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

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

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

By the strength of the analgesic effect comparable to morphine, it significantly exceeds other NSAIDs.

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

Pharmacokinetics:

Bioavailability is 80-100%. Absorption at the / m introduction - complete and fast. After a / m introduction, 30 mg of drug C_mOh - 1,74-3,1 mkg / ml, 60 mg - 3,23-5,77 mkg / ml, the time to reach the maximum concentration, respectively - 15-73 min and 30-60 min. FROM_mOh after intravenous infusion 15 mg - 1.96-2.98 mcg / ml, 30 mg - 3.69-5.61 mcg / ml. Time to reach equilibrium concentration (Css) with parenteral administration - 24 hours when administered 4 times a day (higher than sub-therapeutic) and is 15 mg-0.65-1.13 μg / ml, 30 mg-1.29-2.47 μg / ml; with intravenous infusion of 15 mg - 0.79-1.39 μg / ml, 30 mg - 1.68-2.76 μg / ml. The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the volume of distribution of the drug can be increased 2-fold, and the volume of its distribution R-enantiomer by 20%.

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 (T_1/2) in patients with normal renal function averagely 5.3 hours (3.5-9.2 hours after IM / injection 30 mg). T_1/2lengthens in elderly patients and is shortened in young patients. The function of the liver does not affect T_1/2. In patients with impaired renal function with a creatinine concentration in the blood plasma of 19-50 mg / l (168-442 μmol / l) T_1/2 is 10.3-10.8 hours, with more pronounced renal failure - more than 13.6 hours.

The total clearance is 30 mg to 0.023 l / kg / h (0.019 l / kg / h in elderly patients) with IV IM, 30 mg to 0.03 l / kg / h infusion; 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 moderate and strong intensity of various genesis (including in the postoperative period, with cancer, etc.).

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 acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma); angioedema, hypovolemia (regardless of the cause that caused it), dehydration.

Erosive and ulcerative changes in the gastric mucosa or duodenum, active gastrointestinal bleeding; inflammatory bowel disease; hypocoagulation (including hemophilia).

Severe hepatic impairment or active liver disease; severe renal failure (plasma creatinine above 50 mg / L), progressive kidney disease; confirmed hyperkalemia.

Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, simultaneous administration with other NSAIDs, a high risk of developing or recurring bleeding (including after surgery), a violation of hematopoiesis.

Pregnancy, childbirth and lactation.

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

Period after aortocoronary bypass surgery;

The drug is not used for anesthesia before and during surgery due to high risk of bleeding, as well as for the treatment of chronic pain.

Carefully:

Bronchial asthma; cholecystitis; chronic heart failure; ischemic heart disease, cerebrovascular disease, hypertension; dyslipidemia / hyperlipidemia, diabetes mellitus,diseases of peripheral arteries, smoking, impaired renal function (plasma creatinine below 50 mg / l); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; old age (over 65 years); polyps of the nasal mucosa and nasopharynx.

Anamnestic data on the development of gastrointestinal lesions, the presence of infection Helicobacter pylori, long-term use of NSAIDs, frequent alcohol consumption, severe physical illness, concomitant therapy with the following drugs: anticoagulants (eg, warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, 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 the minimum possible short course.

Dosing and Administration:

Drive deep into the muscle, slowly (or intravenously) for at least 15 seconds in minimum effective doses, selected according to the intensity of the pain and the patient's reaction.If necessary, it is also possible to additionally prescribe opioid analgesics in reduced doses.

Single doses for single intramuscular or intravenous administration:

- patients up to 65 years -10-30 mg, depending on the severity of the pain syndrome,

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

Doses with multiple parenteral administration:

intramuscularly

- 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;

intravenously

- patients under 65 years of age are injected 10-30 mg, then 10-30 mg every 6 hours, with a continuous infusion with an infusomator, the initial dose is 30 mg, and then the infusion rate is 5 mg / h;

- patients over 65 years of age or with a violation of the kidney function injected 10-15 mg every 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 for both intramuscular and intravenous routes of administration.

Continuous intravenous infusion should not last more than 24 hours.

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, 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 genesis.

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

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, 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 or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, shortness of breath, chest pain, wheezing).

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

Overdose:

Symptoms: vomiting, renal dysfunction, metabolic acidosis, erosive-ulcerative gastrointestinal lesions.

Treatment: the conduct of symptomatic therapy (maintenance of vital body functions). 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.Co-administration of ketorolac and methotrexate is possible only with the use of low doses of ketorolac (control the concentration of methotrexate in the blood plasma).

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 administration 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.

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

Co-administration with sodium valproate causes disruption of platelet aggregation. Increases the concentration in the blood plasma of verapamil and nifedipine.

When appointed with other nephrotoxic drugs (incl.with preparations of gold) the risk of development of 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 injection is compatible with saline solution, 5% dextrose solution, Ringer's and Ringer's lactate solution, hydroxyethyl starch solution, and also with infusion solutions containing aminophylline, lidocaine hydrochloride, dopamine hydrochloride, short-acting human insulin and heparin sodium salt.

Special instructions:

When combined with other NSAIDs, fluid retention, cardiac decompensation, and hypertension may occur. The effect on platelet aggregation stops after 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys. If necessary, you can prescribe in combination with narcotic analgesics.

Ketofril® is not recommended as a means for premedication, supporting anesthesia and anesthesia in obstetric practice.

Do not use simultaneously with paracetamol for more than 5 days. Patients with blood clotting disorder are prescribed a drug only with a constant control of the number of platelets, it is especially important in the post-operation period, which require careful monitoring of hemostasis.

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

It is recommended to avoid performing work that requires increased attention and quick response (driving vehicles, working with mechanisms, etc.).

Form release / dosage:

Solution for intravenous and intramuscular injection 30 mg / ml.

Packaging:

1 ml of the drug in a glass ampoule (USP type 1).

5 ampoules per blister of PVC film of amber color and aluminum foil.

1 or 2 blisters with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C in a dark place.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-007067/08

Date of registration:04.09.2008

Expiration Date:Unlimited

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp08.01.2018

Illustrated instructions

Instructions

Ketofril® (Ketofreel®)