Ketanov - instructions for use, dose, side effects, contraindications

The mechanism of action is associated with a non-selective inhibition of the activity of cyclooxygenase type 1 (COX-1) and COX-2 catalyzing the formation of prostaglandins from arachidonic acid, which play an important role in the pathogenesis of pain, inflammation, fever. Ketorolac is a racemic mixture [-]S and [+]R enantiomers, while the analgesic effect is due to [-]S form.By the strength of the analgesic effect comparable to morphine, it significantly exceeds other NSAIDs.

After intramuscular injection and oral administration, the beginning of analgesic effect is noted respectively after 0.5 and 1 hour, the maximum effect is achieved in 2-3 hours.

Pharmacokinetics:

Absorption at the / m introduction - complete, fast. After a 30 mg dose, the maximum concentration (Cmax) - 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, the time to reach the maximum concentration of 15-73 min and 30-60 min, respectively. The equilibrium concentration (Css) is achieved with parenteral administration after 24 hours when applied 4 times a day and is 30 mg -1.29-2.47 μg / ml for IM.

The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the volume of distribution of the drug can be increased 2-fold, and the volume of its distribution R-enantiomer by 20%.

Penetrates into breast milk: after taking the mother 10 mg ketorolac Cmah in milk is achieved 2 hours after the first dose and is 7.3 ng / ml, 2 hours after the second dose of ketorolac (using the drug 4 times a day) - is 7.9 ng / l.

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-hydroxycetorolac. It is excreted 91% by the kidneys, 6% by the intestine.

The half-life (T₁/₂) in patients with normal renal function is 3.5-9.2 hours after a / m administration of 30 mg. T₁/₂lengthens in elderly patients and is shortened in young patients. The function of the liver does not affect T₁/₂. In patients with impaired renal function with a creatinine concentration in the blood plasma of 19-50 mg / l (168-442 μmol / l) T₁/₂ is 10.3-10.8 hours, with more pronounced renal failure - more than 13.6 hours. The total clearance is 30 mg / 0.033 l / kg / h (0.019 l / kg / h in elderly patients with IM) , in patients with renal insufficiency with a creatinine concentration in the blood plasma of 19-50 mg / l with a / m injection of 30 mg - 0.015 l / kg / h.

It is not excreted during hemodialysis.

Indications:

Pain syndrome of severe and moderate severity: trauma, toothache, pain in the postpartum and postoperative period, oncological diseases, myalgia, arthralgia, neuralgia, sciatica, dislocations, distension, rheumatic diseaseandI.

It is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

Hypersensitivity to the active substance or ancillary components.

Anamnestic data on an attack of bronchial obstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete combination of bronchial asthma, polyposis of nose and intolerance to acetylsalicylic acid and other NSAIDs).

Erosive-ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, bleeding or high risk of their development, hypocoagulation (including hemophilia), inflammatory bowel disease (Crohn's disease, ulcerative colitis).

Severe hepatic impairment or active liver disease.

Severe renal insufficiency (creatinine clearance less than 30 ml / min), progressive kidney disease.

Confirmed hyperkalemia.

Decompensated heart failure.

Contraindicated in the period after aortocoronary bypass surgery.

The drug is not used for anesthesia before and during surgical operations because of the high risk of bleeding.

III trimester of pregnancy, childbirth, lactation period (should be abandoned from feeding for the period of drug use).

Children under 16 years of age (efficacy and safety not established).

Carefully:

Bronchial asthma, the presence of factors that increase toxicity in relation to the gastrointestinal tract, alcoholism and cholecystitis; chronic heart failure, edematous syndrome, hypertension; renal dysfunction, cholestasis, sepsis, simultaneous intake with other NSAIDs, advanced age (over 65 years), pregnancy (I-II trimester). Ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, creatinine clearance 30-60 ml / min.

Anamnestic data on the development of gastrointestinal lesions, the presence of infection Helicobacter pylori, long-term use of NSAIDs, severe somatic diseases, concomitant therapy with the following drugs:

- anticoagulants (for example, warfarin);

- antiaggregants (for example, acetylsalicylic acid, clopidogrel);

- oral glucocorticosteroids (for example, prednisolone);

- selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, paroxetine, sertraline).

To reduce the risk of developing adverse events on the part of the gastrointestinal tract, a minimum effective dose should be used with a minimum short course.

Pregnancy and lactation:

It penetrates into breast milk in small amounts.

Use in the III trimester of pregnancy and the period of breastfeeding is contraindicated (should be abandoned from feeding for the period of application of the drug).

Dosing and Administration:

Ketanov® is administered intramuscularly, in minimally effective doses, selected according to the intensity of the pain and the response of the patient.

