Ketorolac - SOLOfarm - instructions for use, dose, side effects, contraindications

Ketorolac belongs to non-steroidal anti-inflammatory drugs (NSAIDs), has a pronounced analgesic effect, and has an anti-inflammatory and moderate antipyretic effect. The mechanism of action is associated with nonselective inhibition of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2) activity catalyzing the formation of prostaglandins (Pg) from arachidonic acid, which play an important role in the pathogenesis of pain, inflammation and fever. Ketorolac is a racemic mixture [-] S and [+] R enantiomers, while the analgesic effect is due to [-] S form.By the strength of analgesic action comparable to morphine, it is significantly superior to other NSAIDs. The onset of analgesic action is observed after 0.5 h, the maximum effect is achieved after 1 -2 h and lasts about 4-6 h.

Pharmacokinetics:

Suction

Bioavailability is complete and fast. After intramuscular injection, 30 mg maximum concentration (Cmax) - 1.74-3.1 μg / ml, 60 mg - 3.23-5.77 μg / ml, time to reach the maximum concentration (T_Cmax) - 15-73 min and 30-60 min respectively. After intravenous administration at a dose of 15 mg Cmax is 1.96-2.98 μg / ml, in a dose of 30 mg - Cmax is 3.69-5.61 μg / ml.

Distribution

The connection with plasma proteins is 99%. Time to reach the equilibrium concentration (C_ss) - 24 hours, C_ss when administered intramuscularly 15 mg 4 times a day - 0.65-1.13 μg / ml, 30 mg - 1.29-2.47 μg / ml.

The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the distribution of ketorolac may increase by a factor of 2, and the volume of distribution of ketorolac R-enantiomer by 20%.

Penetrates into breast milk: after the administration of 10 mg ketorolac Cmax in milk is achieved after 2 hours and is 7.3 ng / ml, 2 hours after the second dose of ketorolac (with the drug 4 times a day) - is 7.9 ng / l.

Metabolism

More than 50% of the administered dose is metabolized in the liver with formation 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.

Excretion

The half-life (T_1/2) in patients with normal renal function averaged 5.3 hours (3.5-9.2 hours after intramuscular injection of 30 mg). T_1/2increases in elderly patients and decreases 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 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 for intramuscular injection of 30 mg is 0.023 l / h / kg, with intravenous injection of 30 mg - 0.03 l / kg / h.

Ketorolac is not excreted by hemodialysis.

Indications:

Pain syndrome of strong and moderate severity: trauma, toothache, pain in the postoperative period, oncological diseases, myalgia, arthralgia, neuralgia, sciatica, dislocations, sprains, rheumatic diseases. It is intended for symptomatic therapy, reducing pain and inflammation at the time of application, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to any component of the drug;

- anamnestic data on an attack of bronchial obstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete combination of bronchial asthma, nasal polyposis and paranasal sinuses and intolerance - acetylsalicylic acid and other NSAIDs);

- Hypovolemia (regardless of the cause that caused it);

- erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, bleeding or high risk of their development, hypocoagulation (including hemophilia), inflammatory bowel disease (Crohn's disease, ulcerative colitis);

severe hepatic insufficiency or active liver disease;

- severe renal failure (serum creatinine> 700 μmol / l), progressive kidney disease;

- confirmed hypokalemia;

- Decompensated heart failure, condition after aortocoronary shunting;

- The drug is not used for anesthesia before and during surgery because of the high risk of bleeding;

- intracranial hemorrhage or suspicion of it;

- confirmed hyperkalemia;

- pregnancy, the period of childbirth, the period of breastfeeding;

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

Carefully:

Hypersensitivity to other NSAIDs, bronchial asthma, the presence of factors that increase toxicity in relation to the gastrointestinal tract (alcoholism, smoking, cholecystitis); postoperative period; chronic heart failure (CHF), ischemic heart disease (IHD), edematous syndrome, hypertension; renal failure of moderate severity (serum creatinine 300-700 μmol / l); cholestasis; sepsis; systemic lupus erythematosus; simultaneous reception with other NSAIDs, long-term intake of NSAIDs; cerebrovascular diseases; Dyslipidemia, hyperlipidemia, diabetes mellitus; diseases of peripheral arteries; ulcerative lesions of the gastrointestinal tract in the anamnesis, the presence of infection N. pylori; severe physical illness; systemic connective tissue diseases; inflammatory bowel disease without exacerbation; simultaneous administration of oral glucocorticosteroid agents (including prednisolone), anticoagulants (including warfarin), antiaggregants (including clopidogrel),selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), elderly age (over 65 years).

