Lornoxicam-Trivium, lyophilizate 8 mg 5 pcs

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID).

ATX code: M01AC05

Indications

Short-term treatment of mild to moderate acute pain syndrome.

Symptomatic therapy of pain and inflammation against osteoarthritis.

Symptomatic therapy of pain and inflammation against rheumatoid arthritis.

Active ingredient

Composition

One vial of lyophilizate contains:

The active ingredient:

lornoxicam – 8.0 mg

Excipients:

Mannitol – 100.0 mg, trometamol – 12.0 mg, disodium edetate – 0.2 mg.

One ampoule with solvent contains:

Water for injection – 2 ml.

How to take, the dosage

Parenterally.

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

After preparation of the solution the needle is replaced. Intramuscular injections are done with a long needle.

The solution prepared this way is given intravenously or intramuscularly for postoperative pain and intramuscularly for an acute attack of lumbago/ischialgia.

The duration of intravenous injection of the solution should be at least 15 seconds, intramuscular – at least 5 seconds.

The recommended single dose is 8 mg intravenously or intramuscularly. The daily dose should not exceed 16 mg. Some patients may require an additional dose of 8 mg for the first 24 hours.

The lowest effective dose should be used for the shortest possible course.

Additional information for special patient groups

Children and adolescents

Lornoxicam is not indicated for use in children and adolescents younger than 18 years because there is insufficient data on its safety and effectiveness.

Elderly people

There is no need to specifically adjust the dose in elderly patients (over 65 years) if there is no renal or hepatic impairment. The drug should be used with caution because the gastrointestinal adverse events are less well tolerated in this age group.

Renal dysfunction

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

Hepatic dysfunction

Patients with moderate hepatic dysfunction may require dose adjustment. Undesirable effects can be minimized by using the lowest effective dose of the drug for the shortest amount of time sufficient to control symptoms.

Interaction

Simultaneous use of the drug Lornoxicam – TRIVIUM® and:

– cimetidine – increases the concentration of lornoxicam in plasma. No interaction with ranitidine and antacids was found;

– anticoagulants or platelet aggregation inhibitors – possible increase in bleeding time (increased risk of bleeding, it is necessary to control the international normalized ratio (INR);

Phenprocoumon – decreases the effectiveness of phenprocoumon treatment;

Heparin – NSAIDs increase the risk of spinal/epidural hematoma when used concurrently with heparin during spinal or epidural anesthesia;

– Beta-adrenoblockers – decreases the hypotensive effectiveness of angiotensin II receptor blockers;

– Diuretics – decreases the diuretic effect and hypotensive effect of loop thiazide and potassium-saving diuretics;

digoxin – decreases the renal clearance of digoxin;

– quinolone antibiotics – increases the risk of seizure syndrome;

– antiaggregants – increases the risk of gastrointestinal bleeding;

– other NSAIDs or glucocorticoids – increases the risk of gastrointestinal ulceration or bleeding;

– methotrexate – increases the serum concentration of methotrexate. This may lead to increased toxicity. Close monitoring of the patient is required if simultaneous administration of these drugs is necessary;

– selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline) – increases the risk of GI bleeding;

Lithium salts – NSAIDs inhibit renal clearance of lithium ions, so serum lithium concentrations may exceed the toxicity limit. Therefore, continuous monitoring of serum lithium ion levels is necessary, especially during initial treatment, dose changes, and discontinuation of treatment;

– cyclosporine – increases cyclosporine nephrotoxicity;

– Sulfonylurea derivatives – may increase the hypoglycemic effect of the latter;

– cefamandole, cefoperazone, cefotetan, valproic acid – increases the risk of bleeding;

– substances that are inducers and inhibitors of cytochrome P450 isoenzyme CYP2C9 lornoxicam (like other NSAIDs metabolized by cytochrome P450 isoenzyme CYP2C9) – interacts with its inducers and inhibitors;

Tacrolimus – increases the risk of nephrotoxic effects due to inhibition of prostacyclin synthesis in the kidneys;

– pemetrexed – NSAIDs may decrease renal clearance of pemetrexed, resulting in increased nephrotoxicity and gastrointestinal toxicity of the drug, as well as inhibition of hematopoiesis.

