Zornica (Tablets) Instructions for Use

Marketing Authorization Holder

Micro Labs Limited (India)

ATC Code

M01AC05 (Lornoxicam)

Active Substance

Lornoxicam (Rec.INN registered by WHO)

Dosage Forms

	Zornica	Film-coated tablets, 4 mg: 30 pcs.
		Film-coated tablets, 8 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, round, biconvex.

Excipients : lactose monohydrate – 47.05 mg, croscarmellose sodium – 3.5 mg, povidone K30 – 1.1 mg, microcrystalline cellulose – 12 mg, magnesium stearate – 0.35 mg.

Shell composition hypromellose – 0.75 mg, titanium dioxide (E171) – 0.6 mg, talc – 0.4 mg, quinoline yellow dye (E104) – 0.1 mg, macrogol 6000 – 0.15 mg.

10 pcs. – blisters (3) – cartons.

Film-coated tablets yellow, round, biconvex.

Excipients : lactose monohydrate – 94.1 mg, croscarmellose sodium – 7 mg, povidone K30 – 2.2 mg, microcrystalline cellulose – 24 mg, magnesium stearate – 0.7 mg.

Shell composition hypromellose – 1.5 mg, titanium dioxide (E171) – 1.2 mg, talc – 0.8 mg, quinoline yellow dye (E104) – 0.2 mg, macrogol 6000 – 0.3 mg.

10 pcs. – blisters (3) – cartons.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

Lornoxicam belongs to the oxicam class and has a pronounced analgesic and anti-inflammatory effect.

Lornoxicam has a complex mechanism of action, which is based on the suppression of prostaglandin synthesis due to inhibition of the activity of COX isoenzymes. In addition, Lornoxicam inhibits the release of oxygen free radicals from activated leukocytes.

The analgesic effect of lornoxicam is not associated with a narcotic effect. The drug does not have an opiate-like effect on the central nervous system and, unlike narcotic analgesics, does not depress respiration and does not cause drug dependence.

Pharmacokinetics

Absorption

Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration.

C_max in blood plasma is reached in about 1-2 hours. Food intake reduces C_max of the drug in plasma by 30% and increases T_max to 2.3 hours. With repeated administration, the drug does not accumulate in the body. The absolute bioavailability of lornoxicam is 90-100%.

Metabolism

Lornoxicam is present in blood plasma mainly unchanged and to a lesser extent in the form of a hydroxylated metabolite (5'-hydroxylornoxicam), which has no pharmacological activity.

Lornoxicam rapidly penetrates into the synovial fluid. The AUC of lornoxicam in synovial fluid is 0.5 after taking a dose of 4 mg 2 times/day.

Lornoxicam is completely metabolized in the liver. The isoenzyme CYP2C9 is involved in metabolism. The binding of lornoxicam to plasma proteins, mainly the albumin fraction, is 99% and does not depend on its concentration.

Excretion

T_1/2 averages 4 hours and does not depend on the concentration of the drug. Approximately 1/3 of metabolites are excreted from the body by the kidneys and 2/3 with bile.

T_1/2 of glucuronidated metabolites of lornoxicam is about 11 hours.

In elderly individuals, as well as in patients with renal or hepatic insufficiency, no significant changes in the pharmacokinetics of lornoxicam were found.

Indications

• Short-term treatment of pain syndrome of various origins;
• Symptomatic therapy of rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, joint syndrome in acute gout, rheumatic soft tissue lesions).

ICD codes

Dosage Regimen

Orally. The drug should be taken before meals with a glass of water.

For severe pain syndrome the recommended dose is 8-16 mg/day, divided into 2-3 doses. The maximum daily dose is 16 mg.

For inflammatory and degenerative rheumatic diseases the recommended initial dose is 12 mg. The standard dose is 8-16 mg/day, depending on the patient’s condition. The duration of therapy depends on the nature and course of the disease.

For gastrointestinal diseases, patients with impaired renal or hepatic function, elderly persons (over 65 years of age), after extensive surgery, the maximum daily dose is 12 mg, in 3 doses.

