Instructions Larfix film-coated tablets 8 mg blister No. 100
Composition
active ingredient: lornoxicam;
1 tablet contains 4 mg or 8 mg of lornoxicam;
excipients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium, magnesium stearate, Opadry white 03F58750*.
*Opadry white 03F58750: talc, polyethylene glycol, hydroxypropylmethylcellulose, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties:
4 mg tablets: oval, oblong, white to yellowish tablets, coated, smooth on both sides;
8 mg tablets: oval, oblong, white to yellowish film-coated tablets, embossed with “L8” on one side and plain on the other side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A C05.
Pharmacological properties
Pharmacodynamics
Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties and belongs to the oxicam class.
Mechanism of action. Lornoxicam inhibits prostaglandin synthesis (inhibition of the enzyme cyclooxygenase), which leads to desensitization of peripheral nociceptors and inhibition of inflammation. Lornoxicam also has a central effect on nociceptors, which is not associated with anti-inflammatory action. Lornoxicam does not affect vital signs (e.g., body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry).
Pharmacokinetics
Absorption. Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma (Cmax) is reached 1-2 hours after taking the drug. The absolute bioavailability of lornoxicam is 90-100%. No first-pass effect was observed. The average half-life is 3-4 hours.
When lornoxicam is taken with food, Cmax is reduced by approximately 30% and Tmax is increased from 1.5 hours to 2.3 hours. The absorption of lornoxicam (calculated according to the area under the pharmacokinetic curve "concentration-time" (AUC)) may be reduced by up to 20%.
Distribution: Lornoxicam is present in plasma in an unchanged state and in the inactive form of its hydroxylated metabolite. The binding of lornoxicam to plasma proteins is 99% and does not depend on its concentration.
Biotransformation. Lornoxicam is extensively metabolized in the liver by hydroxylation, first to the inactive 5-hydroxylornoxicam. Lornoxicam undergoes biotransformation with the participation of cytochrome CYP2C9. As a result of genetic polymorphism, there are individuals with slow and intensive metabolism of this enzyme, which can be expressed in a noticeable increase in plasma levels of lornoxicam in individuals with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. Approximately 2/3 is excreted through the liver and 1/3 through the kidneys in the form of an inactive compound.
Lornoxicam did not induce hepatic enzymes in preclinical studies. There is no evidence of accumulation of lornoxicam after repeated administration of recommended doses.
Elimination. The elimination half-life of the parent compound is 3-4 hours. After oral administration, about 50% is excreted in the feces and 42% through the kidneys, mainly as 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam is about 9 hours after parenteral administration of the drug 1 or 2 times a day.
Special patient populations.
In elderly patients (over 65 years of age), clearance is reduced by 30-40%. Apart from the reduction in clearance, there are no significant changes in the kinetic profile of lornoxicam in elderly patients.
There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic insufficiency, with the exception of accumulation in patients with chronic liver disease, after 7 days of therapy with daily doses of 12 mg and 16 mg.
Indication
- Short-term treatment of acute pain of mild to moderate severity.
- Symptomatic relief of pain and inflammation in osteoarthritis.
- Symptomatic relief of pain and inflammation in rheumatoid arthritis.
Contraindication
- Hypersensitivity to lornoxicam or to any of the components of the drug.
- Thrombocytopenia.
- Hypersensitivity (symptoms similar to those of asthma, rhinitis, angioedema or urticaria) to other NSAIDs, including acetylsalicylic acid.
- Severe heart failure.
- Gastrointestinal bleeding, cerebral vascular bleeding or other blood clotting disorders.
- History of gastrointestinal bleeding or ulcer perforation related to previous NSAID therapy.
- History of acute or recurrent chronic peptic ulcer/bleeding (two or more separate proven episodes of ulceration or bleeding).
- Severe liver failure.
- Severe renal failure (serum creatinine level > 700 μmol/l).
- 3rd trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
Cimetidine: increased plasma concentrations of lornoxicam (no interaction between lornoxicam and ranitidine or lornoxicam and antacids has been identified).
Effect of lornoxicam on other drugs.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4). The international normalized ratio should be closely monitored.
Phenprocoumon: The effectiveness of phenprocoumon treatment is reduced.
ACE inhibitors: may reduce the effect of ACE inhibitors.
Diuretics: weakening of the diuretic and hypotensive effect of loop, thiazide and potassium-sparing diuretics.
Beta-adrenergic blockers: reduced hypotensive effect.
Angiotensin II receptor blockers: reduction of the hypotensive effect.
