Ketonof-LF

General characteristics. Structure:

Active ingredient: 10 mg of a ketorolak of a trometamin (in terms of 100% dry matter).

Excipients: cellulose microcrystallic, starch corn, aerosil, magnesium stearate, lactose, опадрай II (talc, polyethyleneglycol, titanium dioxide, polyvinyl alcohol).

It is considered choice drug for stopping of a megalgia, especially at an injury, its short-term use is possible also at an exacerbation of chronic pain - at patients with degenerative and dystrophic diseases

Pharmacological properties:

Pharmacodynamics. Has the expressed analgeziruyushchy effect, possesses also antiinflammatory and moderate febrifugal action.

Does not influence opioid receptors, breath does not oppress, does not cause medicinal dependence, does not possess sedative and anxiolytic action. On force of analgeziruyushchy effect it is comparable to morphine, considerably surpasses other NPVS.

After intake the beginning of analgeziruyushchy action is noted in 1 h, the maximum effect is reached in 1-2 h.

Pharmacokinetics. After intake кеторолак it is well soaked up from digestive tract. The maximum concentration in a blood plasma is reached in 40 min. after administration of drug on an empty stomach in a dose of 10 mg. Food rich with fats reduces Cmax of a ketorolak in blood and time of achievement of Cmax for 1 h detains.

Gets into breast milk.

The elimination half-life at patients with normal function of kidneys averages 5,3 h. The elimination half-life is extended at elderly patients and shortened at young patients. Function of a liver does not exert impact on an elimination half-life. At patients with a renal failure at concentration of creatinine in a blood plasma of 19-50 mg/l (168-442 µmol/l) the elimination half-life makes 10,3-10,8 h, at more expressed renal failure - more than 13,6 h.

Indications to use:

Stopping of a pain syndrome of average and strong intensity of various genesis: acute pain syndromes of a traumatic origin (dislocations, fractures, gaps and sprains, bruises); postoperative pains after band, abdominal, gynecologic, orthopedic, urological and other operations; for short-term reception for removal of an acute pain syndrome at an osteoarthrosis, osteochondrosis, neuralgia, oncological diseases; a dentagra, pain after dental interventions, at a pericoronitis, a pulpitis.

Route of administration and doses:

Accept once in a dose 10 mg or repeatedly depending on weight and expressiveness of a pain syndrome on 10 mg to 4 times/days. The maximum daily dose – 40 mg. Course duration – no more than 7 days.

Upon transition from parenteral administration of drug to intake the total daily dose of both dosage forms in day of transfer for patients aged up to 65 years should not exceed 90 mg, for patients 65 years or with renal failures – 60 mg are aged more senior. At the same time the drug dose for intake in day of transition should not exceed 30 mg.

Features of use:

It is not recommended to apply as means to premedication, the supporting anesthesia and anesthesia in obstetric practice because of high risk of development of bleedings.

It is not shown for treatment of chronic pain.

With care it is necessary to appoint drug at bronchial asthma, cholecystitis, chronic heart failure, arterial hypertension, renal failures, a cholestasia, active hepatitis, sepsis, a system lupus erythematosus, polyps of a mucous membrane of a nose and nasopharynx, to patients 65 years are aged more senior.

Influence of drug on aggregation of thrombocytes remains during 24-48 h.
The hypovolemia increases risk of development of side reactions from kidneys.

It is not recommended to use кеторолак along with paracetamol more than 5 days.

As at a considerable part of patients at use of a ketorolak side effects from TsNS develop, it is recommended to avoid performance of work, the requiring special attention and bystry reaction (driving of motor transport, work with mechanisms).

Hypersensitivity to other NPVP; bronchial asthma; existence of the factors increasing toxicity of drug for a GIT; alcoholism, tobacco smoking and cholecystitis; the postoperative period, chronic heart failure, an edematous syndrome, arterial hypertension, a renal failure (creatinine of plasma is lower than 50 mg/l), a cholestasia, active hepatitis, a system lupus erythematosus, a concomitant use with other NPVP, at patients of senile age (65 years are more senior) arise more often the side reactions characteristic of NPVP therefore this category of patients is recommended to appoint the doses which are at the lower bound of therapeutic range.

Influence on fertility. Use of a ketorolak can weaken fertility and is not recommended for use by women who plan to become pregnant or there take place inspections concerning fertility, it is necessary to consider a question of cancellation of a ketorolak.

Disturbances from kidneys and a liver. With care appoint drug to patients with disturbances of kidneys, a liver. To patients with insignificant renal failures appoint smaller doses of a ketorolak, and also it is necessary to control a condition of kidneys of patients carefully. As well as for other drugs which inhibit synthesis of prostaglandins, it was reported about increase cases in serum cuts of urea, creatinine and potassium during reception of a ketorolak that can occur after reception of one dose.

