Pharmacology Acular LS
Pharmacological action – analgesic, anti-inflammatory, antipyretic, antiplatelet.
Acular LS Inhibits the activity of cyclooxygenase (COX-1 and COX-2) and inhibits the synthesis of PG. Has a pronounced analgesic activity, associated with an S-shape. The maximum analgesic effect occurs within 2-3 h. It inhibits platelet aggregation, the effect is reversible. Unlike antiagregatsionnogo effect of acetylsalicylic acid (maintained for the lifetime of the platelet), ketorolac tromethamine effect on platelet aggregation is terminated after 24-48 hours of ketorolac tromethamine has no sedative or anxiolytic effect.
Comparison of the pharmacokinetics of ketorolac tromethamine after a / c, / m and oral administration showed that the bioavailability in adults is 100% regardless of the mode of administration. After i / m administration is rapidly and completely absorbed. Cmax is achieved within 50 min after a single i / m injection of 30 mg and 2.2-3.0 mg / ml. When i / v infusion of 10 mg maximum plasma levels (2.4 mg / ml) is defined by 5.4 min. Time to reach equilibrium concentration in parenteral and oral – 24 hours when applied every 6 hours when administered rapidly and completely absorbed. Cmax is achieved, on average, 40 minutes and constitutes 0.7-1.1 ug / ml after a dose of 10 mg. Food rich in fat reduces Cmax and delays the achievement of her for 1 hour Antacids do not affect the absorption. Binding to plasma proteins – 99.2%. The degree of binding is independent of concentration in the bloodstream. Metabolized in the liver with the formation of hydroxylated and conjugated forms. The main metabolite – gidroksiketorolak – pharmacologically active. Eliminated primarily by the kidneys. In patients with impaired renal function, excretion is slowed down. The rate decreases in proportion to its degree of renal dysfunction, except for patients with severe renal insufficiency (plasma clearance is slightly higher that expected for a given degree of kidney damage). The urine reveals 92% of the administered dose in feces – 6%. When multiple doses of ketorolac clearance does not change.
There have been reports on the effectiveness of ketorolac tromethamine in migraine attacks. Exhibits anti-inflammatory properties when used in ophthalmology in the form of eye drops.
Carcinogenesis, Mutagenesis, effects on fertility
In the 18-month study in mice after oral administration at doses up to 2 mg / kg / day (0,9 AUC person) and a 24-month study in rats at doses up to 5 mg / kg / day (0,5 AUC person) carcinogenic effects.
There were no ketorolac tromethamine mutagennocti in a number of bacterial in vitro tests at concentrations of 1590 micrograms / ml and above, ketorolac tromethamine caused increased frequency of chromosomal aberrations in Chinese hamster ovary cells.
In studies of reproduction in two generations at dose levels up to 0.5 mg / kg / day had no effect on fertility in mice and rats.
Application of the substance Acular LS
Pain syndrome of moderate to severe intensity, including in the postoperative period (after abdominal, gynecological, orthopedic, urologic and other operations), pain in trauma (sprain, fracture, fractures and sprains), pain in osteoarthritis, osteochondrosis, neuralgia, pain for cancer, tooth pain, after dental procedures, with perikoronite, pulpitis, back pain and muscle aches.
Contraindications Acular LS
Hypersensitivity (including to other NSAIDs), “Aspirin” asthma (a combination of asthma, recurrent nasal polyposis, and paranasal sinuses, as well as intolerance of aspirin and drugs pirazolonovogo series), bronchospasm, angioedema, erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, hypovolemia, dehydration, hypocoagulation (including hemophilia), a high risk of bleeding or its recurrence (including after operations), impairment of hematopoiesis, hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis , renal and / or liver failure (plasma creatinine above 50 mg / l), concomitant use with other NSAIDs, labor and delivery, the age of 16 years. Do not use for pain relief before and during surgery because of the high risk of bleeding, as well as for the treatment of chronic pain.
Restrictions apply Acular LS
Bronchial asthma, cholecystitis, cholestasis, active hepatitis, chronic heart failure, hypertension, renal failure (plasma creatinine below 50 mg / l), sepsis, systemic lupus erythematosus, and polyps of the nasal mucosa and nasopharynx, advanced age (65 years) .