Methotrexate: Increased serum concentrations of methotrexate, leading to increased toxicity. Careful monitoring is required with concomitant use.
Digoxin: decreased renal clearance of digoxin.
Lithium: NSAIDs reduce the renal clearance of lithium, so serum lithium concentrations may exceed the threshold for toxicity. Serum lithium levels should be monitored, especially at the beginning of treatment, during dose adjustments and during discontinuation of treatment.
Cyclosporine: increased serum cyclosporine concentrations. Possible increased nephrotoxicity of cyclosporine due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy.
Known inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs dependent on cytochrome P450 2C9 (CYP2C9 isoenzyme)) interacts with known inducers and inhibitors of CYP2C9 isoenzymes (see section "Pharmacological properties").
Pemetrexed: NSAIDs may reduce the renal clearance of pemetrexed, resulting in increased renal and gastrointestinal toxicity and myelosuppression.
Other significant information.
Heparin: NSAIDs increase the risk of spinal/epidural hematoma when used concomitantly with heparin during spinal or epidural anesthesia (see section "Special warnings and precautions for use").
Corticosteroids: increased risk of gastrointestinal ulcers or bleeding (see section "Special warnings and precautions for use").
Quinolone antibacterial agents: increased risk of seizures.
Antiplatelet drugs: increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Other NSAIDs: increased risk of gastrointestinal bleeding.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Sulfonylureas (e.g. glibenclamide): increased risk of hypoglycemia.
Tacrolimus: increased risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be monitored during combination therapy (see section 4.4).
Other forms of interaction. Eating.
Since food intake slows down the absorption of lornoxicam, Larfix tablets should not be taken with food if a rapid onset of their effective action (pain relief) is required.
Food intake reduces absorption by approximately 20% and increases Tmax.
Application features
In patients with the following diseases and conditions, the drug should be prescribed only after careful assessment of the expected benefit of therapy and the possible risk:
– Mild (serum creatinine level 150-300 μmol/l) and moderate (serum creatinine level 300-700 μmol/l) renal insufficiency. Lornoxicam should be used with caution due to the important role of prostaglandins in maintaining renal blood flow. In case of deterioration of renal function, treatment with lornoxicam should be discontinued.
– Condition after extensive surgery; heart failure; taking diuretics or drugs that can cause kidney damage. When using lornoxicam, kidney function should be carefully monitored.
– Blood coagulation disorders. Careful clinical examination and evaluation of laboratory parameters (e.g. activated partial thrombin time) are recommended, as lornoxicam inhibits platelet aggregation, increasing blood clotting time. The drug should be administered with caution to patients with a tendency to bleeding.
– Liver failure (e.g. cirrhosis). After using the drug in a dose
12-16 mg per day, it is recommended to regularly conduct laboratory tests due to the possibility of accumulation of lornoxicam in the body (increased AUC); there is no data on deviations in pharmacokinetic parameters in patients with hepatic insufficiency.
Long-term use of the drug
Adverse reactions can be minimized by taking the lowest effective dose of the drug for the shortest period necessary to control the symptoms of the disease. With prolonged treatment (more than 3 months), it is recommended to assess the blood condition (hemoglobin determination), kidney function (creatinine determination) and liver enzymes.
Elderly patients.
Concomitant use with other NSAIDs.
The concomitant use of lornoxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Gastrointestinal complications.
Gastrointestinal bleeding, ulceration or perforation, which may be fatal, may occur with any NSAID at any time during treatment. The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, in patients with a history of ulcer, particularly if complicated by bleeding or perforation (see section 4.3), and in the elderly. In these patient groups, treatment with the drug should be initiated with particular caution at the lowest therapeutic dose.
NSAIDs should be used with caution in the above patient groups and in patients taking concomitant low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (see section 4.5). For patients requiring such concomitant therapy, treatment may be carried out with concomitant protective agents (e.g. misoprostol or proton pump inhibitors). Clinical monitoring at regular intervals is recommended.
Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) during the initial stages of treatment.
The drug should be prescribed with particular caution to patients who are concomitantly using medications that may increase the risk of ulceration or bleeding, for example, oral corticosteroids, anticoagulants - warfarin, selective serotonin reuptake inhibitors or antithrombotic drugs - acetylsalicylic acid (see section "Interaction with other medicinal products and other types of interactions").
In the event of gastrointestinal bleeding or ulceration in patients taking lornoxicam, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as their condition may worsen.
Elderly patients are at increased risk of adverse reactions to NSAIDs, including gastrointestinal bleeding and perforation, which can be fatal (see Contraindications).
Cardiovascular diseases.
