Instructions for Nemotan film-coated tablets 30 mg No. 30
Composition
active ingredient: nimodipine;
1 tablet contains nimodipine 30 mg;
excipients: povidone K25, microcrystalline cellulose, corn starch, crospovidone, magnesium stearate;
shell: Opadry white OY-28920 (polyvinyl alcohol, titanium dioxide (E 171), talc, lecithin (E 322), xanthan gum (E 415)).
Dosage form
Film-coated tablets.
Main physicochemical properties: biconvex round tablets of white or almost white color, coated with a film shell with a core diameter of approximately 10.3 mm.
Pharmacotherapeutic group
Selective calcium channel blockers with a predominant effect on blood vessels. Dihydropyridine derivatives. Nimodipine.
ATX code C08C A06.
Pharmacological properties
Pharmacodynamics
Nimodipine has a pronounced selective effect in certain areas of the brain. Its therapeutic properties are associated with the ability to inhibit the contraction of smooth muscle cells caused by calcium ions.
Nimodipine protects neurons and stabilizes their function; it favorably affects cerebral blood flow and increases tolerance to ischemia through interactions with neuronal receptors and cerebrovascular receptors associated with calcium channels. Other studies have shown that it does not lead to an intracerebral hijacking phenomenon.
Nimodipine has been clinically demonstrated to reduce memory impairment and improve concentration in patients with impaired brain function.
Nimodipine has a positive effect on other typical symptoms, as demonstrated by the assessment of general clinical indicators, the assessment of individual disorders, behavioral observations and psychometric tests.
Pharmacokinetics
Absorption.
The active substance nimodipine is almost completely absorbed after oral administration. Peak plasma concentrations and area under the concentration curve (AUC) increase in proportion to the dose up to the highest dose tested (90 mg).
The estimated volume of distribution (Vss, two-chamber model) for intravenous administration is 0.9-1.6 l/kg body weight. The total (total) clearance is 0.6-1.9 l/h/kg.
Protein binding and distribution
Binding to blood proteins reaches 97-99%.
Metabolism, elimination and excretion
Nimodipine is eliminated by metabolism via the cytochrome P450 3A4 system.
Bioavailability
Due to intensive presystemic metabolism (about 85-95%), absolute bioavailability is 5-15%.
Indication
• Prevention and treatment of ischemic neurological disorders caused by cerebral vasospasm after subarachnoid hemorrhage due to aneurysm rupture.
• Treatment of functional brain disorders in elderly patients with severe symptoms.
Contraindication
The use of the drug Nemotan is contraindicated in individuals with individual hypersensitivity to nimodipine or other components of the drug.
The use of Nemotan in combination with rifampicin is contraindicated, since the simultaneous use of these drugs leads to a significant decrease in the effectiveness of Nemotan.
Antiepileptic drugs (phenobarbital, phenytoin, carbamazepine) significantly reduce the bioavailability of nimodipine, therefore the simultaneous use of Nemotan with these drugs is contraindicated.
Nimodipine should not be used in unstable angina and myocardial infarction and/or within 1 month of their occurrence.
Treatment of functional brain disorders.
Severe hepatic impairment, especially in cirrhosis, may lead to increased bioavailability of nimodipine due to reduced completeness of first-pass metabolism and reduced metabolic clearance. Therefore, Nemotan should not be used for the treatment of functional brain disorders in patients with severe hepatic impairment (e.g. cirrhosis).
Interaction with other medicinal products and other types of interactions
Nimodipine is metabolized by the cytochrome P450 3A4 system, which is located in both the intestinal mucosa and the liver. Therefore, drugs that affect this enzyme system may alter the primary metabolism or clearance of nimodipine.
When using nimodipine concomitantly with the following drugs, the degree as well as the duration of the interaction should be taken into account.
Based on experience with other calcium channel antagonists, it is known that rifampicin will enhance the metabolism of nimodipine due to enzyme induction. Thus, the simultaneous use of rifampicin and nimodipine leads to a significant decrease in the effectiveness of the latter. The use of Nemotan in combination with rifampicin is contraindicated.
Antiepileptic drugs (phenobarbital, phenytoin, carbamazepine) significantly reduce the bioavailability of nimodipine tablets, therefore the simultaneous use of Nemotan with these drugs is contraindicated.
