Non-steroidal anti-inflammatory drug Larfix

Larfix is ​​a drug that has a powerful anti-inflammatory effect. It does not contain narcotic components. The basis of the drug is lornoxicam, a component that is part of the oxicam group. The drug suppresses the production of inflammatory mediators prostaglandins, due to which pathogenic changes are stopped.

In addition, the synthesis of cyclooxygenase, a substance that is a substrate for the formation of prostaglandins, is inhibited. The active ingredients are rapidly absorbed by the tissue of the gastrointestinal tract.

Contraindications

• Hypersensitivity to lornoxicam or to the components of the drug.
• Thrombocytopenia.
• Hypersensitivity (symptoms similar to asthma, rhinitis, angioedema or urticaria) to other NSAIDs, including acetylsalicylic acid.
• Severe form of heart failure.
• Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders.
• History of gastrointestinal bleeding or ulcer perforation associated with previous NSAID therapy.
• Acute or recurrent chronic gastric ulcer/bleeding history (two or more separate proven episodes of ulcer or bleeding).
• Severe form of liver failure.
• Severe renal failure (serum creatinine level > 700 µmol/L).
• III trimester of pregnancy.

Larfix 8 mg No. 30 tablet p.o.

Trade name LARFIX® International nonproprietary name Lornoxicam Dosage form Film-coated tablets 4 mg and 8 mg Composition One tablet contains the active substance - lornoxicam 4 mg or 8 mg, excipients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium, magnesium stearate, Opadry white 03F58750.* *Opadry white 03F58750: talc, polyethylene glycol, hydroxypropyl methylcellulose, titanium dioxide (E 171) Description Film-coated tablets, oblong, oval, white to yellowish in color, smooth on both sides (for a dosage of 4 mg) Tablets , coated, oblong, oval, white to yellowish in color with “L8” embossed on one side and smooth on the other side (for a dosage of 8 mg) Pharmacotherapeutic group Anti-inflammatory and antirheumatic drugs. Non-steroidal anti-inflammatory drugs. Oxycams. Lornoxicam. ATC code M01A C05 Pharmacological properties Pharmacokinetics Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in 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. Lornoxicam is found in plasma unchanged and in the form of its hydroxylated metabolite. Hydroxylated metabolites do not exhibit pharmacological activity. Plasma protein binding of lornoxicam is 99% and is independent of concentration. Lornoxicam is completely metabolized and approximately 2/3 is excreted through the liver and 1/3 through the kidneys as inactive substances. Lornoxicam is metabolized by cytochrome P450 2C9. Due to genetic polymorphisms in the rapid and slow metabolizers existing for this drug, which can lead to significant increases in lornoxicam levels if metabolized slowly. Concomitant use of lornoxicam with food reduces Cmax by approximately 30%. Tmax increases from 1.5 to 2.3 hours. Absorption of lornoxicam (calculated by AUC) may be reduced by up to 20%. Concomitant use with antacids does not affect the pharmacokinetics of lornoxicam. In elderly patients, clearance is reduced by 30 to 40%. In addition, the reduced clearance does not significantly change the kinetic profile of lornoxicam in elderly patients or in patients with mild hepatic or renal dysfunction. Pharmacodynamics Lornoxicam is a non-steroidal anti-inflammatory drug with analgesic and anti-inflammatory properties, belongs to the oxicam class. The mechanism of action of lornoxicam is based in part on the inhibition of prostaglandin synthesis (cyclooxygenase inhibition). Inhibition of cyclooxygenase does not increase the formation of leukotrienes. The mechanism of the analgesic effect of lornoxicam, like other NSAIDs, has not yet been fully determined. Indications for use - short-term treatment of moderate or severe pain. Method of administration and dosage Larfix® tablets are taken before meals with water. For moderate or severe pain, a dose of 8–16 mg per day, divided into 2–3 doses, is recommended. For inflammatory and degenerative rheumatic diseases, an initial dose of 12 mg, divided into 2-3 doses, is recommended. The maximum daily dose should not exceed 16 mg per day. The daily dose and duration of therapy are determined individually, depending on the nature and course of the disease. In elderly patients (over 65 years of age), no dose adjustment is required, but Larfix® should be used with caution due to the likelihood of adverse reactions from the gastrointestinal tract. For patients with moderate to severe renal failure and severe liver failure, the recommended daily dose is 12 mg, divided into 2-3 doses. Side effects It is believed that approximately 20% of patients may experience side effects. The most common adverse reactions, which are common to all other non-steroidal anti-inflammatory drugs, are associated with disorders of the digestive tract: gastrointestinal ulcers with intestinal perforation, which can be severe, nausea, vomiting with blood, diarrhea, flatulence, constipation, dyspepsia, pain in abdomen, melena, ulcerative stomatitis, exacerbation of colitis and Crohn's disease. Gastritis was observed less frequently. When using the drug Larfix®, the following undesirable effects may occur: - often ( 1/100,  1/10) - mild short-term headache, dizziness, nausea, abdominal pain, dyspepsia, diarrhea, vomiting; - sometimes ( 1/1 000,  1/100) - loss of appetite, changes in body