Nimotop - instructions for use, dose, side effects, contraindications

Round, biconvex tablets are yellow, covered with a film membrane. On the front side of the tablet - engraving in the form of a Bayer's cross, on the reverse - "SK".

Pharmacotherapeutic group:The blocker of "slow" calcium channels (BCCI).

ATX: & nbsp

C.08.C.A Dihydropyridine derivatives

C.08.C.A.06 Nimodipine

Pharmacodynamics:

Nimodipine has a highly selective antispasmodic effect on cerebral vessels. Nimodipine prevents or eliminates the narrowing of the vessels, provoked by various vasoactive substances (for example, serotonin, prostaglandins).

In patients with acute disorders of the cerebral circulation nimodipine expands the cerebral vessels and improves cerebral blood flow. Increased perfusion is generally more pronounced in areas of the brain that have received insufficient blood supply than in intact tissues. Nimodipine significantly reduces the incidence of ischemic brain damage and mortality in patients with subarachnoid hemorrhage.

Nimodipine, acting on the receptors of the blood vessels of the brain connected to the calcium channels, exerts a protective effect on nerve cells, stabilizes their function, improves the blood supply to the brain, improves the tolerability of ischemia by nerve cells, and the "stealing syndrome" does not develop. Nimodipine has a beneficial effect in memory disorders and concentration of attentionin patients with impaired brain function. At the same time, personal, behavioral reactions and the results of psychometric functional tests are improved.

Pharmacokinetics:

Suction. After ingestion, the active substance nimodipine almost completely absorbed. Nimodipine and primary metabolites are detected in the blood plasma after 10-15 minutes after taking the pill. After repeated oral administration (30 mg 3 times a day), the maximum concentration in elderly patients was achieved in 0.6-1.6 hours and was 7.3-43.2 ng / ml. In young patients, after taking single doses of Nimotope, 30 mg and 60 mg of Stach are 16 ± 8 ng / ml and 31 ± 12 ng / ml, respectively. The increase in the maximum concentration and area under the concentration-time curve is dose-dependent.

In connection with the intensive metabolism at the "first passage" through the liver (85-95%), the absolute bioavailability of nimodipine is 5-15%.

Distribution. Nimodipine intensively binds to blood plasma proteins (97-99%), penetrates through the placental barrier. Concentrations of nimodipine and its metabolites in breast milk significantly exceed the concentration in the blood plasma.

After oral administration, the concentration of nimodipine in the cerebrospinal fluid is about 0.5% of the concentration in the blood plasma.

Metabolism and excretion. Nimodipine is metabolized mainly by dehydrogenation of dihydropyridine ring and oxidative cleavage of esters.The 3 main metabolites found in the blood plasma do not have clinically significant activity.

The effect of nimodipine on the activity of liver enzymes has not been studied. At the person metabolites on 50% are deduced by kidneys and on 30% with bile. The half-life of nimodipine (T1 / 2 initial phase) is 1.1 to 1.7 hours. The final phase of T1 / 2 is 5-10 hours.

Indications:

1. Prevention and treatment of ischemic neurological disorders caused by cerebrovascular spasm amid subarachnoid hemorrhage caused by rupture of the aneurysm (used after previous treatment of the intravenous infusion solution Nimotop).

2. Severe dysfunction of the brain in elderly patients (decreased memory and concentration, emotional instability).

Contraindications:

Hypersensitivity to any of the components of the drug, severe violations of the liver (for example, cirrhosis), concomitant administration with rifampicin or antiepileptic drugs (phenobarbital, phenytoin, carbamazepine), pregnancy, lactation, age under 18 years.

Carefully:

- with arterial hypotension (systolic blood pressure less than 100 mm Hg)

- In patients with unstable angina or during the first 4 weeks after acute myocardial infarction assessment of potential risk (reduction of coronary artery perfusion and myocardial ischemia) and benefits (improvement of cerebral perfusion).

- in elderly patients with a combined pathology with severe impairment of renal function (glomerular filtration rate less than 20 ml / min)

Elderly patients with severe heart failure who receive a drug to treat brain function disorders need regular follow-up.

Pregnancy and lactation:contraindicated

Dosing and Administration:

Inside. Tablets should be swallowed whole, washed down with a small amount of liquid, regardless of food intake. Intervals between receptions should be not less than 4 hours. The following dosing regimen is recommended:

1. Subarachnoid hemorrhage caused by aneurysm rupture. Tablets should be taken after 5-14 days of intravenous therapy with Nimost's infusion solution.Recommended dose: 2 tablets 6 times a day (60 mg of nimodipine 6 times a day) for 7 days.

2. Therapy of disorders of brain functions in elderly patients. Recommended dose: 1 tablet 3 times a day (30 mg nimodipine 3 times a day).

Side effects:

Adverse Reactions (HP), which have been reported in connection with the use of Nimotop® are given in the tables below. In each group, undesirable effects are presented in order of decreasing severity. The frequency is defined as "very often (> = 1/10)", "often (from> = 1/100 to <1/10)", "infrequently (from> = 1/1000 to <1/100)", "rarely (from> = 1/10 000 to <1/1 000)", "very rarely (<1/10 000)".

