Physiotens pills 0,2mg №28

Active substance

Moxonidine

Composition

1 pill film coated with a dosage of 0.2 mg contains:
Active ingredient: 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, ethylcellulose - 1.20 mg, macrogol - 0.25 mg, talc - 0.9975 mg, iron dye red oxide (E 172) - 0.0025 mg, titanium dioxide (E 171) - 1.25 mg.

Mechanism of action

hypotensive agent of central action.

Mechanism of action

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

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

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

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

Pharmacokinetics

Suction:
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 dehydrated moxonidine. The pharmacodynamic activity of dehydrated moxonidine is about 10% compared with moxonidine.

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

Pharmacokinetics in patients with arterial hypertension:
Compared with healthy volunteers, there are no changes in moxonidine pharmacokinetics in patients with arterial hypertension.

Pharmacokinetics in the elderly
Clinically insignificant changes in the pharmacokinetic parameters of moxonidine in elderly patients are 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 persons younger than 18 years, and therefore in this group pharmacokinetic studies have not been conducted.

Pharmacokinetics for renal failure
Moxonidine clearance is significantly correlated with creatinine clearance (CK). In patients with moderate renal insufficiency (CC in the range of 30-60 ml / min) equilibrium plasma concentrations and a 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 insufficiency (CC is less than 30 ml / min.), The equilibrium plasma concentration 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 end-stage renal disease (CC less than 10 ml / min) on hemodialysis, plasma plasma equilibrium 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 the blood plasma is 1.5 - 2 times higher. In patients with impaired renal function, the dosage should be adjusted individually. Moxonidine is slightly excreted during hemodialysis.

Indications

Arterial hypertension.

Contraindications

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

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

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

With care: severe and terminal renal failure; patients on hemodialysis; due to lack of experience in use - severe liver failure (more than 9 points according to Child-Pyuga classification).

Side effects

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

Cardiovascular:
Rarely (<0.1%): excessive blood pressure reduction, 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 rare (<0.01%): angioedema.
Are common:
Often (1-10%): asthenia.

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

Interaction

Moxonidine may be administered 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 moxonidine was administered with hydrochlorothiazide, glibenclamide, or Digoxin, no pharmacokinetic interaction was detected.

Tricyclic antidepressants can reduce the effectiveness of centrally acting antihypertensive drugs, and therefore they are not recommended in conjunction with moxonidine.

Moxonidine can moderately improve impaired cognitive function in patients receiving lorazepam.

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

In the appointment of moxonidine in conjunction with moclobemide pharmacodynamic interaction is absent,

How to take, the course of administration and dosage

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 insufficiency, as well as those on hemodialysis is 0.2 mg. If necessary and with good tolerance, the daily dose may be increased to 0.4 mg.

Overdosage

There are reports of several cases of overdose without fatal outcome, when doses of 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. Short-term elevation of blood pressure, tachycardia, and hyperglycemia are also potential.

Treatment
There is no specific antidote. In the case of lowering blood pressure, it is recommended to restore the circulating blood volume due to the introduction of fluid and the introduction of dopamine.
Bradycardia can be stopped by atropine.
Alpha-adrenoreceptor antagonists can reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose.

Special notes

If you need to cancel simultaneously taken beta-blockers and the drug Physiotens, first cancel the beta-blockers and, only a few days later, Physiotens®.

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

Influence on ability to driving of the car and to control of cars and mechanisms
Studies on the effect of the drug on the ability to drive 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 actions.