Ksefokam lyophilisate for preparation of solution for injection 8mg, No. 5

• Short-term treatment of mild to moderate acute pain syndrome;

• symptomatic therapy of pain and inflammation associated with osteoarthritis;

• symptomatic therapy of pain and inflammation associated with rheumatoid arthritis.

Parenteral

A solution for injection is prepared immediately before use by dissolving the contents of one vial (8 mg of KsefokamЃ powder) with water for injection (2 ml).

After preparing the solution, the needle is replaced. IM injections are made with a long needle.

Cooked so. the solution is administered intravenously or intramuscularly for postoperative pain and intramuscularly for an acute attack of lumbago / sciatica.

The duration of intravenous administration of the solution should be at least 15 s, intramuscularly - at least 5 s.

The starting dose can be 8 or 16 mg. If the analgesic effect of a dose of 8 mg is insufficient, the same dose can be additionally administered.

Supportive therapy: 8 mg 2 times a day. The maximum daily dose should not exceed 16 mg.

The minimum effective dose should be used in the smallest possible short course.

Lyophilisate for the preparation of a solution for intravenous and intramuscular administration

1 fl.

active substance:

lornoxicam 8 mg

excipients: mannitol (E421) - 100 mg; trometamol - 12 mg; disodium edetate - 0.2 mg

• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose or paranasal sinuses, rhinitis, angioedema, urticaria and intolerance to acetylsalicylic acid and other NSAIDs (including a history);

• thrombocytopenia;

• hemorrhagic diathesis or bleeding disorders, as well as those who have undergone surgery associated with the risk of bleeding or incomplete hemostasis;

• period after coronary artery bypass grafting;

• decompensated heart failure;

• erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding;

• cerebrovascular or other bleeding;

• a history of gastrointestinal bleeding or ulcer perforation associated with NSAIDs;

• a history of active peptic ulcer or recurrent peptic ulcer;

• inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the acute phase;

• severe liver failure;

• severe renal failure (serum creatinine level more than 700 ?mol / l), progressive kidney disease, confirmed hyperkalemia;

• pregnancy;

• breastfeeding period;

• patients under the age of 18 (due to insufficient clinical experience);

• hypersensitivity to lornoxicam or any of the excipients.

pharmachologic effect

NSAIDs, belongs to the oxicam class. It has a pronounced analgesic and anti-inflammatory effect.

The mechanism of action is based on the suppression of prostaglandin synthesis (inhibition of the COX enzyme), leading to suppression of inflammation.

Lornoxicam does not affect the main indicators of the state of the body: body temperature, heart rate, blood pressure, ECG data, spirometry.

The analgesic effect of lornoxicam is not drug-related.

The drug Ksefokam does not have an opiate-like effect on the central nervous system and, unlike narcotic analgesics, does not depress respiration, does not cause drug dependence.

Due to the presence of a local irritant effect on the gastrointestinal tract and a systemic ulcerogenic effect associated with the suppression of prostaglandin synthesis, complications from the gastrointestinal tract are frequent undesirable effects in the treatment of NSAIDs.

Pharmacokinetics

Absorption and distribution

Cmax of lornoxicam in plasma with i / m administration is achieved in approximately 0.4 hours. The absolute bioavailability (calculated by AUC) after i / m administration is 97%.

The degree of binding of lornoxicam to plasma proteins is about 99% and does not depend on the concentration.

Metabolism and excretion

Lornoxicam is extensively metabolized in the liver, mainly via hydroxylation to the inactive 5-hydroxylornoxicam. Lornoxicam is found in plasma unchanged and as a hydroxylated metabolite. Biotransformation of lornoxicam is carried out by the isoenzyme CYP2C9. Due to the polymorphism of the gene encoding this enzyme, there are people with a slow and fast metabolism of the drug, which can lead to a significant increase in plasma levels of lornoxicam in those with a slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized: about 2/3 of the drug is excreted by the liver, and 1/3 by the kidneys as an inactive metabolite.

T1 / 2 of lornoxicam averages 3 to 4 hours.

