Instructions for use Nitresan tablets 10 mg blister No. 30
Composition
active ingredient: nitrendipine;
1 tablet contains 10 mg of nitrendipine;
Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, magnesium stearate, povidone, docusate sodium.
Dosage form
Pills.
Main physicochemical properties:
10 mg tablets: yellow flat tablets with a score on one side and embossed "10" on the other side, with a diameter of approximately 7 mm.
Pharmacotherapeutic group
Selective calcium antagonists with a predominant effect on blood vessels. ATC code C08C A08.
Pharmacological properties
Pharmacodynamics
Nitrendipine is a selective 1,4-dihydropyridine type calcium channel blocker with a predominant effect on peripheral blood vessels, a calcium antagonist. It exhibits pharmacological effects: hypotensive due to selective dilation of peripheral vessels, antianginal, nephroprotective, vasodilator. The mechanism of antihypertensive action is associated with inhibition of the influx of calcium ions through the cell membranes of smooth muscle cells of the blood vessel walls. By reducing the intracellular calcium concentration in the cells, nitrendipine reduces the contractility of vascular muscles, dilating peripheral arteries; reduces total peripheral resistance and pathologically elevated blood pressure. Nitrendipine exhibits a moderate natriuretic effect, especially at the beginning of treatment.
Pharmacokinetics
Absorption
When administered orally, nitrendipine is rapidly and completely absorbed from the gastrointestinal tract. The degree of absorption is 88%. The biological half-life of absorption is from 30 to 60 minutes. The maximum concentration in the blood plasma (Cmax) is reached 1-3 hours after administration of the drug. The average Cmax is approximately 6.1-19 μg/l. Taking into account the significant influence of the first passage through the liver (first-pass effect), the systemic bioavailability of nitrendipine is 20-30%.
Distribution
Nitrendipine is 96-98% bound to plasma proteins (albumin) and is therefore not dialyzable. Nitrendipine cannot be removed by hemodialysis or peritoneal dialysis. In the steady-state phase, the volume of distribution of nitrendipine is up to 5-9 l/kg body weight.
Metabolism/elimination
When administered orally, nitrendipine is extensively metabolized during the first passage through the liver (first-pass effect) and is almost completely metabolized by oxidation in the liver to form inactive metabolites. Approximately 77% of the oral dose is excreted by the kidneys, less than 0.1% in unchanged form, the rest in the form of metabolites with bile and feces.
The half-life of nitrendipine from blood plasma is approximately 8-12 hours.
No accumulation of the active substance or metabolites in the body is detected after reaching a stable state.
Since nitrendipine is mainly biotransformed through metabolic transformations in the liver, in patients with chronic liver diseases its elimination from the body is much slower: the biological half-life is slowed down by 2-3 times.
No dose adjustment is required for patients with mild to moderate renal impairment.
Indication
Treatment of essential hypertension.
Contraindication
Hypersensitivity to nitrendipine or to any other 1,4-dihydropyridine calcium antagonist or to any of the excipients of the drug; cardiogenic shock; severe aortic valve stenosis; unstable angina; acute myocardial infarction within the previous 4 weeks; concomitant use with rifampicin.
Interaction with other medicinal products and other types of interactions
Nitrendipine is metabolized by the cytochrome P450 3A4 enzyme system, which is located in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may modify the first-pass effect or clearance of nitrendipine.
Beta-blockers and/or other antihypertensive agents
The antihypertensive effect of nitrendipine may be enhanced by beta-blockers and/or other antihypertensive drugs.
Diuretics
Concomitant use of diuretics may lead to increased urinary sodium excretion.
Muscle relaxation
The duration and intensity of interactions with muscle relaxants such as pancuronium or vecuronium may be increased in patients taking nitrendipine.
Cimetidine, ranitidine
Cimetidine and ranitidine may cause an increase in the concentration of nitrendipine in the blood plasma, enhancing the effect of nitrendipine.