No interaction studies have been conducted between nimodipine and macrolide antibiotics. Some macrolide antibiotics (e.g. erythromycin) are known to inhibit the cytochrome P450 3A4 system and the possibility of drug interactions at this stage cannot be excluded. Therefore, macrolide antibiotics should not be used with nimodipine.
Azithromycin, although structurally belonging to the macrolide antibiotic class, does not inhibit CYP3A4.
No formal studies have been conducted to investigate the potential interaction between nimodipine and anti-HIV protease inhibitors (e.g. ritonavir). Drugs of this class are known to be potent inhibitors of the cytochrome P450 3A4 system. Therefore, the possibility of a marked and clinically significant increase in nimodipine plasma concentrations when co-administered with protease inhibitors cannot be excluded.
No formal studies have been conducted to investigate the potential interaction between nimodipine and ketoconazole. Azole antifungals are known to inhibit the cytochrome P450 3A4 system and various interactions have been reported for other dihydropyridine calcium channel antagonists. Therefore, a significant increase in the systemic bioavailability of nimodipine due to a decrease in first-pass metabolism cannot be excluded when co-administered with nimodipine tablets.
No formal studies have been conducted to investigate the potential interaction between nimodipine and nefazodone. The antidepressant has been reported to be a potent inhibitor of cytochrome P450 3A4. Therefore, the possibility of increased plasma concentrations of nimodipine when co-administered with nefazodone cannot be excluded.
Long-term co-administration of Nemotan and fluoxetine resulted in an increase in the plasma concentration of nimodipine by almost 50%. The effect of fluoxetine was significantly reduced, but the effect of its active metabolite norfluoxetine was not.
Based on experience with nifedipine, its simultaneous use with quinupristin/dalfopristin may lead to an increase in the concentration of nimodipine in the blood plasma.
Concomitant use of Nemotan and the H2-receptor antagonist cimetidine or valproic acid preparations may lead to an increase in the concentration of nimodipine in the blood plasma.
Long-term use of nimodipine with the antidepressant nortriptyline leads to a slight increase in the concentration of nimodipine in the blood plasma; the concentration of nortriptyline remains unchanged.
Nimodipine may enhance the hypotensive effect of the following antihypertensive drugs when administered concomitantly:
- diuretics;
- β-blockers;
- ACE inhibitors (angiotensin converting enzyme inhibitors);
- α1- antagonists;
- other calcium antagonists;
- α-adrenergic blocking substances;
- phosphodiesterase-5 inhibitors;
- α-methyldopa.
However, if combinations of this type cannot be avoided, the patient's condition should be closely monitored.
In a study in monkeys, it was found that concomitant intravenous administration of nimodipine and the HIV drug zidovudine resulted in a significant increase in the AUC of zidovudine and a decrease in its volume of distribution and clearance.
Grapefruit juice inhibits the cytochrome P450 3A4 system. The use of dihydropyridines - calcium channel antagonists - simultaneously with grapefruit juice leads to increased plasma concentrations and prolonged action of nimodipine due to reduced first-pass metabolism or clearance.
This may increase the hypotensive effect of the drug. After consumption of grapefruit juice, this effect may last for at least 4 days, therefore the simultaneous use of grapefruit/grapefruit juice and nimodipine is not recommended.
Application features
Special warnings and precautions.
Treatment of functional brain disorders.
When treating the elderly, patients with severe renal impairment (glomerular filtration rate less than 20 ml/min) or severe cardiovascular disease, the need for treatment with the drug should be carefully considered and the patient should be systematically examined.
Prevention and treatment of ischemic neurological disorders caused by cerebral vasospasm after subarachnoid hemorrhage due to aneurysm rupture.
Although the use of nimodipine is not associated with an increase in intracranial pressure, in these cases or when the water content in the brain tissues is increased (generalized cerebral edema), careful monitoring of the patient is recommended.
Treatment of functional brain disorders or prevention and treatment of ischemic neurological disorders caused by cerebral vasospasm after subarachnoid hemorrhage due to aneurysm rupture.
The use of nimodipine requires special caution in cases of arterial hypotension with a systolic pressure level of less than 100 mm Hg.
Nimodipine is metabolized via the cytochrome P450 3A4 system. Therefore, drugs that affect this enzyme system may alter the primary metabolism or clearance of nimodipine.
Drugs that are inhibitors or inducers of the cytochrome P450 3A4 system may therefore lead to increased plasma concentrations of nimodipine:
-macrolides (e.g. erythromycin);
-anti-HIV protease inhibitors (e.g. ritonavir);
- antidepressants nefazodone and fluoxetine;
-quinupristin/dalfopristin;
-cimetidine;
-valproic acid.