Pharmacokinetics in special patient groups

In elderly people (over 65 years old), the clearance of the drug is reduced by 30-40%.

In patients with impaired liver or kidney function, no significant changes in the kinetics of lornoxicam are observed, with the exception of cumulation in patients with chronic liver disease after 7 days of treatment at a daily dose of 12 mg or 16 mg.

Side effect

Infectious and parasitic diseases: rarely - pharyngitis.

From the side of the blood and lymphatic system: rarely - anemia, thrombocytopenia, leukopenia, increased bleeding time; very rarely - ecchymosis. It has been reported that NSAIDs can cause potentially severe hematological disorders, such as neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia (class-specific effects).

From the immune system: rarely - hypersensitivity, anaphylactoid and anaphylactic reactions.

From the side of metabolism and nutrition: infrequently - anorexia, change in body weight.

Mental disorders: infrequently - sleep disturbance, depression; rarely - confusion, nervousness, agitation.

From the nervous system: often - short-term headaches of mild intensity, dizziness; rarely - doubtfulness, paresthesias, taste disturbances, tremors, migraines; very rarely - aseptic meningitis in patients with SLE and mixed connective tissue diseases.

From the side of the organ of vision: infrequently - conjunctivitis; rarely - visual disturbances.

On the part of the organ of hearing and labyrinth disorders: infrequently - dizziness, tinnitus.

From the side of the heart: infrequently - palpitations, tachycardia, edema, heart failure.

From the side of the vessels: infrequently - flushing of the face, edema; rarely - arterial hypertension, bleeding, hematoma.

From the respiratory system: infrequently - rhinitis; rarely - dyspnea, cough, bronchospasm.

From the digestive system: often - nausea, abdominal pain, dyspeptic symptoms, diarrhea, vomiting; infrequently - constipation, flatulence, belching, dry mouth, gastritis, stomach ulcer, pain in the epigastric region, duodenal ulcer, ulceration in the oral cavity; rarely - melena, bloody vomiting, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, perforated peptic ulcer, gastrointestinal bleeding.

From the liver and biliary tract: infrequently - an increase in liver function tests, ALT or AST; rarely - liver dysfunction; very rarely - damage to hepatocytes, hepatotoxicity, which can lead to liver failure, hepatitis, jaundice and cholestasis.

Skin and subcutaneous tissue disorders: infrequently - rash, itching, sweating, erythematous rash, urticaria, Quincke's edema, alopecia; rarely - dermatitis and eczema, purpura; very rarely - edema, bullous reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the musculoskeletal system: infrequently - arthralgia; rarely - bone pain, muscle spasms, myalgia.

From the urinary system: rarely - nocturia, urinary disorders, increased levels of urea and creatinine in the blood; very rarely - in patients with pre-existing renal impairment, who need renal prostaglandins to maintain renal blood flow, lornoxicam can provoke acute renal failure. Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is a class-specific effect of NSAIDs.

General disorders and disorders at the injection site: infrequently - malaise, swelling of the face; rarely asthenia.

Application during pregnancy and lactation

Due to the lack of data on the use of the drug Ksefokam during pregnancy and lactation, the drug should not be used.

Suppression of prostaglandin synthesis can have side effects on pregnancy and / or fetal development.

The use of inhibitors of prostaglandin synthesis in early pregnancy increases the risk of miscarriage or the development of heart disease. The risk is considered to be proportional to the dose and duration of treatment.

The appointment of inhibitors of prostaglandin synthesis in the third trimester of pregnancy can lead to toxic effects on the heart and lungs of the fetus (premature closure of the ductus arteriosus and the development of pulmonary hypertension), as well as impaired renal function and, consequently, a decrease in amniotic fluid. Application in late terms can cause prolongation of bleeding time in the mother and fetus, as well as suppression of the contractile activity of the uterus, which can delay or lengthen the period of labor.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency.

Patients with moderate hepatic impairment may require dose adjustment.

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure (serum creatinine level more than 700 ?mol / l), progressive kidney disease, confirmed hyperkalemia.

Patients with mild to moderate renal impairment may require dose adjustment.