To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used for the shortest possible short course.

Adverse Reactions

Depending on the frequency of occurrence, the following groups of side effects are distinguished: very common (>1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), including isolated reports.

From the nervous system: common – headache, dizziness; uncommon – sleep disorders, depression; rare – drowsiness, agitation, tremor, paresthesia; very rare – aseptic meningitis.

From the digestive system: common – dyspepsia, abdominal pain, nausea, vomiting, diarrhea, heartburn; uncommon – gastritis, erosive and ulcerative lesions of the gastric and intestinal mucosa (including with perforation and bleeding), constipation, flatulence, increased levels of “liver” transaminases; rare – dry mouth, esophagitis, melena, impaired liver function, stomatitis.

From the skin: uncommon – skin rash, itching, urticaria, alopecia; rare – edematous syndrome, Stevens-Johnson syndrome, Lyell’s syndrome, angioedema; very rare – ecchymosis.

From the urinary system: rare – dysuria, decreased glomerular filtration, interstitial nephritis, glomerulonephritis, papillary necrosis, nephrotic syndrome, peripheral edema, acute renal failure.

From the senses: uncommon – tinnitus; rare – visual impairment.

From the cardiovascular system: uncommon – development or worsening of heart failure, tachycardia; rare – increased blood pressure.

From the hematopoietic organs: rare – agranulocytosis, leukopenia, anemia, thrombocytopenia, increased bleeding time.

From the respiratory system: uncommon – rhinitis; rare – pharyngitis, dyspnea, cough, bronchospasm.

Other uncommon – anorexia, increased sweating, change in body weight, arthralgia; rare – myalgia.

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Contraindications

• Hypersensitivity to lornoxicam or to one of the components of the drug;
• Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinusitis and intolerance to acetylsalicylic acid and other NSAIDs (including in history);
• Hemorrhagic diathesis or bleeding disorders, as well as patients who have undergone surgery associated with a risk of bleeding or incomplete hemostasis;
• Period after coronary artery bypass grafting;
• Cerebrovascular or other bleeding;
• Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding;
• Recurrent gastric ulcer or repeated gastrointestinal bleeding;
• Gastrointestinal bleeding associated with NSAID use in history;
• Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase;
• Decompensated heart failure;
• Severe hepatic insufficiency or active liver disease;
• Severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases;
• Confirmed hyperkalemia;
• Hypovolemia or dehydration;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Pregnancy, breastfeeding period;
• Children under 18 years of age (due to the lack of clinical data on the use of lornoxicam in this age group).

With caution

Erosive and ulcerative lesions and gastrointestinal bleeding (in history), moderately severe renal failure, conditions after surgical interventions, age over 65 years, coronary heart disease, in patients with hemostasis defects, with a risk of developing cardiovascular thrombosis (myocardial infarction, acute cerebrovascular accidents (ischemic, hemorrhagic stroke)), chronic heart failure (II-IV functional class according to NYHA classification), cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery diseases, smoking, systemic lupus erythematosus, creatinine clearance less than 60 ml/min, presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe somatic diseases. simultaneous use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy. During lactation, breastfeeding should be discontinued during treatment with the drug.

Use in Hepatic Impairment

The use of the drug in patients with severe hepatic insufficiency or active liver disease is contraindicated.

Use in Renal Impairment

Use the drug with caution in patients with moderately severe renal insufficiency.

The use of the drug in patients with severe renal failure (creatinine clearance less than 30 ml/min) and progressive kidney diseases is contraindicated.

Pediatric Use

The use of the drug in children and adolescents under 18 years of age is contraindicated (due to the lack of clinical data on the use of lornoxicam in this age group).

Geriatric Use

Use the drug with caution in patients over 65 years of age.

Special Precautions

The risk of the ulcerogenic effect of the drug can be reduced by the simultaneous administration of proton pump inhibitors and synthetic prostaglandin analogues.