Pregnancy and lactation:

Do not take the drug during pregnancy (adverse effects on the fetal cardiovascular system - premature closure of the arterial duct), during labor, in the early postpartum period (inhibits the synthesis of prostaglandins, the drug can adversely affect the fetal blood circulation and weaken the contractile activity of the uterus, which increases risk of uterine bleeding) and during breastfeeding (the drug penetrates into breast milk). If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intramuscularly, intravenously.

The drug is intended for short-term use.

The drug is administered intravenously struino for at least 15 seconds or intramuscularly slowly, deep into the gluteal muscle, in minimally effective doses, by a minimally short course. If necessary, it is also possible to additionally use opioid analgesics in reduced doses.

Single doses for single administration:

- patients from 16 to 65 years old and weighing more than 50 kg - 60 mg (2 ml) intramuscularly or 30 mg (1 ml) intravenously;

- patients older than 65 years, or with renal insufficiency (serum creatinine 170-442 μmol / l), or with a body weight of less than 50 kg - 30 mg (1 ml) intramuscularly or 15 mg (0.5 ml) intravenously.

Doses with repeated administration:

- patients from 16 to 65 years old and weighing more than 50 kg - 30 mg (1 ml) intramuscularly or intravenously if necessary every 6 hours. The maximum daily dose should not exceed 90 mg (3 ml);

- patients older than 65 years, or with renal insufficiency (serum creatinine 170-442 μmol / l), or with a body weight of less than 50 kg - 15 mg (0.5 ml) intramuscularly or intravenously as needed every 6 hours. The maximum daily dose is not should exceed 60 mg (2 ml).

The maximum duration of treatment should not exceed 2 days. When switching from parenteral administration of the drug to 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 renal insufficiency or with a body weight of less than 50 kg. In this case, the dose of the drug in tablets on the day of transition should not exceed 30 mg.

Side effects:

According to the World Health Organization (WHO), adverse events are classified according to their frequency of development as follows: very frequent (> 10%), frequent (> 1% and <10%), infrequent (> 0.1 % and <1%), rare (> 0.01% and <0.1%), very rare (<0.01%), the frequency is unknown (the frequency can not be determined from the available data).

Allergic reactions: infrequent - anaphylaxis or anaphylactoid reactions (skin discoloration, skin rash, hives, skin itch, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, shortness of breath, heaviness in the chest).

Local reactions: frequent - burning or pain at the injection site.

From the central nervous system: very frequent - headache; frequent - dizziness, drowsiness, increased sweating; infrequent - tremor, unusual dreams, hallucinations, euphoria, extrapyramidal symptoms, vertigo, paresthesia, depression, insomnia, nervousness, pathological thinking, loss of concentration, hyperkinesis, confusion (stupor), aseptic meningitis (fever, severe headache, seizures, rigidity of neck muscles and / or back), psychosis, fainting.

From the skin: frequent - itching, rash (including maculopapular rash); infrequent - urticaria, toxic epidermal necrolysis (Lyell's syndrome), malignant exudative erythema (Stevens-Johnson syndrome), exfoliative dermatitis (fever with chills or without, hyperemia, densification or flaking of the skin, enlargement and / or soreness of the tonsils).

From the urinary system: infrequent - haematuria, proteinuria, urinary retention, oliguria, polyuria, frequent urination, acute renal failure, back pain with or without hematuria and / or azotemia, interstitial nephritis, hyponatremia, hyperkalemia, hemolytic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura).

From the digestive system: very frequent - gastralgia, dyspepsia, nausea; frequent - diarrhea, constipation, flatulence, a feeling of fullness of the stomach, vomiting, stomatitis; infrequent - increased or decreased appetite, anorexia, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and / or bleeding - abdominal pain, spasm or burning in the epigastric region, blood in the feces or melena,vomiting with blood or the type of "coffee grounds", nausea, heartburn), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis, polydipsia, dry mouth; frequency unknown - exacerbation of ulcerative colitis or Crohn's disease.

From the hematopoiesis: frequent - purple; infrequent - anemia, eosinophilia.

From the respiratory system: infrequent - bronchospasm or dyspnea, pulmonary edema, rhinitis, laryngeal edema (difficulty breathing).