Pregnancy and breastfeeding Acular LS
Teratogenic effects. In studies of reproduction, performed during organogenesis using daily oral doses of ketorolac tromethamine 3.6 mg / kg (0.37 MRDCH) in rabbits and 10 mg / kg (1.0 MRDCH) in rats showed no teratogenic effects on the fetus . However, reproductive studies in animals do not always predict effects in humans.
Adequate and well controlled studies in pregnant women has not been conducted. Pregnancy is possible if the effect of therapy outweighs the potential risk to the fetus.
Neteratogennye effects. Since it is known adverse effects of NSAIDs on the cardiovascular system of the fetus (premature closure of the ductus arteriosus), should be avoided during pregnancy (especially in the later stages). Ketorolac tromethamine oral doses of 1.5 mg / kg (0.14 MRDCH) in rats after 17 days are used pregnancy, caused dystocia and calves increased mortality.
Childbirth and delivery. The use of ketorolac tromethamine is contraindicated, since by inhibiting prostaglandin synthesis, it can adversely affect fetal circulation and reduce uterine contractions, which increases the risk of uterine bleeding.
Category of the fetus by FDA – S.
After a single oral dose of 10 mg of ketorolac tromethamine maximum concentration determined in breast milk in humans is 7.3 ng / ml, the maximum ratio of milk / plasma – 0.037, after one day of admission (4 times a day), the corresponding figures are 7.9 ng / ml, 0.025. Because drugs that inhibit the synthesis of PG, may cause adverse effects in newborns, at the time of treatment should stop breastfeeding.
Side effects of substance Acular LS
The frequency of side effects increases with dose. In clinical trials were marked by the following side effects possibly related to the use of ketorolac tromethamine:
From the digestive tract: stomachalgia (13%), nausea (12%), dyspepsia (12%), diarrhea (7%)> 1% – constipation, bloating, feeling of fullness, vomiting, stomatitis; ≤ 1% – gastritis , belching, anorexia, increased appetite, dry mouth.
Since the nervous system and sense organs: headache (17%), dizziness (7%), somnolence (6%); ≤ 1% – asthenia, tremor, abnormal dreams, insomnia, hallucinations, euphoria, extrapyramidal symptoms, vertigo, paresthesia depression, anxiety, disturbances in thinking, inability to concentrate, hyperkinesis, stupor, excessive thirst, taste disturbances, visual disturbances (including blurred vision), hearing loss, ringing in the ears.
Cardio-vascular system and blood (hematopoiesis, hemostasis):> 1% – increased blood pressure; ≤ 1% – palpitations, pallor, syncope, anemia, eosinophilia.
The respiratory system: ≤ 1% – dyspnea, rhinitis, pulmonary edema, cough.
Genitourinary: ≤ 1% – hematuria, proteinuria, oliguria, urinary retention, urinary frequency.
For the skin:> 1% – pruritus, rash.
Allergic reactions:1% – purpura, sweating; ≤ 1% – nosebleeds, rectal bleeding, weight gain, fever, infection.
Local reactions: pain at the injection site (2% – with multiple doses).
In post-marketing studies have noted the following side effects:
From the digestive tract: erosive and ulcerative lesions of the gastrointestinal tract (including perforation and / or bleeding – abdominal pain, spasm or burning sensation in the epigastric region, melena, vomiting on the type of “coffee ground”, nausea, heartburn, etc.) , cholestatic jaundice, hepatic dysfunction, hepatitis, hepatomegaly, acute pancreatitis.
The nervous system and sensory organs: seizures, psychosis, aseptic meningitis (fever, severe headache, seizures, stiff neck and / or back).
Cardio-vascular system and blood (hematopoiesis, hemostasis): hypotension, flushing, thrombocytopenia, leukopenia.
The respiratory system: ≤ 1% – asthma, bronchospasm.
Genitourinary: acute renal failure, lower back pain with or without hematuria and / or azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia), hyponatremia, hyperkalemia, nephritis, edema of renal origin.