weight, insomnia, depression, conjunctivitis, vertigo, ringing in the ears, palpitations, tachycardia, edema, fluid retention, heart failure, facial flushing, rhinitis, constipation, flatulence, belching, dry mouth, gastritis, stomach and duodenal ulcers, abdominal pain, bleeding gums, ulcerative stomatitis, increased levels of liver enzymes (ALT, AST), rashes, itching, increased sweating, erythematous rashes, urticaria and angioedema, alopecia, arthralgia, malaise, facial swelling; - rarely ( 1/10,000,  1/1,000) - pharyngitis, anemia, thrombocytopenia, eosinophilia, leukopenia, coagulation disorders, pancytopenia, hypersensitivity reactions, fever, chills, anaphylactoid reactions, anaphylaxis, hyponatremia, anxiety, impaired consciousness, increased excitability, impaired ability to concentrate, changes in attention, cognitive disorders, drowsiness, paresthesia, dysgeusia, tremor, migraine, hyperkinesia, hypoesthesia, visual impairment, including blurred vision, impaired color vision, visual field defects, scotoma, amblyopia, diplopia, iridocyclitis , arterial hypertension, hot flashes, hemorrhage, vasculitis, hematomas, dyspnea, cough, bronchospasm, melena, vomiting with blood, stomatitis, esophagitis, gastroesophageal reflux disease, dysphagia, aphthous stomatitis, glossitis, perforation of peptic ulcers, hemorrhoids, gastrointestinal bleeding , dermatitis, eczema, maculopapular rash, purpura, pain in the bones and back, muscle spasms, muscle weakness, myalgia, synovitis, nocturia, urinary disorders, increased levels of urea nitrogen and creatinine in the blood, asthenia. - very rarely (1/10,000) - ecchymosis, aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue diseases, toxic effects on the liver, which may result in the development of liver failure, hepatitis, jaundice, cholestasis, edema and bullous reactions, changes nails, psoriasis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, lornoxicam may cause acute renal failure in patients with pre-existing kidney disease. Contraindications - hypersensitivity to lornoxicam or to the components of the drug - pregnancy and lactation - children under 18 years of age - thrombocytopenia - hypersensitivity (symptoms similar to those of bronchial asthma, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid - severe form of heart failure - gastrointestinal bleeding, cerebrovascular bleeding or other hematological disorders - history of gastrointestinal bleeding or perforation associated with previous use of non-steroidal anti-inflammatory drugs - active peptic ulcer or recurrent peptic ulcer / bleeding history (two or more) more than a proven episode of ulceration or bleeding) - severe liver failure - severe renal failure (serum creatinine level >700 µmol/l) Drug interactions - Cimetidine: increased plasma concentrations of lornoxicam (interactions between lornoxicam and ranitidine or lornoxicam and antacids are not found) - Anticoagulants: non-steroidal anti-inflammatory drugs can increase the effect of anticoagulants (for example, warfarin, anisindione, dicumarol, fenedione), which leads to an increase in bleeding time - Fenprocoumon: the effectiveness of treatment with phenprocoumon is reduced. - Heparin: Non-steroidal anti-inflammatory drugs increase the risk of spinal/epidural hematoma when used concomitantly with heparin during spinal or epidural anesthesia - 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 receptor blockers: decreased hypotensive effect. — Angiotensin II receptor blockers: decreased hypotensive effect. - Digoxin: decreased renal clearance of digoxin. - Corticosteroids: increased risk of gastrointestinal ulcers and bleeding. — Antibacterial drugs of the quinolone group: the risk of epileptic phenomena increases. - Antiplatelet drugs: increases the risk of gastrointestinal bleeding. — Other NSAIDs: the risk of gastrointestinal bleeding increases. - Methotrexate: an increase in the concentration of methotrexate in the blood serum, leading to an increase in its toxicity. Careful monitoring is necessary during concurrent use. — Serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding. - Lithium preparations: Non-steroidal anti-inflammatory drugs can reduce the renal clearance of lithium with a further increase in its concentration in the blood serum. It is necessary to monitor the level of lithium in the blood serum, especially at the beginning of treatment, when adjusting the dose and stopping treatment. - Cyclosporine: an increase in the concentration of cyclosporine in the blood serum, possibly increasing the nephrotoxicity of cyclosporine. During combination therapy, it is necessary to monitor renal function. - Sulfonylurea derivatives (for example, glibenclamide): the hypoglycemic effect may be enhanced. - Lornoxicam (like other NSAIDs that are metabolized by cytochrome CYP2C9) interacts with known inducers and inhibitors of CYP2C9 isoenzymes (for example, tranylcypromine and rimfamycin). - Tacrolimus: Concomitant use of NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. With such combination therapy, it is necessary to carefully monitor renal function - Pemetrexed: NSAIDs may reduce the renal clearance of pemetrexed, resulting in increased renal and gastrointestinal toxicity, myelosuppression. Special instructions for patients with renal failure (serum creatinine level 150-300 µmol/l) and moderate renal impairment. deficiency (serum creatinine level 300–700 µmol/l), the drug should be prescribed only after