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

Composition:10.0 ml concentrate for solution for infusion contains:
Active substance: nitroglycerin 10.0 mg.
Excipients: propylene glycol 10.3 mg, dextrose (glucose) 494.4 mg, 1M hydrochloric acid 0 - 0.006%, water for injection 9663.3 mg.

Description:Clear, colorless, odorless solution.

Pharmacotherapeutic group:Vasodilator - nitrate.

ATX: & nbsp

C.01.D.A.02 Nitroglycerine

Pharmacodynamics:Venodilating agent from the group of nitrates. Nitrates are able to release from their molecule nitric oxide, which is a natural endothelial relaxing factor - a mediator of the direct activation of guanylate cyclase. An increase in the concentration of cyclic guanosine monophosphate results in the relaxation of smooth muscle fibers, predominantly venules and veins. Has antianginal and spasmolytic effect, relaxes the smooth muscles of the vascular walls, bronchi, gastrointestinal tract, bile ducts, ureters.With intravenous administration, a rapid decrease in preload on the heart is caused by the widening of the peripheral veins. Reducing the flow of blood to the right atrium, helps to reduce pressure in the small circle of blood circulation and regression of symptoms with pulmonary edema; reduces postnagruzku, the need for myocardium in oxygen (due to reduced preload, postnagruzki and stress of the walls of the ventricles due to a decrease in the volume of the heart).
Promotes the redistribution of coronary blood flow to the zones of the ischemic myocardium. Has a central inhibitory effect on sympathetic vascular tone, inhibiting the vascular component of the formation of pain syndrome. Causes the expansion of cerebral vessels, which explains the headache when it is used.

Pharmacokinetics:Getting into the systemic bloodstream, 60% binds to blood plasma proteins. It has high lipophilicity, has a large volume of distribution (3.3 - 1.2 l / kg). Rapidly metabolized in the liver by glutathione reductase, which affects organic nitrates, with the formation of di- and mononitrates (only isosorbide-5-mononitrate is active), the final metabolite is glycerin. It is excreted by the kidneys in the form of metabolites.The total ground clearance is 30 - 78 l / min, the elimination half-life is 1-3 minutes.

Indications:- Acute myocardial infarction (including complicated by acute left ventricular failure).
- Severe forms of angina, incl. unstable and postinfarction angina.
- Pulmonary edema, acute heart failure, incl. against the background of a hypertensive crisis.
- Controlled arterial hypotension during surgical interventions to reduce bleeding in the operating theater.

Contraindications:- Hypersensitivity to the active substance, other organic nitrates or excipients.
- Acute circulatory disturbance (shock, vascular collapse).
- Cardiogenic shock (if no measures are taken to maintain the end diastolic pressure).
- Severe arterial hypotension (systolic blood pressure (BP) below 90 mmHg).
- Severe hypovolemia.
- Severe anemia.
- Heart failure due to obstruction, aortic, subaortic or mitral stenosis, hypertrophic obstructive cardiomyopathy, or constrictive pericarditis.
- Cardiac tamponade.
- Simultaneous administration of inhibitors of phosphodiesterase-5 (including sildenafil, varde-nafil, tadalafil).
- Simultaneous reception with a stimulant of soluble guanylate cyclase with rhyociguate.
- Age under 18 years (efficiency and safety not established).
- Craniocerebral injury.
- Toxic pulmonary edema.
- Intracranial hypertension.
- Hemorrhage in the brain.

Carefully:Perlinterate® should be used with extreme caution and with careful medical supervision in the following cases:
- Low filling pressure of the left ventricle, including acute myocardial infarction (systolic blood pressure below 90 mm Hg should be avoided).
- Violation of the function of the left ventricle (for example, with left ventricular failure).
Tendency to orthostatic disorders of vascular regulation.
- Increased intraocular pressure, incl. angle-closure glaucoma.
- Severe renal and / or hepatic insufficiency (risk of development of methemoglobinemia).
- Thyrotoxicosis.
- Diabetes.
- Atherosclerosis.

