotoxicity if NSAIDs are used together with tacrolimus.

NSAIDs may reduce the effect of diuretics and antihypertensive drugs. When ACE = ACE inhibitors and/or angiotensin II receptor antagonists are used in combination with NSAIDs, the risk of acute renal failure, which is usually reversible, may be increased in some patients with impaired renal function (eg, dehydrated patients). patients or in elderly patients).

Therefore, combining drugs should be done with caution, especially in the elderly. Patients should be dosed appropriately (as accurately as possible), with attention paid to monitoring renal function at the initiation of concomitant therapy and periodically thereafter.

NSAIDs may worsen heart failure, decrease GFR = GFR (glomerular filtration rate), and increase plasma levels of cardiac glycosides when coadministered with cardiac glycosides.

Ketorolac has been shown to reduce the need for concomitant opioid analgesia when used to relieve postoperative pain.

Animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones concomitantly may be at increased risk of developing seizures.

The use of NSAIDs with zidovudine increases the risk of hematological toxicity. There is evidence that there is an increased risk of hemarthrosis (accumulation of blood in the joint cavity) and hematomas in HIV (+) = HIV patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

When taken with antiepileptic drugs (phenytoin, carbamazepine), the frequency of attacks increases. When taken simultaneously with psychotropic drugs (fluoxetine, thiotixine, alprazolam), patients experience hallucinations.

When taking ketorol and non-depolarizing muscle relaxants simultaneously, patients experience shortness of breath.

special instructions

Since NSAIDs reduce platelet aggregation, ketorolac should be administered with caution to patients with blood coagulation disorders.

Adverse effects can be minimized by using the minimum effective dose for the shortest period of time according to control symptoms.

Gastrointestinal ulcers, bleeding and perforation

Gastrointestinal ulcers, bleeding and perforation, which may be fatal, have been reported with non-steroidal anti-inflammatory drug therapy, including ketorolac, and may occur at any time during treatment, with or without warning symptoms or previous serious gastrointestinal problems. tract in the anamnesis.

Increased rates of clinically serious gastrointestinal bleeding were observed in patients younger than 65 years of age who received a mean daily dose of greater than 90 mg of ketorolac intramuscularly compared with patients who received parenteral opioids.

In older people, there is an increased incidence of side effects due to the use of non-steroidal anti-inflammatory drugs, especially gastrointestinal bleeding and perforation, which can be fatal.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with increasing doses of nonsteroidal anti-inflammatory drugs, including intravenous ketorolac, in patients with a history of ulcers, especially complicated by bleeding or perforation, or in the elderly. The risk of clinically serious gastrointestinal bleeding is dose dependent. In these patients, treatment should be started with the lowest available dose. For such patients, as well as for patients requiring concomitant use of low-dose aspirin or other drugs that may also increase gastrointestinal risks, combination therapy with cytoprotectors (eg misoprostol or proton pump inhibitors) should be prescribed. This age-related risk group for gastrointestinal bleeding is characteristic of all non-steroidal anti-inflammatory drugs. Compared with young patients, elderly patients have an increased plasma half-life and reduced plasma clearance of ketorolac. A longer interval between doses of the drug is recommended.

Nonsteroidal anti-inflammatory drugs should be prescribed with caution to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease), as these conditions may worsen. Patients with a history of gastrointestinal toxicity, especially in the elderly, should report any unusual intra-abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment. If gastrointestinal bleeding or ulceration occurs in patients taking ketorolac intravenously, treatment should be discontinued.

Precautions are recommended in patients concomitantly receiving drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, certain serotonin reuptake inhibitors, or antiplatelet drugs such as aspirin.

The use of the drug in patients taking anticoagulants such as warfarin is contraindicated.

As with other non-steroidal anti-inflammatory drugs, the percentage of patients and the degree of gastrointestinal complications they experience may increase due to an increase in the dose and duration of treatment with ketorolac when administered intravenously. The risk of clinically serious gastrointestinal bleeding depends on the dose of the drug. This is especially true for elderly patients who take an average daily dose of more than 60 mg of ketorolac intravenously. A history of peptic ulcer disease increases the likelihood of serious gastrointestinal complications during ketorolac therapy.