a careful assessment of the expected benefits of therapy and the possible risks. If renal function deteriorates, treatment with the drug should be discontinued. Patients undergoing major surgery, with heart failure, or taking diuretics or drugs that may cause kidney damage should be closely monitored for renal function. In patients with bleeding disorders, careful clinical examination and evaluation of laboratory parameters (eg, partial thrombin time) are recommended because lornoxicam inhibits platelet aggregation, increasing blood clotting time. In patients with liver failure (for example, with cirrhosis), laboratory tests are recommended after using the drug at a dose of 12-16 mg per day due to the possibility of accumulation of lornoxicam in the body (increased AUC). However, no deviations in pharmacokinetic parameters were found in patients with liver failure compared to healthy volunteers. During long-term treatment (more than 3 months), it is recommended to assess blood status (hemoglobin determination), kidney function (creatinine determination) and liver enzymes. Elderly patients (over 65 years of age) are advised to monitor renal and liver function and use the drug with caution after surgery. Concomitant use of lornoxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Adverse reactions can be minimized by taking the lowest effective dose of the drug. During the use of NSAIDs, gastrointestinal bleeding, ulcers and perforation may occur, which can be fatal. Patients with a history of ulcers complicated by bleeding or perforation, as well as elderly patients, should begin treatment with the drug at the lowest possible therapeutic doses with extreme caution. Larfix® should be used with caution to treat patients taking medications that increase the risk of ulcers and bleeding (see section “Drug Interactions”). For patients who require concomitant therapy, treatment can be done while taking proton pump inhibitors concomitantly and closely monitored. In elderly patients, the risk of adverse reactions during the use of NSAIDs increases, in particular gastrointestinal bleeding and perforation. If any adverse reactions from the digestive tract occur, you should stop taking the drug and consult a doctor. The drug should be used with caution and after careful analysis in patients with arterial hypertension and/or heart failure, since edema and fluid retention in the body are possible due to the use of NSAIDs. In patients with uncontrolled arterial hypertension, congestive heart failure, coronary heart disease, cerebrovascular disorders, as well as patients with increased risk factors for cardiovascular diseases (arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), treatment should begin after a thorough analysis. Concomitant use of NSAIDs and heparin increases the risk of spinal/epidural hematoma during spinal or epidural anesthesia. Serious skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in rare cases in association with NSAIDs, especially early in treatment. Treatment with the drug must be stopped at the first symptoms (skin rashes, lesions of the mucous membranes and other symptoms of hypersensitivity). Patients with bronchial asthma, including a history of asthma, should use NSAIDs with caution, since there are cases of bronchospasm. In patients with systemic lupus erythematosus and mixed connective tissue diseases, the risk of aseptic meningitis increases. Lornoxicam inhibits platelet aggregation, increasing blood clotting time. The drug should be prescribed with caution to patients with a tendency to bleeding. Coadministration of NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function must be carefully monitored during this combination therapy. Like other NSAIDs, Larfix® can cause episodic increases in transaminases, bilirubin in the blood serum, as well as an increase in the concentration of urea and creatinine in the blood. If the deviations in laboratory parameters are significant and continue for a long time, treatment must be stopped and the necessary examination must be carried out. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use the drug. Lornoxicam, like other drugs that inhibit cyclooxygenase synthesis, can impair fertility. Not recommended for use by women who are planning pregnancy. Patients with chickenpox should not use the drug. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms If dizziness and/or drowsiness occurs after taking the drug, you should not drive vehicles or operate other mechanisms. Overdose Symptoms: nausea, vomiting, cerebral symptoms (dizziness, blurred vision), ataxia leading to coma and convulsions, possible changes in liver and kidney function, blood clotting disorders. Treatment: symptomatic. Not amenable to dialysis. There is no specific antidote. Gastric lavage is recommended. The use of activated coal, provided that it is taken immediately after an overdose of the drug, Larfix® can reduce the absorption of the drug. The output and packaging forms are placed in a contour cell package. 3 or 10 contour cell packages along with the instructions for medical use in the state and Russian languages ​​are placed in cardboard packaging. Storage conditions are stored in a dry place protected from light, at a temperature of not higher than 25ºС. Keep out of the reach of children! The shelf life of 2 years is not used after the expiration date indicated on the package. Conditions of vacation from pharmacies according to the recipe