The drug should be used with caution in patients with a history of hypertension and/or heart failure, as NSAIDs may cause edema and fluid retention in the body.
Patients with a history of hypertension and/or mild to moderate congestive heart failure should be monitored, as NSAID therapy may be associated with phenomena such as fluid retention and edema.
There is evidence to suggest that the use of some NSAIDs (especially long-term therapy and at high doses) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is insufficient data to exclude such a risk with lornoxicam.
Lornoxicam should only be prescribed to patients with uncontrolled hypertension, chronic heart failure, ischemic heart disease, peripheral arterial disease and/or cerebrovascular disorders after careful evaluation of the indications. Evaluation is also required before prescribing long-term treatment to patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
Concomitant treatment with NSAIDs and heparin increases the risk of spinal/epidural hematoma during spinal or epidural anesthesia (see section "Interaction with other medicinal products and other types of interactions").
Adverse skin reactions.
Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which have been fatal, have occurred with the use of NSAIDs (see section "Adverse reactions").
The risk of developing such reactions is highest at the beginning of treatment: in most cases, such reactions occur within the first month of taking the drug. Lornoxicam should be discontinued at the first signs of skin rash, mucosal lesions, or other manifestations of hypersensitivity.
Bronchial asthma.
Use with caution in patients with bronchial asthma or a history of this disease, as NSAIDs provoke bronchospasm in these patients.
Connective tissue disease.
Patients with systemic lupus erythematosus and mixed connective tissue disease may be at increased risk of developing aseptic meningitis.
Concomitant use of tacrolimus.
Concomitant treatment with NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be closely monitored during such combination therapy (see section 4.5).
Like other NSAIDs, lornoxicam may cause occasional elevations in transaminases, serum bilirubin, and blood urea and creatinine concentrations, as well as other laboratory abnormalities. If laboratory abnormalities are significant and persist for a long time, treatment should be discontinued and appropriate investigations should be performed.
Fertility.
Lornoxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Lornoxicam should be discontinued in women who have difficulty conceiving or are undergoing investigation of infertility.
Varicella.
In the presence of chickenpox, severe skin and soft tissue infections may develop in exceptional cases. At this time, the effect of NSAIDs on the worsening of these infectious diseases cannot be excluded. It is recommended to avoid the use of lornoxicam in the presence of chickenpox.
Excipients.
This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Use during pregnancy or breastfeeding
Pregnancy.
Lornoxicam is contraindicated in the third trimester of pregnancy. There are no clinical data on the use of lornoxicam in the first and second trimesters of pregnancy and during labor, therefore the drug is not recommended for use during this period.
There are no adequate data from the use of lornoxicam in pregnant women. Animal studies have shown reproductive toxicity.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development. Epidemiological studies have shown an increased risk of miscarriage and heart defects when prostaglandin synthesis inhibitors are used in early pregnancy. The risk increases with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors has been shown to increase pre- and post-implantation fetal death and embryo-fetal lethality. Prostaglandin synthesis inhibitors should not be used in the first and second trimesters of pregnancy. Use is only possible if absolutely necessary.
During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:
- cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired kidney function, which can progress to kidney failure, and therefore to a decrease in the amount of amniotic fluid.
The pregnant woman and fetus at the end of pregnancy may be exposed to the following effects from the use of prostaglandin synthesis inhibitors:
- possible increase in bleeding duration;
- suppression of uterine contractile function, which may lead to a delay or increase in the duration of labor.
Therefore, the use of lornoxicam is contraindicated during the third trimester of pregnancy (see section "Contraindications").
Breastfeeding. There are no data on the excretion of lornoxicam in human breast milk. Relatively high concentrations of lornoxicam are excreted in the milk of lactating rats. Therefore, lornoxicam should not be used during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
If you experience dizziness and/or drowsiness as a result of taking the drug, you should not drive or operate other machinery.
Method of administration and doses
Larfix tablets should be taken orally with sufficient water.
For all patients, the appropriate dosage regimen should be based on individual response to treatment.
Pain
The dose is 8-16 mg of lornoxicam per day, divided into 2-3 doses. The maximum recommended daily dose is 16 mg.
Osteoarthritis and rheumatoid arthritis
An initial daily dose of 12 mg lornoxicam, divided into 2-3 doses, is recommended.
The maintenance dose should not exceed 16 mg per day.
Elderly patients (over 65 years of age), with the exception of patients with impaired liver or kidney function, do not require dose adjustment, but lornoxicam should be used with caution due to the likelihood of adverse reactions from the gastrointestinal tract.