Hematological effects

Patients with coagulation disorders should not take Ketorolac. Patients receiving anticoagulation therapy are at risk of bleeding when taking Ketorolac simultaneously with these drugs. The simultaneous use of ketorolac and a low prophylactic dose of heparin (2500 - 5000 units every 12 hours), as well as dextran, has not been thoroughly studied, and therefore may also cause a high likelihood of bleeding. Patients already receiving anticoagulants or receiving low-dose heparin should not use ketorolac. Patients taking other drugs that have a negative effect on hemostasis should be monitored when using Ketorolac. In controlled clinical studies, the incidence of clinically significant postoperative bleeding was less than 1%.

Ketorolac inhibits platelet aggregation and prolongs bleeding time. In patients with normal blood clotting, coagulation time increased, but within the normal range from two to eleven minutes. In contrast to the long-lasting effect of aspirin, platelet function returns to normal within 24 to 48 hours after discontinuation of ketorolac.

There are reports of postoperative wound blood loss associated with the perioperative use of Ketorolac when administered intramuscularly or intravenously. Therefore, ketorolac should not be used in patients who have undergone operations with a high risk of bleeding. Particular care should be taken in situations that do not allow deviations in hemostasis, for example, in cosmetic or day surgery, prostate resection or tonsillectomy. Signs of wound bleeding and epistaxis have been reported with Ketorolac use. Physicians should be attentive to the pharmacological similarity of ketorolac and other non-steroidal anti-inflammatory drugs that inhibit cyclooxygenase, as well as the risk of bleeding, especially in the elderly.

Skin reactions

Serious skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of nonsteroidal anti-inflammatory drugs. Patients at risk for such reactions were identified at the very beginning of therapy: such reactions in most cases occurred in the first month of treatment. Treatment with ketorolac should be discontinued at the first appearance of skin rash, mucosal damage or other signs of hypersensitivity to the drug.

Systemic lupus erythematosus and Sharp's syndrome

Patients with systemic lupus erythematosus and Sharpe's syndrome are at risk of aseptic meningitis.

Sodium/fluid retention in cardiovascular pathologies and peripheral edema

Caution should be exercised in patients with a history of hypertension and/or heart failure, as fluid retention and edema have been reported in association with nonsteroidal anti-inflammatory drug therapy.

Fluid retention, hypertension, and peripheral edema have been observed in some patients taking nonsteroidal anti-inflammatory drugs, including ketorolac, so this drug should be used with caution in patients with heart failure, hypertension, or related pathologies.

Cardiovascular and cerebrovascular effects of the drug

For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and counseling is necessary as fluid retention and edema have been reported due to nonsteroidal anti-inflammatory drugs.

Epidemiological data suggest that the use of coxibs or certain non-steroidal anti-inflammatory drugs (especially at high doses) may be associated with a small increase in the risk of arterial thrombotic complications (eg, myocardial infarction or stroke). Although ketorolac has not been shown to increase the incidence of thrombotic complications such as myocardial infarction, there is still insufficient data on which to exclude such a risk when using ketorolac.

Patients with uncontrolled hypertension, chronic heart failure, established coronary artery disease, peripheral arterial disease and/or cerebrovascular disease should take ketorolac only after careful evaluation. A similar decision should be made before starting treatment in patients with a risk factor for cardiovascular disease (eg, hypertension, hyperlipidemia, diabetes mellitus and smoking).

Cardiovascular disorders, renal and liver dysfunction

Caution should be exercised in patients with pathologies that may cause a decrease in blood volume and/or renal blood flow, in which renal prostaglandins play a supporting role in ensuring renal perfusion. In such patients, the use of non-steroidal anti-inflammatory drugs can, depending on the dose of the drug, cause a weakening of the renal prostaglandin structure and can provoke overt renal failure. Patients at greatest risk for this reaction are those who are volume depleted due to blood loss or severe dehydration, patients with impaired renal function, heart failure, impaired liver function, the elderly, and patients taking diuretics. Renal function should be monitored in such patients. Typically, cessation of nonsteroidal anti-inflammatory drug therapy is followed by recovery to pre-treatment levels. Impaired recovery of lost fluid/blood during surgery, causing hypovolemia, may cause renal dysfunction, which in turn may be exacerbated by the use of Ketorolac. Thus, dehydration should be corrected and strict specialist monitoring of serum urea and creatinine and diuresis recommended as long as the patient is normovolemic. For patients on renal dialysis, the clearance of ketorolac was reduced to approximately half the normal value and the temporary half-life was increased by approximately 3-fold.

