Ketorolac
Active material: Ketorolac
When ATH: M01AB15
CCF: NSAIDS with the expressed analgesic effect
ICD-10 codes (testimony): K08.8, M05, M15, M54.1, M79, M79.1, M79.2, R52.0, R52.2, T14.0, T14.3
When CSF: 05.01.01.05
Manufacturer: Synthesis of (Russia)
Pharmaceutical form, composition and packaging
Pills, coated white or nearly white, round, dvoyakovpukla forms; in cross section showed two layers.
| 1 tab. | |
| ketorolaka trometamin | 10 mg |
Excipients: lactose, potato starch, low molecular weight polyvinyl Medical (povidone), magnesium stearate, talc, kollidon CL-M.
The composition of the shell: auxipropilmetilzelluloza or hydroxypropyl methylcellulose (gipromelloza), talc, Titanium dioxide, polyethylene glycol 4000, propylene glycol.
10 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (2) – packs cardboard.
Solution for in / and the / m clear, yellowish.
| 1 ml | |
| ketorolaka trometamin | 30 mg |
Excipients: sodium chloride, disodium edetate (Trilon b), water d / and.
1 ml – vials of dark glass (5) – packings Valium planimetric (1) – packs cardboard.
1 ml – vials of dark glass (5) – packings Valium planimetric (2) – packs cardboard.
1 ml – vials of dark glass (10) – packs cardboard.
1 ml – vials of dark glass (10) – packings Valium planimetric (1) – packs cardboard.
Pharmacological action
NSAID with analgesic, anti-inflammatory and antipyretic action of moderate.
The mechanism of action associated with a non-selective inhibition of the activity of enzymes Cox-1 and Cox-2, mainly in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins – modulators of pain sensitivity, thermoregulation and inflammation.
Ketorolac is a razemicescuu mixture of S(-) and R(+)-enantiomers, When the anesthetic effect due to S(-)-form.
The drug does not affect opioid receptors, It does not suppress breathing, It does not cause drug dependence, possesses sedative and anxiolytic effect.
Strength pain effect is comparable to morphine, vastly superior to other NSAIDs.
Once inside the beginning of pain through actions 1 no, maximum effect is achieved after 1-2 no.
After the/m introduction beginning of pain through actions 30 m, maximum effect is achieved after 1-2 no.
Pharmacokinetics
Absorption
The ingestion well absorbed from the digestive tract Ketorolac. Tmax is 40 minutes after taking the dose on an empty stomach 10 mg. Cmax plasma 0.7-1.1 ug / ml. Rich fat food lowers (C)max the drug in the blood and delay its attainment at the 1 time. Suction with the/m introduction full and quick.
Bioavailability is 80-100%.
After the / m 30 mg Cmax in plasma is 1.74-3.1 ug / ml. After the / m dose 60 mg Cmax in plasma is 3.23-5.77 ug / ml. Tmax Accordingly is 15-73 Mines and 30-60 m.
After the on/in infusion dose 15 mg Cmax is 1.96-2.98 ug / ml, dose 30 mg – Cmax is 3.69-5.61 ug / ml.
Distribution
The binding to plasma proteins – 99%. When gipoalbuminemii number of free stuff in the blood increases. Vd is 0.15-0.33 l / kg.
The time to reach Css ingestion – 24 h when applied 4 times / day (above subterapevticheskoj) and is intake 10 mg – 0.39-0.79 ug / ml.
Css in injecting introduction is achieved through 24 h when applied 4 times / day (above subterapevticheskoj) and when the/m in a dose of 15 mg of 0.65-1.13 ug / ml, When the/m in a dose of 30 mg – 1.29-2.47 ug / ml; the on/in infusions in the dose 15 mg – 0.79-1.39 ug / ml, the on/in infusions in the dose 30 mg – 1.68-2.76 ug / ml.
Poor passes through GEB, It crosses the placental barrier (10%).