Application in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

Elderly patients (over 65 years of age) should be prescribed the drug with caution.

special instructions

The drug should not be used concomitantly with other NSAIDs.

The risk of gastrointestinal bleeding, ulceration or perforation of the gastrointestinal tract increases with increasing doses of NSAIDs in patients with a history of gastric ulcer, especially if it was accompanied by complications such as bleeding or perforation in the elderly. Such patients should begin treatment with the lowest possible dose of the drug. Such patients, as well as patients who need the simultaneous administration of low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal adverse events, are shown the simultaneous administration of drugs that have a protective effect (for example, misoprostol or proton pump inhibitors).

Regular observation is recommended. If signs of liver damage appear (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, dark urine, increased hepatic transaminases), the patient should stop taking the drug and consult a doctor.

The drug can change the properties of platelets, but does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular diseases.

For the disorders described below, Xefocam should be prescribed only after a careful assessment of the expected benefit of therapy and the possible risk.

Mild renal dysfunction (serum creatinine 150-300 ?mol / l) and moderate (serum creatinine 300-700 ?mol / l): maintenance of renal blood flow depends on the level of renal prostaglandins. Ksefokam should be discontinued if renal function deteriorates during treatment.

Monitoring of renal function should be carried out in patients who have undergone major surgery, patients with heart failure receiving diuretics, as well as in the case of drugs with proven or suspected nephrotoxicity.

Disruption of the blood coagulation system: Close clinical observation and evaluation of laboratory parameters, such as APTT, are recommended.

Liver dysfunction (liver cirrhosis): regular clinical observation and evaluation of laboratory parameters should be carried out. in the treatment of lornoxicam in a daily dose of 12-16 mg, cumulation of the drug is possible.

Long-term treatment (more than 3 months): Regular assessment of laboratory parameters of blood (hemoglobin), renal function (creatinine) and liver enzymes is recommended.

Patients over 65 years of age: monitoring of liver and kidney function is recommended. Use with caution in the elderly in the postoperative period.

It is necessary to avoid concomitant use with other NSAIDs, including selective COX-2 inhibitors.

Adverse effects can be minimized by using the lowest effective dose of the drug for the shortest amount of time sufficient to control symptoms.

Gastrointestinal bleeding, ulcer, perforation, which were previously noted with the use of all NSAIDs, at any stage of treatment and can be fatal.

The presence of Helicobacter pylori.

History of gastrointestinal toxicity, particularly in the elderly.

While taking medications such as oral corticosteroids (for example, prednisolone), anticoagulants (for example, warfarin), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline) and antiplatelet drugs (for example, acetylsalicylic acid), ...

With the simultaneous use of NSAIDs and heparin during spinal and epidural anesthesia, the risk of hematoma development increases.

History of gastrointestinal tract pathology (ulcerative colitis, Crohn's disease); the patient's condition may worsen.

History of arterial hypertension and / or heart failure, because with the use of NSAIDs, fluid retention and the development of edema were noted.

In the presence of peripheral arterial disease or cerebrovascular disease, the presence of risk factors for the development of cardiovascular diseases, such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking, Xefocam should be prescribed only after a careful assessment of the expected benefit of therapy and the possible risk.

Ksefokam, like other NSAIDs, may increase the risk of arterial thromboembolic complications (for example, myocardial infarction or stroke).

Care should be taken to prescribe the drug to patients with bronchial asthma in the active phase or in history, since it is known that NSAIDs can provoke bronchospasm in such patients.

In very rare cases, severe skin reactions leading to death are possible, incl. exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

The use of the drug Ksefokam, like any drug that suppresses the synthesis of prostaglandins, can interfere with the ability to fertilize, therefore it is not recommended for women wishing to become pregnant.

Patients with SLE and mixed connective tissue diseases may be at increased risk of aseptic meningitis.

Lornoxicam inhibits platelet aggregation and lengthens bleeding time, so it should be prescribed with caution in case of increased bleeding tendency.

The simultaneous use of NSAIDs and tacrolimus may lead to an increased risk of nephrotoxic effects due to inhibition of prostacyclin synthesis in the kidneys.