Pregnancy and lactation:Fertility
According to the studies, no adverse reactions from fertility or reproductive performance in rats and rabbits were observed with the use of nitroglycerin.Clinical studies on the effect of nitroglycerin on human fertility have not been conducted.
Pregnancy
Clinical studies of the use of the preparation Perlignanit® in pregnant women have not been conducted. The use of the preparation Perlignanit® during pregnancy is possible only strictly according to the doctor's prescription, in case the intended benefit for the mother exceeds the possible risk to the fetus and / or the child. In this case, careful monitoring of the condition of the pregnant woman and fetal development is carried out.
Breastfeeding period
There is information about the penetration of nitrates into breast milk, but the exact content of nitroglycerin in breast milk has not been determined. Also, a possible risk of developing methaemoglobinaemia in infants has been reported, so if it is necessary to administer the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:Treatment should be conducted in a hospital with an individual choice of the speed of infusion of the drug. The solution is administered via an automatic dispenser or through a conventional system for intravenous infusion. Automatic dispenser allows you to enter even an un-diluted 0.1% solution with accurate dosing of the rate of administration and total dose.The introduction through a conventional system for fluid transfusion provides an accurate dose selection by counting the number of drops of the transfused liquid. For the intravenous administration of the preparation Perlignanit®, the following materials are used: polyethylene, polypropylene or polytetrafluoroethylene. Infusion materials made of polyvinyl chloride or polyurethane, reduce the effectiveness of the drug as a result of absorption (up to 60%), which must be made up by increasing the dose. The solution is rapidly destroyed in the light, therefore the vials and the transfusion system must be screened with a lightproof material.
Usually, an infusion solution with a concentration of 100 or 200 μg / ml is used: the concentrated solution is diluted with 0.9% sodium chloride solution, 5% or 10% dextrose (glucose) solution. Dilution - see dilution table.
It is recommended to start treatment with a dose of 0.5-1.0 mg nitroglycerin per hour (8-16 μg / min), if necessary, gradually (every 3-5 minutes) the dose is increased (depending on the effect and response of heart rate, central venous pressure and systolic blood pressure, which can be reduced by 10 - 25% of the initial, but should not be less than 90 mm Hg).If no therapeutic effect is obtained at a rate of 20 μg / min, a further increase in the rate of administration should be 10-20 μg / min. If there is a response (in particular, a decrease in blood pressure) a further increase in the rate of infusion is not carried out or is carried out at longer intervals. The maximum dose is 8 mg of nitroglycerin per hour (133 g / min), in rare cases, 10 mg per hour (166 g / min).
In severe angina, acute left ventricular failure (pulmonary edema) is recommended to start with 1 mg slowly over 3 minutes, subsequently increasing the dose from 2 to 8 mg per hour for 1 - 2 days.
With hypertensive crisis, incl. with cardiac decompensation, the dose ranges from 2 to 8 mg per hour (33 to 133 μg / min).
If hypotension controlled depending on the type of general anesthesia and the level of blood pressure lowering dose of between 2 and 10 ug / kg / min under ECG control and the central intracardiac hemodynamics.
Application in elderly patients
Elderly patients do not need dose adjustment.
Dilution table

The amount of active substance (nitroglycerin)		10 mg	20 mg	30 mg	40 mg	50 mg
Perlinterate® solution		10 ml	20 ml	30 ml	40 ml	50 ml
Infusion solution at dilution	Degree of breeding 1 : 10	100	200	300	400	500
	1 : 20	200	400	600	800	1000
	1 : 40	400	800	1200	1600	2000
Ready Infusion Solution	1 : 10	110	220	330	440	550
	1 : 20	210	420	630	840	1050
	1 : 40	410	820	1230	1640	2050

Dose calculation table

5 ampoules of 10 ml of concentrate Perlignanite® is diluted to 500 ml of the solution (100 μg / ml)		Perlingant® dosage	10 ampoules of 10 ml of Perlinginate ® concentrate diluted to 500 ml of the solution (200 μg / ml)
Infusion rate		Dosage	Infusion rate
ml / hour	drops / min		ml / hour	drops / min
10	3-4	1	5	1-2
20	7	2	10	3
30	10	3	15	5
40	13	4	20	7
50	17	5	25	8
60	20	6	30	10
70	23	7	35	12
80	27	8	40	13
90	30	9	45	15
100	33	10	50	17

1 ml corresponds to 20 drops
Duration of treatment is determined by clinical indications and can be continued up to 3 days.

