NEGIS [Nimodipine] 30 mg Tablets
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NEGIS
instructions for medical use of the medicinal product
Tradename
Negis,
International non-proprietary name
Nimodipine, Nimodipine
Composition
Each film-coated tablet contains:
active substances: nimodipine 30 mg
excipients: starch, dextron, microcrystalline cellulose, hypromellose, sodium carboxymethylcellulose, silicon dioxide, magnesium stearate, talc
Dosage form
Tablets.
Pharmacotherapeutic group
Blockers of slow calcium channels .
Pharmacological properties
Pharmacodynamics
The blocker of slow calcium channels (BMCK), a derivative of 1,4-dihydropyridine, has a predominantly cerebrovasodilating and anti-ischemic effect. May prevent or eliminate vasospasm caused by various vasoactive substances (including serotonin, prostaglandins, histamine). Due to its high lipophilicity, it penetrates through the BBB.
Practically does not affect the conductivity in the sinoatrial and atrioventricular nodes, as well as myocardial contractility. Reflexively increases heart rate in response to vasodilation.
In patients with acute disorders of cerebral circulation, nimodipine, by expanding the vessels of the brain, improves cerebral circulation. At the same time, additional perfusion, as a rule, is expressed in damaged areas and in areas of the brain with insufficient blood supply. The use of nimodipine can significantly reduce mortality and the incidence of ischemic neurological disorders against the background of subarachnoid hemorrhage .
Pharmacokinetics
Absorption - almost complete. Bioavailability - 8-12% (pronounced effect of "first pass" through the liver). T max - 0.5-1 h, C max is 31 ng / ml. C ss (0.6-1.6 hours after the next dose) in plasma is 12.3-17.5 ng / ml in young people and 26 ng / ml in older people. There is a proportional increase in plasma concentration with an increase in a single dose to 90 mg.
Nimodipine is largely bound to plasma proteins (97-99%). Penetrates through the placental barrier. The concentration of nimodipine and its metabolites in breast milk significantly exceeds the concentration in blood plasma.
It is excreted by the kidneys (less than 1% - unchanged) and with bile (99%) in the form of metabolites (dehydrogenation of the dihydropyridine ring and oxidative cleavage of esters play a primary role). Metabolites are practically devoid of pharmacological activity. The kinetics of excretion is linear.
Indications for use
· prevention and treatment of ischemic neurological disorders caused by spasm of cerebral vessels against the background of subarachnoid hemorrhage due to aneurysm rupture (after IV therapy with an infusion solution);
· severe brain dysfunction in elderly patients (including decreased memory and ability to concentrate, emotional lability).
Contraindications
· severe liver dysfunction (for the treatment of brain dysfunction);
· pregnancy;
· breastfeeding period;
· age up to 18 years;
· therapy with antiepileptic drugs;
· simultaneous use with rifampicin;
· individual intolerance to the components of the drug.
Dosage and administration
The drug is taken orally, regardless of the meal. Tablets should be swallowed whole with a small amount of liquid. The intervals between doses should be at least 4 hours.
In the absence of other appointments, it is recommended to observe the following dosing regimen:
subarachnoid hemorrhage after aneurysm rupture: the recommended dose is 60 mg 6 times / day for 7 days.
impaired brain function in elderly patients: the recommended dose is 30 mg 3 times / day.
Special instructions and precautions
The appointment of Negisa in elderly patients with a large number of concomitant diseases, severe renal insufficiency (GFR less than 20 ml / min) and severe cardiovascular diseases should be especially carefully justified. During therapy and after its completion, such patients need regular medical supervision (including neurological).
In patients with impaired liver function, due to a decrease in the intensity of the pronounced "first pass" effect through the liver and a slowdown in metabolic inactivation, the bioavailability of nimodipine may increase. As a result, the main and side effects of the drug, in particular its hypotensive effect, may be enhanced. In such cases, the dose of the drug should be reduced depending on the degree of reduction in blood pressure, and if necessary, the use of the drug should be discontinued.
Despite the absence of a "withdrawal" syndrome in BMCC, a gradual reduction in doses is recommended before stopping treatment.
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist that the patient is taking Negis.
Caution should be given simultaneously with disopyramide and flecainamide (possibly increased severity of negative inotropic action).
Influence on the ability to drive vehicles and mechanisms
During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Use during pregnancy and during breastfeeding
The use of the drug during pregnancy and during breastfeeding is contraindicated.
