Ketanov, 10 mg 100 pcs

Pharmacotherapeutic group:

Non-steroidal anti-inflammatory drug (NSAID).

ATX code: M01AB15

Pharmacological action:

Pharmacodynamics

Ketorolac has a pronounced analgesic effect, also has anti-inflammatory and moderate antipyretic effects.

The mechanism of action is related to non-selective inhibition of activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, mainly in peripheral tissues, with following inhibition of prostaglandin biosynthesis – modulators of pain sensitivity, thermoregulation and inflammation. Ketorolac is a racemic mixture of [-]S and [+]R enantiomers, and the analgesic effect is due to the [-]S form.

The drug does not affect the opioid receptors, does not depress respiration, does not cause addiction and has no sedative and anxiolytic action. Its analgesic effect is comparable with that of morphine; it is considerably superior to other non-steroidal anti-inflammatory drugs.

After oral administration, the onset of analgesic effect is noted after 1 hour, the maximum effect is reached after 1 -2 hours.

Pharmacokinetics

After oral administration, ketorolac is well absorbed in the gastrointestinal tract – maximum concentration (Cmax) in blood plasma (0.7-1.1 mcg/ml) is reached 40 min after an empty stomach dose of 10 mg. Fat-rich food decreases the maximum blood concentration of the drug and delays its achievement by 1 hour. 99% of the drug is bound to plasma proteins, and in case of hypoalbuminemia the amount of free substance in blood increases. Bioavailability is 80-100%). Time of reaching equilibrium concentration (Css) when administered orally is 24 hours when administered 4 times a day (higher than subtherapeutic) and is 0.39-0.79 mcg/ml after 10 mg oral administration.

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

Transfers to breast milk: after maternal administration of the first and second doses of Ketorolac 10 mg, the Cmax in milk is reached after 2 hours and is 7.3 ng/ml and 7.9 g/l, respectively.

More than 50% of the administered dose is metabolized in the liver to form pharmacologically inactive metabolites. The main metabolites are glucuronides, which are excreted by the kidneys, and p-hydroxyketorolac. It is excreted 91% by the kidneys, 6% – through the intestine.

The elimination half-life (T1/2) in patients with normal renal function is 2.4-9 h after oral administration of 10 mg. The T1/2 is longer in elderly patients and shorter in younger patients. Liver function has no effect on the T1/2. In patients with impaired renal function with plasma creatinine concentrations of 19-50 mg/l (168-442 μmol/l)

The T1/2 is 10.3-10.8 h, with more severe renal impairment more than 13.6 h.

The total clearance is 0.025 l/kg/h when administered orally at 10 mg; in renal failure with plasma creatinine concentrations of 19-50 mg/l when administered orally at 10 mg-0.016 l/kg/h.

It is not excreted by hemodialysis.

Indications

Active ingredient

Composition

One coated tablet contains:

The active ingredient: ketorolaca trometamol -10.00 mg.

Auxiliary substances:

Corn starch – 44.76 mg, microcrystalline cellulose – 122.41 mg, colloidal silica – 1.83 mg, magnesium stearate – 1.00 mg.

The film coating:

Hypromellose – 2.91 mg, macrogol-400 – 0.68 mg, purified talc – 0.16 mg, titanium dioxide – 1.25 mg.

How to take, the dosage

In tablet form, Ketanov® is administered orally once or repeatedly depending on the severity of the pain syndrome. A single dose is 10 mg; when repeatedly administered, it is recommended to take 10 mg up to 4 times a day, depending on the severity of pain; the maximum daily dose should not exceed 40 mg.

When taken orally, the duration of the course should not exceed 5 days.

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors), calcium preparations, glucocorticosteroids, ethanol, corticotropin may lead to a significant increase in the risk of adverse reactions, including formation of gastrointestinal ulcers and development of gastrointestinal bleeding. Concomitant use with nonsteroidal anti-inflammatory drugs is contraindicated.

Concomitant use with paracetamol increases nephrotoxicity. with methotrexate – hepatotoxicity and nephrotoxicity.

The concomitant use of ketorolac and methotrexate is only possible with low doses of the latter (control the plasma concentration of methotrexate) and diuretics (reduces the synthesis of prostaglandins in the kidneys).

When combined with opioid analgesics, the doses of the latter can be significantly reduced.
Antacids do not affect absorption of the drug.

Ketorolac increases hypoglycemic effect of insulin and oral hypoglycemic drugs (dose recalculation is necessary). Concomitant use with sodium valproate causes impaired platelet aggregation.

Enhances plasma concentrations of verapamil and nifedipine.

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

Drugs that block tubular secretion decrease clearance of ketorolac and increase its plasma concentrations.

Concomitant use with probenecid leads to increased plasma concentration and half-life of ketorolac. Concomitant use with probenecid is contraindicated.

The concomitant use of lithium salts and some drugs that inhibit the synthesis of prostaglandins leads to impaired excretion and increased plasma concentration of lithium salts.
Concomitant use with lithium salts is contraindicated.
Caution is recommended during concomitant use of cyclosporine, tacrolimus with ketorolac (as well as with other NSAIDs) due to increased risk of nephrotoxicity.

There have been reported cases of hematoma formation in HIV-infected patients with hemophilia who received zidovudine and ibuprofen concomitantly.

