Index of drugs

Treatment of dyslipidemia, especially in patients with mixed dyslipidemia (characterized by elevated levels of LDL and triglycerides and low HDL cholesterol) and in patients with primary hypercholesterolemia (heterozygous familial or non-familial). It should be used in combination with HMG-CoA reductase inhibitors (statins), if the reduction in cholesterol obtained in monotherapy with an HMG-CoA reductase inhibitor is insufficient. It can only be used on its own in patients with HMG-CoA reductase inhibitors that are considered unsuitable or unacceptable. During treatment with the preparation, the diet and other non-pharmacological treatments should be continued (eg physical exercise, weight loss).

1 tabl the modified release contains 1000 mg of nicotinic acid and 20 mg of laropiprant. The preparation contains lactose.

Nicotinic acid reduces the concentration of low density lipoprotein (LDL-C), total cholesterol (TC), very-low-density lipoprotein (VLDL-C), apolipoprotein B (apo B, predominantly LDL proteins), triglycerides (TG) , and lipoprotein (a) (Lp (a), a modified LDL particle), as well as an increase in the concentration of high density lipoprotein (HDL-C) and apolipoprotein AI (apo AI, the main protein component of the HDL fraction). The mechanism of action of nicotinic acid probably consists in inhibiting the release of free fatty acids (FFA) from adipose tissue and inhibiting the lipogenesis processde novo or esterification of fatty acids to triglycerides in the liver. Treatment with nicotinic acid is associated with a reduction in the risk of death and cardiovascular events, as well as inhibition of the progression rate or stimulation of atherosclerotic lesions. After oral administration (regardless of food), bioavailability is at least 72%. Plasma proteins bind to <20%. Nicotinic acid is extensively subject to first-pass metabolism through two dose-related metabolic pathways and dose frequency. The effect of the first pass through the first metabolic pathway is nicotinamide adenine dinucleotide (NAD) - undergoing further transformation and nicotinamide; in the second path, Glycine is coupled with nicotinic acid, resulting in the formation of nicotinuric acid (NUA). Under conditions of low supply of nicotinic acid or a slower rate of nicotinic acid absorption, the first metabolic pathway prevails; in the case of a higher supply or faster absorption rate, the NAD pathway is saturated and an increasing portion of the orally administered nicotinic acid dose in unchanged form is passed into the bloodstream. Nicotinic acid is excreted primarily in the urine in the form of metabolites. Laropiprant is a potent and selective DP antagonist₁ - receptor for PGD₂. It does not inhibit the production of prostaglandins. Laropiprant effectively reduces the symptoms of flushing with flushing caused by nicotinic acid in which PGD is involved₂. Laropiprant does not affect lipid levels or interfere with the effect of nicotinic acid on the lipid profile. Laropiprant is characterized by affinity for the thromboxane A receptor₂ (this effect is much weaker than on DP₁), but in therapeutic doses does not significantly affect clinically bleeding time and collagen-induced platelet aggregation. Following oral administration with food, laropiprant is rapidly absorbed from the gastrointestinal tract, the mean absolute bioavailability of laropiprant after administration of 40 mg in the form of 2 tablets. sustained-release containing nicotinic acid and laropiprant after an overnight non-eating meal is about 71%. To a high degree (> 99%), it binds to plasma proteins. It is metabolized primarily in the glucuronidation process and in a small part in oxidative metabolism processes, and then excreted in the form of glucuronide with faeces and urine.

Hypersensitivity to the components of the preparation. Significant or unexplained liver problems. Active peptic ulcer disease. Bleeding from the artery.

