Xanthinol nicotinate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT XANTINOLNICOTINATE

Composition:

Active substance: 1 tablet contains xantinol nicotinate, calculated as 100% substance – 150 mg;

Excipients: lactose monohydrate (Granulac-70); potato starch; povidone; calcium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: white or almost white tablets, round-shaped, with a flat surface, a score line and bevelled edges.

Pharmacotherapeutic group. Peripheral vasodilators. Purine derivatives.

ATC code C04AD02.

Pharmacological properties.

Pharmacodynamics.

Vasodilating, anti-aggregating, anti-atherosclerotic agent combining properties of theophylline and nicotinic acid.

Blocks adenosine receptors and phosphodiesterase, increasing intracellular levels of cyclic adenosine monophosphate, and substrate-stimulates synthesis of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. Exerts vasodilating effects by reducing total peripheral vascular resistance and improving microcirculation, tissue oxygenation and nutrition; reduces blood viscosity; enhances cerebral circulation; inhibits platelet aggregation and activates fibrinolysis; strengthens myocardial contraction. With prolonged use, it may delay the development of atherosclerotic changes, reduces cholesterol and atherogenic lipid levels, increases lipoprotein lipase activity. With long-term use, it may reduce arterial blood pressure.

Pharmacokinetics.

Well absorbed in the gastrointestinal tract, undergoes biotransformation to form xanthinol and nicotinic acid. Excreted by the kidneys—mainly—as non-toxic metabolites. Therapeutic plasma concentration is 10–20 mg/kg. Elimination half-life is approximately 5 hours.

Clinical characteristics.

Indications. As part of complex therapy in the following diseases and conditions: cerebrovascular disorders, coronary and cerebral atherosclerosis, obliterative atherosclerosis of lower limb vessels, Raynaud's disease, Buerger's disease, obliterative endarteritis, acute arterial thrombosis, diabetic angiopathy and retinopathy, acute thrombophlebitis (of superficial and deep veins), post-thrombophlebitic syndrome, trophic ulcers of lower limbs, pressure sores, migraine, Meniere's syndrome, dermatoses (vascular origin trophic disorders), hypercholesterolemia, hypertriglyceridemia.

The drug in this pharmaceutical form should be used at the end of the acute phase of the disease.

Contraindications.

• Hypersensitivity to any component of the drug, as well as to theophylline and nicotinic acid;
• acute and chronic heart failure of grade II–III;
• acute myocardial infarction;
• acute renal failure;
• acute heart failure or severe congestive heart failure;
• acute hemorrhage;
• gastric and duodenal ulcer in the stage of exacerbation;
• glaucoma;
• mitral stenosis.

Interaction with other medicinal products and other types of interactions. To avoid a sharp drop in arterial pressure, the drug must not be prescribed in combination with antihypertensive agents (beta-adrenoblockers, alpha-adrenoblockers, sympatholytics, ganglion blockers, ergot alkaloids). Concurrent use with strophanthin and other cardiac glycosides may lead to bradycardia and arrhythmias. The drug is also incompatible with MAO inhibitors, alcohol, and coffee. Enhances the anticoagulant effect of heparin, streptokinase, and fibrinolysin.

Use with particular caution in combination with nicotinic acid patches, as flushing, sensation of warmth, and head pulsation may occur.

Special precautions for use

If cardiac glycosides are used concomitantly, treatment should be administered under electrocardiographic monitoring to prevent the development of bradycardia and arrhythmias.

Ten to fifteen minutes after taking the tablet, a sensation of warmth may occur, which may be associated with paresthesia and flushing. These reactions may last 10–20 minutes or longer, and their intensity may decrease within several days after initiating xanthinol nicotinate therapy.

Use with caution in patients with arterial hypertension or labile arterial pressure when xanthinol nicotinate is administered concomitantly with antihypertensive agents or cardiac glycosides due to the potential risk of significant decrease in arterial pressure and/or development of arrhythmias. Postural hypotension may occur due to the vasodilatory effect of the drug. Because of the possible increase in transaminase and alkaline phosphatase levels during prolonged use of xanthinol nicotinate, caution is required when administering the drug to patients with hepatic or renal insufficiency.

Use with caution in patients with severe atherosclerosis of coronary and cerebral vessels, tachysystolic cardiac rhythm disorders, and in elderly patients.