From the sense organs: infrequent - impaired taste, visual impairment (including blurred vision), decreased hearing, ringing in the ears.

From the cardiovascular system: frequent - increased blood pressure; infrequent - a feeling of palpitations, pallor of the skin, fainting, hyperemia; frequency unknown - lowering of arterial pressure, heart failure, myocardial infarction, stroke.

From the side of the hemostasis system: infrequent - bleeding from a postoperative wound, epistaxis, rectal bleeding.

Other: frequent - swelling; infrequent - weight gain, fever, infections, asthenia, increased sweating, swelling of the tongue; the frequency is unknown - an increase in the concentration of urea and creatinine in the blood plasma.

Overdose:

Symptoms: abdominal pain, nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

Treatment: there is no specific antidote, gastric lavage, administration of adsorbents (Activated carbon) and symptomatic therapy (maintenance of vital body functions). Ketorolac is not excreted sufficiently by dialysis.

Interaction:

Simultaneous use of ketorolac with other NSAIDs, glucocorticosteroids, ethanol, corticotropin, calcium preparations increases the risk of ulceration of the gastrointestinal mucosa and the development of gastrointestinal bleeding.

Simultaneous use with paracetamol increases the nephrotoxicity of ketorolac, with methotrexate increases hepato- and nephrotoxicity. Do not use simultaneously with paracetamol for more than 2 days. The combined use of ketorolac and methotrexate is possible only with the use of low doses of the latter and control of its concentration in the blood plasma. When appointed with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases.

Probenecid reduces plasma clearance and the volume of ketorolac distribution, increases its concentration in blood plasma and increases its half-life. Simultaneous use with anticoagulants - derivatives of coumarin and indanediol, heparin, thrombolytics (alteplase, streptokinase, urokinase), antiplatelet drugs, cephalosporins, valproic acid and acetylsalicylic acid increases the risk of bleeding.

Reduces the effect of antihypertensive and diuretic drugs (reduces the synthesis of prostaglandins in the kidneys).

Drugs that block tubular secretion, reduce the clearance of ketorolac and increase its concentration in the blood plasma.

When combined with opioid analgesics, the doses of the latter can be significantly reduced.

Increases hypoglycemic action of insulin and oral hypoglycemic drugs (dose recalculation is necessary). Increases the concentration in the blood plasma of verapamil and nifedipine.

Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

It is not recommended simultaneous use with lithium salts, pentoxifylline, zidovudine, digoxin,tacrolimus, selective serotonin reuptake inhibitors, antacids, mifepristone.

The drug should not be mixed in one syringe with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride (ketorolac precipitated from the solution). Pharmaceutically incompatible with a solution of tramadol, lithium preparations.

Special instructions:

Before prescribing the drug, it is necessary to clarify the question of the previous allergy to ketorolac or other NSAIDs. Because of the risk of developing allergic reactions, the first dose is administered under close supervision of the doctor.

Hypovolemia increases the risk of developing nephrotoxic adverse reactions.

If necessary, can be used with opioid analgesics.

It is not recommended to be used as a means for premedication, maintenance of anesthesia.

When combined with other NSAIDs, fluid retention, cardiac decompensation, and increased blood pressure may occur.

The risk of developing drug complications increases with prolonged treatment (in patients with chronic pain) and an increase in the dose of the drug.

To reduce the risk of developing NSAIDs-gastropathy antacids are used, misoprostol, omeprazole.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 30 mg / ml.

Packaging:

1 ml per ampoule of colored glass with a colored fracture ring or with a colored dot and a notch or without a rift ring, a colored dot and a notch. 5 or 10 vials in blisters of polyvinyl chloride or polyethylene terephthalate film with a polymer film or lacquered aluminum foil or a polymer film without an aluminum foil and lacquer or in the form of cardboard with cells for stacking ampoules.

1 the contour cellular packaging made of cardboard or form with 10 ampoules or blisters 2 or shapes from a cardboard of 5 ampoules together with instructions for use and a lancet ampulnam or without a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-003884

Date of registration:06.10.2016 / 02.08.2017

Expiration Date:06.10.2021

The owner of the registration certificate:GROTEKS, LLC GROTEKS, LLC Russia

Manufacturer: & nbsp

GROTEKS, LLC Russia

Information update date: & nbsp07.01.2018

Illustrated instructions

Instructions

Ketorolac - SOLOFARM (Ketorolac - Solopharm)