Ketorolak

General characteristics. Structure:

Active ingredient: 1 ml of a ketorolak трометамол (a ketorolaka трометамин) - 30 mg;

Excipients: sodium chloride - 4.35 mg, dinatrium эдетат (salt disodium ethylene diamine-N, N,N, acid N-tetrauksusnoy 2-water (Trilonum of B)) - 500 mkg, water for and - to 1 ml.

Description: Solution for in/in and introductions in oil transparent, yellowish color.

Pharmacological properties:

Ketorolak - NPVP, has the expressed analgeziruyushchy (anesthetic) effect, possesses also antiinflammatory and moderate febrifugal action.

The mechanism of action is connected with non-selective oppression of activity of TsOG-1 and TsOG-2 enzymes, mainly in peripheral fabrics, braking of biosynthesis of prostanglandin – modulators of painful sensitivity, an inflammation and thermal control is a consequence of what. Ketorolak represents racemic mix R (+) and S (-) - enantiomer, at the same time analgeziruyushchy (anesthetic) action is caused by S (-) - an enantiomer.

Ketorolak 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 (anesthetic) effect it is comparable to morphine, considerably surpasses other NPVP.

After intake the beginning of analgeziruyushchy (anesthetic) action is noted respectively in 1 h, the maximum effect is reached in 2-3 h.

After introduction in oil the beginning of analgeziruyushchy (anesthetic) action is noted in 0.5 h, the maximum effect is reached in 1-2 h.

 

Pharmacokinetics. Absorption

At intake кеторолак it is well soaked up from a GIT. Bioavailability makes 80-100%. Cmax in a blood plasma makes 0.7-1.1 mkg/ml and 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 drug in blood and achievement on 1 h detains her.

At introduction in oil absorption full and bystry. After administration of drug in oil in a dose of 30 mg of Cmax in a blood plasma makes 1.74-3.1 mkg/ml, in a dose of 60 mg - 3.23-5.77 mkg/ml. Tmax respectively makes 15-73 min. and 30-60 min.

Later in/in infusion of drug in a dose of 15 mg of Cmax makes 1.96-2.98 mkg/ml, in a dose of 30 mg - 3.69-5.61 mkg/ml.

Distribution

Linkng with proteins of a blood plasma - 99%. At a hypoalbuminemia the amount of free substance in blood increases.

Vd makes 0.15-0.33 l/kg.

Time of achievement of Css at intake - 24 h at use 4 (above subtherapeutic). Css after intake in a dose of 10 mg makes 0.39-0.79 mkg/ml.

Css at parenteral administration is reached in 24 h at use 4 (above subtherapeutic) and at introduction in oil in a dose of 15 mg makes 0.65-1.13 mkg/ml, at introduction in oil in a dose of 30 mg - 1.29-2.47 mkg/ml; at in/in infusion in a dose of 15 mg - 0.79-1.39 mkg/ml, at in/in infusion in a dose of 30 mg - 1.68-2.76 mkg/ml.

Badly passes through GEB, gets through a placenta (10%).

It is allocated with breast milk: at intake by mother of 10 mg of a ketorolak of Cmax in breast milk it is reached in 2 h after reception of the first dose and makes 7.3 ng/ml, in 2 h after use of the second dose of a ketorolak (at drug 4 use) Cmax makes 7.9 ng/ml.

At parenteral administration it is allocated with breast milk in small amounts.

Metabolism

More than 50% of the entered dose are metabolized in a liver with formation pharmacological of inactive metabolites. The main metabolites are glucuronides and r-gidroksiketorolak.

Removal

It is removed with urine - 91% (40% in the form of metabolites), with a stake - 6%. It is not removed by a hemodialysis.

After intake of T1/2 at patients with normal function of kidneys makes 2.4-9 h (on average 5.3 h).

After introduction of 30 mg in oil of T1/2 - 3.5-9.2 h, later in/in introductions of 30 mg of T1/2 - 4-7.9 h.

The general clearance at introduction in oil 30 mg make 0.023 l/kg/h, at in/in infusion of 30 mg - 0.03 l/kg/h.

Pharmacokinetics in special clinical cases

At patients with a renal failure of Vd of drug Vd its R-enantiomera - can increase by 20% twice, and. At concentration of creatinine in a blood plasma of 19-50 mg/l at introduction of 30 mg of drug in oil the general clearance makes 0.015 l/kg/h.

At patients with a renal failure at concentration of creatinine in a blood plasma of 19-50 mg/l (168-442 µmol/l) T1/2 makes 10.3-10.8 h, at more expressed renal failure - more than 13.6 h.