For the skin: Lyell’s syndrome, Stevens-Johnson syndrome, exfoliative dermatitis, makulopapulleznaya rash, urticaria.
Allergic Reactions: anaphylaxis or anaphylactoid reactions, laryngeal edema, swelling of the tongue, angioedema.
Other: bleeding from the wound, myalgia.
Interaction
The simultaneous use of aspirin or other NSAIDs, corticosteroids, ethanol, corticotropin may lead to gastrointestinal ulceration and development of gastrointestinal bleeding. Joint appointment with paracetamol increases the nephrotoxicity of methotrexate – a hepato-and nephrotoxicity. Ketorolac tromethamine simultaneous appointment and methotrexate is only possible using low doses of the latter (it is necessary to control the concentration of methotrexate in blood plasma). Against the background of ketorolac tromethamine may decrease the clearance of methotrexate and increased toxicity of lithium, and these substances. Probenecid decreases the plasma clearance and volume of distribution of ketorolac tromethamine, increases its concentration in blood plasma and increases the T1 / 2. Reduces the diuretic effect of furosemide in humans with normovolemiey. Simultaneous with the appointment of indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, and pentoxifylline tsefotetanom increases the risk of bleeding. Reduces the effect of antihypertensive and diuretic drugs (reduced synthesis of PG in the kidney). While the use of ACE inhibitors increases the likelihood of impaired renal function. When combined with opioid analgesics doses of the latter can be reduced substantially.
Antacids do not affect the absorption of ketorolac tromethamine completeness. Increases the hypoglycemic effect of insulin and oral hypoglycemic agents (requires recalculation of the dose). Joint appointment with valproate sodium is a violation of platelet aggregation. Increases the plasma concentrations of verapamil and nifedipine. In the appointment of other nephrotoxic drugs (including drugs with gold) increased risk of nephrotoxicity. Drugs that block tubular secretion, reduced clearance of ketorolac and increase its concentration in blood plasma.
Solution for injection should not be mixed in one syringe with morphine sulfate, promethazine and hydroxyzine for precipitation. Pharmaceutical incompatible with a solution of tramadol, medication lithium. Solution for injection is compatible with a number of solutions, including with saline, 5% dextrose, Ringer’s solution, as well as infusion solutions containing aminophylline, lidocaine hydrochloride, dopamine hydrochloride, a short-acting human insulin and heparin sodium salt.
In post-marketing studies have reported a possible interaction between ketorolac tromethamine (a / c, w / o) with non-depolarizing muscle relaxants, leading to apnea (special study of this interaction is not performed).
Overdose Acular LS
Symptoms: lethargy, drowsiness, nausea, vomiting, abdominal pain, the occurrence of peptic ulcers of stomach and / or erosive gastritis, renal failure, metabolic acidosis.
Treatment: symptomatic therapy, the maintenance of vital body functions. The specific antidote is not found. Not shown sufficiently by dialysis.
Dosage and administration Acular LS
Inside, a / m / in. In children, only by injection. Dose picked individually, taking into account the severity of pain. A single dose is 10-30 mg, dose frequency – up to 4 times a day (every 6-8 hours). The maximum daily dose for elderly patients – 60 mg. The solution was administered i / m or / in the treatment of acute and severe pain for up to 5 days in children – 2 days. The tablets are used no more than 5-7 days.
Precautions Acular LS
Patients receiving NSAIDs, including ketorolac tromethamine, there may be serious complications such treatment as ulceration gastrointestinal bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions, hepatic failure.
The risk of developing complications of drug therapy increases for extending and improving the treatment of oral doses over 40 mg / day. Patients with impaired blood clotting administered only under constant control the number of platelets, which is especially important for post-surgical patients, requiring careful hemostasis. Hypovolemia increases the risk of adverse reactions in the kidneys. Do not use simultaneously with acetaminophen for more than 5 days. It is not recommended to use the drug for pain relief in labor (due to lack of adequate studies and the possible influence of NSAIDs on the contractility of the uterus).
Possible appearance during treatment of sleepiness, dizziness, insomnia or depression requires caution during exercise in potentially hazardous activities that require attention and psychomotor speed of reaction (driving vehicles).