Table 1: HP, which were reported in connection with the use of the drug at ischemic neurological disorders

Class Systems	Infrequently	Rarely
bodies
(MedDRA)
Violations from	Thrombosis-
the sides of the blood and	flooding

lymphatic systems
Immune system disorders	Allergic reactions Rash
Disturbances from the nervous system	Head pain
Heart Disease	Tachycardia	Bradikar dia
Vascular disorders	Reduction of blood pressure Vasodilation
Disorders from the gastrointestinal tract	Nausea	Intestinal impassable bridge
Infringements from hepatobiliary systems		The transitor- no raising hepatic of the Enzymes
Table 2: HP, which were reported in connection with the use of the drug for severe impairment of brain function in elderly patients
System Class bodies (MedDRA)	Frequent	Infrequent
Immune system disorders		Allergic reactions Rash

Disturbances from the nervous system		Headache, vertigo, dizziness, hyperkinetic, tremor
Heart Disease		Feeling heartbeat tion, tachycardia
Violations from	Decrease	Fainting
sides of blood vessels	arterial pressure Vasodilation	Edema
Violations from		Constipation
hand		Diarrhea
gastrointestinal tract		Flatulence

Overdose:

Symptoms: marked reduction in blood pressure, tachycardia or bradycardia, vomiting, pain in the epigastric region, symptoms of impairment of the central nervous system. In case of an overdose, stop taking the medication immediately.

Treatment is symptomatic. First aid includes washing the stomach and taking activated charcoal. If there is a significant reduction in blood pressure, you should enter intravenously dopamine or norepinephrine. Specific antidotes of nimodipine are unknown.

Interaction:

Nimotop is metabolized with the enzymes of the cytochrome P450 3A4 system, so drugs that induce or inhibit the activity of liver enzymes can affect the concentration of nimodipine in plasma.

Based on the experience of using other blockers of slow calcium channels, it can be expected that rifampicin, which is the inducer of the activity of "hepatic" enzymes, is able to accelerate the metabolism of nimodipine. With the simultaneous use of rifampicin and nimodipine, the efficacy of the latter can be reduced. Antiepileptic drugs that induce the cytochrome P450 enzyme system ZA4 (phenobarbital, phenytoin and carbamazepine) significantly reduce the bioavailability of nimodipine, so their combined use is contraindicated.

Drugs that induce the activity of the enzymes of the P450 system of 4A4 can increase the concentration of nimodipine in plasma:

- Macrolides (for example erythromycin). Structurally related azithromycin does not have such properties

- Inhibitors of HIV proteases (eg ritonavir,)

- Azoleptimotics (for example ketoconazole)

- Antidepressants nefazodone and fluoxetine (an increase in the concentration of nimodipine in plasma with a co-administration reaches 50%)

- Quinopristin / dalfopristine

- Cimetidine

- Valproic acid

When co-prescribing such drugs, reduction of nimodipine dose and blood pressure monitoring should be provided

The long-term use of ndModdinhta with the iSynchronous NortmendMy IrtodShk nota significant reduction in the concentration of nimodipine in the blood plasma; the concentration of norptiptyline remains unchanged.

Nimodipine can lower blood pressure when co-administered with:

- diuretics

- beta-blockers

- with ACE inhibitors

- blockers of AT-1 receptors

- other calcium antagonists

- alpha-blockers

- methyldopa

- inhibitors of phosphodiesterase.

With the joint use of nimodipine with drugs from these groups, careful monitoring of blood pressure is required.

In patients on long-term therapy with haloperidol, no drug interaction of nimodipine with haloperidol was observed.

Simultaneous intravenous administration of zidovudine and nimodipine results in a significant increase AUC for zidovudine and a decrease in the volume of its distribution and clearance.

Calcium preparations reduce the effectiveness of nimodipine.

Grapefruit juice suppresses the metabolism of oxidation of dihydropyridines. Combinations of grapefruit juice and nimodipine should be avoided, as this can lead to an increase in the concentration of nimodipine in the blood plasma.

Special instructions:

The appointment of nimodipine to elderly patients with a large number of concomitant diseases, severe hepatic insufficiency (glomerular filtration value less than 20 ml / min) and severe cardiovascular diseases should be especially carefully justified. During and after therapy, these patients need regular medical supervision.

In patients with violations function of the liver due to a decrease in the intensity of primary metabolism and slowing down the metabolic inactivation bioavailability of nimodipine may increase. As a consequence, the basic and side effect, in particular its hypotensive effect, may be intensified.

In such cases, the dose should be reduce depending on the degree decrease in blood pressure; Nimodipine should be taken to cease.

Fertility

In some cases, when carrying out fertilization in vitro Against the background of the use of blockers of "slow" calcium channels, reversible chemical changes in the head of spermatozoa were observed, which can lead to a disruption of sperm function.

Effect on the ability to drive transp. cf. and fur:

The use of nimodipine may disrupt the ability to control vehicles and mechanisms, in connection with the possible decrease in blood pressure and occurrence of dizziness.

Form release / dosage:

Film-coated tablets, 30 mg. 10 tablets in a blister pack. 3 or 10 blisters together with instructions for use in a cardboard box.

Packaging:(10) - blister (3) / Blisters - 10 N3 / - Cardboard tutu
(10) - blisters (10) / Blisters - 10 N10 / - Cardboard tutu

Storage conditions:In dry and protected from light and out of reach of children at a temperature not exceeding 30 ° C.

Shelf life:5 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013667 / 01

Date of registration:27.03.2008

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp17.08.2015

Illustrated instructions

Instructions

Nimotop® (Nimotop®)