In patients with diabetes mellitus receiving xanthinol nicotinate, blood glucose levels should be monitored more frequently than usual.

Prolonged use of high doses of the drug may lead to changes in glucose tolerance, increased levels of liver enzymes, and changes in blood biochemical parameters, which may necessitate discontinuation of the drug.

Xanthinol nicotinate should be prescribed with particular caution to patients who have recently suffered from liver disease. This includes patients with Gilbert's syndrome, who are sensitive to the hepatic effects of nicotinic acid and prone to more pronounced increases in unconjugated bilirubin levels.

Baseline tests should be performed to determine the presence of elevated lipid levels in blood serum. Regular monitoring is required to assess serum lipid levels. If there is an insufficient clinical response to the drug, treatment should be discontinued.

Since the drug contains lactose, it should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Xanthinol nicotinate should be prescribed with extreme caution to patients with a history of peptic ulcer disease, and, if possible, the use of maximum doses should be avoided. Nicotinate promotes histamine release from mast cells and enhances gastric hydrochloric acid secretion. Therefore, caution is advised in patients with increased gastrointestinal tract sensitivity, bronchial asthma, or predisposition to allergic reactions.

Use during pregnancy or breastfeeding. The drug should not be administered during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery. Caution should be exercised when driving or operating machinery due to the potential for dizziness.

Dosage and Administration

Administer orally to adults after meals. Swallow tablets whole, without chewing.

The usual initial dose is 1 tablet (150 mg) three times daily. If necessary, the single dose may be increased to 2–3 tablets (300–450 mg) three times daily. Then, as the patient's condition improves, the dose should be reduced to 1 tablet 2–3 times daily. The maximum daily dose, provided the therapy is well tolerated, is 12 tablets (1800 mg).

The duration of treatment is determined by the physician according to the course of the disease and the patient's tolerance to the drug.

In acute disorders of cerebral and peripheral circulation, the injectable form of the drug is preferred.

Children. The efficacy and safety of the drug in pediatric patients have not been established; therefore, the drug should not be used in this patient population.

Overdose. Symptoms: pronounced arterial hypotension, tachycardia, sensation of warmth, skin flushing and tingling of the skin on the head and neck, feeling of pressure in the head, weakness, dizziness, loss of consciousness, nausea, vomiting, diarrhea, gastralgia.

Treatment: lay the patient down; the above symptoms usually resolve spontaneously within 10–15 minutes and do not require specific treatment. In case of pronounced arterial hypotension, symptomatic therapy should be administered.

Adverse Reactions.

Immune system disorders: allergic reactions, including skin rashes (urticarial, erythematous-papular), itching, sensation of warmth, tingling, hyperemia of the skin in the upper part of the body, especially neck and head; in isolated cases – angioneurotic edema.

Central and peripheral nervous system disorders: increased fatigue, weakness, dizziness, headache.

Cardiovascular system disorders: flushing, sensation of warmth, arterial hypotension; palpitations; in isolated cases, possible provocation of angina attacks, cardiac arrhythmias, development of steal syndrome.

Gastrointestinal disorders: rarely – nausea, vomiting, diarrhea, anorexia, gastralgia, abdominal distension, meteorism, abdominal discomfort, heartburn, recurrent ulcer, increased activity of liver transaminases and alkaline phosphatase.

Musculoskeletal system disorders: muscle cramps, weakness, arthritis due to development of gout.

Skin and mucous membrane disorders: dry skin, epidermal peeling, pigmentation, hyperkeratosis.

Eye disorders: blurred vision, eye swelling, exophthalmos, amblyopia, cystoid and macular edema.

Endocrine system disorders: with prolonged use of high doses – decreased glucose tolerance.

Biochemical abnormalities: increased alkaline phosphatase, LDH and BSE (blood formed elements), elevated uric acid levels predisposing to gout, hyperglycemia.

Shelf life. 4 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

Tablets 150 mg, 10 tablets per blister, 6 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Halychfarm" or JSC "Kyivmedpreparat".

Manufacturer's name and address.

79024, Ukraine, Lviv, Opryshkivska St., 6/8
or
01032, Ukraine, Kyiv, Saksahanskoho St., 139.