Renal impairment: For patients with mild to moderate renal impairment, the maximum recommended daily dose is 12 mg, divided into 2-3 doses.
Hepatic impairment: For patients with moderate hepatic impairment, the maximum recommended daily dose is 12 mg, divided into 2-3 doses (see section "Special warnings and precautions for use").
Adverse reactions can be minimized by using the lowest effective dose of the drug and for the shortest period of time necessary to control symptoms (see section "Special warnings and precautions for use").
Children.
Lornoxicam is not recommended for use in children under 18 years of age due to insufficient data on the efficacy and safety of the drug.
Overdose
Symptoms: symptoms such as nausea, vomiting, cerebral symptoms (dizziness, visual disturbances) may occur. In severe cases: ataxia, with transition to coma and convulsions; liver and kidney damage; possible blood clotting disorders.
Treatment: In case of actual or suspected overdose, the drug should be discontinued. Due to its short half-life, lornoxicam is rapidly eliminated from the body. It is not dialyzable. There is currently no specific antidote. Standard emergency measures should be taken, including gastric lavage. The use of activated charcoal, if administered immediately after an overdose of lornoxicam, may reduce the absorption of the drug. For the treatment of gastrointestinal disorders, a prostaglandin analogue or ranitidine can be used, for example.
Adverse reactions
The most common adverse reactions of NSAIDs were related to the gastrointestinal tract. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, especially in the elderly, may occur with NSAIDs (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported with NSAIDs. Gastritis has been observed less frequently.
It is estimated that approximately 20% of patients treated with lornoxicam may experience adverse reactions. The most common adverse reactions of lornoxicam are nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed less frequently than in
10% of patients who participated in the study. Edema, hypertension, and heart failure were reported during treatment with NSAIDs.
There is clinical and epidemiological evidence that the use of some NSAIDs, especially at high doses and in long-term use, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction or stroke (see section "Special warnings and precautions for use").
Exceptionally, serious infectious complications of the skin and soft tissues have been reported during the course of chickenpox.
Infections and infestations: pharyngitis.
Blood and lymphatic system disorders: Anemia, thrombocytopenia, leukopenia, prolonged bleeding time, ecchymosis. NSAIDs can cause class-specific potentially severe hematological disorders such as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Immune system disorders: hypersensitivity reactions, anaphylactoid reactions and anaphylaxis.
Metabolic disorders: loss of appetite, changes in body weight.
Mental disorders: insomnia, depression, confusion, nervousness, agitation.
Nervous system: mild and transient headache, dizziness, drowsiness, paresthesia, taste disturbance (dysgeusia), tremor, migraine, aseptic meningitis in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (see section "Special warnings and precautions for use").
From the organs of vision: conjunctivitis, visual impairment.
From the organs of hearing and balance: vertigo, tinnitus.
Cardiovascular system: palpitations, tachycardia, edema, heart failure, facial flushing, hypertension, hot flashes, hemorrhages, hematomas.
From the respiratory system: rhinitis, dyspnea, cough, bronchospasm.
On the part of the digestive system: nausea, abdominal pain, dyspepsia, diarrhea, vomiting, constipation, flatulence, belching, dry mouth, gastritis, gastric ulcer, abdominal pain in the upper abdomen, duodenal ulcer, oral mucosal ulcers, melena, vomiting with blood, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, peptic ulcer perforation, gastrointestinal bleeding.
On the part of the liver and biliary tract: increased levels of liver enzymes (ALT, AST); toxic effect on the liver, resulting in the possible development of liver failure, hepatitis, jaundice, cholestasis.
Skin and subcutaneous tissue disorders: rash, itching, increased sweating, erythematous rash, urticaria, angioedema, alopecia, dermatitis, eczema, purpura, edema and bullous reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: arthralgia, bone pain, muscle spasms, myalgia.
Renal and urinary disorders: nocturia, urinary disorders, increased blood urea nitrogen and creatinine; lornoxicam may cause acute renal failure in patients with renal diseases that depend on renal prostaglandins and play an important role in maintaining renal blood flow (see section "Special warnings and precautions for use").
Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is a class-specific effect of NSAIDs.
General disorders: malaise, facial edema, asthenia.
Expiration date.
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Packaging
10 tablets in a blister. 3 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
KUSUM HEALTHCARE PVT. LTD.
Location of the manufacturer and its business address
SP 289 (A), RIICO Indl. Area, Chopanki, Bhiwadi (Raj.), India.
SP 289 (A), RIICO Indl. Area, Chopanki, Bhiwadi (Raj.), India.
