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

Excipients: cellulose microcrystalline 42.5 mg, magnesium stearate 1 mg, talc 2 mg, crospovidone (kollidone TSL) 1 mg, lactose monohydrate (sugar milk) to obtain a core of 100 mg;

sheath: hypromellose (hydroxypropylmethylcellulose) 1.8 mg, talc 0.1 mg, titanium dioxide 0.9 mg, propylene glycol 1 mg, macrogol-4000 (polyethylene glycol 4000, polyethylene oxide-4000) 1.2 mg.

Description:Round biconvex tablets covered with a film coat, white or almost white. Two layers are visible on the cross-section.

Pharmacotherapeutic group:non-steroidal anti-inflammatory drug (NSAID)

ATX: & nbsp

M.01.A.B.15 Ketorolac

Pharmacodynamics:

Non-steroidal anti-inflammatory drug (NSAID) with pronounced analgesic effect. Ketorolac has also an anti-inflammatory and moderate antipyretic effect.

The mechanism of action is associated with a nonselective inhibition of the activity of cyclooxygenase 1 and 2 enzymes,mainly in peripheral tissues, the consequence of which is the inhibition of the biosynthesis of prostaglandins - modulators of pain sensitivity, thermoregulation and inflammation. Ketorolac is a racemic mixture [-]S- and [+]R enantiomers, while the analgesic effect is due to [-] S-enantiomer. The drug does not affect opioid receptors, does not depress respiration, does not cause drug dependence, does not have sedative and anxiolytic effects.

By the strength of the analgesic effect comparable to morphine, it is much superior to other non-steroidal anti-inflammatory drugs.

After oral administration, the beginning of analgesic effect is observed after 1 h, the maximum effect is achieved in 2-3 hours.

Pharmacokinetics:

Suction. PWhen taken internally ketorolac well absorbed in the gastrointestinal tract tract, bioavailability - 80-100%. The maximum concentration (C_ma_x) in blood plasma (0.7-1.1 μg / ml) is achieved 40 minutes after taking the drug on an empty stomach at a dose of 10 mg. Fat-rich food reduces the maximum concentration of ketorolac in the blood and delays its achievement by 1 h.

Distribution. 99% of the drug binds to blood plasma proteins and the hypoalbuminemia increases the amount of free substance in the blood.

The time to reach the equilibrium concentration with oral administration is 24 hours when administered 4 times a day (above the subtherapeutic level) and is 10 mg to 0.39-0.79 μg / ml after ingestion.

The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency The volume of distribution of the drug can be increased 2 times, and the volume of its distribution R-enantiomer by 20%.

Penetrates into breast milk: when a mother receives 10 mg of ketorolac, the maximum concentration in milk is reached 2 hours after taking the first dose 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 / ml.

Metabolism. More than 50% of the administered dose is metabolized in the liver with the formation of pharmacologically inactive metabolites. The main metabolites are glucuronides, which are excreted by the kidneys and p-hydroxycetorolac. It is excreted on 91% by kidneys, 6% through the intestine.

Excretion. PThe half-life (T_1/2) in patients with normal renal function is 2.4-9 hours (an average of 5.3 hours). The elimination half-life increases in elderly patients and is shortened in young patients.The function of the liver does not affect T_1/2It is not excreted by hemodialysis;

Pharmacokinetics in special clinical cases

In patients with impaired renal function with a creatinine concentration in the blood plasma of 19-50 mg / l (168-442 μmol / L), the half-life is 10.3-10.8 hours, with more pronounced renal failure more than 13.6 hours.

Indications:

Pain syndrome of strong and moderate severity: trauma, toothache, myalgia, arthralgia, neuralgia, sciatica, dislocations, sprains, rheumatic diseases, postoperative pain, oncological diseases.

Contraindications:

- Hypersensitivity to ketorolac or other non-steroidal anti-inflammatory drugs;

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis);

- urticaria, rhinitis caused by taking an NSAID (in history);

- intolerance of drugs pyrazolone series;

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

- confirmed hyperkalemia;

- erosive and ulcerative lesions of the gastrointestinal tract in the phase of exacerbation;

- Inflammatory bowel disease;

- hypocoagulation (including hemophilia);

- severe renal failure (creatinine clearance less than 30 ml / min);

- severe hepatic insufficiency or active liver disease;

- simultaneous reception with other non-steroidal anti-inflammatory drugs;

- high risk of bleeding (including after operations);

- children and adolescents under 16 years of age (efficacy and safety not established);

- Pregnancy;

lactation period.

Ketorolac is not recommended for use as a means for premedication, supporting anesthesia and anesthesia in obstetric practice because of the high risk of bleeding.

