Ketorol ampoules 1ml №10

Active ingredient and dosage form

Coated Tablets green, round, biconvex, with the letter "S" on one side; on the break - the core is white or almost white.
1 pill contains Ketorolaka tromethamine 10 mg;
Excipients: MCC, lactose, corn starch, Magnesium stearate, anhydrous colloidal silicon, sodium starch glycolate, hypromellose, propylene glycol, titanium dioxide, green olive;
in a blister strip package 10 pcs.; in a pack of cardboard 2 packs.

transparent colorless or pale yellow liquid, free from visible foreign particles.
1 ml contains ketorolaka tromethamine 30 mg;
Excipients: sodium chloride, alcohol, disodium edetate, octoxynol, propylene glycol, sodium hydroxide, water for injection;
in 1 ml ampoules; in a blister strip package 10 pcs.

tab., pokr. the shell - P No. 015823/02 07/08/04
rr d / injection. - P No. 015823/01 07.07.04

Mechanism of action

nonsteroidal anti-inflammatory agent (NSAID) with a pronounced analgesic effect.
Ketorolac has a pronounced analgesic effect, also has anti-inflammatory and moderate antipyretic effect.
The mechanism of action is associated with non-selective inhibition of the activity of the enzyme 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 racemic mixture of -S- and + R-enantiomers, with the analgesic effect due to the -S-enantiomer.
The drug does not affect opioid receptors, does not inhibit respiration, does not cause drug dependence, does not have a sedative and anxiolytic effect.
The strength of the analgesic effect is comparable with morphine, far superior to other NSAIDs.
After intramuscular administration and administration of the drug inside, the beginning of the analgesic effect is noted, respectively, after 30 minutes and 1 hour, the maximum effect is achieved in 1-2 hours.

Suction
After oral administration, Ketorolac is well absorbed from the gastrointestinal tract. C_max in blood plasma is reached 40 minutes after taking the drug on an empty stomach at a dose of 10 mg and is 0.7-1.1 mcg / ml. High-fat food lowers C_max Ketorolaka in the blood and delays the time to reach C_max for 1 hour
Bioavailability - 80-100%.
After i / m administration, ketorolac is rapidly and completely absorbed from the injection site into the systemic circulation. After i / m administration of the drug in a dose of 30 mg C_max in blood plasma is 1.74-3.1 mcg / ml, in a dose of 60 mg - 3.23-5.77 mcg / ml, the time to reach C_max, respectively, 15-73 minutes and 30-60 minutes.
Distribution
Plasma protein binding is 99%. With hypoalbuminemia, the amount of free substance in the blood increases.
Time to reach C_ss with parenteral and oral administration - 24 hours with the appointment of the drug 4 times / day (above subtherapeutic) and is with the / m administration of the drug in a dose of 15 mg - 0.65-1.13 mcg / ml, in a dose of 30 mg - 1.29-2.47 mg / ml; after ingestion of the drug in a dose of 10 mg - 0.39-0.79 mg / ml. V_d makes 0.15-0.33 l / kg.
Penetrates into breast milk. When prescribing the drug in a dose of 10 mg 4 times / day C_max in breast milk, it is reached 2 hours after the first dose and is 7.3 ng / ml, 2 hours after the second dose C_max is 7.9 ng / l.
Metabolism
More than 50% of the administered dose is metabolized in the liver to form pharmacologically inactive metabolites. The main metabolites are glucuronides and p-hydroxyketolac.
Removal
Excreted by the kidneys (91%) and through the intestines (6%). Glucuronides are excreted in the urine.
T_1/2 in patients with normal renal function, it averages 5.3 hours (3.5–9.2 hours after i / m administration of the drug at a dose of 30 mg and 2.4–9 hours after ingestion at a dose of 10 mg).
Total clearance is when i / m administration of the drug in a dose of 30 mg - 0.023 l / kg / h, when taken orally in a dose of 10 mg - 0.025 l / kg / h.
Pharmacokinetics in special clinical situations
In patients with renal failure V_d Ketorolaka can increase by 2 times, and V_d R-enantiomer - 20%.
T_1/2 lengthens in elderly patients and shortened in young patients. Liver function has no effect on T_1/2. In patients with impaired renal function when plasma creatinine concentration is 19-50 mg / l (168-442 μmol / l) T_1/2 is 10.3-10.8 h, with more severe renal failure - more than 13.6 h.
General clearance in patients with renal insufficiency with plasma creatinine concentration of 19-50 mg / l with i / m administration of the drug in a dose of 30 mg - 0.015 l / kg / h (0.019 l / kg / h in elderly patients), with ingestion in a dose of 10 mg - 0.016 l / kg / h.
It is not displayed during hemodialysis.