Features of application

Use during pregnancy and lactation

Lornoxicam is contraindicated in the third trimester of pregnancy. There are no clinical data on the use of lonoxicam in the first and second trimesters of pregnancy and during childbirth, so the drug is not recommended for use during this period.

There is insufficient data regarding the use of lornoxicam in pregnant women. Animal studies have shown reproductive toxicity.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Data from epidemiological studies indicate an increased risk of miscarriage, as well as the development of heart defects when using prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors leads to an increase in pre- and post-implantation fetal death and embryofetal mortality. Prostaglandin synthesis inhibitors should not be used in the first and second trimesters of pregnancy. Use is possible only when absolutely necessary.

In the third trimester of pregnancy, when using any prostaglandin synthesis inhibitors, the following effects on the fetus are possible:

• cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension)
• impaired renal function, which can progress to renal failure and then to a decrease in the amount of amniotic fluid.

The pregnant woman and the fetus at the end of pregnancy may be exposed to the following effects from the use of prostaglandin synthesis inhibitors:

• possible increase in the duration of bleeding;
• inhibition of contractile function of the uterus, which can lead to a delay or increase in the duration of labor.

Thus, the use of lornoxicam is contraindicated in the third trimester of pregnancy.

Breastfeeding period

There are no data on the excretion of lornoxicam into human breast milk. Relatively high concentrations of lornoxicam are excreted in the milk of lactating rats. Therefore, lornoxicam should not be used during breastfeeding.

Children

Lornoxicam is not recommended for use in children under 18 years of age due to insufficient data on the effectiveness and safety of the drug.

The ability to influence the reaction rate when driving vehicles or other mechanisms

If dizziness and/or drowsiness occurs as a result of taking the drug, you should not drive vehicles or operate other machinery.

Directions for use and doses

Take Larfix tablets orally with plenty of water.

For all patients, the appropriate dosage regimen should be based on individual response to treatment.