Digoxin
With simultaneous use, an increase in the level of digoxin in the blood plasma and the appearance of symptoms of overdose are possible. If it is necessary to prescribe such a combination, patients should be under constant supervision of a physician who can make appropriate adjustments to the doses of digoxin.
Rifampicin significantly stimulates the cytochrome P450 3A4 enzyme system. The simultaneous use of rifampicin and nitrendipine can cause a significant decrease in the bioavailability of nitrendipine (as well as other dihydropyridine calcium channel blockers) and weaken its antihypertensive effect, therefore, nitrendipine should not be used simultaneously with rifampicin.
Grapefruit juice
Grapefruit juice inhibits the oxidative metabolism of nitrendipine. Concomitant use with the drug may cause an increase in the level of nitrendipine in the blood plasma, which is accompanied by an increase in the antihypertensive effect of nitrendipine.
With regular use of grapefruit juice or grapefruit, the effect may appear even 3 days after the last dose of nitrendipine.
Theoretically possible combinations
Phenytoin, phenobarbital, carbamazepine
Detailed studies of the potential interaction between nitrendipine and anticonvulsants have not been conducted. However, it is known that phenytoin, phenobarbital, carbamazepine are potential inducers of the cytochrome P450 3A4 enzyme system. The simultaneous use of these drugs and drugs similar in structure to nitrendipine significantly reduced their bioavailability. Based on these assumptions, a clinical decrease in the bioavailability of nitrendipine and, as a result, a decrease in the effect of nitrendipine should be expected. If the dose of nitrendipine was increased due to simultaneous use with phenytoin, phenobarbital, carbamazepine, then after discontinuation of these anticonvulsants, the dose of nitrendipine should be reduced again.
Ketoconazole, itraconazole, fluconazole
No specific studies of the potential interaction between nitrendipine and azole antifungals (ketoconazole, itraconazole, fluconazole) have been conducted.
These agents are known to inhibit the cytochrome P450 3A4 enzyme system. Interactions of these agents with other dihydropyridine calcium channel blockers have been described. Therefore, when administered orally with nitrendipine, a significant increase in the bioavailability of nitrendipine as a result of its first-pass metabolism cannot be ruled out.
If it is necessary to prescribe such a combination with nitrendipine, patients should be under constant supervision of a physician who can make appropriate adjustments to the doses of nitrendipine after monitoring blood pressure.
Nefazodone
No controlled studies of the potential interaction between nitrendipine and nefazodone have been conducted to date. This antidepressant is a potent inhibitor of cytochrome P450 3A4. Therefore, when administered orally with nitrendipine, a significant increase in nitrendipine plasma levels cannot be excluded.
Fluoxetine
It is known that simultaneous use of the structurally similar dihydropyridine calcium antagonist nimodipine with the antidepressant fluoxetine leads to a 50% increase in nimodipine plasma concentrations.
With simultaneous use, the plasma level of fluoxetine was significantly reduced, but the concentration of its main metabolite, norfluoxetine, did not change.
Therefore, the possibility of an increase in the concentration of nitrendipine in the blood plasma with simultaneous use with fluoxetine cannot be ruled out.
Valproic acid
To date, no controlled studies of the potential interaction between nitrendipine and valproic acid have been conducted. Since it is known that the simultaneous use of valproic acid with a structurally similar analogue of nimodipine as a result of enzymatic inhibition led to an increase in its plasma concentration and increased efficacy, an increase in the efficacy of nitrendipine when used simultaneously with valproic acid cannot be excluded.
Erythromycin, troleandomycin, clarithromycin, roxithromycin
No studies have been conducted to date on the potential interaction between nitrendipine and these macrolide antibiotics. These antibiotics are known to inhibit the cytochrome P450 3A4 enzyme system, which metabolizes other drugs with a similar structure. Therefore, the possibility of increasing the plasma concentration of nitrendipine when used simultaneously with macrolide antibiotics cannot be ruled out.
Amprenavir, atazanavir, ritonavir, indinavir, nelfinavir, saquinavir
No detailed studies of the potential interaction between nitrendipine and protease inhibitors have been conducted. Drugs of this type have been described as potent inhibitors of the cytochrome P450 3A4 enzyme system. Therefore, the possibility of an increase in nitrendipine plasma concentrations when used simultaneously with protease inhibitors cannot be excluded.