Indications and usage

- pain syndrome of medium and strong intensity of various genesis (including pain in the postoperative period, with cancer).

Contraindications

- hypersensitivity to ketorolac or other NSAIDs;
- "Aspirin Triad";
- bronchospasm;
- angioedema;
- hypovolemia (regardless of the cause that caused it);
- dehydration;
- erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;
- peptic ulcers;
- hypocoagulation (including hemophilia);
- hepatic and / or renal failure (plasma creatinine above 50 mg / l);
- hemorrhagic stroke (confirmed or suspected);
- hemorrhagic diathesis;
- simultaneous reception with other NSAIDs;
- high risk of bleeding (including after surgery);
- violation of blood formation;
- pregnancy, childbirth;
- lactation (breastfeeding);
- children's and teenage age up to 16 years.
Ketorol is not recommended as a means for sedation, supportive anesthesia and anesthesia in obstetric practice because of the high risk of bleeding.
Ketorol is not indicated for the treatment of chronic pain.
WITH caution It should be prescribed for 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, in elderly patients over 65 years old.

Dosage and administration

Inside Ketorol is prescribed once in a dose of 10 mg or repeatedly, depending on the severity and severity of pain, 10 mg up to 4 times / day. The maximum daily dose is 40 mg. Course duration - no more than 5 days.
V / m Ketorol prescribed in the minimum effective doses, selected in accordance with the intensity of pain and the response of the patient. If necessary, at the same time, it is possible to additionally prescribe opioid analgesics in reduced doses.
Patients under 65 years old the drug is prescribed in a / m dose of 10–30 mg once or depending on the severity of the pain syndrome, 10–30 mg every 4–6 h.
Patients over the age of 65 or with impaired renal function the drug is prescribed in a / m dose of 10–15 mg once or depending on the severity of the pain syndrome, 10–15 mg every 4–6 h.
When i / m administration maximum daily dose for patients under the age of 65 - 90 mg, for patients older than 65 years or with impaired renal function - 60 mg. Duration of treatment is no more than 5 days.
When switching from parenteral administration to oral administration, the total daily dose of both dosage forms on the day of transfer for patients under the age of 65 should not exceed 90 mg, for patients over the age of 65 years or with impaired renal function - 60 mg. In this case, the dose of the drug for oral administration on the day of transition should not exceed 30 mg.

Often - more than 3%, less often - 1-3%, rarely - less than 1%.
From the digestive system: often (especially in elderly patients older than 65 years, with a history of erosive and ulcerative lesions of the gastrointestinal tract) - gastralgia,diarrhea; less often - stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach; rarely - nausea, erosive and ulcerative lesions of the gastrointestinal tract (including perforation and / or bleeding - abdominal pain, spasm or burning in the epigastric region, melena, vomiting like "coffee grounds", nausea, heartburn), cholestatic jaundice hepatitis, hepatomegaly, acute pancreatitis.
From the urinary system: rarely, acute renal failure, back pain with or without hematuria and / or azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased urine volume, nephritis, edema of renal genesis.
On the part of the respiratory system: rarely - bronchospasm or dyspnea, rhinitis, laryngeal edema (shortness of breath, difficulty breathing).
From the side of the central nervous system: often - headache, dizziness, drowsiness, rarely - aseptic meningitis (fever, severe headache, convulsions, neck and / or back muscle stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis, hearing loss, ringing ears, visual disturbances (including blurred vision).
Since the cardiovascular system: less often - increased blood pressure; rarely - pulmonary edema, fainting.
From the side of blood-forming organs: rarely - anemia, eosinophilia, leukopenia.
From the blood coagulation system: rarely - bleeding from a postoperative wound, epistaxis, rectal bleeding.
Dermatological reactions: less often, skin rash (including maculo-papular rash), purpura; rarely - exfoliative dermatitis (fever with or without chills, redness, hardening or peeling of the skin, swelling and / or tenderness of the tonsils), urticaria, Stevens-Johnson syndrome, Lyell's syndrome.
Allergic reactions: rarely, anaphylaxis or anaphylactoid reactions (discoloration of skin, skin rash, urticaria, skin itching, tachypnea or dyspnea, eyelid edema, periorbital edema, shortness of breath, difficulty breathing, chest pain, wheezing).
Local reactions: less often - burning or pain at the injection site.
Other: often - swelling of the face, legs, ankles, fingers, feet, weight gain; less often, excessive sweating; rarely - swelling of the tongue, fever.