Provided with breast milk. The ingestion of mother 10 mg ketorolac (C)max the milk is 7.3 ng / ml, Tmax is 2 hours after the first dose. Through 2 hours after the use of a second dose of ketorolac (in applying the drug 4 times / day) Cmax is 7.9 ng / ml. When injecting is the breast milk in small amounts.
Metabolism
More 50% the dose imposed metabolised in the liver with the formation of pharmacologically active metabolites. The main metabolites are glukuronida and r-gidroksiketorolak.
Deduction
Excreted in the urine – 91% (40% as metabolites), with feces – 6%. Not displayed by hemodialysis.
T1/2 in patients with normal renal function averages 5.3 no (After the / m 30 mg – 3.5-9.2 no, After i / v administration 30 mg – 4-7.9 no).
Total clearance in the/m introduction 30 mg of 0.023 L / kg / h, the on/in infusion 30 mg of 0.03 L / kg / h.
Pharmacokinetics in special clinical situations
In patients with renal insufficiency (V)d the drug can increase 2 times, and (V)d his R-enantiomer – on 20%. When the concentration of creatinine in the blood plasma 19-50 mg/l in the/m introduction 30 mg drug generic clearance is 0.015 L / kg / h.
In patients with impaired kidney function when the concentration of creatinine in the blood plasma 19-50 mg / l (168-442 mmol / l) T1/2 is 10.3-10.8 no, a more pronounced renal insufficiency – more 13.6 no.
Liver function has no effect on T1/2.
In patients older total clearance in the/m in a dose of 30 mg of 0.019 L / kg / h. T1/2 longer in patients older and shortened in young.
Testimony
-syndrome pain of moderate to severe intensity different Genesis (incl. injury, toothache, pain in the postpartum and postoperative period, oncological diseases, myalgia, arthralgia, neuralgia, radiculitis, sprains, stretching, rheumatic diseases).
Dosage regimen
Orally
Ketorolac should be applied inside once or repeatedly, depending on the severity of pain.
Odnokratnaya dose – 10 mg, If readmission is recommended to take on 10 mg to 4 times/day depending on the severity of pain. The maximum daily dose should not exceed 40 mg.
The ingestion duration should not exceed 5 days.
Parenteral
The drug should be introduce/m (deep in the muscle) or / (spray) slowly for at least 15 s minimum effective dose, selected in accordance with the intensity of pain and the patient's response.
Injecting a single dose
One-time single dose in the/m or/in the introduction: adults up to the age of 65 years – 10-30 mg depending on the severity of the pain syndrome; elderly patients over the age of 65 years or with impaired renal function – by 10-15 mg every 4-6 no.
In repeated dose injecting a
At in/m introduction adults up to the age of 65 years injected i / m 10-60 mg in the first introduction, then – by 10-30 mg every 6 no (usually 30 mg every 6 no); Polder acientam (senior 65 years) or with impaired renal function – by 10-15 mg every 4-6 no.
At in/in the introduction of adults up to the age of 65 years Jet injected in a dose 10-30 mg, then – by 10-30 mg every 6 no. In continuous infusions using infusomat initial dose of 30 mg, then the infusion rate is 5 mg / h.
At in/in the introduction patients older older 65 years or with impaired renal function Jet injected in a dose 10-15 mg every 6 no.
As with the/m, and/in the way the introduction of the maximum daily dose for adults up to the age of 65 years is 90 mg; for polder acientov (senior 65 years) or with impaired renal function – 60 mg.
Continuous/cefuroxim should not last for more than 24 no.
In injecting a duration of treatment should not exceed 5 days.
When switching from injecting the drug at its ingesting total daily dose of the drug in two dosage forms on the day of transfer should not exceed 90 mg for adults up to the age of 65 years and 60 mg – to elderly patients (senior 65 years) or with impaired renal function. When this dose tablets a day of transition should not exceed 30 mg.