In case of gastrointestinal bleeding, the drug should be discontinued immediately and appropriate emergency measures taken. Particular attention should be paid to monitoring the condition of those patients with gastrointestinal pathology who are receiving lornoxicam treatment for the first time.

Like other oxicams, Lornoxicam inhibits platelet aggregation and therefore may increase bleeding time.

When using this drug, it is necessary to carefully monitor the condition of patients who require absolutely normal functioning of the blood coagulation system (for example, patients who are to undergo surgery), who have blood coagulation disorders or are receiving drugs that inhibit blood coagulation (including low-dose heparin), in order to detect signs of bleeding in a timely manner.

If signs of liver damage appear (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, increased levels of “liver” transaminases), you should stop taking the drug and consult your doctor.

The drug should not be used simultaneously with other NSAIDs.

The drug may change platelet properties, but does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

In patients with impaired renal function caused by large blood loss or severe dehydration, Lornoxicam, as an inhibitor of prostaglandin synthesis, can be prescribed only after hypovolemia and the associated danger of reduced renal perfusion have been eliminated.

Like other NSAIDs, Lornoxicam can cause an increase in the concentration of urea and creatinine in the blood plasma, as well as retention of water and sodium, peripheral edema, arterial hypertension and other early signs of nephropathy. Long-term treatment of such patients with lornoxicam can lead to the following consequences: glomerulonephritis, papillary necrosis and nephrotic syndrome with transition to acute renal failure. The drug should not be prescribed to patients with a pronounced decrease in renal function. In elderly patients, as well as in patients suffering from arterial hypertension and/or obesity, blood pressure levels should be monitored.

It is especially important to monitor renal function in elderly patients, as well as in patients

• Simultaneously receiving diuretics;
• Simultaneously receiving drugs that can cause kidney damage.

With long-term use of the drug, hematological parameters, as well as renal and liver function, should be periodically monitored. The use of the drug may adversely affect female fertility and is not recommended for women planning a pregnancy.

Effect on ability to drive vehicles, mechanisms

Caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, because the drug may cause dizziness and other side effects that may affect these abilities.

Overdose

Symptoms possible intensification of the described side effects.

Treatment symptomatic. Taking activated charcoal immediately after taking the drug may help reduce the absorption of lornoxicam. To prevent damage to the gastrointestinal mucosa, antiulcer drugs (prostaglandin analogues or ranitidine) can be used. Hemodialysis is ineffective.

Drug Interactions

Simultaneous use of lornoxicam and

• Cimetidine increases the concentration of lornoxicam in blood plasma;
• Anticoagulants or platelet aggregation inhibitors – possible increase in bleeding time (increased risk of bleeding, INR control is necessary);
• Beta-blockers and ACE inhibitors may reduce their hypotensive effect;
• Diuretics – reduces the diuretic effect and hypotensive effect;
• Digoxin – reduces the renal clearance of digoxin;
• Quinolone antibiotics – increases the risk of convulsive syndrome;
• Other NSAIDs or glucocorticosteroids – increases the risk of gastrointestinal bleeding;
• Mifepristone – Lornoxicam may reduce the effectiveness of mifepristone. The drug should be started no earlier than 8-12 days after taking mifepristone;
• Methotrexate – increases the concentration of methotrexate in blood plasma;
• Selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline) – increases the risk of gastrointestinal bleeding;
• Lithium salts – may cause an increase in the maximum concentrations of lithium in blood plasma and thereby enhance the known side effects of lithium;
• Cyclosporine – increases the nephrotoxicity of cyclosporine;
• Oral hypoglycemic agents – may enhance the hypoglycemic effect of the latter;
• Alcohol, corticotropin, potassium preparations – increases the risk of side effects from the gastrointestinal tract;
• Cefamandole, cefoperazone, cefotetan, valproic acid – increases the risk of bleeding;
• Cholestyramine – accelerates the excretion of lornoxicam from the gastrointestinal tract;
• Rifampicin – reduces the concentration of lornoxicam in blood plasma.

No interaction with ranitidine and antacid drugs has been identified.

Storage Conditions

The drug should be stored in a place protected from light and out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.