Nitromint, sublingual spray 0.4 mg/dose 180 doses 10 g

Pharmgroup:

Vasodilating agent – nitrate.

Pharmic action:

Nitromint is a peripheral vasodilator with predominant effect on venous vessels, an antianginal drug. Nitroglycerin is an organic nitrogen-containing compound with predominant venodilatory action.
The effects of nitroglycerin are due to the ability to release from its molecule nitric oxide, which is a natural endothelial-relaxing factor. Nitric oxide activates the enzyme guanylate cyclase, which leads to an increase in intracellular levels of cGMP, this prevents the penetration of calcium ions into the smooth muscle cells and causes them to relax.

The relaxation of smooth muscle in the vascular wall causes vasodilation, which reduces venous return to the heart (preload) and the resistance of the large circulatory system (postload). This reduces heart function and myocardial oxygen demand. Dilation of the coronary vessels improves coronary blood flow and promotes its redistribution to areas with reduced blood supply, which increases oxygen delivery to the myocardium.

The reduction of venous return leads to reduction of filling pressure, improvement of subendocardial blood supply, reduction of pressure in the small circle of circulation and regression of symptoms in pulmonary edema. Nitroglycerin has a central inhibitory effect on sympathetic vascular tone, depressing the vascular component of pain syndrome formation. Nitroglycerin also relaxes smooth muscle cells of bronchi, urinary tract, gall bladder, bile ducts, esophagus, small and large intestine as well as their sphincters.

The action of Nitromint starts quickly, the effect develops within 1-1.5 minutes and lasts about 30 minutes.

Pharmacokinetics:

Absorption
Nitromint® aerosol is rapidly and completely absorbed from the oral cavity into the systemic bloodstream. Bioavailability of Nitromint® is 100% when administered sublingually, because in this case nitroglycerin is not metabolized during “first passage” through the liver. Cmax in plasma is reached after 4 min.

Distribution
Binding to plasma proteins is 60%.
Circulating nitroglycerin is firmly bound to erythrocytes and accumulates in vascular walls.

Metabolism
Fast metabolized with the participation of nitrate reductase, with the formation of di- and mononitrates (only isosorbide-5-monononitrate is pharmacologically active), the final metabolite is glycerol.

Elimation
After drug administration under tongue T1/2 from blood plasma is 2.5-4.4 min. Total clearance is 25-30 l/min.
It is excreted mainly with urine as metabolites, less than 1% is excreted unchanged.

Indications

– angina (relief and prevention of attacks, including before exercise);
– acute left ventricular failure (as part of combination therapy).

Active ingredient

Composition

1 dose:

– nitroglycerin (as 1% solution) 400 mcg

Associates:

ethanol,

propylene glycol.

How to take, the dosage

Nitromint is used sublingually.

Before using the product for the first time, the dispensing pump should be filled by removing the protective cap and pressing the dispensing valve several times until an aerosol appears. After an extended period of disuse it may be necessary to refill the pump. The can must be held upright with the dispensing head upwards when in use.
Each time the dispensing valve is pressed one dose (400 mcg nitroglycerin) is dispensed from the can fitted with a mechanical pump as an aerosol.

There is no need to shake the bottle before use.

To stop an attack of angina, sublingually apply 400-800 mcg (1-2 doses) by pressing on the dosing valve, preferably while sitting, while holding your breath at 30-second intervals; then close your mouth for a few seconds. If needed, Nitromint should be repeated, but not more than 1.2 mg (3 doses) for 15 minutes.

To prevent seizure development, sublingually apply 400 mcg (1 dose) 5-10 minutes before exercise.

In acute left ventricular failure, developing pulmonary edema, 1.6 mg (4 doses) or more is applied sublingually over a short period of time with strict hemodynamic control (systolic BP must be greater than 100 mmHg.
If therapeutic effect is insufficient the same dose may be repeated in 10 min.
No dosage correction is required if the drug is used in elderly patients.

Interaction

Other vasodilators and antihypertensive drugs (beta-adrenoblockers, slow calcium channel blockers), ACE inhibitors, neuroleptics, tricyclic antidepressants, MAO inhibitors, phosphodiesterase inhibitors, procainamide and ethanol may increase the hypotensive effect of NitroMint®.

Nitromint® increases the effect of dihydroergotamine and decreases the effectiveness of heparin.

Special Instructions

Nitromint® increases excretion of catecholamines and vanillinic acid in the urine.

The patient should avoid alcohol consumption while using the drug.

Pediatric use

The drug is contraindicated in children and adolescents under 18 years of age because there is insufficient data on the safety of Nitromint in this patient population.

Impact on driving and operating machinery

In the beginning of treatment, it is necessary to refrain from driving and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions. Thereafter, the degree of restriction is determined individually for each patient.

Contraindications

– shock;
– collapse;
– age under 18 years;
– hypersensitivity to nitroglycerin and other organic nitrates.

The drug should be used with caution in acute circulatory failure accompanied by severe arterial hypotension (systolic blood pressure less than 90 mm Hg).), in orthostatic hypotension, hemorrhagic stroke, acute myocardial infarction and chronic heart failure with low left ventricular filling pressure, hypertrophic cardiomyopathy, Severe renal and/or hepatic insufficiency, severe anemia and thyrotoxicosis, alcoholism, epilepsy, craniocerebral trauma, intracranial hypertension, closed-angle glaucoma (risk of increased intraocular pressure), migraine.

Side effects

Cardiovascular system: dizziness, headache, tachycardia, fever; BP decrease; rarely (especially in overdose) – orthostatic collapse, cyanosis.

Digestive system disorders: dry mouth; nausea, vomiting, abdominal pain are rare.

CNS disorders: weakness, rarely – anxiety, psychotic reactions, lethargy, disorientation.

Allergic reactions: rare – skin rash, itching.

Local reactions: skin hyperemia, burning under the tongue.

Others: rare – blurred vision, hypothermia, methemoglobinemia.

Overdose

Symptoms: headache, decreased BP, orthostatic hypotension, reflex tachycardia, dizziness, facial flushing, vomiting and diarrhea, asthenia, increased somnolence, fever. At excessively high doses (more than 20 mg/kg) methemoglobinemia, cyanosis, dyspnea and tachypnea, orthostatic collapse are observed.

The treatment: in mild cases – transfer the patient to the supine position with elevated legs; in severe cases – symptomatic and supportive therapy to eliminate intoxication and shock (including BCC replacement, administration of norepinephrine (noradrenaline) and/or dopamine). The use of epinephrine (adrenaline) is contraindicated.

The following antidotes and treatments may be used if methemoglobinemia develops:

1. Ascorbic acid – 1 g in the form of sodium salt internally or intravenously.
2. Methylene blue intravenously at a dose of up to 50 ml of 1% solution.
3. Toluidine blue v/v, first dose 2-4 mg/kg, then repeatedly 2 mg/kg.
4. Oxygen therapy, hemodialysis, blood transfusion (exchange).

Pregnancy use

In pregnancy and during lactation, the use of Nitromint is possible under strict medical supervision in cases where the anticipated benefit of therapy to the mother exceeds the potential risk to the fetus or the infant.

It is unknown whether Nitroglycerin is excreted with the breast milk.

Similarities