When using these drugs simultaneously, blood pressure should be monitored and, if necessary, a reduction in the dose of nimodipine should be considered.
Use during pregnancy or breastfeeding
Pregnancy
Appropriate studies on the effects on pregnant women have not been conducted. If it is necessary to use the drug during pregnancy, the benefits and potential risks of taking the drug should be carefully weighed depending on the severity of the clinical picture.
Breast-feeding
It has been found that the concentration of nimodipine and its metabolites in breast milk corresponds in order of magnitude to that in maternal plasma. Mothers are not recommended to breastfeed their infants while taking the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
The ability to drive and use machines may be impaired due to possible dizziness.
Method of administration and doses
Treatment of functional brain disorders.
When treating functional brain disorders in elderly patients, the recommended dose, unless otherwise prescribed by a doctor, is 1 tablet of Nemotan three times a day (30 mg of nimodipine 3 times a day).
In patients with significantly reduced renal function (glomerular filtration rate less than 20 ml/min), the need for treatment with the drug should be carefully considered and the patient should be systematically examined.
Prevention and treatment of ischemic neurological disorders caused by cerebral vasospasm after subarachnoid hemorrhage due to aneurysm rupture.
After a course of infusion therapy, Nemotan should be administered orally at a dose of 60 mg (2 film-coated tablets) 6 times a day.
In case of adverse reactions, the dose should be reduced, and if necessary, the drug should be discontinued.
Impaired liver function, especially in cirrhosis, may lead to increased bioavailability of nimodipine due to reduced completeness of first-pass metabolism and reduced metabolic clearance. Adverse reactions (e.g., decreased blood pressure) may be more pronounced. In such cases, the dose should be reduced and, if necessary, the drug should be discontinued.
When used concomitantly with CYP 3A4 inhibitors or inducers, dose adjustment may be required (see section "Interaction with other medicinal products and other types of interactions").
Swallow the tablets whole, without chewing, with a small amount of liquid, regardless of food intake, at intervals of at least 4 hours. It is not recommended to use grapefruit juice simultaneously with the drug.
Children
The drug should not be used in children.
Overdose
Symptoms: in acute overdose, severe arterial hypotension, tachycardia or bradycardia, nausea, and gastrointestinal disorders are observed.
Treatment: in case of acute overdose, immediate withdrawal of the drug is recommended. In case of emergency care, symptomatic therapy is indicated. As emergency therapy, gastric lavage is recommended, followed by the use of activated charcoal.
If blood pressure continues to fall, intravenous noradrenaline or dopamine should be administered. Since there is no specific antidote, symptomatic therapy is also provided for other adverse reactions.
Adverse reactions
Below is a list of adverse drug reactions based on clinical trials of nimodipine for the indication "subarachnoid hemorrhage due to aneurysm".
From the blood and lymphatic system: changes in blood test parameters, thrombocytopenia.
Immune system disorders: acute hypersensitivity reactions, allergic reaction,
rash.
Nervous system: nonspecific cerebrovascular symptoms, headache.
Cardiac: nonspecific arrhythmias, tachycardia, bradycardia.
From the vascular system: nonspecific cardiovascular symptoms, hypotension, vasodilation.
Gastrointestinal: gastrointestinal disorders, nausea, intestinal obstruction.
Liver and biliary tract: mild to moderate liver reactions, transient increase in liver enzyme activity.
Below is a list of adverse drug reactions based on clinical studies of nimodipine for the indication "treatment of functional brain disorders".
Immune system disorders: acute hypersensitivity reactions, allergic reaction,
rash.
Nervous system: nonspecific cerebrovascular symptoms, headache, vertigo.
Nonspecific neurological symptoms: dizziness, hyperkinesia, tremor.
Cardiac: nonspecific arrhythmias, palpitations, tachycardia.
Vascular disorders: nonspecific cardiovascular symptoms, hypotension, vasodilation, syncope, edema.
Gastrointestinal: gastrointestinal disorders, constipation, diarrhea, flatulence.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging, out of the reach of children.
Incompatibility
Unknown.
Packaging
10 tablets in a blister; 3 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Medochemie LTD.
Location of the manufacturer and its business address
2 Michael Erakleous Street, Agios Athanassios Industrial Area, Limassol, 4101, Cyprus (Factory AZ).