The safety and efficacy of the medicine in children has not been established, which is why it is not recommended in this age group. In patients switching from long-acting nicotinic acid to long-acting (contained in the product) cases of severe hepatic toxicity, including fulminant hepatic necrosis have been reported, therefore the treatment should be started with the lowest dose.Caution should be exercised in people who consume significant amounts of alcohol and / or liver disease. Patients who develop transaminase elevations should be followed up until the symptoms subside; if ALT or AST elevations are> 3 x ULN, dose reduction or discontinuation is recommended. In cases of concomitant use of statins and nicotinic acid (at doses ≥ 1000 mg / day), cases of myopathy / rhabdomyolysis have rarely occurred, therefore when considering combination therapy with these drugs, careful consideration should be given to the potential benefits and risks and whether patients show any signs or symptoms muscle pain, tenderness or weakness, especially in the first months of treatment and after increasing the dose of one of the preparations. In such cases, periodic determination of serum creatine kinase (CK) should be considered, but there is no certainty that such treatment will prevent severe myopathy. Caution should be exercised in patients with predisposing factors for rhabdomyolysis, i.e. in patients> 70 years of age, with renal impairment, uncontrolled hypothyroidism, hereditary muscular disease in an individual or family history, abusing alcohol, and if toxic effects occur muscles using a statin or a fibrate history. If muscle pain, weakness or cramps occur while taking the product simultaneously with the statin, the creatine kinase activity should be determined; if its concentration is significantly increased (> 5 x ULN), treatment should be discontinued. Caution should be exercised when using the product in Chinese patients in combination with Simvastatin or ezetimibe and simvastatin (especially at simvastatin doses of 40 mg or greater), due to the increased incidence of myopathy in this patient group. The use of Chinese patients with Simvastatin 80 mg or with ezetimibe 10 mg and simvastatin 80 mg is not recommended in Chinese patients. Caution should be exercised in patients with impaired renal function, with gout or at risk of gout, and in patients with unstable angina or in the acute phase of myocardial infarction, especially if such patients also take vascular preparations such as nitrates, Calcium channel blockers or antagonists of the adrenergic receptors. Due to the risk of increased fasting blood Glucose, careful observation of patients or potentially diabetic patients; it may be necessary to adjust the diet and / or the hypoglycemic treatment. Due to the risk of reducing the number of platelets during treatment with nicotinic acid, the condition of patients undergoing surgery should be carefully assessed. Patients at risk of hypophosphataemia and patients with past history of jaundice, hepatobiliary disorders or peptic ulcer should be carefully monitored. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

There are no studies on the combined use of nicotinic acid and laropiprant in pregnant and breast-feeding women. Do not use during pregnancy unless clearly necessary. The decision to continue or terminate breastfeeding or to continue or discontinue treatment should be made taking into account the benefit of breastfeeding for the child and the benefits of the preparation for the woman.

Very often: hot flushes with redness. Common: dizziness and headache, paraesthesia; diarrhea, indigestion, nausea, vomiting; erythema, pruritus, rash, urticaria; feeling hot. Uncommon: angioneurotic edema, loss of consciousness, shortness of breath, incontinence and stool, cold sweats, tremors, chills, increased blood pressure, swelling of the lips, burning sensation, drug eruptions, arthralgia, swelling of the lower limbs, increased heart rate. In addition, <1% of patients had atrial fibrillation and other arrhythmias, palpitations, tachycardia; migraine, fainting; cystic macular edema, toxic amblyopia; dyspnoea; abdominal pain, swollen lips, belching, peptic ulcer; keratosis, darkening, dry skin, discoloration; bladder rash,weakness and muscle pain; impaired Glucose tolerance, gout; runny nose; hypotension, orthostatic hypotension; weakness, chills, facial swelling, generalized edema, pain, peripheral edema; angioneurotic edema, type I hypersensitivity; jaundice, anxiety, insomnia.

Orally. The initial dose is 1 tablet. with modified release (1000 mg nicotinic acid / 20 mg laropiprant) once a day. After 4 weeks, it is recommended to increase the dose in patients to the maintenance dose of 2000 mg / 40 mg taken as 2 tablets. with modified release once a day. Due to the lack of testing, it is not recommended to use higher daily doses than 2000 mg / 40 mg. If the preparation has not been taken for less than 7 consecutive days, patients may resume treatment from the last applied dose. If the preparation was not taken for 7 or more consecutive days, the treatment should be resumed at a dose of 1000 mg / 20 mg for one week, before increasing the dose to a maintenance dose of 2000 mg / 40 mg. Patients using up to 2000 mg or higher prolonged-release nicotinic acid can start treatment at 2,000 mg / 40 mg. Patients using up to 2000 mg of sustained release nicotinic acid should start treatment with an initial dose of 1000 mg / 20 mg, which should be increased to a maintenance dose of 2000 mg / 40 mg for 4 weeks. For patients using immediate-release nicotinic acid, treatment should be started with the 1,000 mg / 20 mg dose, which should be increased to a maintenance dose of 2000 mg / 40 mg for 4 weeks. If bile-acid-binding preparations are used concomitantly, it is recommended to administer Tredaptive for> 1 h before or> 4 h after the bile acid sequestrant.
The tablets should be taken whole, with food, in the evening or at bedtime. To maintain the properties of the modified-release tablets, the tablets must not be divided, broken, crushed or chewed.