Side effects:Possible side effects are given below for body systems and frequency of occurrence (classification of the World Health Organization):
Very often - more than 1/10;
Often - more than 1/100 and less than 1/10;
Infrequently - more than 1/1000 and less than 1/100;
Rarely more than 1/10000 and less than 1/1000;
Very rarely - less than 1/10000;
The frequency is unknown - the frequency can not be estimated from the available data.
From the central nervous system
Very often: "nitrate" headache.
Often: drowsiness, dizziness, incl. postural.
Heart Disease
Often: tachycardia.
Infrequently: the "paradoxical" increase in angina attacks.
The frequency is unknown: heart palpitations.
Vascular disorders
Often: orthostatic hypotension.
Infrequently: vascular collapse (sometimes accompanied by bradyarrhythmia and syncope); transient hypoxemia due to the relative redistribution of blood flow to hypo-ventilated alveolar areas (in patients with coronary heart disease, may lead to myocardial hypoxia).
Rarely: cyanosis.
The frequency is unknown: marked decrease in blood pressure, hyperemia of the facial skin.
From the gastrointestinal tract
Infrequent: nausea, vomiting.
Very rarely: heartburn.
From the skin and subcutaneous tissues
Infrequent: skin allergic reactions (including rash), allergic contact dermatitis.
The frequency is unknown: exfoliative dermatitis, generalized skin rash.
General disorders and disorders at the site of administration
Often: asthenia.
The frequency is unknown: itching, burning, erythema, irritation.
Other
Infrequent: blurred vision.
Rarely: methemoglobinemia.
For organic nitrates, there have been cases of the development of a marked decrease in blood pressure, accompanied by nausea, vomiting, anxiety, pallor and increased sweating.
The use of the drug may cause transient hypoxemia due to the relative redistribution of blood flow to hypoventilation alveolar sites (in patients with coronary heart disease - may lead to myocardial hypoxia).
Like other forms of nitrates, nitroglycerine often can cause dose-related headaches due to the expansion of cerebral vessels. As a rule, the headaches go away on their own in a few days, despite the continued therapy with Perlinnit®. In the case of persistent headaches against intermittent therapy with nitroglycerin, weak analgesics should be used to stop them. Headaches that are not amenable to treatment are an indication for reducing the dose of Perlinnit® or stopping treatment.
A slight reflex-induced increase in heart rate, if necessary, can be prevented with combined therapy with beta-blockers.

Overdose:Symptoms: marked decrease in blood pressure (less than 90 mm Hg), with orthostatic dysregulation, pallor, increased sweating, "threadlike" pulse, reflex tachycardia, fainting, throbbing headache, asthenia, dizziness, incl.postural, nausea, vomiting, diarrhea, increased drowsiness, a feeling of heat. When high doses are used (more than 20 mg / ml), methemoglobinemia, cyanosis with subsequent development of tachypnea and dyspnea, anxiety, loss of consciousness and cardiac arrest, collapse, increased intracranial pressure, which can cause cerebral symptoms. Treatment: discontinue further administration of the drug. If there is a pronounced decrease in blood pressure, give the patient a horizontal position with raised legs (or, if necessary, put a compression bandage on their legs) and carry out measures to replenish the volume of circulating blood and provide oxygen therapy. As a rule, blood pressure is normalized within 15-20 minutes after discontinuation of the drug administration. The introduction can be continued after a re-selection of the infusion rate.
In exceptional cases, to maintain blood circulation, you can enter norepinephrine (noradrenaline) and / or dopamine. The introduction of epinephrine (adrenaline) and related compounds is contraindicated! If there are signs of stopping breathing and heart, immediately begin resuscitation (if necessary, the patient is placed in the intensive care unit).
With methemoglobinemia - depending on the degree of severity, ascorbic acid is used in the form of a sodium salt IV / 0.1-0.15 ml / kg of 1% solution up to 50 ml; oxygenate-rupiah, artificial ventilation, hemodialysis.
Treatment of methaemoglobinemia with methylene blue is contraindicated in patients with deficiency of glucose-6-phosphate dehydrogenase or methaemoglobin reductase. If treatment is contraindicated or ineffective, exchange transfusion and / or transfusion of erythrocyte mass are recommended.

Interaction:Use of nitroglycerin with antihypertensive agents (e.g., beta-blockers, diuretics, blockers "slow" calcium channel vaso-dilators (e.g., 5-phosphodiesterase inhibitors, including sildenafil, Tadao-Phil, vardenafil), inhibitors of angiotensin converting enzyme) , neuroleptics, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, ethanol and ethanol-containing agents can lead to a marked decrease in blood pressure.
Simultaneous use of nitroglycerin and phosphodiesterase-5 inhibitors (incl.
sildenafil, tadalafil, vardenafil) is contraindicated in view of the possibility of a marked decrease in blood pressure. Patients who have recently taken phosphodiesterase-5 inhibitors, the administration of Perlin- nate® solution is contraindicated. Simultaneous application of the preparation Perlinnagit® with a stimulant of soluble guanilatclycium rhyociguate can cause the development of arterial hypotension.
With simultaneous intravenous injection of tissue plasminogen activator (TPA) and nitroglycerin, the plasma clearance of TPA can be accelerated by increasing blood circulation in the liver.
With simultaneous application with dihydroergotamine, an increase in the concentration and increase in the action of dihydroergotamine is possible. Special care should be taken when using in patients with cardiovascular diseases, since dihydroergotamine is a nitroglycerin antagonist and can lead to coronary vasoconstriction.
Simultaneous administration of nitroglycerin and heparin reduces the effectiveness of the latter (after drug cancellation, a reduction in the dose of heparin may be required).Simultaneous use of nitroglycerin and acetylsalicylic acid can enhance the antihypertensive effect of nitroglycerin.
Simultaneous use of nitroglycerin and non-steroidal anti-inflammatory drugs, with the exception of acetylsalicylic acid, may lead to a decrease in the therapeutic effect of nitroglycerin.
Sapropterin is a cofactor of nitric oxide synthase. It is advisable to use caution while using sapropterine-containing medications with all vasodilating agents that are associated with nitric oxide (NO), including classical NO donors (for example, nitroglycerine, isosorbide dinitrate, isosorbide mononitrate) and others.
Against the background of quinidine and procainamide, development of orthostatic collapse is possible.

