Nitsergolin

General characteristics. Structure:

Active agent: ницерголин – 4 mg,
excipients: lactoses monohydrate – 40 mg, tartaric acid – 1,04 mg.

Pharmacological properties:

Pharmacodynamics. An alpha adrenceptor blocking agent – synthetic derivative ergot alkaloids, with the attached bromzameshchenny rest of niacin. Improves cerebral circulation, activates metabolism of a brain. Reduces brain vascular resistance, increases an arterial blood stream and consumption of oxygen and glucose brain tissues. Reduces resistance of pulmonary vessels. Increases blood-groove speed in vessels of upper and lower extremities, especially at blood circulation disturbance. Reduces aggregation of thrombocytes and improves haemo rheological indicators. With arterial hypertension can cause a gradual lowering of arterial pressure in patients. The contained rest of niacin has myotropic spasmolytic effect on resistive vessels (it is especially active concerning vessels of a brain and extremities), increases their permeability for glucose. Blocks the vasoconstrictive reactions of brain vessels caused by serotonin. Improves a renal blood stream, normalizes blood circulation of extremities at spastic arteriopatiya.

Pharmacokinetics. Key products of metabolism of a nitsergolin: 1,6 диметил-8-гидроксиметил-10-метоксиэрголин (MMDL, a hydrolysate) and 6-метил-8-гидро-ксиметил-10-метоксиэрголин (MDL, a demethylation product under the influence of CYP2D6 isoenzyme). The ratio of values of the area under a curve "concentration - time" for MMDL and MDL at intravenous administration of a nitsergolin indicates (AUC) the expressed metabolism at the first passing. Researches confirm lack of accumulation of other metabolites (including MMDL) in blood. Nitsergolin it is active (> 90%) contacts proteins of plasma, and degree of his affinity to α-acid of a glycoprotein is more, than to a seralbumin. It is shown that ницерголин and its metabolites can be distributed in blood cells. The pharmacokinetics of a nitsergolin at use of doses to 60 mg has linear character and does not change depending on age of the patient.
Bioavailability – 60%. The maximum concentration is defined by 1 – 1,5 h.
Drug elimination half-life - 2,5 h. It is removed in the form of metabolites, generally by kidneys (about 80% of the general dose), and in small quantity – intestines (10-20%). At patients with a heavy renal failure considerable decrease in extent of removal of products of metabolism in comparison with patients with normal function of kidneys was observed.
 
With care the Hyperuricemia or gout in the anamnesis and/or in combination with medicines which break metabolism and removal of uric acid.

Indications to use:

Acute and chronic cerebral metabolic and vascular disorders
(owing to atherosclerosis, arterial hypertension, thrombosis or a vascular embolism of a brain, including the tranzitorny cerebral attack, vascular dementia and a headache caused by a vasospasm).
Acute and chronic peripheral metabolic and vascular disorders (the organic and functional arteriopatiya of extremities, Raynaud's disease, syndromes caused by disturbance of a peripheral blood-groove).
As an additional tool at treatment of hypertensive crises.

Route of administration and doses:

Intramusculary: the recommended dose of 2-4 mg of drug 2 times a day. 4 mg of drug dissolve in 2 or 4 ml of sodium of chloride of solution for injections 0,9%, the received solution has concentration respectively 2 mg/ml and 1 mg/ml.
Intravenously: the recommended dose of 4-8 mg of drug, enter kapelno, to destination the doctor it is possible to repeat infusion several times in days.
4 or 8 mg of drug dissolve in 100 ml of solution of sodium of chloride 0,9% or solution of a dextrose (glucose) of 5-10%, the prepared solution has concentration respectively 0,04 mg/ml and 0,08 mg/ml.
Vnutriarterialno: the recommended dose of 4 mg of drug, enter 4 mg of drug within 2 min. dissolve 0,9% in 10 ml of solution of sodium of chloride, the prepared solution has concentration of 0,4 mg/ml.
The dose, duration of therapy and way of introduction depend on character and weight of a disease. It is in certain cases preferable to begin therapy with parenteral administration with the subsequent transition to oral administration.
At a chronic renal failure (creatine of blood serum of 2 mg/dl and more) it is recommended to use drug in lower therapeutic doses.

Features of use:

After intravenous administration for prevention of orthostatic hypotension the patient is recommended to be in horizontal position within 10-15 minutes. Drug works gradually therefore it should be accepted for a long time, at the same time the doctor has to periodically (at least each 6 months) to estimate effect of treatment and expediency of its continuation.
Influence on ability to manage vehicles and mechanisms 
 During treatment it is necessary to be careful at control of vehicles and mechanisms, and also the performance of work demanding the increased concentration of attention and speed of psychomotor reaction.

Side effects:

From a nervous system and sense bodys: headache, dizziness, sleep disorder (drowsiness or sleeplessness), feeling of fatigue, excitement, concern, syncope.
From cardiovascular system and system of blood: orthostatic hypotension, stenocardia attack, reduction of viscosity of blood, cold snap of extremities.
From bodies of digestive tract: nausea, vomiting, decrease in appetite, diarrhea, abdominal pain, increase in acidity of a gastric juice.
Allergic reactions: itch and hyperemia of the person and upper half of a trunk, erythema, small tortoiseshell.
Others: perspiration, extremity pain, heat.
If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Strengthens effects of hypotensive medicines.
It is impossible to exclude a possibility of interaction of a nitsergolin with medicinal means, metabolized under the influence of CYP2D6 cytochrome.

Contraindications:

Hypersensitivity to a nitsergolin or other components of drug, recently postponed myocardial infarction, acute bleeding, the expressed bradycardia, disturbance of orthostatic regulation, age up to 18 years. 
Use at pregnancy during pregnancy should be applied only with explicit need and under direct control of the doctor. For the period of treatment it is necessary to refuse breastfeeding as ницерголин and products of his metabolism get into mother's milk.

Overdose:

Symptoms: the passing expressed lowering of arterial pressure.
Treatment: to lay the patient on several minutes in horizontal position. In exceptional cases at sharp disturbance of blood supply of a brain and heart introduction of sympathomimetic means under constant control of arterial pressure is recommended.

Storage conditions:

To store at a temperature not above 25 °C. To store in the places unavailable to children. To store the prepared solution for intramuscular introduction in the place protected from light at a temperature not above 30 °C during 48 h. To use the prepared solutions for intravenous and intra arterial administration only freshly cooked. 
Period of validity 2 years. Not to apply after the period of validity specified on the label.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for пригот. solution for инъекц. 4 mg: amp. 5 in set. with solvent.