If necessary, you can further assign opioid analgesics in small doses.
Side effect
Often – >3%; less frequently – 1-3%; rarely – < 1%.
From the digestive system: often (particularly in elderly patients over the age of 65 years, have a history of erosivno-azwenne shock syndrome) – gastralgia, diarrhea; less frequently – stomatitis, flatulence, constipation, vomiting, a feeling of fullness; rarely – nausea, erosive and ulcerative lesions of the gastrointestinal tract (incl. with perforation and/or bleeding – abdominal pain, spasm, or a burning sensation in the epigastric region, ground, vomiting blood or by type “coffee grounds”, nausea, heartburn), cholestatic jaundice, hepatitis, gepatomegaliya, acute pancreatitis.
From the urinary system: rarely – acute renal failure, low back pain with or without hematuria and/or азотемии, hemolytic uremic syndrome (gemoliticheskaya anemia, renal failure, thrombocytopenia, purpura), frequent urination, increase or decrease the amount of urine, jade, edema of renal origin.
From the central and peripheral nervous system: often – headache, dizziness, drowsiness; rarely – aseptic meningitis (incl. fever, Strong headache, convulsions, stiff neck and / or back), hyperactivity (incl. mood changes, anxiety), hallucinations, depression, psychosis.
Cardio-vascular system: sometimes – increased blood pressure; rarely – pulmonary edema, fainting.
The respiratory system: rarely – bronchospasm or dyspnoea, rhinitis, laryngeal edema (incl. breathlessness, difficulty breathing).
From the senses: rarely – hearing loss, tinnitus, blurred vision (incl. blurred vision).
From the hematopoietic system: rarely – anemia, eozinofilija, leukopenia, bleeding from the surgical wound, nose bleed, rectal bleeding.
Allergic reactions: sometimes – skin rash (incl. macular-papular), purpura; rarely – exfoliative dermatitis (incl. fever with or without fever, redness, seal or peeling skin, swelling and/or tenderness Palatine tonsils), hives, Stevens-Johnson syndrome, Lyell's syndrome, anafilaktoidnыe reactions or anaphylaxis (incl. discoloration of skin, skin rash, hives, itchy skin, tachypnea or Dyspnea, swelling of the eyelids, periorbital edema, breathlessness, labored breathing, heaviness in the chest, wheezing).
Local reactions: less frequently – burning or pain at the injection.
Other: often – swelling (incl. person, goleneй, ankles, fingers, Foot), weight gain; less frequently – increased sweating; rarely – swelling of the tongue, fever.
Contraindications
- “Aspirin” asthma;
-bronchospasm;
- Angioedema;
- Gipovolemiя (regardless of the underlying causes of);
- Degidratatsiya;
- Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;
-peptic ulcers;
— gipokoagulyatsia (incl. hemophilia);
- Liver failure;
- Renal failure (sыvorotochnыy creatinine >5 mg / dL);
- Hemorrhagic stroke (confirmed or suspected);
- Gyemorragichyeskii diatyez;
-the simultaneous use of other NSAIDS;
is a high risk of recurrence of bleeding (incl. after surgery);
-blood;
- Pregnancy;
-childbirth;
- Lactation;
- Childhood and adolescence up 16 years (efficacy and safety have not been established);
- Hypersensitivity to the drug;
-hypersensitivity to ketorolaku and other NSAIDS.
The drug is not administered for pain before and during surgery due to the high risk of bleeding, and for the treatment of chronic pain.
FROM caution use in patients with asthma, holetsistite, chronic heart failure, hypertension, impaired renal function (sыvorotochnыy creatinine < 5 mg / dL), Cholestasis, active hepatitis, sepsis, SLE, Polyps of nasal mucous membrane and Chair, in elderly patients (senior 65 years).
Pregnancy and lactation
The drug is contraindicated in pregnancy, during childbirth and breastfeeding.
