Ketanov, 30 mg/ml 1 ml 10 pcs

Ketanov – means improving cerebral circulation, vasodilator, neuroprotective, anti-aggregative, anti-hypoxic.

It selectively increases cerebral blood flow and microcirculation, improves the supply of oxygen to the brain.

It has a neuroprotective effect, increases the tolerance of cerebral hypoxia by activating aerobic utilization of glucose and metabolism of adrenaline and serotonin in the brain tissue.

It improves the transport of oxygen to the tissues.

Reduces platelet aggregation and increased blood viscosity, increases the plasticity of red blood cells.

Indications

Pain syndrome of moderate and severe intensity of various origins (including in the postoperative period, with cancer).

Pharmacological effect

Pharmacotherapeutic group: non-steroidal anti-inflammatory drug.

ATX code: M01AB15

Pharmacological properties

Pharmacodynamics

A non-steroidal anti-inflammatory drug (NSAID), has a pronounced analgesic effect, also has anti-inflammatory and moderate antipyretic effects.

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

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

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

Pharmacokinetics

After oral administration, ketorolac is well absorbed from the gastrointestinal tract – the maximum concentration (Cmax) in the blood plasma (0.7-1.1 μg/ml) is achieved 0.4 hours after taking 10 mg of ketorolac on an empty stomach in the dosage form of tablets dispersible in the oral cavity. Food rich in fat reduces the maximum concentration of the drug in the blood and delays its achievement by 1 hour. 99% of the drug is bound to plasma proteins; with hypoalbuminemia, the amount of free substance in the blood increases. Bioavailability – 80-100%. The time to reach equilibrium concentration – Css (0.39-0.79 µg/ml), with oral administration of 10 mg of ketorolac 4 times a day (dose higher than subtherapeutic), is 24 hours.

The volume of distribution is 0.15-0.33 l/kg. In patients with renal failure, the volume of distribution of the drug may increase by 2 times, and the volume of distribution of its R-enantiomer by 20%.

Penetrates into breast milk: after the mother takes 10 mg of ketorolac, Cmax in breast milk is reached after 2 hours and is 7.3 ng/ml after the first dose and 7.9 ng/ml after the second dose of the drug.

More than 50% of the administered dose is metabolized in the liver with the formation of pharmacologically inactive metabolites. The main metabolites are glucuronides, which are excreted by the kidneys, and p-hydroxyketorolac. Excreted by the kidneys (91%) and through the intestines (6%).

The half-life (T1/2) in patients with normal renal function is 2.4-9 hours after oral administration of a 10 mg dose. T1/2 lengthens in elderly patients and shortens in young ones. Impaired liver function does not affect T1/2. In patients with impaired renal function with a plasma creatinine concentration of 19-50 mg/l (168-442 µmol/l), T1/2 is 10.3-10.8 hours, with more severe renal failure – more than 13.6 hours.

When taking a dose of 10 mg orally, the total clearance is 0.025 l/h/kg; for renal failure (plasma creatinine concentration 19-50 mg/l) – 0.016 l/h/kg.

Not excreted during hemodialysis.

Special instructions

The effect on platelet aggregation ceases after 24–48 hours.

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

Ketanov® is not recommended for use as a means for premedication, maintenance of anesthesia and pain relief in obstetric practice.

Do not use simultaneously with paracetamol for more than 5 days. Patients with bleeding disorders are prescribed the drug only with constant monitoring of the platelet count, which is especially important in the postoperative period, when careful monitoring of hemostasis is required.

Since a significant proportion of patients who are prescribed Ketanov® 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 (driving a vehicle, working with machinery, etc.).

Active ingredient

Ketorolac

Composition

1 ampoule contains ketorolac tromethamine 30 mg,

sodium chloride 4.35 mg,

alcohol 10% w/v,

sterile water for injection 1 ml

Contraindications

hypersensitivity to ketorolac or other NSAIDs, “aspirin asthma”, bronchospasm, angioedema, hypovolemia (regardless of the cause), dehydration;
erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, hypocoagulation (including hemophilia);
liver and/or renal failure (plasma creatinine above 50 mg/l);
hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, concomitant use with other NSAIDs, high risk of development or recurrence of bleeding (including after surgery), impaired hematopoiesis;
pregnancy, childbirth and lactation;
children under 16 years of age (efficacy and safety have not been established);
pain relief before and during surgery (due to the high risk of bleeding);
treatment of chronic pain.

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

Side Effects

The incidence of side effects is determined as follows: often – more than 3%; less often – 1–3%; rarely – less than 1%.

From the digestive system: often (especially in elderly patients over 65 years of age with a history of erosive and ulcerative lesions of the gastrointestinal tract) – gastralgia, diarrhea; less often – stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach; rarely – nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and/or bleeding – abdominal pain, spasm or burning in the epigastric region, melena, vomiting like “coffee grounds”, nausea, heartburn, etc.), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

From the urinary system: rarely – acute renal failure, lower back pain with or without hematuria and/or azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased 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 respiratory system: rarely – bronchospasm or dyspnea, rhinitis, laryngeal edema (shortness of breath, difficulty breathing).

From the side of the central 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 cardiovascular system: less often – increased blood pressure; rarely – pulmonary edema, fainting.

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

From the hemostasis system: rarely – bleeding from a postoperative wound, nosebleeds, rectal bleeding.

From the skin: less often – 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.

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

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

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

Interaction

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

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

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

Antacids do not affect the complete absorption of the drug.

The hypoglycemic effect of insulin and oral hypoglycemic drugs increases (dose recalculation is necessary).

Co-administration with sodium valproate causes disruption 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. Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in the blood plasma.

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

The injection solution is compatible with saline, 5% dextrose solution, Ringer’s solution and Ringer-lactate, Plasmalit solution, as well as infusion solutions containing aminophylline, lidocaine hydrochloride, dopamine hydrochloride, short-acting human insulin and heparin sodium salt.

Overdose

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

Treatment: gastric lavage, administration of adsorbents (activated carbon) and symptomatic therapy (maintaining vital functions in the body). Not cleared sufficiently by dialysis.

Storage conditions

store in a dry place, protected from light, at a temperature not exceeding 25°C.

Shelf life

5 years.

Manufacturer

S.K. Therapy S.A., Romania