Special instructions:In acute myocardial infarction or acute heart failure should be used only under the condition of careful clinical observation of the patient.
To prevent the increase in angina attacks, sharp abolition should be avoided. If it is known that the patient is taking phosphodiesterase-5 inhibitors, therapy with Perlinnitol is contraindicated.Patients receiving treatment with Perlinnit® should be warned about the inadmissibility of taking phosphodiesterase-5 inhibitors (eg sildenafil, tadalafil, vardenafil).
Against the background of the intravenous administration of Perlinnit®, a significant reduction in blood pressure and the appearance of dizziness can occur with a sharp transition from the "lying" or "sitting" position to the "standing" position; hot weather, as well as increased angina (with a sharp decrease in blood pressure) and myocardial ischemia until myocardial infarction and sudden death (paradoxical nitrate reactions). To prevent undesirable blood pressure lowering, it is necessary to select the speed of the drug administration individually and methodically. Reduction of blood pressure can be observed not only during the selection of the rate of administration of the preparation Perlinhinat®, but also later against a background of stabilized blood pressure. Therefore, monitoring of blood pressure should be carried out at least 3-4 times per hour during the entire infusion time. Possible development of tolerance and cross tolerance to other drugs of the nitrate group with prolonged use, especially in high doses. Patients previously treated with organic nitrates (eg, isosorbide dinitrate, isosorbide-5-mononitrate) may require a higher dose.
In the treatment of patients with concomitant type 1 diabetes mellitus, it should be borne in mind that 1 ampoule of the preparation Perlinnagit® contains 0.48 g of glucose.
If blurred vision is retained or strongly pronounced, treatment should be discontinued.
In patients with severe hepatic insufficiency and severe renal insufficiency, dose adjustment is required depending on the severity of the disease (especially when using high doses), it is recommended to start with the lowest possible dose. Careful monitoring of the patient is necessary.
Hypoxemia
Care should be taken when using in patients with arterial hypoxemia due to severe anemia (including glucose-6-phosphate dehydrogenase (G6PD) induction failure), because nitroglycerin metabolism in such patients is reduced.
Also caution is necessary when used in patients with hypoxemia and impaired ventilation / perfusion due to lung disease or heart failure; as well as in patients with angina pectoris, myocardial infarction or cerebral ischemia, having respiratory tract disorders (especially alveolar hypoxia).Under these conditions, the vessels in the lungs contract in order to move the perfusion of the alveolar hypoxia region to the part of the lung with better ventilation (Euler-Lilestrand reflex). As a powerful vasodilator, nitroglycerine can prevent this protective narrowing of the vessels and, consequently, lead to an increase in the perfusion of poorly ventilated areas, a deterioration of the ventilation-perfusion imbalance, and a further decrease in the arterial partial pressure of oxygen.
Methemoglobinemia
After the use of the drug, the development of methemoglobinemia was reported. Treatment of methaemoglobinemia with methylene blue is contraindicated in patients with deficiency of glucose-6-phosphate dehydrogenase or methaemoglobin reductase.

Effect on the ability to drive transp. cf. and fur:Nitroglycerine can reduce the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. This effect is exacerbated by alcohol.

Form release / dosage:Concentrate for the preparation of a solution for infusions 1 mg / ml.

Packaging:For 10 ml of solution in ampoules of colorless transparent glass (type I, Ph.Eur.) With two color coding rings and a notch on the neck of the ampoule, the place of which is indicated by a colored dot on top. For 10 ampoules installed in the cells along with instructions for use in a cardboard bundle.

Storage conditions:At a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:5 years.
Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013654 / 01

Date of registration:17.11.2011 / 30.11.2012

Expiration Date:Unlimited

The owner of the registration certificate:YUSB Pharma GmbHYUSB Pharma GmbH Germany

Manufacturer: & nbsp

EVER Pharma Jena, GmbH Germany

Representation: & nbspYUSB FARMA LLC YUSB FARMA LLC Russia

Information update date: & nbsp2016-12-15

Illustrated instructions

Instructions

Perlingant® (Perlinganit®)