Pain

Dose of 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 dose of 12 mg of lornoxicam, divided into 2-3 doses, is recommended.

The maintenance dose should not exceed 16 mg per day.

Drug interactions

When Larfix enters the body, it rapidly reacts with other chemical elements. This feature must be taken into account in order to prevent the development of any side effects. Doctors need to remember the following:

• The use of Larfix together with Cimetidine causes an increase in the concentration of the active substances of anti-inflammatory tablets.
• Larfix increases the effectiveness of anticoagulants, which can cause small blood clots.
• Larfix reduces the effectiveness of treatment with Phenprocoumon.
• Larfix weakens the effect of diuretics, ACE inhibitors, loop, thiazide and potassium-sparing drugs.
• Reduces the hypotensive effect during simultaneous treatment with beta-adrenergic blockers.
• The hypotensive effect is reduced when Larfix is ​​used together with angiotensin receptor blockers.

Overdose

Currently, there is no data regarding overdose that would allow us to determine its consequences or suggest specific treatment.

Symptoms

Symptoms such as nausea, vomiting, and cerebral symptoms (dizziness, blurred vision) may occur. In severe cases: ataxia, with transition to coma and convulsions, damage to the liver and kidneys; Possible blood clotting disorder.

Treatment

If there is an existing or expected overdose, you should stop using the drug. Due to its short half-life, lornoxicam is rapidly eliminated from the body. Not amenable to dialysis. There is currently no specific antidote. The usual emergency measures, including gastric lavage, should be carried out. The use of activated carbon when taken immediately after an overdose of lornoxicam may lead to a decrease in absorption of the drug. For the treatment of gastrointestinal disorders, you can, for example, use a prostaglandin analogue or ranitidine.

Adverse reactions

The most common adverse reactions of NSAIDs were related to the gastrointestinal tract. When taking NSAIDs, peptic ulcers, perforation or gastrointestinal bleeding may occur, sometimes resulting in death, especially in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, grinding, vomiting of blood, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported with NSAID treatment. Gastritis was observed less frequently.

It is believed that approximately 20% of patients treated with lornoxicam may experience side effects. The most common side effects of lornoxicam are nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed in less than 10% of patients in the study. Edema, hypertension, and heart failure have been reported with NSAID treatment.

There are clinical and epidemiological data that indicate that the use of some NSAIDs, especially in high doses and long-term use, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction or stroke.

Side effects

Improper use of Larfix can cause serious side effects. They most often occur when the dosage of the drug is incorrectly selected. The greatest danger is the possibility of developing ulcerative stomatitis, which requires immediate treatment. Patients often experience the following side effects:

• Attachment of a secondary infection - pharyngitis;
• Anemia, increased levels of platelets, leukocytes, eosinophils in the blood, blood clotting disorders;
• Neutropenia, agranulocytosis, hypersensitivity;
• Increased body temperature, chills, anaphylactic shock;
• Complete lack of appetite, sudden loss of body weight;
• Slowing down the production of thyroid hormones;
• Depression, psychosis, increased excitability, excessive fatigue, impaired consciousness, cognitive disorders;
• Headache, dizziness, drowsiness, migraine, aseptic meningitis;
• Conjunctivitis, decreased visual acuity, diplopia, scotoma, ringing in the ears;
• Increased or decreased blood pressure, swelling, arrhythmia, tachycardia, swelling, heart failure;
• Rhinitis, shortness of breath, cough, spasms in the bronchi;
• Nausea, vomiting, pain in the stomach, dry mouth, flatulence, belching;
• Stomatitis, glossitis, perforation, hemorrhoids;
• Increased levels of liver enzymes, development of jaundice or liver failure;
• Rashes, itching, burning, peeling, swelling, dermatitis, eczema, changes in the shape of nails, psoriasis, erythema, Stevens-Jones syndrome;
• Bone pain, neuralgia, muscle weakness, synovitis;
• Nocturia, difficulty urinating, increased levels of urea and creatinine in the blood;
• Malaise, swelling of the face, asthenia.

Note!

Description of the drug Larfix table. p/o 8 mg No. 100 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.