Cautions
The combined application with other NSAIDS may experience fluid retention, cardiac decompensation, arterial hypertension.
Do not use simultaneously with paracetamol more than Ketorolac 5 days.
You can optionally assign Ketorolac in combination with opioid analgesics.
Hypovolemia increase the risk of adverse reactions from the kidneys.
The influence of the drug on platelet aggregation stops after 24-48 no.
Patients with impaired blood clotting drug appoint only keeping the number of platelets, This is especially important in the post-period, that requires careful monitoring of hemostasis.
The risk of medical complications increases with the duration of treatment (in patients with chronic pain) and oral dosage >40 mg / day.
Ketorolac is not recommended as a means for then, maintenance of anesthesia and analgesia in obstetrics.
Effects on ability to drive vehicles and management mechanisms
Because a large part of patients when prescribing Ketorolac develop side effects from the CENTRAL NERVOUS SYSTEM (incl. drowsiness, dizziness, headache), It is recommended to avoid the execution of works, requiring attention and quick reactions (incl. driving vehicles, using machinery).
Overdose
Symptoms: abdominal pain, nausea, vomiting, the emergence of chronic stomach ulcers, or erosive gastritis, impairment of renal function, metabolic acidosis.
Treatment: in the case of the reception of the drug inside – gastric lavage, introduction of adsorbents (Activated carbon); ingestion and parenteral administration – symptomatic therapy (maintenance of the vital functions of the body). It is not displayed sufficiently by dialysis.
Drug Interactions
The simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDS, calcium supplementation, GCS, ethanol, corticotropin may lead to gastrointestinal ulcers and development of gastrointestinal bleeding.
Combined use of ketorolac with paracetamolom increases nefrotoksicnosti, with methotrexate – improves liver- and Nephrotoxicity and is only possible when using low doses of the latter (methotrexate concentration should be monitored in blood plasma).
Together with the use of Probenecid decreases plasma clearance and Vd Ketorolac, increases its concentration in the blood plasma and increases its T1/2.
With the use of ketorolac may reduce clearance of methotrexate and lithium, toxicity of these substances.
The simultaneous use of ketorolac with indirect antikoagulyantami, geparinom, thrombolytics, antiplatelet, cefoperazone, cefotetanom and pentoksifillinom increases the risk of bleeding.
The combined application with Ketorolakom dropping effect gipotenziveh and diuretic drugs (decreased renal prostaglandin synthesis).
With simultaneous use of Ketorolac with opioid analgesics last dose can be significantly reduced, tk. intensified their action.
Antacids do not affect the completeness of absorption of Ketorolac.
While the use of ketorolac increases the hypoglycemic effect of insulin and oral hypoglycemic drugs (recalculation of the dose needed).
Combined ketorolac with sodium valproate causes a disturbance of platelet aggregation; increases concentration in the blood plasma of nifedipine and verapamil.
Together with the use of ketorolac with other nefrotoksicnami drugs (incl. with the drugs gold) It increases the risk of nephrotoxicity.
Together with the use of medicines, block tubular secretion, reduce clearance of ketorolac and increase its concentration in the blood plasma.
Ketorolac injection should not be mixed in the same syringe with morphine sulfate, promethazine and Hydroxyzine of precipitation.
Farmatsevticeski incompatible with the solution of ketorolac tramadol, lithium preparations.
Ketorolac injection is compatible with saline solution, 5% dextrose (Glucose), Ringer solution and Ringer-lactate, solution “Plazmalit”, as well as infusion solutions, containing aminophylline, Lidocaine hydrochloride, dopamine hydrochloride, Short-acting human insulin and heparin sodium salt.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. Tablets should be stored in a place inaccessible to children, dry, dark place at a temperature of 15 ° to 25 ° C. Solution to the in/m and/in the introduction should be stored in a dark place at a temperature between 15° to 25° c. Shelf life – 2 year.
