Ketorolac

When ATH:
M01AB15

Characteristic.

NSAIDs. Ketorolac tromethamine is razemical mixture (-)With and (+)R forms. Ketorolac tromethamine may exist in three crystalline forms of. All forms are equally soluble in water. Ketorolac tromethamine has a pKa 3,5 and the distribution coefficient n-octanol / water 0,26. Molecular weight 376,41.

Pharmacological action.
Analgesic, anti-inflammatory, pyretic, antiagregantnoe.

Application.

Pain syndrome moderate to strong expression, incl. postoperatively (after abdominal, gynecological, orthopedic, urological and other operations), pain in trauma (dislocation, fracture, fractures and sprains), pain in osteoarthritis, osteochondrosis, neuralgia, pain in oncology, toothache, pain after dental surgery, when Pericoronitis, pulpitis, back pain and muscle.

Contraindications.

Hypersensitivity (incl. to other NSAIDs), «Aspirinovaya» asthma (a combination of asthma, recurrent nasal polyposis, and paranasal sinuses, and intolerance of aspirin and drugs pirazolonovogo series), bronchospasm, angioedema, erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, peptic ulcers, gipovolemiя, degidratatsiya, hypocoagulation (incl. hemophilia), a high risk of bleeding or a recurrence (incl. after surgery), hemodyscrasia, hemorrhagic stroke (confirmed or suspected), gyemorragichyeskii diatyez, kidney and / or liver failure (plasma creatinine above 50 mg / l), concomitant use of other NSAIDs, labor and delivery, Age to 16 years. Not used for anesthesia before and during surgery because of the high risk of bleeding, and for the treatment of chronic pain.

Restrictions apply.

Bronchial asthma, cholecystitis, cholestasis, active hepatitis, congestive heart failure, arterial hypertension, impairment of renal function (plasma creatinine below 50 mg / l), sepsis, systemic lupus erythematosus, polyps of the mucous membrane of the nose and nasopharynx, advanced age (senior 65 years).

Pregnancy and breast-feeding.

Teratogenic effects. In reproduction studies, made in the period of organogenesis, with daily oral doses of ketorolac tromethamine 3,6 mg / kg (0,37 MRDC) rabbits and 10 mg / kg (1,0 MRDC) in rats showed no teratogenic effects on the fetus. However, reproductive studies in animals do not always predict effects in humans.

There are no adequate and well-controlled studies in pregnant women have not held. Application during pregnancy is possible, if the effect of therapy outweighs the potential risk to the fetus.

Nonteratogenic effects. As it is well known adverse effects of NSAIDs on the cardiovascular system of the fetus (premature closure of the ductus arteriosus), should be avoided in pregnancy (especially in the later stages). Oral doses of ketorolac tromethamine 1,5 mg / kg (0,14 MRDC) rats, applied after 17 day of pregnancy, caused dystocia and higher pup mortality.

Labor and delivery. The use of ketorolac tromethamine is contraindicated, because, inhibiting the synthesis of prostaglandins, it may adversely affect fetal circulation and reduce uterine activity, which increases the risk of uterine bleeding.

Category actions on the fetus by the FDA — with. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

After a single oral administration 10 mg of ketorolac tromethamine maximum concentration, determined in human breast milk, is 7,3 ng / ml, maximum ratio of milk/plasma — 0,037; after one day of admission (4 once a day) Similar figures are 7,9 ng / ml, after 0,025. Since PM, ingibiruyushtie synthesis NG, can cause adverse effects in newborns, at the time of treatment should stop breastfeeding.

Side effects.

The frequency of side effects increases with the dose. In clinical trials, the following were noted side effects, possibly associated with the use of ketorolac tromethamine:

From the digestive tract: gastralgia (13%), nausea (12%), dyspepsia (12%), diarrhea (7%); >1% - Constipation, flatulence, a feeling of fullness, vomiting, stomatitis; ≤ 1%-gastritis, belching, anorexia, increased appetite, dry mouth.

From the nervous system and sensory organs: headache (17%), dizziness (7%), drowsiness (6%); ≤ 1%-asthenia, tremor, unusual dreams, insomnia, hallucinations, euphoria, extrapyramidal symptoms, vertigo, paraesthesia, depression, nervousness, thought disorders, inability to concentrate, hyperkinesis, stupor, hyperdipsia, taste disturbances, blurred vision (incl. blurred vision), hearing loss, tinnitus.

Cardio-vascular system and blood (hematopoiesis, hemostasis): >1% - Increase in blood pressure; ≤ 1%-heartbeat, paleness, fainting, anemia, eozinofilija.

From the respiratory system: ≤ 1%-Dyspnea, rhinitis, pulmonary edema, cough.

With the genitourinary system: ≤ 1%-hematuria, proteinuria, oligurija, urinary retention, frequent urination.

For the skin: >1% -itching, rash.

Allergic reactions: <1% - Urticaria.

Other: swelling (4%), >1% -Purpura, increased sweating; ≤ 1% of nosebleeds, rectal bleeding, weight gain, fever, infection.

Local reactions: pain at the injection site (2% — repeated introduction).