If necessary, it is also possible to additionally use opioid analgesics in reduced doses.

Single doses for single intramuscular injection:

- patients under 65 years of age -10-30 mg, depending on the severity of the pain syndrome;

- patients over 65 years of age or with renal dysfunction 10-15 mg.

Doses with multiple intramuscular injection:

- patients under 65 years of age are given 10-30 mg, then 10-30 mg every 4-6 hours;

- patients older than 65 years or with impaired renal function - 10-15 mg every 4-6 hours.

The maximum daily dose for patients under 65 years of age should not exceed 90 mg, and for patients older than 65 years or with impaired renal function, 60 mg with an intramuscular route of administration.

For parenteral administration, the duration of treatment should not exceed 5 days.

When switching from parenteral administration of the drug to its oral administration, the total daily dose of both dosage forms on the day of transfer should not exceed 90 mg for patients under 65 years of age 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.

Side effects:

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

From the digestive system: often (especially in elderly patients over 65 years of age, having a history of erosive and ulcerative lesions of the gastrointestinal tract) - gastralgia, diarrhea; less often - stomatitis, flatulence, constipation, vomiting, sensation of stomach overflow; 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, low back pain with or without hematuria and / or azotemia, haemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased urine volume,nephritis, edema of renal genesis.

From the sense organs: rarely - hearing loss, ringing in the ears, visual impairment (including blurred vision).

From the respiratory system: rarely - bronchospasm, 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, neck and / or neck stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

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

On the part of the organs of hematopoiesis: rarely - anemia, eosinophilia, leukopenia.

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

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

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

Allergic reactions: rarely - Anaphylaxis or anaphylactoid reactions (skin color change of the face, skin rash, hives, skin itch, tachypnea, edema of the eyelids, periorbital edema, shortness of breath, shortness of breath, heaviness in the chest, wheezing).

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

Overdose:

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

Treatment: gastric lavage, administration of adsorbents (Activated carbon) and the conduct of symptomatic therapy (maintenance of vital functions in the body). It is not excreted sufficiently by dialysis.

Interaction:

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

Co-administration with paracetamol increases nephrotoxicity, with methotrexate-hepato- and nephrotoxicity.

Joint application of ketorolac and methotrexate is possible only with the use of low doses of the latter (control the concentration of methotrexate in the blood plasma).

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

Probenecid reduces plasma clearance and the volume of ketorolac distribution, increases its concentration in blood plasma and increases its half-life.

Against the background of the use of ketorolac, a decrease in the clearance of methotrexate and lithium and the increased toxicity of these substances are possible.

Simultaneous use with indirect anticoagulants, heparin, thrombolytic agents, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

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

When combined with opioid analgesics, the doses of the latter can be significantly reduced.

Antacids do not affect the full absorption of the drug.

Increased hypoglycemic effect of insulin and oral hypoglycemic drugs (necessaryrecalculation of the dose).

Joint application with valproic acid causes disruption of platelet aggregation.

Increases the concentration in the blood plasma of verapamil and nifedipine.

When used with other nephrotoxic drugs (including with 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.

Solution for injection should not be mixed in one syringe with morphine sulfate, promethazine and hydroxyzine due to precipitation.

Pharmaceutically incompatible with a solution of tramadol, lithium preparations.

The solution for injections is compatible with saline solution, 5% dextrose solution, Ringer's and Ringer's lactate solution, Plasma-Lit 148 solution, and infusion solutions containing aminophylline, lidocaine hydrochloride, dopamine hydrochloride, short-acting insulin and heparin sodium salt.

Special instructions:

Hypovolemia increases the risk of adverse reactions from the kidneys.

If necessary, can be used in combination with opioid analgesics.

It is not recommended to be used as a means for premedication, maintenance of anesthesia.

In patients with blood clotting disorder, the drug is used only with a constant control of the number of platelets, especially important in the postoperative period, which requires careful control of hemostasis.

The risk of developing drug complications increases with prolonged treatment (in patients with chronic pain) and an increase in the dose of the drug more than 40 mg / day.

To reduce the risk of developing NSAIDs-gastropathy antacids are used, misoprostol, omeprazole.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Solution for intramuscular injection 30 mg / ml.

Packaging:

1 ml in an ampoule of transparent, colorless glass, type I, marked with a blue stripe and a red dot.

5 or 10 ampoules in a plastic contour pack.

1 pack together with instructions for use in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012170 / 02

Date of registration:04.05.2010

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

S.C. TERAPIA, S.A. Romania

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp04.05.2010

Illustrated instructions

Instructions

Ketanov® (Ketanov®)