Function of a liver does not exert impact on T1/2.

At patients of advanced age the general clearance at introduction in oil in a dose of 30 mg makes 0.019 l/kg/h of T1/2 is extended at patients of advanced age and shortened at young people.

Indications to use:

— pain syndrome of strong and moderate expressiveness: injuries, a dentagra, pains in the postoperative period, oncological diseases, a mialgiya, an arthralgia, neuralgia, radiculitis, dislocations, stretchings, rheumatic diseases.

It is intended for symptomatic therapy, reduction of pain and an inflammation at the time of use, does not influence progressing of a disease.

Route of administration and doses:

For intake

Ketorolak it is necessary to apply inside once or repeatedly depending on weight of a pain syndrome.

The single dose - 10 mg, at repeated reception is recommended to accept on 10 mg to 4 times/days depending on expressiveness of pain. The maximum daily dose should not exceed 40 mg.

At intake duration of a course should not exceed 5 days.

Features of use:

At combined use with other NPVP the liquid delay, a decompensation of cordial activity, arterial hypertension can be observed.

For decrease in risk of development of NPVP-gastropathies antacids, мизопростол, омепразол are appointed.

Influence on aggregation of thrombocytes remains during 24-48 h.

The hypovolemia increases risk of development of side reactions from kidneys.

If necessary it is possible to appoint in a combination with opioid analgetics.

Not to use along with paracetamol more than 5 days.

The patient with disturbance of a blood coagulation appoint drug only at constant control of number of thrombocytes, especially in the postoperative period, demanding careful control of a hemostasis.

Influence on ability to driving of motor transport and to control of mechanisms

As at a considerable part of patients at Ketorolak's appointment side effects from the central nervous system (drowsiness, dizziness, a headache) develop, it is recommended to avoid performance of work, the requiring special attention and bystry reaction (driving of motor transport, work with mechanisms).

Side effects:

Often-> 3%; less often - 1-3%; seldom - <1%.

From the alimentary system: often (especially at patients of advanced age 65 years having GIT erosive cankers in the anamnesis are more senior) - 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 - abdominal pain, a spasm or burning in epigastric area, a melena, vomiting with blood or as "a coffee thick", nausea, heartburn), cholestatic jaundice, hepatitis, a hepatomegalia, acute pancreatitis.

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

From TsNS and peripheral nervous system: often - a headache, dizziness, drowsiness; seldom - aseptic meningitis (including fever, a severe headache, spasms, muscle tension of a neck and/or back), a hyperactivity (including change of mood, concern), hallucinations, a depression, psychosis.

From cardiovascular system: less often - increase in the ABP; seldom - a syncope.

From respiratory system: seldom - a bronchospasm, диспноэ, rhinitis, a fluid lungs, throat hypostasis (including an asthma, breath difficulty).

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

From system of a hemopoiesis: seldom - anemia, an eosinophilia, a leukopenia.

From coagulant system of blood: seldom - bleeding from a postoperative wound, nasal bleeding, rectal bleeding.

From integuments: less often - skin rash (including makulopapulezny), a purpura; seldom - exfoliative dermatitis (including fever with/without fever, reddening, consolidation or a peeling of skin, swelling and/or morbidity of palatine tonsils), a small tortoiseshell, Stephens-Johnson's syndrome, a Lyell's disease.

Allergic reactions: seldom - an anaphylaxis or anaphylactoid reactions (including 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).

Local reactions: less often - burning or pain in an injection site.

Others: often - hypostases (including persons, shins, anklebones, fingers, a foot), increase in body weight; less often - the increased perspiration; seldom - a paraglossa, fever.

Interaction with other medicines:

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

Joint appointment with paracetamol increases nephrotoxicity, with a methotrexate - gepato-and nephrotoxicity.

Joint purpose of a ketorolak and methotrexate is possible (to control only when using low doses of the last concentration of a methotrexate in a blood plasma).

Against the background of use of a ketorolak reduction of clearance of a methotrexate and lithium and strengthening of toxicity of these substances is possible.

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

Reduces effect of hypotensive and diuretic drugs (synthesis of prostaglandins in kidneys goes down).

At simultaneous use with opioid analgetics of a dose of the last can be significantly reduced since their action amplifies.

At simultaneous use strengthens hypoglycemic effect of insulin and peroral hypoglycemic drugs (recalculation of a dose is necessary).

Joint appointment with valproic acid causes disturbance of aggregation of thrombocytes.

Increases concentration in a blood plasma of verapamil and nifedipine.

