Ketanov

General characteristics. Structure:

Active agent: ketorolaka трометамин-10 mg.
Excipients: starch corn, cellulose microcrystallic, silicon dioxide colloid, magnesium stearate.
Film cover: a gidroksipropilmetiltsellyuloza, polyethyleneglycol-400 (a macrogoal 400), the talc purified titanium dioxide, the water purified (it is lost in the course of production).
1 ml of solution for intramuscular introduction contains:
Active agent: a ketorolaka трометамин - 30 mg
Excipients: sodium chloride, dinatrium эдетат, ethanol, sodium hydroxide, water for injections.
Description
Tablets: round biconvex tablets coated, white or almost white color with an engraving of "KVT" on one party.
Solution for injections: transparent colourless or pale yellow  solution.

Pharmacological properties:

Pharmacodynamics. Ketorolak has the expressed analgetic effect, possesses also antiinflammatory and moderate febrifugal action.
The mechanism of action is connected with non-selective oppression of activity of enzyme of cyclooxygenase 1 and 2, mainly, in peripheral fabrics, the investigation of what
braking biosynthase of prostaglandins – modulators of painful sensitivity, thermal control and an inflammation is. Ketorolak represents racemic mix [-] of S and [+] R of enantiomer at the same time anesthetizing action is caused [-] S by a form.
Drug does not influence opioid receptors, does not oppress breath, 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 NPVP.
After intramuscular introduction and intake the beginning of the anesthetizing action is noted respectively in 0,5 and 1 h, the maximum effect is reached in 1-2 h. 

Pharmacokinetics. After intake of Ketanov® it is well soaked up in digestive tract – the maximum concentration (With max) in a blood plasma (0,7-1,1 mkg/ml) is reached in 40 min. after reception on an empty stomach of a dose of 10 mg. Food rich with fats reduces the maximum concentration of drug in blood and detains her achievement on 1 hour of 99% of drug contacts proteins of a blood plasma, and at a hypoalbuminemia the amount of free substance in blood increases. Bioavailability - 80-100%. Absorption at introduction in oil – full bystry. After maintaining 30 mg in oil drug With max - 1.74 – 3.1 mkg/ml, 60 mg – 3.23 - 5.77 mkg/ml, time of achievement of the maximum concentration respectively 15-73 min. and 30-60 min. Time of achievement of equilibrium concentration (Css) at parenteral and peroral administration – 24 h at appointment 4 times a day (above subtherapeutic) also makes at introduction in oil 15 mg – 0.65 - 1.13 mkg/ml, 30 mg – 1.29-2.47 mkg/ml; after intake of 10 mg – 0.39 - 0.79 mkg/ml. The volume of distribution makes 0.15-0.33 l/kg. At patients with a renal failure the volume of distribution of drug can increase twice, and the volume of distribution of its R - an enantiomer – by 20%.
Gets into breast milk: after reception by mother of 10 mg of a ketorolak With max in 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 (when using drug 4 times a day) - makes 7.9 ¡ú/l.
More than 50% of the entered dose are metabolized in a liver about formation pharmacological of inactive metabolites. The main metabolites are glucuronides which are removed by kidneys, and r-gidroksiketorolak. 6% - through intestines are brought to 91% by kidneys.
The elimination half-life (T ½) at patients with normal function of kidneys averages 5.3 h (3.5-9.2 h after introduction of 30 mg in oil and 2.4 - 9 h after intake of 10 mg). The t ½ is extended at elderly patients and shortened at young people. Function of a liver does not exert impact on T ½. At patients with a renal failure at concentration of creatinine in a blood plasma of 19-50 mg/l (168-442 µmol/l)  of T ½ makes 10.3 – 10.8 h, at more expressed renal failure – more than 13.6 h.
The general clearance makes at introduction in oil 30 mg - 0.023 l/kg/h (elderly patients have 0.019 l/kg/h), intake of 10 mg – 0.025 l/kg/h; at a renal failure with concentration of creatinine in a blood plasma of 19-50 mg/l at introduction of 30 mg in oil – 0.015 l/kg/h, at intake of 10 mg – 0.016 l/kg/h.
It is not removed during a hemodialysis.

Indications to use:

Pain syndrome of average and strong intensity of various genesis (including in the postoperative period, at oncological diseases and др).

Route of administration and doses:

In the form of the tablets Ketanov® 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 a day 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.
In the form of solution for injections of Ketanov® enter deeply intramusculary in minimum effective doses which are picked up according to intensity of pain and reaction of the patient. If necessary it is at the same time possible to appoint in addition opioid analgetics in the reduced doses.
Single doses at single intramuscular introduction:
• The patient up to 65 years - 10-30 mg depending on weight of a pain syndrome,
• The patient 65 years or with a renal failure – on 10-15 mg are more senior each 4-6 hours.
Doses at repeated intramuscular introduction:
• The patient up to 65 years enter 10-30 mg, then – on 10-30 mg each 4-6 hours,
• The patient 65 years or with a renal failure – on 10-15 mg are more senior each 4-6 hours
The maximum daily dose for patients up to 65 years should not exceed 90 mg, and for patients 65 years or with an impaired renal function – 60 mg are more senior at an intramuscular way of introduction.
At parenteral administration duration of a course of treatment should not exceed 5 days.
Upon transition from parenteral administration of drug to its intake the total daily dose of both dosage forms in day of transfer should not exceed 90 mg for patients up to 65 years and – for patients 65 years or with an impaired renal function are more senior than 60 mg. At the same time the drug dose in tablets in day of transition should not exceed 30 mg.