Quinupristin/dalfopristin
Studies conducted with another calcium channel blocker, nifedipine, have shown that concomitant use of quinupristin/dalfopristin may increase nifedipine plasma concentrations. Given this fact, it is recommended that patients' blood pressure be monitored closely and, if necessary, the dose of nitrendipine should be reduced in a timely manner when quinupristin/dalfopristin is used concomitantly.
Application features
The drug should be used with caution in patients with:
In patients with mild or moderate hepatic impairment (especially in elderly patients over 65 years of age), the elimination of the active substance is slowed down, which may lead to undesirable arterial hypotension. In patients with severe hepatic impairment, the effect of nitrendipine may be enhanced and/or prolonged. In such cases, treatment should be started with a lower dose, the patient should be under close medical supervision during therapy, and constant monitoring of blood pressure is also recommended. In the event of a sudden decrease in blood pressure, the drug should be discontinued.
Cardiac dysfunction
When nitrendipine and beta-blockers are used simultaneously in patients with impaired cardiac function, careful monitoring of blood pressure is necessary, since a sudden decrease in blood pressure is possible.
In cases of decompensated heart failure, as well as in sick sinus syndrome, in the absence of cardiac pacing support, special attention to the patient's condition and careful monitoring of cardiac activity are necessary when using the drug Nitresan.
Angina pectoris
According to spontaneous reports, angina attacks occurred very rarely (usually at the beginning of treatment). According to clinical trial data, angina occurred infrequently.
Cytochrome P450 3A4 system
Nitrendipine is metabolized by the cytochrome P450 3A4 enzyme system. Drugs that inhibit or induce this enzyme system may modify the first-pass effect or the elimination of nitrendipine from the body.
The following drugs, known as inhibitors of the cytochrome P450 3A4 enzyme system, may increase the level of nitrendipine in the blood plasma:
macrolide antibiotics; AIDS protease inhibitors; azole antifungals; antidepressants nefazodone and fluoxetine; quinupristin/dalfopristin; valproic acid; cimetidine and ranitidine.
Therefore, when nitrendipine is used concomitantly with one of these drugs, blood pressure should be monitored. If necessary, a reduction in the nitrendipine dose should be considered.
Elderly patients should be especially careful when using increased doses of the drug.
The drug contains lactose as an excipient, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use this drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
At the beginning of treatment or when using increased doses, or in combination therapy with other antihypertensive agents, or when drinking alcohol simultaneously, it is recommended to refrain from driving vehicles and potentially hazardous activities that require increased attention and speed of psychomotor reactions, since the level of attention may decrease with a decrease in blood pressure.
Use during pregnancy or breastfeeding
Pregnancy.
The drug is contraindicated during pregnancy.
Breastfeeding period.
Nitrendipine passes into breast milk. If necessary, breastfeeding should be discontinued.
Method of administration and doses
Prescribed for adults orally in the morning after meals. The tablets should be swallowed whole, without chewing, with a sufficient amount of water (for example, a glass).
It is strictly forbidden to drink grapefruit juice!
The active ingredient nitrendipine is sensitive to light, so the tablets should be removed from the blister only before use.
Nitresan 10 mg
1 tablet of Nitresan 10 mg twice a day (morning and evening), which is 20 mg of nitrendipine per day. If blood pressure is not sufficiently reduced during treatment, the doctor may double the daily dose and prescribe 2 tablets twice a day, which is equivalent to a daily dose of 40 mg.
The maximum daily dose is 40 mg.
The dose and number of doses are determined by the doctor individually. In order to achieve the maximum therapeutic effect, individual dosage of the drug is recommended depending on the patient's condition, his reaction to the drug and tolerability. The duration of treatment is determined by the patient's clinical condition.