Effects on the kidneys

As with other non-steroidal anti-inflammatory drugs, ketorolac should be used with caution in patients with impaired renal function or a history of renal disease, as it is a potent inhibitor of prostaglandin synthesis. Caution should be exercised as nephrotoxicity has been identified with the use of ketorolac and other non-steroidal anti-inflammatory drugs in patients with pathologies that cause a reduction in circulating blood volume and/or renal blood flow, in which renal prostaglandins play a supportive role in maintaining renal perfusion.

In such patients, the use of ketorolac or other nonsteroidal anti-inflammatory drugs may, depending on the dosage, provoke a reduction in renal prostaglandin formation and may cause overt renal failure or decompensated renal failure. At greater risk of this reaction are patients who have impaired renal function, hypovolemia, heart failure, liver dysfunction, as well as those taking diuretics and the elderly. Stopping ketorolac or other non-steroidal anti-inflammatory drugs usually results in recovery to pre-drug levels.

As with other drugs that inhibit prostaglandin synthesis, increases in serum urea, creatinine and potassium have been reported with ketorolac trometamol, which may occur after a single dose of the drug.

Patients with renal impairment: Since ketorolac trometamol and its metabolites are eliminated primarily by the kidneys, patients with moderate to severe renal impairment (serum creatinine greater than 160 µmol/L) are contraindicated to take Ketorolac. Patients with milder renal impairment should receive a reduced dose of ketorolac (not exceeding 60 mg/day intramuscularly or intravenously) and their renal status should be closely monitored by a physician.

Use in Patients with Hepatic Impairment: In patients with hepatic impairment due to cirrhosis, no clinically important changes in ketorolac clearance or terminal half-life were observed.

Borderline increases in one or more measures of liver function may occur. These disturbances may be variable, may remain unchanged, or may progress with continued therapy. Significant increases (3 times higher than normal) in serum alanine aminotransferase or aspartate aminotransferase were observed in control clinical trials in less than 1% of patients. If clinical signs or symptoms associated with liver disease develop, or if systemic manifestations of the disease occur, Ketorolac should be discontinued.

Anaphylactic (pseudo-anaphylactic) reactions

Anaphylactic (pseudo-anaphylactic) reactions (including, but not limited to, anaphylaxis, bronchospasm, flushing, rash, hypotension, laryngeal edema, and angioedema) may occur in patients with a history of hypersensitivity to aspirin, other nonsteroidal anti-inflammatory drugs, or intravenous ketorolac. in patients without such a history. Such phenomena may also occur in patients with a history of angioedema, bronchospastic reactivity (eg asthma) or nasal polyps. Pseudo-anaphylactic reactions, such as anaphylaxis, can be fatal. Thus, ketorolac should not be used in patients with a history of asthma, as well as in patients with severe or partial nasal polyp syndrome, angioedema and bronchospasm.

Precautions and non-reproductive effects

The use of Ketorolac, as well as other drugs that slow down the synthesis of cyclooxygenase/prostaglandin, can impair reproductive function, and therefore the drug is not recommended for women trying to become pregnant. Women who have difficulty conceiving or undergoing fertility research should discontinue the use of Ketorolac.

Fluid retention and swelling

Fluid retention, hypertension, and edema have been reported with ketorolac use and should therefore be used with caution in patients with heart failure, hypertension, or similar conditions.

Drug abuse and dependence

Ketorolac is not addictive. No symptoms associated with drug withdrawal were observed after sudden cessation of intravenous ketorolac use.

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

Since patients prescribed ketorol develop side effects from the central nervous system (dizziness, drowsiness) and from the sensory organs (hearing loss, ringing in the ears, blurred vision), it is recommended to avoid performing work that requires increased attention and quick reaction.

Overdose

Symptoms: abdominal pain, nausea, vomiting, peptic ulcer of the stomach and duodenum, erosive gastritis, impaired renal function, metabolic acidosis. Rarely, but gastrointestinal bleeding and acute renal failure are possible.