At appointment with other nefrotoksichny medicines (including with gold drugs) the risk of development of nephrotoxicity increases.

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

Miyelotoksichny medicines strengthen manifestations of a gematotoksichnost of drug.

Solution for injections should not be mixed in one syringe from morphine sulfate, promethazine and Hydroxyzinum because of loss of a deposit.

Pharmaceutical it is incompatible with solution of a tramadol, lithium drugs.

Solution for injections is compatible from 0.9% solution of sodium of chloride, 5% solution of a dextrose (glucose), Ringer's solution and Ringera-laktata, Plazmalit solution, and also to the infusion solutions containing Aminophyllinum, lidocaine a hydrochloride, a dopamine a hydrochloride, insulin of the person of short action and heparin sodium salt.

Contraindications:

— a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid or other NPVP (including in the anamnesis);

— the urticaria, rhinitis caused by reception of NPVP (in the anamnesis);

— intolerance of medicines of a pyrazolon row;

— dehydration, a hypovolemia (irrespective of the reason which caused it);

— bleedings or high risk of their development;

— a state after performing aortocoronary shunting;

— the confirmed hyperpotassemia;

— inflammatory diseases of intestines;

— GIT erosive cankers in aggravation stages, round ulcers;

— hypocoagulation (including hemophilia);

— heavy renal failure (KK less than 30 ml/min.);

— heavy liver failure or active disease of a liver;

— the hemorrhagic stroke (confirmed or suspected);

— hemorrhagic diathesis;

— hemopoiesis disturbance;

— pregnancy;

— childbirth;

— period of a lactation (breastfeeding);

— children's age up to 16 years (efficiency and safety are not established);

— hypersensitivity to a ketorolak and other NPVP.

Drug is not used as means for premedication, the supporting anesthesia, by anesthesia before and during surgeries (including in obstetric practice) because of high risk of bleeding.

Drug is not shown for treatment of chronic pains.

With care: bronchial asthma; cholecystitis; chronic heart failure; arterial hypertension; a renal failure (creatinine of plasma is lower than 50 mg/l); cholestasia; active hepatitis; sepsis; system lupus erythematosus; advanced age (65 years are more senior); polyps of a mucous membrane of a nose and nasopharynx, concomitant use with other NPVP; existence of the factors increasing toxicity of a GIT: alcoholism, tobacco smoking; the postoperative period, an edematous syndrome, an ischemic heart disease, cerebrovascular diseases, дислипидемия / a lipidemia, a diabetes mellitus, diseases of peripheral arteries, clearance of creatinine less than 60 ml/min., GIT cankers in the anamnesis, existence of an infection of Helicobacter pylori, long use NPVP, heavy somatopathies, a concomitant use of peroral GKS (including Prednisolonum), anticoagulants (including warfarin), antiagregant (including klopidogret), selective serotonin reuptake inhibitors (including a tsitaloprama, fluoxetine, a paroksetin, sertraline).

 

Use of drug KETOROLAK at pregnancy and feeding by a breast

Use of drug at pregnancy, in the course of childbirth and during breastfeeding is contraindicated.

 

Use at abnormal liver functions

The drug priyemeneniye at a liver failure is contraindicated.

With care it is necessary to use drug at cholecystitis, a cholestasia, active hepatitis.

 

Use at renal failures

The drug priyemeneniye at a renal failure (plasma creatinine> of 50 mg/l is contraindicated).

With care it is necessary to use drug at a renal failure (plasma creatinine <50 mg/l).

 

Use for elderly patients

With care it is necessary to use drug at patients of advanced age (65 years are more senior).

 

Use for children

Contraindication: children's and teenage age up to 16 years (efficiency and safety are not established).

Overdose:

Symptoms: abdominal pains, nausea, vomiting, GIT erosive cankers, renal failure, metabolic acidosis.

Treatment: in case of administration of drug inside - a gastric lavage, administration of adsorbents (absorbent carbon); at intake and parenteral administration - performing symptomatic therapy (maintenance of the vital functions of an organism). It is not removed sufficiently by means of dialysis.

Storage conditions:

List B. Solution for in/in and introductions in oil should be stored in the unavailable to children, protected from light place at a temperature from 15 °C to 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

1 ml - ampoules of dark glass (5) - planimetric strip packagings (1) - packs cardboard.
1 ml - ampoules of dark glass (5) - planimetric strip packagings (2) - packs cardboard.
1 ml - ampoules of dark glass (10) - planimetric strip packagings (1) - packs cardboard.
1 ml - ampoules of dark glass (10) - a box cardboard.