Special Instructions

With caution

The following disorders should be treated with Lornoxicam-TRIVIUM® only after careful evaluation of the expected benefit of therapy and possible risk:

– Renal dysfunction: mild (serum creatinine 150-300 μmol/L) and moderate (serum creatinine 300-700 μmol/L), because maintenance of renal blood flow depends on renal prostaglandin levels. Lornoxicam-TRIVIUM® should be discontinued if renal function deteriorates during treatment.

– Renal function should be monitored in patients who have undergone major surgery, patients with heart failure, patients receiving diuretics, and if drugs with proven or suspected nephrotoxicity are used.

– Disorders of the clotting system: close clinical monitoring and evaluation of laboratory parameters, such as activated partial thrombin time (APT), is recommended.

– Liver dysfunction (cirrhosis): regular clinical monitoring and evaluation of laboratory parameters should be performed because the drug may cumulate when treated with lornoxicam at a daily dose of 12-16 mg.

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

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

– Avoid concomitant administration with other NSAIDs, including selective cyclooxygenase-2 inhibitors.

– Unwanted 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, ulceration, perforation, which have been reported previously with all NSAIDs at any stage of treatment and may be fatal. Presence of Helicobacter pylori.

– A history of gastrointestinal toxicity, particularly in the elderly.

. – Concomitant use of medications such as oral glucocorticosteroids (e.g., prednisolone), anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline) and antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel).

– The simultaneous use of NSAIDs and heparin during spinal and epidural anesthesia increases the risk of hematoma.

– A history of gastrointestinal pathology (ulcerative colitis, Crohn’s disease), as the patient’s condition may worsen.

– A history of arterial hypertension and/or heart failure, since fluid retention and edema have been reported with NSAIDs.

– In the presence of peripheral arterial disease or cerebrovascular disease, the presence of cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, smoking, Lornoxicam-TRIVIUM® should be prescribed only after careful evaluation of the expected benefit of therapy and the possible risk.

– Lornoxicam-Trivium®, like other NSAIDs, may increase the risk of arterial thromboembolic complications (e.g., myocardial infarction or stroke).

– Caution should be exercised when prescribing the drug in patients with bronchial asthma in the active phase or with a history of bronchial asthma because it is known that NSAIDs may provoke bronchospasm in these patients.

– In very rare cases, severe skin reactions leading to death may occur, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

– Use of Lornoxicam-Trivium®, like any drug that inhibits prostaglandin synthesis, may interfere with fertility, so it is not recommended for women who want to become pregnant.

– Patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease may have an increased risk of aseptic meningitis.

– Lornoxicam suppresses platelet aggregation and prolongs bleeding time, so caution should be exercised when it is prone to bleeding.

– Concomitant use of NSAIDs and tacrolimus may increase the risk of nephrotoxic effects due to inhibition of prostacyclin synthesis in the kidneys.

– It is recommended to avoid the use of lornoxicam in infections caused by varicella zoster virus.

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 the dose of NSAIDs in patients with a history of peptic ulcer, especially if it was accompanied by complications such as bleeding or perforation in the elderly. Such patients should start treatment with the lowest possible dose of the drug. Such patients, as well as patients who require concomitant administration of low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal adverse events, concomitant administration of drugs with a protective effect (e.g., misoprostol or proton pump inhibitors) is indicated.

The regular monitoring is recommended. If signs of liver damage occur (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkened urine, increased “liver transaminases”), the drug should be stopped and the patient should see a physician.

The drug may change platelet properties, but it does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular disease.

Influence on driving and operating machinery

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

Contraindications

– hypersensitivity to lornoxicam or any of the excipients;

– complete or incomplete combination of bronchial asthma, recurrent nasal or paranasal sinus polyposis, rhinitis, angioedema, urticaria and intolerance to acetylsalicylic acid and other NSAIDs (including history of

– thrombocytopenia;

– hemorrhagic diathesis or clotting disorders and those who have had surgery with a risk of bleeding or incomplete hemostasis;

– the period after coronary artery bypass grafting;

– decompensated heart failure;

– erosive-ulcerative changes in gastric or 12 duodenal mucosa, active gastrointestinal bleeding; cerebrovascular or other bleeding;

– gastrointestinal bleeding or ulcer perforation in history associated with NSAID use;

– history of active peptic ulcer or recurrent peptic ulcer;

– Inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute phase;

– severe hepatic impairment;

– Severe renal insufficiency (serum creatinine greater than 700 μmol/L), advanced renal disease, confirmed hyperkalemia;

Pregnancy and breast-feeding;

Patients under 18 years of age (due to lack of clinical experience).