Elderly patients and patients with impaired liver function
The metabolism of nitrendipine may be slowed down, leading to an undesirable decrease in blood pressure. Since the therapeutic effect of the drug may be enhanced and/or prolonged, it is recommended to start treatment with lower doses (10 mg nitrendipine per day) under close medical supervision.
In cases of significant reduction in blood pressure, even when using low doses, treatment should be changed.
Kidney dysfunction
Patients with mild to moderate renal impairment do not require special dose adjustments.
Children
The drug is not used in children due to the lack of data on its effects and safe use.
Overdose
Symptoms of acute intoxication.
Hot flashes, headache, hypotension (circulatory collapse), changes in heart rate (tachycardia or bradycardia).
It is necessary to remove the drug from the body: wash the gastrointestinal tract, use activated charcoal. Carefully monitor the patient's vital functions. If blood pressure drops significantly, dopamine and noradrenaline should be administered. Attention should be paid to the possible negative effects of catecholamines (especially with regard to heart rhythm disturbances).
In case of bradycardia, intravenous administration of atropine or orciprenaline (similarly to the treatment of intoxication with other calcium channel blockers). Repeated intravenous administration of 10 ml of 10% calcium gluconate or 10% calcium chloride is possible, followed by calcium infusion (it is necessary to prevent the possible development of hypercalcemia). In such cases, catecholamines are also effective, but in much higher doses. Further treatment is symptomatic.
Nitrendipine is not dialyzable, so hemoperfusion and plasmapheresis will not be effective.
Adverse reactions
Adverse reactions occurring with the use of nitrendipine are classified by organ system class and frequency of occurrence:
very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), including isolated cases.
On the part of the immune system:
uncommon - allergic reactions, including skin reactions and allergic edema/angioedema.
From the cardiovascular system:
very often - peripheral edema (especially at the beginning of treatment, usually transient); often - at the beginning of treatment, angina attacks or an increase in the frequency, duration and severity of angina attacks in patients suffering from this disease are possible; palpitations, tachycardia; infrequently - arterial hypotension; rarely - leukocytoclastic vasculitis; very rarely - myocardial infarction.
From the blood and lymphatic system:
very rarely - leukocytopenia, agranulocytosis. The composition of peripheral blood normalized after discontinuation of the drug.
From the nervous system:
very often - headache (especially at the beginning of treatment, usually mild and transient); infrequently - anxiety, sleep disturbances, paresthesia, dizziness, fatigue, tremor (at high doses), drowsiness, nervousness, migraine, hypoesthesia.
On the part of the organs of vision:
infrequently - visual disturbances, blurred vision.
From the side of the organs of hearing and vestibular apparatus:
infrequently - dizziness, tinnitus, vertigo.
On the part of the respiratory system:
infrequently - shortness of breath, nosebleeds.
From the digestive system:
often - feeling of fullness of the stomach; infrequently - nausea, diarrhea, vomiting, abdominal pain, dry mouth, constipation, gastroenteritis; very rarely - gingival hyperplasia.
From the kidneys and urinary tract:
infrequently - peripheral edema of the lower extremities; rarely - urge to urinate; polyuria.
On the skin:
very often - hot flashes (especially at the beginning of treatment, usually transient); infrequently - hypersensitivity reactions (itching, urticaria, erythema, rash, photosensitivity); very rarely - exfoliative dermatitis, angioedema, maculopapular exanthema.
From the musculoskeletal system:
uncommon – arthralgia; myalgia.
From the reproductive system and mammary glands:
very rarely - erectile dysfunction, gynecomastia (in elderly patients), menorrhagia.
From the liver and biliary tract:
rarely - impaired liver function, increased levels of certain laboratory parameters (slight or moderate increase in transaminases).
Other:
infrequently - rhinitis, nonspecific pain, weight gain, increased sweating; very rarely - fever.
Expiration date
4 years.
Storage conditions
Store in the original packaging, protected from light and out of the reach of children, at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister, 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
PRO.MED.CS Praha a.s.
Location of the manufacturer and its business address
Telčska 377/1, Michle, Prague 4, 140 00, Czech Republic.
