Physiotens (Moxonidin)

Active substance:

moxonidine 0.2 mg.

Excipients:

 lactose monohydrate - 95.80 mg,

povidone - 0.70 mg

crospovidone - 3.00 mg,

magnesium stearate - 0.30 mg.

Shell:

 hypromellose - 1.30 mg, ethyl cellulose - 1.20 mg, macrogol - 0.25 mg, talc - 0.9975 mg, dye iron oxide red (E 172) - 0.0025 mg, titanium dioxide (E 171) - 1 , 25 mg.

Moxonidine is a hypotensive agent with a central mechanism of action. In the stem structures of the brain (the rostral layer of the lateral ventricles), moxonidine selectively stimulates imidazoline-sensitive receptors involved in the tonic and reflex regulation of the sympathetic nervous system. Stimulation of imidazoline receptors reduces peripheral sympathetic activity and blood pressure (BP).

Moxonidine differs from other sympatholytic antihypertensive drugs in its lower affinity for a2-adrenergic receptors, which explains the lower likelihood of developing a sedative effect and dry mouth.

The use of moxonidine leads to a decrease in systemic vascular resistance and blood pressure. The hypotensive effect of moxonidine is confirmed in double-blind, placebo-controlled, randomized trials.

Moxonidine improves the insulin sensitivity index (compared with placebo) by 21% in patients with obesity, insulin resistance and moderate arterial hypertension.

Pharmacokinetics

Absorption: 
After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. The time to reach maximum concentration is about 1 hour. Eating does not affect the pharmacokinetics of the drug.

Distribution 
Communication with plasma proteins is 7.2%.

Metabolism 
The main metabolite is dehydrogenated moxonidine. The pharmacodynamic activity of dehydrogenated moxonidine is about 10% compared with moxonidine.

Withdrawal 
The half-life (T1 / 2) of moxonidine and the metabolite is 2.5 and 5 hours, respectively. Within 24 hours, over 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% in the form of dehydrromoxonidine, other metabolites in the urine do not exceed 8% of the dose). Less than 1% of the dose is excreted through the intestines.

Pharmacokinetics in patients with arterial hypertension: 
Compared with healthy volunteers, in patients with arterial hypertension there is no change in the pharmacokinetics of moxonidine.

Pharmacokinetics in the elderly 
Clinically insignificant changes in the pharmacokinetic parameters of moxonidine in elderly patients have been noted, probably due to a decrease in the intensity of its metabolism and / or slightly higher bioavailability.

Pharmacokinetics in children 
Moxonidine is not recommended for use in people under 18 years of age, and therefore pharmacokinetic studies have not been conducted in this group.

Pharmacokinetics in renal failure 
Excretion of moxonidine is largely correlated with creatinine clearance (CC). In patients with moderate renal failure (CC in the range of 30-60 ml / min), equilibrium plasma concentrations and final T1 / 2 are approximately 2 and 1.5 times higher than in individuals with normal renal function (CC more than 90 ml / min.). In patients with severe renal failure (CC less than 30 ml / min.), Equilibrium plasma concentrations and final T1 / 2 are 3 times higher than in patients with normal renal function. The administration of multiple doses of moxonidine leads to predictable cumulation in the body of patients with moderate and severe renal failure. In patients with terminal renal failure (CC less than 10 ml / min) undergoing hemodialysis, the equilibrium plasma concentrations and final T1 / 2 are 6 and 4 times higher, respectively than in patients with normal renal function. In all groups, the maximum concentration of moxonidine in blood plasma is 1.5 to 2 times higher. In patients with impaired renal function, the dosage should be selected individually. Moxonidine is slightly excreted during hemodialysis.

Arterial hypertension.

Hypersensitivity to the active substance and other components of the drug; sick sinus syndrome, severe bradycardia (heart rate (heart rate) of rest less than 50 beats / min).

Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Due to the lack of safety and efficacy data, the administration of moxonidine to persons under 18 years of age is not recommended.

Precautions: severe and terminal renal failure; hemodialysis patients; due to a lack of experience in use, severe hepatic insufficiency (more than 9 points according to the Child-Pyug classification).

From the central nervous system: 
Often (1-10%): headache, dizziness, drowsiness. 
Infrequently (<1%): insomnia.

From the cardiovascular system: 
Rarely (<0.1%): excessive decrease in blood pressure, orthostatic hypotension.

From the gastrointestinal tract: 
Often (1-10%): dry mouth. 
Infrequently (<1%): nausea.

From the skin and subcutaneous fat 
Infrequently (<1%): skin rash, itching. 
Very rarely (<0.01%): angioedema. 
General: 
Often (1-10%): asthenia.

The most common side effects in patients taking moxonidine are dry mouth, headache, dizziness, asthenia, and drowsiness. These symptoms often diminish after the first weeks of therapy.

Moxonidine can be prescribed with thiazide diuretics, “slow” calcium channel blockers and other antihypertensive drugs. The combined use of moxonidine with these and other antihypertensive agents leads to an additive effect.

When prescribing moxonidine with hydrochlorothiazide, glibenclamide or digoxin, no pharmacokinetic interaction was found.

Tricyclic antidepressants can reduce the effectiveness of central antihypertensive drugs, and therefore it is not recommended to take them together with moxonidine.

Moxonidine is able to moderately improve impaired cognitive function in patients receiving lorazepam.

The appointment of moxonidine together with benzodiazepines may be accompanied by an increase in the sedative effect of the latter.

When prescribing moxonidine together with moclobemide, there is no pharmacodynamic interaction,

Inside, regardless of the meal.

In most cases, the initial dose of Physiotens® is 0.2 mg per day. The maximum single dose is 0.4 mg. The maximum daily dose, which should be divided into 2 doses, is 0.6 mg.

The daily dose for patients with moderate or severe renal failure, as well as those on hemodialysis, is 0.2 mg. If necessary and with good tolerance, the daily dose can be increased to 0.4 mg.

There are reports of several cases of overdose without fatal outcome, when doses up to 19.6 mg were simultaneously applied.

Symptoms

headache, sedation, drowsiness, marked decrease in blood pressure, dizziness, fatigue, asthenia, bradycardia, dry mouth, vomiting and pain in the epigastric region. A short-term increase in blood pressure, tachycardia, hyperglycemia are also potentially possible.

Treatment

There is no specific antidote. In the case of lowering blood pressure, it is recommended that the volume of circulating blood be restored through the introduction of fluid and the introduction of dopamine.

Bradycardia can be stopped with atropine.

Alpha-adrenergic antagonists can reduce or eliminate the paradoxical hypertensive effects of an overdose of moxonidine.

If it is necessary to cancel the simultaneously taken beta-blockers and the Physiotens drug, first beta-blockers and, only after a few days, Physiotens® are canceled.

During treatment, regular monitoring of blood pressure, heart rate and ECG is necessary. Stop taking the drug "Physiotens" should be gradual.

Influence on the ability to drive a car and to control machines and mechanisms 
Studies of the effect of the drug on the ability to drive a car and other mechanisms have not been conducted. 
There are reports of drowsiness and dizziness during treatment with moxonidine. This should be considered when performing the above steps.