Side effects

In each private category, side effects are grouped by system-organ class and presented in decreasing order of frequency: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); infrequent (≥ 1/1000 to < 1/100); rare (≥ 1/10 000 to < 1/1000); very rare (< 1/10 000), unknown (cannot be estimated based on available data).

Infectious and parasitic diseases

Rare: pharyngitis.

Blood and lymphatic system disorders

Rare: anemia, thrombocytopenia, leukopenia, increased bleeding time.

Very rare: ecchymoses. It has been reported that NSAIDs can cause potentially severe hematologic disorders, such as neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia (class-specific effects).

Immune system disorders

Rarely: hypersensitivity, anaphylactoid and anaphylactic reactions.

Metabolic and nutrition disorders

Infrequent: anorexia, weight changes.

Mental disorders

Infrequent: sleep disorders, depression.

Rarely: confusion, nervousness, anxious agitation.

Nervous system disorders

Often: transient headaches of mild intensity, dizziness.

Rarely: somnolence, paresthesias, taste disturbance, tremor, migraine.

Very rare: aseptic meningitis in patients with SLE and mixed connective tissue diseases.

Visual organ disorders

Infrequent: conjunctivitis.

Rarely: visual disorders.

Hearing organ and labyrinth disorders

Infrequent: dizziness, tinnitus.

Cardiac disorders

Infrequent: palpitations, tachycardia, edema, heart failure.

Vascular disorders

Infrequent: flushing of the face, edema.

Rarely: arterial hypertension, bleeding, hematoma.

Respiratory system, thorax and mediastinum disorders

Infrequent: rhinitis.

Rarely: dyspnea, cough, bronchospasm.

Gastrointestinal disorders

Often: nausea, abdominal pain, dyspeptic complaints, diarrhea, vomiting.

Infrequent: constipation, flatulence, belching, dry mouth, gastritis, peptic ulcer, epigastric pain, duodenal ulcer, oral ulcers.

Rarely: melena, bloody vomiting, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, perforative peptic ulcer, gastrointestinal bleeding.

Liver and biliary tract disorders

Infrequent: increased liver function tests, alanine aminotransferase (ALT) or aspartate aminotransferase (ACT).

Rarely: impaired liver function.

Very rare: damage to hepatocytes. Hepatotoxicity, which may lead to liver failure, hepatitis, jaundice and cholestasis.

Skin and subcutaneous tissue disorders

Infrequent: rash, itching, sweating, erythematous rash, urticaria, Quincke’s edema, alopecia.

Rare: dermatitis and eczema, purpura.

very rarely: edema, bullous reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Muscular and connective tissue disorders

Infrequent: arthralgia.

Rarely: bone pain, muscle cramps, myalgia.

Rare: renal and urinary tract disorders

Rarely: nycturia, urinary disorders, increased blood levels of urea and creatinine.

Very rarely: in patients with pre-existing renal dysfunction who require renal prostaglandins to maintain renal blood flow, lornoxicam may 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 site of administration

Infrequent: malaise, facial edema.

Rarely: asthenia.

Overdose

There are currently no data on overdose to assess its effects or suggest specific treatment.

In case of overdose of the drug Lornoxicam-Trivium® the following symptoms may be observed: nausea and vomiting, cerebral symptoms (dizziness, visual disturbances, ataxia turning into coma and seizures). Changes in liver and kidney function and blood clotting disorders are possible.

In case of overdose or suspected overdose the drug therapy should be stopped immediately. Due to its short half-life, lornoxicam is rapidly eliminated from the body. Dialysis is ineffective.

To date, the existence of a specific antidote is not known. Prostaglandin analogues or ranitidine may be used to treat gastrointestinal disorders.

Pregnancy use

Because of the lack of data on the use of the drug Lornoxicam – TRIVIUM® during pregnancy and lactation, the drug should not be used.

The suppression of prostaglandin synthesis may have adverse effects on pregnancy and/or fetal development.

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

The administration of prostaglandin synthesis inhibitors in the third trimester of pregnancy may result in toxic effects on the fetal heart and lungs (premature closure of the arterial duct and development of pulmonary hypertension) as well as impaired renal function and, consequently, a decrease in amniotic fluid. Late-term use may cause prolongation of maternal and fetal bleeding time, as well as suppression of uterine contractile activity, which may delay or lengthen the period of labor.

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