With care appoint drug to patients with states which lead to reduction of volume of blood and/or a renal blood flow. At these patients it is necessary to control functions of kidneys. Reduction of volume should be adjusted and to carefully control the content in blood serum of urea and creatinine, and also volume of urine which is removed until at the patient there comes the normovolemia. At patients who are on renal dialysis the clearance of a ketorolak was reduced approximately twice in comparison with normal speed, and time of final semi-removal was tripled approximately. Patients with an abnormal liver function as a result of cirrhosis had no clinically significant changes in clearance of a ketorolak or a final elimination half-life. Boundary increases in values according to one or bigger number of functional tests of a liver can be observed. These aberrations can be temporary, can be left without change or can progress at treatment continuation. If clinical signs and symptoms indicate development of a disease of a liver or if system manifestations are observed, drug should be cancelled.

Cardiovascular and cerebrovascular effects. At use of a ketorolak monitoring of the ABP is necessary for the patients having arterial hypertension and heart failure. It is caused by a delay of liquid and development of hypostases at use of NPVS.

Clinical trials and epidemiological data demonstrate that use of koksib and some other NPVS (especially in high doses) can increase risk of arterial thrombosis (for example, a myocardial infarction or a stroke). In spite of the fact that кеторолак does not lead to increase in frequency of trombotichesky events, such as a myocardial infarction, there is no enough data completely to exclude such risk.

At patients with uncontrollable arterial hypertension and heart failure, an ischemic heart disease, diseases of peripheral arteries and/or cerebrovascular diseases it is necessary to appoint кеторолак after careful assessment of a ratio risk/advantage. Similar approach prior to treatment needs to be applied to patients with risk factors of cardiovascular diseases (for example, arterial hypertension, a lipidemia, a diabetes mellitus, smoking).

Disturbances from a GIT: gastrointestinal ulcers, bleedings and perforation which can lead to a lethal outcome develop at reception of all NPVS including a ketorolaka, at any time during treatment, it is frequent without preliminary symptoms or without existence in the anamnesis of serious complications from a GIT. Elderly people, persons with existence in the anamnesis of gastrointestinal bleeding, at the weakened patients or patients receiving high doses of a ketorolak, risk of development of side reactions from a GIT higher, and can have fatal effects of these side reactions. These patients have to begin treatment with purpose of the lowest dose; the recommended therapy with mizoprostoly or inhibitors of a proton pomp can be it. The combination therapy is appointed also to the patients receiving at the same time low doses of aspirin or its analogs. For elderly people it is recommended to increase an interval between receptions of a ketorolak.

NPVS should appoint with care to patients with inflammatory diseases of intestines (nonspecific ulcer colitis, a disease Krone). Patients with development of side reactions from a GIT in the anamnesis, especially elderly people, have to report about any unusual abdominal symptoms, especially at the initial stages of treatment. At identification of side reactions from a GIT, it is necessary to cancel кеторолак. With care appoint кеторолак to patients, receiving the accompanying treatment by oral corticosteroids, selective serotonin reuptake inhibitors or antithrombocytic means.

System lupus erythematosus and the mixed diseases of connecting fabric. At patients with a system lupus erythematosus and the different mixed diseases of connecting fabric the risk of development of aseptic meningitis increases.

Dermatological effects. Ketorolak it is necessary to cancel in cases of the first symptoms of rash on skin, damages of mucous membranes or any other signs of hypersensitivity.

Hematologic effects. Patients with disturbances of a blood coagulation should not appoint кеторолак. The patients receiving anticoagulating therapy can have the increased risk of bleeding if at the same time apply кеторолак. In controlled clinical trials the frequency of cases of considerable postoperative bleeding made less than 1%. Ketorolak inhibits aggregation of thrombocytes and prolongs a bleeding time. At patients with a normal bleeding time duration of bleeding increased, but did not go beyond the normal range of values of 2-11 minutes. Unlike long influence as a result of use of acetylsalicylic acid, function of thrombocytes is returned to normal within 24-48 hours after cancellation of a ketorolak.

Drug is not means for anesthesia and has no sedative or anxiolytic properties, therefore, it is not recommended as means of premedication before operation for anesthesia maintenance.

With care apply at patients with rare hereditary diseases: inborn galactosemia, deficit of lactase, glucose/galactose sprue.

Side effects:

From the alimentary system: often meet – a gastralgia, diarrhea; less often – stomatitis, a meteorism, a lock, vomiting, feeling of overflow of a stomach; seldom – a loss of appetite, nausea, GIT erosive cankers (including with perforation and/or bleeding – an abdominal pain, a spasm or burning in epigastric area, blood in Calais or a melena, vomiting with blood or as "a coffee thick", nausea, heartburn, etc.), cholestatic jaundice, hepatitis, a hepatomegalia, acute pancreatitis.

From an urinary system: acute renal failure, back pain, hamaturia, azotemia, gemolitiko-uraemic syndrome (hemolitic anemia, renal failure, thrombocytopenia, purpura), increase of an urination, increase or decrease in volume of urine, nephrite, hypostases of renal genesis.

