Niselat^® (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

M01AB (Acetic acid derivatives and related compounds)

Active Substance

Amtolmetin guacil (Rec.INN registered by WHO)

Dosage Form

Niselat®

Film-coated tablets, 600 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from white to almost white, capsule-shaped, biconvex, with a characteristic odor.

Excipients : lactose monohydrate – 40.1 mg, hypromellose 15 cps – 6 mg, lactose monohydrate (Flowlac 100) – 120.3 mg, colloidal silicon dioxide – 1.6 mg, sodium carboxymethyl starch (type-A) – 24 mg, magnesium stearate – 8 mg.

Film coating composition hypromellose 5 cps – 12.5 mg, titanium dioxide – 6.25 mg, macrogol 400 – 1.25 mg.

10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic agents; non-steroidal anti-inflammatory and antirheumatic agents; acetic acid derivatives and related substances

Pharmacological Action

NSAID, non-selective COX inhibitor. Amtolmetin guacil is a precursor of tolmetin. It has anti-inflammatory, analgesic, antipyretic, desensitizing action, and possesses a gastroprotective effect.

It suppresses pro-inflammatory factors, reduces platelet aggregation; inhibits COX-1 and COX-2, disrupts arachidonic acid metabolism, reduces the formation of prostaglandins (including at the site of inflammation), suppresses the exudative and proliferative phases of inflammation.

It reduces capillary permeability; stabilizes lysosomal membranes; inhibits the synthesis or inactivates inflammatory mediators (prostaglandins, histamine, bradykinins, cytokines, complement factors).

It blocks the interaction of bradykinin with tissue receptors, restores impaired microcirculation and reduces pain sensitivity at the site of inflammation. It affects the thalamic centers of pain sensitivity; reduces the concentration of biogenic amines with algogenic properties; increases the pain sensitivity threshold of the receptor apparatus.

It eliminates or reduces the intensity of pain syndrome, reduces morning stiffness and swelling, increases the range of motion in affected joints after 4 days of treatment.

The protective effect of amtolmetin guacil on the gastric mucosa is realized by stimulating capsaicin receptors (also called vanilloid receptors) present in the walls of the gastrointestinal tract.

Due to the presence of a vanillic group in the composition of amtolmetin guacil, it can stimulate capsaicin receptors, which, in turn, causes the release of the peptide encoded by the calcitonin gene (CGRP) and a subsequent increase in the production of nitric oxide (NO).

Both of these actions counteract the negative effect caused by the decrease in prostaglandins due to COX inhibition. Amtolmetin guacil was well tolerated by patients during long-term use (for 6 months).

Pharmacokinetics

Absorption and Distribution

The absorption of amtolmetin guacil after oral administration is rapid and complete. Mainly, the drug is concentrated in the walls of the stomach and intestines, where its very high concentration is maintained for 2 hours after administration. Time to reach C_max after oral administration – 20-60 min.

Plasma protein binding – 99%.

Metabolism

After absorption, Amtolmetin guacil immediately undergoes hydrolysis by plasma esterases to form three metabolites: MED5, tolmetin, and guaiacol, which are transformed into the active metabolite tolmetin; the latter penetrates into tissues, exerting a pharmacological action. The main pathway of tolmetin metabolism is the oxidation of the methyl group at the benzene ring to a carboxyl group.

Excretion

T_1/2 in adults – about 5 h. Within 24 hours, the drug is almost completely eliminated from the body in the form of glucuronides (with urine – 80%, with bile – 20%).

Indications

• Rheumatoid arthritis;
• Osteoarthritis;
• Ankylosing spondylitis;
• Articular syndrome during gout exacerbation;
• Bursitis, tenosynovitis;
• Pain syndrome of mild to moderate intensity (arthralgia, myalgia, neuralgia, migraine, toothache and headache, algodysmenorrhea, pain from injuries, burns).

Intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

ICD codes

Dosage Regimen

Administer the recommended dose of 600 mg twice daily.

For maintenance therapy, reduce the dose to 600 mg once daily once symptom control is achieved.

Do not exceed the maximum daily dose of 1800 mg.

Take tablets on an empty stomach to preserve the gastroprotective effect.

Swallow the film-coated tablets whole with a sufficient amount of liquid.

Use the lowest effective dose for the shortest duration necessary to control symptoms.

Monitor renal and hepatic function during long-term therapy.