Interaction with other drugs
Xenobiotics that affect the activity of the CYP3A4 isoenzyme can change the metabolic clearance of nimodipine.
Rifampicin, inducing the activity of liver enzymes, is able to accelerate the metabolism of nimodipine and, with their simultaneous use, the effectiveness of nimodipine decreases.
Previous long-term administration of microsomal oxidation inducers (phenobarbital, phenytoin or carbamazepine) increases the metabolism of nimodipine.
Grapefruit juice inhibits the metabolism of dihydropyridines. Combinations of grapefruit juice and nimodipine should be avoided as this may lead to an unpredictable increase in plasma concentrations of nimodipine.
Simultaneous use of nimodipine with cimetidine or valproic acid may also lead to an increase in plasma concentrations of nimodipine.
The combined use of nimodipine and fluoxetine is accompanied by an increase in the plasma concentration of nimodipine (by 50%), while the concentration of fluoxetine is significantly reduced, and the concentration of its active metabolite norfluoxetine remains unchanged.
Simultaneous long-term use of nimodipine and nortriptyline leads to a slight decrease in the concentration of nimodipine (while the concentration of nortriptyline in the blood plasma does not change).
Nimodipine with simultaneous intravenous administration with zidovudine leads to a significant increase in the AUC of the latter and a decrease in its V d and clearance.
Suppresses the metabolism of prazosin and other alpha-blockers, as a result of which an increase in the hypotensive effect is possible.
In patients taking antihypertensive drugs (diuretics, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, other BMCCs, alpha-blockers, methyldopa, sympatholytics, and others), nimodipine enhances the severity of the hypotensive effect.
Caution should be given simultaneously with disopyramide, flecainide, procainamide, quinidine and other drugs that cause a prolongation of the QT interval (possibly increased severity of negative inotropic action and prolongation of the QT interval).
Co-administration of potentially nephrotoxic drugs (eg, aminoglycosides, cephalosporins, furosemide) with nimodipine may lead to impaired renal function. If necessary, their simultaneous use, as well as in patients with renal insufficiency, treatment should be carried out under close monitoring of renal function. If impaired renal function is detected, nimodipine should be discontinued.
Enhances the arrhythmogenic effect of drugs that promote the excretion of potassium ions.
Increases the risk of side effects of cardiac glycosides, quinidine, carbamazepine, cyclosporine, theophylline, valproic acid, lithium preparations.
The hypotensive effect is enhanced with simultaneous administration with inhalation anesthetics.
The hypotensive effect is reduced by sympathomimetics, NSAIDs (suppression of prostaglandin synthesis, sodium and fluid retention in the body), estrogens (fluid retention in the body).
Side effect
From the side of the cardiovascular system: lowering blood pressure, bradycardia or tachycardia, arrhythmias, flushing of the skin of the face, development or aggravation of existing heart failure and myocardial ischemia (especially in patients with severe obstructive lesions of the coronary arteries).
From the digestive system: nausea, diarrhea or constipation, flatulence, dry mouth, change in appetite (usually increased), gingival hyperplasia (bleeding, soreness, swelling), in rare cases, paralytic ileus.
From the nervous system: headache, dizziness, asthenia, extrapyramidal disorders (ataxia, mask-like face, muscle rigidity, tremor, difficulty swallowing), symptoms of CNS excitation (insomnia, increased motor activity, agitation, aggressiveness), depression, excessive fatigue, drowsiness .
From the respiratory system: cough, shortness of breath.
From the musculoskeletal system: soreness and swelling of the joints.
From the hemopoietic system: thrombocytopenia, agranulocytosis.
Allergic reactions: skin itching, rash.
Influence on laboratory parameters: increased activity of hepatic transaminases, alkaline phosphatase and GGT, increased plasma urea concentration, hypercreatininemia.
Others: peripheral edema, increased sweating, decreased kidney function, galactorrhea, weight gain.
If any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
Symptoms : a significant decrease in blood pressure, tachycardia or bradycardia, epigastric pain, various neurological disorders.
Treatment: gastric lavage, activated charcoal, symptomatic therapy. Specific antidotes are unknown.
Storage conditions
Store in a cool and dry place, at a temperature not exceeding 30 0 C.
Keep out of the reach of children.
Best before date
3 years. Do not use after the expiry date stated on the package.
Holiday conditions
Released by prescription.
Release form
10 tablets in an aluminum foil blister. 3 blisters with instructions for use in a cardboard box.