Moxonidine

Pharmacological properties

Moxonidine has been proven to be an effective antihypertensive agent. Available experimental data indicate that the place of the antihypertensive effect of moxonidine is central nervous system. moxonidine is a selective agonist of imidazoline receptors. these imidazoline-sensitive receptors are concentrated in the rostral section of the ventrolateral part of the medulla oblongata - a site that is considered the center of regulation of the peripheral sympathetic nervous system. stimulation of imidazoline receptors reduces the activity of the sympathetic nervous system and reduces hell.

Moxonidine differs from other sympatholytic antihypertensive agents in relatively low affinity for known α₂-adrenoreceptors compared with imidazoline receptors. Due to this, sedation and dry mouth with the use of moxonidine are rare.

In humans, the use of moxonidine leads to a decrease in OPSS with a subsequent decrease in blood pressure. The antihypertensive effect of moxonidine was demonstrated in double-blind, placebo-controlled, randomized trials. The published data indicate that the use of the angiotensin II antagonist (AAII) together with moxonidine in hypertensive patients with left ventricular hypertrophy with a decrease in the same level of blood pressure allowed an increase in regression of left ventricular hypertrophy compared with the free combination of thiazide and calcium channel blocker.

In therapeutic studies lasting 2 months, compared with placebo, moxonidine increased the insulin sensitivity index by 21% in patients with moderate hypertension, obesity, and insulin resistance.

Pharmacokinetics Absorption. Following oral administration of moxonidine rapidly (time to reach C_max in blood plasma - about 1 h) and is almost completely absorbed in the upper gastrointestinal tract. The absolute bioavailability is about 88%, which indicates the absence of significant metabolism during the initial passage through the liver. Simultaneous eating does not affect the pharmacokinetics of moxonidine.

Distribution. The degree of binding to plasma proteins, determined in vitro, is about 7.2%.

Biotransformation. In human plasma samples, only dehydrogenated moxonidine was identified. The pharmacodynamic activity of dehydrogenated moxonidine is about ¹/₁₀ moxonidine activity.

Within a 24-hour period, 78% of the total dose of moxonidine is excreted in the urine as an unchanged compound and 13% in the form of dehydrogenated moxonidine. Other minor metabolites in urine make up about 8% of the dose. Less than 1% is excreted in the feces. T_½ moxonidine and its metabolite is about 2.5 and 5 hours, respectively.

In patients with hypertension compared with healthy individuals, the pharmacokinetics of moxonidine did not differ significantly.

In the elderly, changes in pharmacokinetics were noted, most likely due to a reduced level of metabolism and / or slightly greater bioavailability. However, these changes are not considered clinically significant.

Since moxonidine is not recommended for the treatment of children, pharmacokinetic studies in this subpopulation have not been conducted.

Excretion of moxonidine is largely dependent on creatinine clearance. In patients with moderate renal failure (glomerular filtration rate of 30-60 ml / min), a stable plasma concentration and T_½ approximately 2 and 1.5 times higher than in patients with normal renal function (glomerular filtration rate of 90 ml / min). In patients with severe renal failure (glomerular filtration rate of 30 ml / min), a stable plasma concentration and T_½ about 3 times higher. In these patients, no accumulation of moxonidine was detected after repeated use.In patients with end-stage renal failure (glomerular filtration rate of 10 ml / min) who are on hemodialysis, plasma AUC and T_½ approximately 6 and 4 times higher, respectively, compared with hypertensive patients with normal renal function. In patients with moderate renal failure C_max moxonidine in blood plasma is only 1.5–2 times higher.

Based on the above data, the dose of moxonidine for patients with renal failure should be selected individually. During hemodialysis, moxonidine is excreted to a small extent.

Preclinical safety data. The preclinical data did not reveal a particular risk to humans based on the results of standard studies on pharmacological safety, chronic toxicity, genotoxicity, carcinogenic potential and reproductive toxicity. Animal studies have shown toxic effects on embryonic development when using doses that are toxic to the mothers body. Studies of reproductive toxicity have not revealed an effect on fertility and teratogenic potential. Toxic effects on embryonic development were observed in rats at doses of ≥9 mg / kg / day and in rabbits at doses above 0.7 mg / kg / day. In studies of peri- and postnatal development in rats, effects on development and viability were noted at doses of ≥3 mg / kg / day.

Indications

Ag

Application

The standard initial dose of moxonidine is 0.2 mg / day. maximum single dose - 0.4 mg. the maximum daily dose is 0.6 mg in 2 divided doses. the dose should be selected individually, depending on the response of the patient.

Physiotens can be taken regardless of food intake, washed down with a small amount of liquid.

For patients with moderate or severe renal failure, the initial dose of moxonidine is 0.2 mg / day. If necessary, and if the drug is well tolerated, the dose can be increased to 0.4 mg / day for patients with moderate renal failure and to 0.3 mg / day for patients with severe renal failure (see SPECIAL INSTRUCTIONS).

For patients on hemodialysis, the initial dose of Physiotens is 0.2 mg / day. If necessary, and in case of good tolerability of the drug, the dose can be increased to 0.4 mg / day.

Contraindications

Physiotens is contraindicated in:

• hypersensitivity to the active substance or to any component of the drug;
• sick sinus syndrome;
• bradycardia (at rest 50 bpm);
• AV blockade II and III degree;
• heart failure.