Therefore, caution should be exercised when concomitant use of NSAIDs and zidovudine. Ketorolac has no effect on the binding of digoxin to blood proteins.

According to animal studies, the simultaneous use of NSAIDs with quinolone antibiotics increases the risk of seizures.

The use of NSAIDs is not recommended for 8-12 days after mifepristone administration, because the effect of mifepristone may diminish.

Special Instructions

Ketorolac inhibits platelet aggregation and increases blood clotting time. The effect on platelet aggregation stops after 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys.
If necessary, can be administered in combination with narcotic analgesics.

Ketanow® is not recommended for use as a premedication and maintenance anesthesia.
Fluid retention, arterial hypertension and edema have been reported during the use of ketorolac. Caution should be exercised when prescribing to patients with heart failure, arterial hypertension.

Simultaneous use with other nonsteroidal anti-inflammatory drugs may lead to such disorders as decompensation of heart failure, increased blood pressure. In patients with blood coagulation disorders the drug is prescribed only with continuous monitoring of platelet count, which is especially important in postoperative period when careful hemostasis control is required.

According to clinical studies, use of some nonsteroidal anti-inflammatory drugs in high doses may increase the risk of arterial thrombotic complications (e.g., myocardial infarction, stroke). Although no such complications have been reported with ketorolac, there is insufficient data to exclude the risk of such complications. The risk of adverse reactions increases with longer duration of treatment and higher oral doses over 40 mg/day.

The use of antacids, misoprostol, and drugs that reduce gastric secretion (histamine Hg-receptor blockers, proton pump inhibitors) is recommended to reduce the risk of NSAID gastropathy.

The effect of the medicinal product for medical use on the ability to drive vehicles and machines

. During the treatment period, the development of side effects of the central nervous system (drowsiness, dizziness, headache) which reduces the speed of mental and motor reactions and for this reason it is necessary to refrain from driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

The drug is not used:

– for prophylactic analgesia before and during extensive surgical procedures because of the high risk of bleeding.

– for the treatment of chronic pain.

Gastric and duodenal ulcers, ulcerative colitis, Crohn’s disease, history of liver disease, hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, significant decrease in
circulating blood volume (including after surgery), elderly patients (including those receiving diuretics, weakened patients and those with low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes, peripheral artery disease, smoking, Helicobacter pylori infection, long-term use of non-steroidal anti-inflammatory drugs, tuberculosis, significant osteoporosis, alcoholism, severe somatic diseases, hypotension, hypertension.

Side effects

CNS disorders: frequent – headache, dizziness, somnolence; rarely aseptic meningitis (fever, severe headache, neck muscle stiffness), hyperactivity, mood changes, anxiety, hallucinations, depression, psychosis.

Cardiovascular system disorders: infrequent increase in BP; rarely – pulmonary edema, fainting.

Respiratory system disorders: rarely – bronchospasm, shortness of breath, rhinitis, laryngeal edema.

Disorders of the digestive system: frequently (especially in elderly patients aged over 65 years old with a history of gastrointestinal erosive ulcers) gastralgia, diarrhea; infrequently – stomatitis, flatulence, constipation, vomiting, feeling of stomach overflow; rarely – nausea, erosive-ulcerative lesions of the gastrointestinal tract (including perforation [perforation], gastric ulcers.including with perforation [severe abdominal pain] and bleeding [coffee grounds type vomiting, melena] – conditions that can lead to death), cholestatic jaundice, hepatitis, hepatomegaly. acute pancreatitis.

Disorders of the excretory system: rarely – acute renal failure, lumbar pain with or without hematuria and/or azotemia, hemolytic-uremic syndrome (hemolytic anemia. renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased daily diuresis, nephritis, edema of renal genesis.

Sensory system disorders: rare – hearing loss, tinnitus, vision disorders (including blurred vision).
Haemostatic disorders: rare – bleeding from the postoperative wound, nasal bleeding, rectal bleeding.

Hematopoietic disorders: rarely anemia, eosinophilia, leukopenia.

Skin disorders: infrequent skin rash (including maculopapular rash), purpura, rarely exfoliative dermatitis, urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Allergic reactions: rare anaphylactic reactions, anaphylactoid reactions (skin hyperemia, rash, urticaria, skin itching, shortness of breath, difficulty breathing, angioedema).

Other disorders: frequently – edema (face, shins, weight gain); infrequently – increased sweating: rarely – swelling of the tongue, fever.

Overdose

Symptoms: abdominal pain, nausea, vomiting, occurrence of peptic ulcers of the stomach or erosive gastritis, impaired renal function, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents (activated charcoal) and symptomatic therapy (maintenance of vital body functions).

It is not eliminated sufficiently by dialysis.

Pregnancy use

Safety of use during pregnancy of this drug has not been established. The use during the third trimester of pregnancy of drugs that disrupt the synthesis of prostaglandins may cause premature closure of the arterial duct and weaken the contractility of the uterus. As a consequence of impaired uterine contractions, labor is delayed and the risk of uterine bleeding increases.

Ketorolac penetrates the mother’s milk. Both the mother and the baby have an increased risk of bleeding.

The use of the drug Ketonov® is contraindicated in pregnancy and during breastfeeding.

Similarities