Ketorolac is not indicated for the treatment of chronic pain.

Carefully:With bronchial asthma, cholecystitis, chronic heart failure, arterial hypertension, impaired renal function (plasma creatinine below 50 mg / l), cholestasis, active hepatitis, sepsis, systemic lupus erythematosus, polyps of the nasal mucosa and nasopharynx, patients over the age of 65 .

Pregnancy and lactation:The drug is contraindicated for use during pregnancy and during breastfeeding.

Dosing and Administration:

Ketorolac is administered orally once in a dose of 10 mg or repeatedly, depending on the severity of the pain syndrome, 10 mg up to 4 times a day.

The maximum daily dose should not exceed 40 mg.

If taken internally, the duration of the course should not exceed 5 days.

Side effects:

Often - 1/100 appointments (> 1% and <10%), infrequently - 1/1000 appointments (> 0.1% and <1%).

Allergic reactions: infrequently anaphylaxis or anaphylactoid reactions (change face color, skin rash, urticaria, skin itch, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest, wheezing).

From the central nervous system: often - headache, dizziness, drowsiness; rarely aseptic meningitis (fever, severe headache, convulsions, rigidity of the neck and / or back muscles), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis, fainting.

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

From the urinary system: infrequently - acute renal failure, back pain, hematuria, azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia purpura), frequent urination, increased or decreased urine volume, nephritis, renal edema genesis.

From the digestive system: often - gastralgia, diarrhea, stomatitis, flatulence, constipation, vomiting, sensation of stomach overflow; infrequently - decreased appetite, nausea, erosive and ulcerative lesions of the gastrointestinal tract (including perforation and / or bleeding - abdominal pain, cramping or burning sensation in the epigastric region, melena, vomiting, according to the "coffee grounds '', nausea, heartburn), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

From the side of the blood coagulation system: infrequently - bleeding from the postoperative wounds, epistaxis, rectal bleeding.

From the respiratory system: infrequently - bronchospasm or shortness of breath, rhinitis, pulmonary edema, laryngeal edema (shortness of breath, difficulty breathing).

From the sense organs: infrequent - hearing loss, ringing in the ears, impaired vision (including blurred vision).

From the side of the cardiovascular system: often - increased blood pressure.

From the side of the hemostasis system: infrequently - anemia, eosinophilia, leukopenia.

Other: often - swelling of the face, legs, ankles, fingers, feet, weight gain, increased sweating; infrequently - swelling of the tongue, fever.

Overdose:

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

Treatment: gastric lavage, administration of adsorbents (Activated carbon) and symptomatic therapy. Ketorolac is not excreted sufficiently by dialysis.

Interaction:

Simultaneous use of ketorolac with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

Co-administration with paracetamol increases the risk of developing nephrotoxicity, with methotrexate-hepato-and nephrotoxicity.

Against the background of the use of ketorolac, a decrease in the clearance of methotrexate and lithium and

increased toxicity of these substances. The joint administration of ketorolac and methotrexate is possible only with the use of low doses of the latter (in this case, the concentration of methotrexate in the blood plasma should be monitored).

Simultaneous administration with indirect anticoagulants, heparin, thrombolytic agents, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of

bleeding.

Increases the effect of narcotic analgesics.

When administered with other nephrotoxic drugs (including drugs gold) increases the risk of developing nephrotoxicity.

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

Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

Special instructions:

It should be borne in mind that the effect of the drug on platelet aggregation persists for 24-48 hours. Hypovolemia increases the risk of developing adverse reactions from the kidneys. If necessary ketorolac can be prescribed in combination with narcotic analgesics.

It is not recommended to use ketorolac simultaneously with paracetamol for more than 5 days.

To reduce the risk of NSAID-gastropathy, antacid medicinal facilities, misoprostol, omeprazole.

Patients with a violation of blood clotting drug prescribed only with a constant control of the number of platelets; This is especially important in the postoperative period and requires careful monitoring of hemostasis.

Effect on the ability to drive transp. cf. and fur:Since a significant part of patients with the use of ketorolac develop side effects from the central nervous system (drowsiness, dizziness,headache), it is recommended to avoid work that requires increased attention and quick reaction (driving vehicles, working with mechanisms).

Form release / dosage:Tablets, film-coated, 10 mg.

Packaging:

10 tablets in a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered.

1, 2, 3, 4, 5 or 10 contour cell packs with instructions for use are placed in a pack of cardboard.

Storage conditions:In dry, dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001005

Date of registration:26.08.2010

The owner of the registration certificate:SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp11.04.2012

Illustrated instructions

Instructions

Ketorolac (Ketorolac)