In post-marketing studies have noted the following side effects:

From the digestive tract: erosive and ulcerative lesions of the gastrointestinal tract (incl. with perforation and/or bleeding is abdominal pain, spasm, or a burning sensation in the epigastric region, ground, vomiting on the type of "coffee grounds", nausea, heartburn and others.), cholestatic jaundice, abnormal liver function, hepatitis, gepatomegaliya, acute pancreatitis.

From the nervous system and sensory organs: convulsions, psychosis, aseptic meningitis (fever, Strong headache, convulsions, stiff neck and / or back).

Cardio-vascular system and blood (hematopoiesis, hemostasis): gipotenziya, flushing, thrombocytopenia, leukopenia.

From the respiratory system: ≤ 1%-asthma, bronchospasm.

With the genitourinary system: acute renal failure, back pain with or without hematuria and / or azotemia, hemolytic uremic syndrome (gemoliticheskaya anemia, renal failure, thrombocytopenia), giponatriemiya, hyperkalemia, jade, edema of renal origin.

For the skin: Lyell's syndrome, Stevens-Johnson syndrome, exfoliative dermatitis, makulopapulleznaya rash, hives.

Allergic reactions: anafilaktoidnыe reactions or anaphylaxis, laryngeal edema, swelling of the tongue, angioedema.

Other: bleeding from the surgical wound, myalgia.

Cooperation.

The simultaneous use of acetylsalicylic acid or other NSAIDs, gljukokortikoidami, ethanol, corticotropin may lead to gastrointestinal ulcers and development of gastrointestinal bleeding. Co-administration with paracetamol enhances nephrotoxicity, with methotrexate is liver- and nephrotoxicity. Co-administration of ketorolac tromethamine and methotrexate is only possible when using low doses of the latter (necessary to control the concentration of methotrexate in plasma). Against the background of ketorolac tromethamine may decrease the clearance of lithium and methotrexate and increased toxicity of these substances. Probenecid decreases the plasma clearance and volume of distribution of ketorolac tromethamine, increases its concentration in blood plasma and increases T_1/2. Reduces the diuretic effect of furosemide in people with normovolemia. Co-administration with indirect anticoagulants, geparinom, thrombolytics, antiplatelet, cefoperazone, tsefotetanom and pentoxifylline increases the risk of bleeding. Reduces the effect of antihypertensive drugs and diuretics (decreased PG synthesis in the kidneys). While the use of ACE inhibitors increases the likelihood of renal impairment. When combined with the last dose of opioid analgesics can be significantly reduced.

Antacids do not affect the completeness of absorption of ketorolac tromethamine. It increases the hypoglycemic effect of insulin and oral hypoglycemic drugs (recalculation of the dose needed). Co-administration with sodium valproate causes a disturbance of platelet aggregation. It increases plasma concentration of nifedipine, and verapamil. In the appointment of other nephrotoxic drugs (incl. with the drugs gold) It increases the risk of nephrotoxicity. PM, block tubular secretion, ketorolac reduce clearance and increase its concentration in blood plasma.

The solution for injection should not be mixed in the same syringe with morphine sulfate, promethazine and Hydroxyzine of precipitation. Pharmaceutical incompatible with a solution of tramadol, lithium preparations. The solution for injection is compatible with a range of solutions, incl. saline, 5% dextrose, Ringer, as well as infusion solutions, containing aminophylline, Lidocaine hydrochloride, dopamine hydrochloride, Short-acting human insulin and heparin sodium salt.

In post-marketing studies have reported on the possible interaction of ketorolac tromethamine (I /, / m) with non-depolarizing muscle relaxants, leading to apnea (special studies of this interaction is not performed).

Overdose.

Symptoms: slackness, drowsiness, nausea, vomiting, abdominal pain, the occurrence of peptic ulcers of the stomach and / or erosive gastritis, impairment of renal function, metabolic acidosis.

Treatment: simptomaticheskaya therapy, maintenance of the vital functions of the body. The specific antidote is not found. It is not displayed sufficiently by dialysis.

Dosing and Administration.

Inside, / m, I /. Children only as injections. Dose picked individually, taking into account the severity of pain. A single dose of 10-30 mg, the frequency is up to 4 once a day (every 6-8 hours). The maximum daily dose for elderly patients is 60 mg. The solution was administered / m or / in the treatment of acute and severe pain in not more than 5 days, children — 2 days. The tablets are used no more than 5-7 days.

Precautions.

Patients, receiving NSAIDs, incl. ketorolaka trometamin, are possible severe complications of treatment, both gastrointestinal ulceration, bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, hepatic failure.

The risk of complications increases with drug therapy treatment and elongation increase oral dose more 40 mg / day. Patients with impaired blood clotting appointed only with constant monitoring of the number of platelets, This is especially important for post-operative patients, requiring careful hemostasis. Hypovolemia increase the risk of adverse reactions from the kidneys. Do not use simultaneously with paracetamol more 5 d. It is not recommended to use the drug for pain relief in labor (due to the lack of adequate research and the possible influence of NSAIDs on the contractile ability of the uterus).

Possible appearance during the treatment period of drowsiness, dizziness, insomnia or depression necessitates compliance with caution during activities potentially hazardous activities, require increased attention and psychomotor speed reactions (driving vehicles).

Cooperation