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

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 adverse reactions from the kidneys.
If necessary, Ketorol can be prescribed in combination with opioid analgesics.
It is not recommended to use Ketorol along with Paracetamol for more than 5 days.
Patients with impaired blood coagulation drug is prescribed only with constant monitoring of the number of platelets; This is especially important in the postoperative period and requires careful control of hemostasis.
Influence on ability to drive motor transport and control mechanisms
Since a significant proportion of patients with Ketorol use develop side effects from the central nervous system (drowsiness, dizziness, headache), it is recommended to avoid performing work requiring increased attention and quick reaction (driving vehicles, working with mechanisms).

Symptoms: abdominal pain, nausea, vomiting, the development of peptic ulcers of the stomach or erosive gastritis, renal dysfunction, metabolic acidosis.
Treatment: gastric lavage, the introduction of adsorbents (activated carbon) and symptomatic therapy. Ketorolac is not adequately excreted through dialysis.

The simultaneous use of ketorolac with Acetylsalicylic acid or other NSAIDs, Calcium supplements, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of Gastrointestinal bleeding.
Co-administration of Ketorol with paracetamol increases the risk of nephrotoxicity, with Methotrexate, hepato-and nephrotoxicity.
Against the background of the use of Ketorolac, the clearance of methotrexate and lithium may be reduced and the toxicity of these substances may increase. The joint appointment of ketorolac and methotrexate is possible only when using low doses of the latter (in this case, the concentration of methotrexate in the blood plasma should be monitored).
Probenecid reduces plasma clearance and distribution of ketorolac, increases plasma concentration and increases the half-life of the latter.
Co-administration with indirect anticoagulants, Heparin, thrombolytic agents, antiplatelet agents, cefoperazone, cefotetan and Pentoxifylline increases the risk of bleeding.
Ketorol reduces the effect of antihypertensive and diuretic drugs (as the synthesis of prostaglandins in the kidneys is reduced).
When combining Ketorol with opioid analgesics, the dose of the latter can be significantly reduced.
Antacids do not affect the absorption of Ketorolac.
With simultaneous use with Ketorol, the hypoglycemic effect of insulin and oral hypoglycemic drugs is increased (therefore, dose recalculation is necessary).
The joint appointment of Ketorol with sodium valproate causes a violation of platelet aggregation.
Ketorolac increases plasma concentrations of Verapamil and Nifedipine.
When prescribing Ketorol with other nephrotoxic drugs (including with gold medications), the risk of nephrotoxicity increases.
Drugs that block tubular secretion, reduce the clearance of ketorolac and increase its concentration in the blood plasma.
Pharmaceutical Interaction
The solution for injection should not be mixed in the same syringe with morphine sulfate, promethazine and hydroxyzine due to precipitation.
Pharmaceutically incompatible with tramadol solution, lithium preparations.
The solution for injection is compatible with saline, 5% dextrose solution, Ringer's solution and Ringer-lactate solution,solution of plasmalite, as well as with infusion solutions containing aminophylline, Lidocaine hydrochloride, dopamine hydrochloride, short-acting human insulin and heparin sodium salt.

List B. The drug should be stored in a dry, dark place, out of reach of children at a temperature not exceeding 25 ° C.

3 years.
Pharmacy sales terms
The drug is available on prescription.