Nitsergolin

General characteristics. Structure:

Active ingredient: 4 mg of a nitsergolin in 1 ampoule.

Excipients: tartaric acid, sugar milk (lactose).

Pharmacological properties:

Pharmacodynamics. Nitsergolin — synthetic derivative ergot alkaloids with the attached bromzameshchenny rest of niacin.

Renders vazodilatiruyushchy (including concerning brain arteries) action. Improves microcirculation. The contained rest of niacin has direct myotropic spasmolytic effect on a muscular coat of resistive vessels, increases their permeability for glucose (leveling opposite effect of an ergolinovy ring) that is most brightly shown concerning vessels of a brain and extremities. Improves a brain, pulmonary and renal blood stream, increases delivery of oxygen and glucose. Improves blood supply in extremities, especially at a circulatory unefficiency owing to functional arteriopatiya.

Pharmacokinetics. Absorption — high. Bioavailability — about 60%. The maximum concentration in a blood plasma in 2-4 hours. Nitsergolin actively contacts proteins of plasma, showing at the same time more expressed affinity to an acid alfa1-glycoprotein, than to a seralbumin. Concentration of glycoproteins in a blood plasma increases as a result of acute inflammatory processes, malignant new growths or a stress with age. Such states cause decrease in concentration of a nitsergolin in a blood plasma. 90% of the entered dose are exposed to metabolism, generally by hydrolysis and demethylation. Process of demethylation is caused by catalytic activity of an isoenzyme of CYP2D6.

Nitsergolin is exposed to presistemny metabolism. The main metabolites of a nitsergolin which are formed during presistemny metabolism are MMDL (1,6-диметил-8-гидроксиметил-10-метоксиэрголин) and MDL (6-метил-8-гидроксиметил-10-метоксиэрголин). It is shown that ницерголин and its metabolites can be distributed in blood cells. About 80% of a nitsergolin and its metabolites are removed with urine, the rest — with a stake. Nitsergolin and MMDL are exposed to bystry elimination (biological T1/2 makes 2,5 h for a nitsergolin and 2-4 h for MMDL) whereas MDL is removed more slowly (biological T1/2 makes 10-12 h).

The pharmacokinetics at use of doses to 60 mg has linear character and does not change depending on age of the patient. At patients with a heavy renal failure considerable decrease in extent of removal of products of metabolism with urine in comparison with patients with normal function of kidneys was observed.

Indications to use:

• Disturbance of peripheric circulation.
• Cognitive disturbances at elderly.

Route of administration and doses:

Drug dissolve 0,9% in the enclosed chloride sodium solution. Intramusculary on 4 mg 2 times a day. Intravenously: slow infusion — on 4-8 mg on 100 ml of sodium of chloride of solution for infusions of 0,9%; on doctor's orders this dose can be entered several times in days. Vnutriarterialno — on 4 mg in 10 ml of sodium of chloride of solvent for preparation of dosage forms for injections of 0,9%, the drug is administered within 2 minutes.

olny with a renal failure (serumal creatinine of 2 mg/dl and more) it is recommended to use drug in lower therapeutic doses.

Solution of drug is recommended to be used right after preparation.

The dose, duration of treatment, way of introduction depend on disease severity.

It is preferable to begin with parenteral treatment with the subsequent transition to oral administration.

Features of use:

After intravenously го administrations of drug for prevention of orthostatic hypotension the patient is recommended to be in horizontal position within 10-15 minutes.

At the expressed by-effects reduce a dose or stop administration of drug.

In therapeutic doses ницерголин does not influence system arterial pressure. However drug can cause gradual moderate pressure decrease in patients with arterial hypertension.

The fibrosis cases (for example, lungs, heart, heart valves, or retroperitoneal fibrosis) connected with effect of alkaloids of an ergot on serotoninovy 5-Nt2v-retseptory were revealed.

At use of alkaloids of an ergot and their derivatives ergotism symptoms were registered (including nausea, vomiting, diarrhea, abdominal pains, vasoconstriction of peripheral vessels).

During treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reaction.

Side effects:

Very seldom (<0,01%) the following side reactions can develop: a hyperemia of a cat of the person and an upper half of a trunk, heat, psychomotor arousing, a sleep disorder, a lowering of arterial pressure, a headache, dizziness, confusion of consciousness, stenocardia, a skin itch, skin rash, allergic reactions, increase in concentration of uric acid in a blood plasma (the effect does not depend on a dose and duration of therapy), ergotism symptoms: dyspepsia (nausea, vomiting, diarrhea, abdominal pains), vasoconstriction of peripheral vessels, cold snap of extremities, extremity pain, paresthesias, concern, fear, loss of consciousness, change in mood or behavior, development of spasms.

Interaction with other medicines:

Nitsergolin can strengthen effect of hypotensive drugs, tranquilizers and neuroleptics.

Adrenomimetiki at simultaneous use can cause an idiosyncrasy.

At simultaneous use with acetylsalicylic acid, other antiagregant, and also anticoagulants increase in time of bleedings is possible.

Nitsergolin is metabolized under the influence of CYP2D6 isoenzyme therefore it is impossible to exclude a possibility of its interaction with medicines which are metabolized with the participation of this enzyme.

It is necessary to be careful at simultaneous use with the drugs influencing metabolism of uric acid.

Nitsergolin exponentiates effect of beta adrenoblockers on heart.

Contraindications:

Hypersensitivity, arterial hypotension, the expressed atherosclerosis of peripheral vessels, organic lesions of heart, myocardial infarction, angina of exertion, deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption, pregnancy, the breastfeeding period, children's age up to 18 years, acute bleeding, heavy bradycardia, simultaneous use with sympathomimetics (alpha and beta-adrenergic agonists).

With care. A hyperuricemia or gout in the anamnesis and/or a combination to the medicines breaking metabolism and removal of uric acid.

Overdose:

Symptoms: the passing expressed lowering of arterial pressure (ABP).

Treatment: to lay the patient in horizontal position, if necessary sympathomimetics under control of the ABP.

Storage conditions:

In the place protected from light at a temperature not above 10 °C. Freezing is not allowed. To store in the place, unavailable to children. A period of validity - 3 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for injections on 4 mg in ampoules. On 5 ampoules of drug and 5 ampoules of solvent ("Sodium chloride solvent for preparation of dosage forms for injections of 0,9%" - on 5 ml in an ampoule) in a pack from a cardboard together with the application instruction and a knife ampoule or the scarificator ampoule. When packaging the ampoules having a ring of a break or a point for opening the knife ampoule or the scarificator ampoule is not put.