Discontinue treatment if signs of gastrointestinal bleeding or ulceration occur.

Adverse Reactions

The frequency of side effects is classified depending on the incidence of the case: common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (less than 0.01%), including isolated reports, and frequency unknown.

From the digestive system common – nausea; uncommon – dyspepsia, discomfort in the stomach and intestines, abdominal bloating; rare – abdominal pain, diarrhea, vomiting, constipation, gastritis; very rare – peptic ulcer, impaired liver function.

From the urinary system frequency unknown – increased blood urea nitrogen, urinary tract infections.

From the organ of vision: rare – visual disturbances.

From the organ of hearing and labyrinthine disorders rare – tinnitus.

From the respiratory system: rare – bronchospasm, dyspnea, rhinitis, laryngeal edema.

From the nervous system: common – dizziness, headache, drowsiness; rare – depression.

From the cardiovascular system: common – increased BP.

From the hematopoietic organs rare – anemia, thrombocytopenia, agranulocytosis, leukopenia.

From the skin uncommon – skin rash (including maculopapular rash), purpura; rare – exfoliative dermatitis (fever with or without chills, redness, induration or peeling of the skin, swelling and/or soreness of the palatine tonsils), urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

From the immune system rare – anaphylaxis or anaphylactoid reactions (facial skin discoloration, skin rash, urticaria, skin itching, tachypnea or dyspnea, eyelid edema, periorbital edema, shortness of breath, difficulty breathing, chest tightness, wheezing).

Other common – weakness; uncommon – edema (face, shins, ankles, fingers, feet, weight gain); rare – increased sweating, fever, lymphadenopathy; very rare – tongue edema.

Contraindications

• Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or sinusitis and intolerance to acetylsalicylic acid and other NSAIDs (including history);
• Erosive and ulcerative changes in the mucous membrane of the stomach and duodenum;
• Active gastrointestinal bleeding;
• Cerebrovascular or other bleeding;
• Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase;
• Hemophilia and other bleeding disorders;
• Decompensated heart failure;
• Hepatic insufficiency or active liver disease;
• Severe renal insufficiency (creatinine clearance less than 30 ml/min);
• Progressive kidney diseases;
• Confirmed hyperkalemia;
• Period after coronary artery bypass surgery;
• Arterial hypertension;
• Congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Glucose-6-phosphate dehydrogenase deficiency;
• Pregnancy;
• Lactation period;
• Age under 18 years;
• Hypersensitivity to amtolmetin, tolmetin.

With caution the drug should be prescribed for hyperbilirubinemia, chronic heart failure, coronary artery disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, chronic renal failure (creatinine clearance 30-60 ml/min), history of ulcerative gastrointestinal lesions, presence of Helicobacter pylori infection, severe somatic diseases, long-term use of NSAIDs, simultaneous use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), alcoholism, smoking, elderly patients.

Use in Pregnancy and Lactation

The safety of the drug during pregnancy and breastfeeding has not been established.

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency or active liver disease.

Use in Renal Impairment

Contraindicated in severe renal insufficiency (creatinine clearance less than 30 ml/min), progressive kidney diseases.

Should be prescribed with caution in chronic renal failure (creatinine clearance 30-60 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

During treatment, monitoring of the peripheral blood picture and functional state of the liver and kidneys is necessary.

Treatment should be discontinued 48 hours before the determination of 17-ketosteroids.

Effect on the ability to drive vehicles and mechanisms

During treatment, one should refrain from engaging in potentially hazardous activities that require increased attention and speed of mental and motor reactions.

Overdose

Symptoms abdominal pain, nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents (activated charcoal) and symptomatic therapy (maintenance of vital body functions). There is no specific antidote.

Drug Interactions

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites.

Reduces the effectiveness of uricosuric, antihypertensive drugs and diuretics.

Enhances the hypoglycemic effect of sulfonylurea derivatives, the action of anticoagulants, antiplatelet agents, fibrinolytics, the side effects of estrogens, glucocorticoids and mineralocorticoids.

Antacids and cholestyramine reduce absorption.

Increases the blood concentration of lithium and methotrexate drugs.

In some patients with impaired renal function, the combined use of NSAIDs and ACE inhibitors may lead to further deterioration of renal function.

Myelotoxic drugs enhance the manifestations of hematotoxicity of the drug.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date printed on the package.

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.