Features of use:

Influence on aggregation of thrombocytes stops in 24-48 hours. The hypovolemia increases risk of development of side reactions from kidneys. If necessary it is possible to appoint in a combination with narcotic analgetics. Кетанов® it is not recommended to apply as means to premedication, the supporting anesthesia and anesthesia in obstetric practice. Not to use along with paracetamol more than 5 days. To patients with disturbance of a blood coagulation appoint drug only at constant control of number of thrombocytes that is especially important in the post-operational period when  careful control of a hemostasis is required.
As at a considerable part of patients at purpose of Ketanova® 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 and so forth).

Side effects:

Often – more than 3%, are less frequent – 1-3%, is rare – less than 1%.
From the alimentary system: often (especially at elderly patients 65 years having digestive tract 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 – nausea, digestive tract erosive cankers (including with perforation and/or bleeding – abdominal pain, a spasm or burning in epigastric area, a melena, vomiting as "a coffee thick", nausea, heartburn, etc.), cholestatic jaundice, hepatitis, a hepatomegalia, acute pancreatitis.
From an urinary system: seldom – an acute renal failure, a back pain with or without hamaturia and/or azotemias, a hemolitic uraemic syndrome (hemolitic anemia, a renal failure, thrombocytopenia, a purpura), a frequent urination, increase or decrease in volume of urine, nephrite, hypostases of renal genesis.
From sense bodys: seldom - decrease in hearing, a ring in ears, a vision disorder (including an illegibility of visual perception).
From respiratory system: seldom - a bronchospasm or диспноэ, rhinitis, throat hypostasis (an asthma, breath difficulty),
From TsNS: often – a headache, dizziness, drowsiness; seldom – aseptic meningitis (fever, a severe headache, spasms, muscle tension of a neck and/or back), a hyperactivity (change of mood, concern), hallucinations, a depression, psychosis.
From cardiovascular system: less often – increase in the ABP; seldom – a fluid lungs, a syncope.
From bodies of a hemopoiesis: seldom – anemia, an eosinophilia, a leukopenia.
From system of a hemostasis: seldom - bleeding from a postoperative wound, nasal bleeding, rectal bleeding.
From integuments: less often – skin rash (including makulopapullezny rash), a purpura; seldom - exfoliative dermatitis (fever with a fever or without, 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.
Local reactions: less often – burning or pain in an injection site.
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: often – hypostases (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 non-steroidal anti-inflammatory drugs, calcium drugs, glucocorticosteroids, ethanol, corticotropin can lead to formation of ulcers of digestive tract 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).
Probenitsid reduces plasma clearance and volume of distribution of a ketorolak, increases its concentration in a blood plasma and increases the period of its semi-removal. 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 developing of bleeding. Reduces effect of hypotensive and diuretic drugs (synthesis of prostaglandins in kidneys goes down). At a combination with opioid analgetics of a dose of the last can be significantly reduced.
Antiacid means do not influence completeness of absorption of medicine.
Hypoglycemic effect of insulin and peroral hypoglycemic drugs increases (recalculation of a dose is necessary). Joint appointment with Valproatum of sodium causes disturbance of aggregation of thrombocytes. Increases concentration in a blood plasma of verapamil and nifedipine.
At appointment with other nephrotoxic medicines (in т.ч 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.
Solution for injections should not be mixed in one syringe with morphine sulfate, promethazine and Hydroxyzinum because of loss of a deposit. Pharmaceutical it is not compatible to solution of a tramadol, lithium drugs.
Solution for injections is compatible to normal saline solution, 5% dextrose solution, 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:

Hypersensitivity to a ketorolak or other non-steroidal anti-inflammatory drugs, "aspirinovy" asthma, a bronchospasm, a Quincke's disease, a hypovolemia (irrespective of the reason which caused it), dehydration. 
Digestive tract erosive cankers in aggravation stages, round ulcers, hypocoagulation (including hemophilia). 
Liver and/or renal failure (creatinine of plasma is higher than 50 mg/l). 
The hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, a concomitant use with other NPVP, high risk of development or a recurrence of bleeding (including after operations), hemopoiesis disturbance. 
Pregnancy, childbirth and period of a lactation. Children's age up to 16 years (efficiency and safety are not established). 
Drug is not used for anesthesia before and during surgeries because of high risk of bleeding, and also 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.

Overdose:

Symptoms: abdominal pains, nausea, vomiting, emergence of round ulcers of a stomach or erosive gastritis, renal failure, metabolic acidosis.
Treatment: a gastric lavage, administration of adsorbents (absorbent carbon) and performing symptomatic therapy (maintenance of the vital functions in an organism). It is not removed sufficiently by means of dialysis. 

Storage conditions:

List B. Tablets: at a temperature not above 25 °C in the dry place protected from light.
Solution for intramuscular introduction: at a temperature not above 25 °C in the place protected from light.
To store in the place, unavailable to children.

Period of validity - 3 years. Solution for intramuscular introduction – 3 years. Not to use after the period of validity specified on packaging

Issue conditions:

According to the recipe

Packaging:

Tablets on 10 mg: 10 tablets  in the blister from aluminum foil and PVC of a film; on 1,2,3 or 10 blisters together with the application instruction in a cardboard pack.
Solution for intramuscular introduction of 30 mg/ml: on 1 ml of drug in ampoules from transparent colourless glass I of type with marking by a blue strip and a blue point; on 5 or 10 ampoules together with the application instruction in a cardboard pack.