Side effects

The most common side effects of taking moxonidine include dry mouth, dizziness, asthenia, and drowsiness. the severity of these symptoms often decreases after the first few weeks of treatment.

Adverse reactions grouped by classes of body systems and frequency-distributed are noted in placebo-controlled clinical trials in 886 patients who used moxonidine: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100).

From the nervous system: often - headache *, dizziness / vertigo, drowsiness; infrequently - fainting *.

From the cardiovascular system: infrequently - bradycardia, hypotension * (including orthostatic hypotension).

From the side of the organ of hearing and the labyrinth: infrequently - ringing in the ears.

From the digestive tract: very often - dry mouth; often - diarrhea, nausea / vomiting / dyspepsia.

On the part of the skin and subcutaneous tissue: often - rash, itching; infrequently - angioedema.

From the musculoskeletal system and connective tissue: often - back pain; infrequently - pain in the neck.

From the psyche: often - insomnia; infrequently - nervousness.

General disorders and reactions at the injection site: often - asthenia; infrequently - edema.

* Frequency not increased compared to placebo.

special instructions

In the post-registration period, cases of av-blockade of varying severity were reported in patients taking moxonidine. therefore, the causative role of moxonidine in delaying av conduction cannot be completely ruled out. therefore, caution is advised in treating patients with a tendency to develop av-blockade.

Patients with grade I AV blockade should use moxonidine with extreme caution to avoid bradycardia. Moxonidine cannot be used in patients with a higher degree of AV blockade (see CONTRAINDICATIONS).

Moxonidine should be used with caution in patients with severe coronary artery disease or unstable angina pectoris, since experience with the drug in such patients is limited.

It is recommended to use moxonidine with caution in patients with impaired renal function, since moxonidine is excreted primarily by the kidneys. Such patients are advised to carefully titrate the dose, especially at the beginning of therapy. Treatment should begin with a dose of 0.2 mg / day; the dose can be increased to a maximum of 0.4 mg / day for patients with moderate renal failure (glomerular filtration rate of 30 ml / min, but 60 ml / min) and a maximum of 0.3 mg / day for patients with severe renal failure (glomerular rate filtration 30 ml / min) if clinically indicated and the drug is well tolerated.

If Physiotens is used in combination with a β-adrenergic receptor blocker and both drugs must be discontinued, the β-adrenergic receptor blocker should be withdrawn first, and then Physiotens after a few days.

At present, there have been no manifestations of the effects of withdrawal from blood pressure after stopping the use of moxonidine. However, abrupt discontinuation of moxonidine therapy is not recommended; instead, the dose should be gradually reduced over 2 weeks.

Patients with single hereditary diseases, such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption, should not take this drug.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Studies on the effect of the drug on the ability to drive vehicles or work with mechanisms have not been conducted. Reported cases of drowsiness and dizziness when using the drug. This should be considered when performing these actions.

Use during pregnancy or lactation

Pregnancy. There are no relevant data on the use of moxonidine in pregnant women. Animal studies have shown an embryotoxic effect. The possible risk to humans is unknown. Moxonidine should not be used during pregnancy unless there is a clear need.

Lactation. Moxonidine passes into breast milk, therefore it should not be used during lactation. If moxonidine therapy is considered absolutely necessary, breast-feeding should be discontinued.

Children. Physiotens is not recommended for use in children due to insufficient data on the safety and effectiveness of the drug in this group.

Interactions

The simultaneous use of the drug with other antihypertensive agents leads to an additive effect.

Since tricyclic antidepressants can reduce the effectiveness of centrally acting antihypertensive drugs, the simultaneous administration of these drugs with Physiotens is not recommended.

Moxonidine may enhance the sedative effect of tricyclic antidepressants (simultaneous administration should be avoided), tranquilizers, alcohol, sedatives and hypnotics.

Moxonidine moderately increases cognitive impairment in patients receiving lorazepam. Moxonidine may enhance the sedative effect of benzodiazepines with simultaneous use.

Moxonidine is excreted by tubular excretion.Interactions with other agents that are excreted by tubular excretion cannot be ruled out.

Overdose

Symptoms of an overdose. in some cases, an overdose of moxonidine, even at a dose of 19.6 mg, taken at a time, did not lead to death. signs and symptoms of overdose include headache, sedation, drowsiness, arterial hypotension, dizziness, asthenia, bradycardia, dry mouth, vomiting, fatigue, pain in the upper abdomen. in case of severe overdose, careful monitoring of impaired consciousness and respiratory depression is recommended. based on studies of the use of high doses of the drug in animals, we can additionally expect the appearance of temporary hypertension, tachycardia and hyperglycemia.

Necessary measures in case of overdose. Specific antidotes are unknown. In case of hypotension, dopamine and the introduction of plasma-replacing solutions are recommended to support hemocirculation. When bradycardia occurs, atropine can be used.

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

Storage conditions

Physiotens tablets of 0.2 mg should be stored at a temperature not exceeding 25 ° c, physiotherapy tablets of 0.3 and 0.4 mg should be stored at a temperature not exceeding 30 ° c. Keep out of the reach of children.

Conditions of dispensing from pharmacies: by prescription.