From sense bodys: decrease in hearing, a ring in ears, a vision disorder (including an illegibility of visual perception).

From respiratory organs, a thorax and mediastinum: bronchospasm or диспноэ, rhinitis, fluid lungs, throat hypostasis (asthma, breath difficulty), nasal bleeding.

From TsNS: headache, dizziness, drowsiness, aseptic meningitis (fever, severe headache, spasms, stiffness of muscles of a neck and/or back), hyperactivity (change of mood, concern), hallucinations, depression, psychosis, unconscious states.

From vessels: arterial hypertension, hypotension, hematomas, reddening, pallor, postoperative bleedings.

From heart: heartbeat, bradycardia, heart failure.

From bodies of a hemopoiesis: seldom – anemia, an eosinophilia, a leukopenia.

From system of a hemostasis: bleeding from a postoperative wound, rectal bleeding.

From integuments: skin rash (including makulopapullezny rash), a purpura, exfoliative dermatitis (fever with a fever or without, a hyperemia, consolidation or a peeling of skin, swelling and/or morbidity of palatine tonsils), a small tortoiseshell, a malignant exudative erythema (Stephen-Johnson's syndrome) and a toxic epidermal necrolysis (Lyell's disease) – it is very rare.

From a musculoskeletal system and connecting fabric: mialgiya, functional frustration.

From a metabolism and food: anorexia, hyperpotassemia, hyponatremia.

Allergic reactions: seldom – an anaphylaxis or anaphylactoid reactions (face skin discoloration, skin rash, a small tortoiseshell, an itch of skin, a tachypnea or диспноэ, swell a century, periorbital hypostasis, an asthma, the complicated breath, weight in a thorax, goose breathing).

Others: hypostases (persons, shins, anklebones, fingers, a foot, increase in body weight), the increased sweating, a paraglossa, fever.

Interaction with other medicines:

Simultaneous use with acetylsalicylic acid or other NPVS, calcium drugs, glucocorticosteroids, ethanol, corticotropin can lead to formation of ulcers of a GIT and development of gastrointestinal bleedings.

Joint appointment with paracetamol increases risk of development of nephrotoxicity, with a methotrexate – gepato-and nephrotoxicity.

Probenetsid reduces plasma clearance and volume of distribution of a ketorolak, increases its concentration in a blood plasma and increases an elimination half-life.

Co-administration with indirect anticoagulants, heparin, trombolitika, antiagregant, tsefoperazony, tsefotetany and pentoksifilliny increases risk of development of bleeding.

Reduces effect of anti-hypertensive and diuretic drugs.

At a combination with opioid analgetics of a dose of the last can be reduced.

At simultaneous use hypoglycemic effect of insulin and peroral hypoglycemic drugs increases.

Increases concentration of verapamil and nifedipine in a blood plasma.

Appointment from sodium as Valproatum causes disturbance of aggregation of thrombocytes.
At appointment with other nefrotoksichny medicines (including with gold drugs) the risk of development of nephrotoxicity increases.

The medicines blocking canalicular secretion reduce clearance of a ketorolak and increase its concentration in a blood plasma.

Contraindications:

Hypersensitivity to a ketorolak or other NPVS, a "aspirinovy" triad, a bronchospasm, a Quincke's disease, a hypovolemia, dehydration, GIT erosive cankers in an aggravation phase, round ulcers, hypocoagulation (including hemophilia), a liver and / or renal failure (creatinine of plasma is higher than 50 mg/l), a hemorrhagic stroke, hemorrhagic diathesis, a concomitant use with other NPVS, high risk of development of bleeding, hemopoiesis disturbance, pregnancy, childbirth, the lactation period, age up to 16 years.

Overdose:

Symptoms: the overdose of a ketorolak at single use is shown by abdominal pains, nausea vomiting, a hyperventilation, symptoms of stomach ulcer and/or erosive gastritis, renal failures which pass after medicine cancellation.

Gastrointestinal hemopoiesis, arterial hypertension, acute renal failure, respiratory depression and coma can seldom develop. The overdose can be shown by a headache, pain in epigastriums, a disorientation, excitement, drowsiness, dizziness, a sonitus and a faint. Seldom diarrhea, an attack of spasms develops. Anaphylactoid reactions were registered at use of a ketorolak in therapeutic doses and at overdose.

The symptomatic treatment directed to maintenance of the vital functions. There is no specific antidote. Dialysis significantly does not lower the level of a ketorolak in blood. Within the first hour after reception of potentially toxic dose of a ketorolak the gastric lavage and purpose of absorbent carbon is necessary. It is necessary to provide a sufficient diuresis, to constantly control functions of a liver and kidneys. It is necessary to watch a condition of patients, at least, within 4 hours after reception of potentially toxic dose. Frequent or long spasms need to be stopped intravenous administration of diazepam. Other actions are appointed depending on a condition of the patient.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the places protected from children. Period of storage 2 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in blister strip packagings. On 2, 3 or 5 blister strip packagings in a cardboard pack together with the application instruction.