It is recommended that lornoxicam be avoided for varicella-zoster virus infections.

Influence on the ability to drive vehicles and mechanisms

Patients who experience dizziness and / or drowsiness during treatment with lornoxicam should refrain from driving and operating equipment.

Overdose

At present, there is no data on overdose that would allow assessing its consequences or suggesting specific treatment.

In case of an overdose of Ksefokam, the following symptoms may occur: nausea and vomiting, cerebral symptoms (dizziness, blurred vision, ataxia, turning into a coma, and convulsions). Changes in liver and kidney function, blood clotting disorders are possible.

Ћечение: в случае передозировки или подозрени¤ на передозировку терапию препаратом немедленно прекращают. ¬следствие короткого “1/2 лорноксикам быстро удал¤етс¤ из организма. ?иализ неэффективен. ?о насто¤щего времени о существовании специфического антидота неизвестно. ?л¤ лечени¤ желудочно-кишечных расстройств могут примен¤тьс¤ аналоги простагландина или ранитидин.

Ћекарственное взаимодействие

ѕри одновременном применении препарата  сефокам с циметидином повышаетс¤ концентраци¤ лорноксикама в плазме. ¬заимодействие с ранитидином и антацидными препаратами не вы¤влено.

ѕри одновременном применении препарата  сефокам с антикоагул¤нтами или ингибиторами агрегации тромбоцитов возможно увеличение времени кровотечени¤ и повышение риска кровотечени¤ (необходим контроль MHO).

ќдновременное применение с фенпрокумоном уменьшает его эффективность.

ѕри одновременном применении Ќѕ¬— и гепарина в сочетании со спинальной/эпидуральной анестезией увеличиваетс¤ риск возникновени¤ спинальных или эпидуральных гематом.

ѕри одновременном применении  сефокама уменьшаетс¤ гипотензивный эффект бета-адреноблокаторов и антагонистов рецепторов ангиотензина II.

 сефокам уменьшает мочегонный эффект и гипотензивное действие 'петлевых', тиазидных и калийсберегающих диуретиков.

 сефокам снижает почечный клиренс дигоксина.

ѕри одновременном применении с антибиотиками группы хинолонов повышаетс¤ риск развити¤ судорожного синдрома.

ѕри одновременном применении с антиагрегантами повышаетс¤ риск желудочно-кишечного кровотечени¤.

ѕри одновременном применении с другими Ќѕ¬— или v — повышаетс¤ риск кровотечени¤ из ? “.

 сефокам повышает концентрацию метотрексата в сыворотке. Ёто может привести к усилению токсичности. ѕри необходимости одновременного назначени¤ этих препаратов требуетс¤ пристальное наблюдение за пациентом.

ѕри одновременном применении с селективными ингибиторами обратного захвата серотонина (например, циталопрам, флуоксетин, пароксетин, сертралин) повышаетс¤ риск кровотечений из ? “.

Ќѕ¬ѕ подавл¤ют почечный клиренс ионов лити¤, поэтому концентраци¤ лити¤ в сыворотке может превысить предел токсичности. ѕоэтому необходимо посто¤нное наблюдение за уровнем ионов лити¤ в сыворотке, особенно на первоначальном этапе лечени¤, при изменении дозы и прекращении лечени¤.

 сефокам повышает нефротоксичность циклоспорина.

 сефокам способен усиливать гипогликемический эффект производных сульфонилмочевины.

With the simultaneous use of Xefocam with cefamandol, cefoperazone, cefotetan, valproic acid, the risk of bleeding increases.

With the simultaneous use of substances that are inducers and inhibitors of the CYP2C9 isoenzyme of cytochrome P450, lornoxicam (like other NSAIDs metabolized by the CYP2C9 isoenzyme of cytochrome P450) interacts with its inducers and inhibitors.

With simultaneous use with tacrolimus, the risk of nephrotoxicity increases due to inhibition of prostacyclin synthesis in the kidneys.

NSAIDs can reduce the renal clearance of pemetrexed, which leads to an increase in nephrotoxicity and gastrointestinal toxicity of the drug, as well as inhibition of hematopoiesis.