Moxarel, 0.4 mg 30 pcs

Pharmacotherapeutic group

Hypotensive agent of central action.

Code ATX: C02AC05

Pharmacological properties

Pharmacodynamics

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

Moxonidine differs from other sympatholytic hypotensive agents in its lower affinity for α₂-adrenoreceptors, which explains the lower probability of developing sedation and dry mouth when using it.

The administration of moxonidine is accompanied by a decrease in systemic vascular resistance and BP. The hypotensive effect of moxonidine has been confirmed in double-blind placebo controlled randomized trials.

. Results from a clinical trial involving 42 patients with arterial hypertension and left ventricular hypertrophy (LVH) demonstrated that with similar blood pressure reductions, use of a combination of angiotensin II receptor antagonists with moxonidine reduces LVH to a greater extent than the combination of a thiazide diuretic and a calcium channel blocker (15% versus 11%; p < 0.5).

Moxonidine improves insulin sensitivity index by 21% (compared with placebo) 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%, indicating no significant “first pass” effect. Time of reaching maximum concentration is about 1 hour. Food intake has no effect on the pharmacokinetics of the drug.

Distribution

The binding to plasma proteins is 7.2%.

Metabolism

The main metabolite is a dehydrated moxonidine derivative. The pharmacodynamic activity of the main metabolite is about 10% of the activity of moxonidine.

Elimation

The elimination half-life (T_1/2) of moxonidine and the dehydrated 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 dehydromoxonidine, the level of other metabolites in the urine does not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestine.

Pharmacokinetics in special patient groups

Patients with arterial hypertension

In comparison with healthy volunteers, patients with arterial hypertension show no changes in the pharmacokinetics of moxonidine.

Elderly patients

Clinically insignificant changes in moxonidine pharmacokinetic parameters have been observed in elderly patients, probably due to decreased metabolic rate and/or slightly higher bioavailability.

Children

Moxonidine is contraindicated for use in patients younger than 18 years, and therefore no pharmacokinetic studies have been performed in this group.

Patients with renal impairment

The excretion of moxonidine is highly correlated with creatinine clearance (CK). In patients with moderate renal impairment (CK between
30-60 ml/min), equilibrium plasma concentrations and final T_1/2 are approximately 2 and 1.5 times higher than in patients with normal renal function (CK greater than 90 ml/min).

In patients with severe renal impairment (CKI less than 30 mL/min), equilibrium plasma concentrations and final T_1/2 are 3 times higher than in patients with normal renal function. Administration of multiple doses of moxonidine results in predictable cumulation in patients with moderate to severe renal impairment. In patients with terminal renal failure (CKR less than 10 mL/min) on hemodialysis, equilibrium plasma concentrations and final T_1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function. In patients with moderate renal impairment, the maximum plasma concentration of moxonidine 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

Active ingredient

Composition

Effective ingredient: moxonidine – 0.40 mg;

Ancillary substances: lactose monohydrate – 64.00 mg, microcrystalline cellulose 101 – 14.80 mg, microcrystalline cellulose 102 – 14.80 mg, povidone K-30 – 2.00 mg, croscarmellose sodium – 2.00 mg, colloidal silicon dioxide – 1.00 mg, magnesium stearate – 1.00 mg.

Film coating: .[hypromellose – 1.80 mg, talc – 0.60 mg, titanium dioxide – 0.31 mg, macrogol 4000 (polyethylene glycol 4000) – 0.27 mg, iron oxide yellow dye – 0.02 mg] or [dry film coating mixture, containing hypromellose (60%), talc (20%), titanium dioxide (10.33%), macro-gol 4000 (polyethylene glycol 4000) (9%), iron oxide yellow dye (0.67%)] – 3.00 mg.

How to take, the dosage

Ingestion, regardless of meals.

In most cases, the starting dose of Moxarel® is 0.2 mg per day. The maximum single dose is 0.4 mg. The maximum daily dose to be divided into 2 doses is 0.6 mg.

An individual adjustment of the daily dose is necessary depending on the patient’s tolerance to the current therapy.

Dose adjustment is not required for patients with hepatic insufficiency.

The starting dose for patients on hemodialysis is 0.2 mg/day. If necessary and if well tolerated, the daily dose can be increased to a maximum of 0.4 mg per day.

Patients with renal insufficiency are recommended to choose the dose cautiously, especially at the beginning of treatment. The initial dose should be 0.2 mg per day. If necessary and in case of good tolerability daily dose of the preparation can be increased up to maximum 0.4 mg for patients with moderate renal insufficiency (CKD more than 30 ml/min but less than 60 ml/min) and 0.3 mg for patients with severe renal insufficiency (CKD less than 30 ml/min).

Interaction

Special Instructions

At regular BP control is required during treatment.

In post-marketing surveillance, cases of atrioventricular block of varying severity have been reported in patients taking moxonidine. The association between Moxarel® and atrioventricular conduction slowing cannot be completely excluded. Thus, caution is recommended when treating patients with a probable predisposition to develop atrioventricular blockade.

There is currently no evidence that discontinuation of Moxarel® leads to an increase in BP. However, it is not recommended that Moxarel® be stopped abruptly; instead, the dose should be reduced gradually over a period of two weeks.

If it is necessary to stop the beta-adrenoblockers and Moxarel® at the same time, the beta-adrenoblockers should be stopped first and only after several days with moxonidine.

In elderly patients there may be an increased risk of cardiovascular events due to the use of hypotensive drugs, therefore Moxarel® treatment should be started with the lowest dose.

At the time of treatment, BP, HR and electrocardiography (ECG) should be monitored regularly. Moxarel® should be stopped gradually.

At the time of treatment with Moxarel® , alcohol consumption should be avoided.

Influence on the ability to drive vehicles, mechanisms

The effect of the drug Moxarel® on the ability to drive vehicles and mechanisms has not been studied. However, taking into account the possible occurrence of dizziness and somnolence, patients should exercise caution when engaged in potentially dangerous activities requiring increased attention.

Synopsis

Contraindications

Side effects

The most common side effects in patients taking moxonidine are: dry mouth, dizziness, asthenia, somnolence. These symptoms usually decrease after the first weeks of therapy.

The frequency of side effects is classified according to the World Health Organization (WHO) recommendations:

very often ≥ 1/10;

often from ≥ 1/100 to < 1/10;

infrequently from ≥ 1/1000 to < 1/100;

rarely from ≥ 1/10000 to < 1/1000;

very rarely < 1/10000, including individual reports;

frequency is unknown – it is not possible to determine the frequency of occurrence from the available data.

Nervous system disorders:

often – headache*, dizziness (vertigo), somnolence, insomnia;

infrequently – fainting*, hyperexcitability.

Cardiac disorders:

infrequent – bradycardia.

vascular disorders:

infrequent – marked BP decrease, orthostatic hypotension.

Hearing and labyrinth disorders:

infrequent – tinnitus.

Gastrointestinal disorders:

very often – dry mouth;

often – nausea, diarrhea, vomiting, dyspepsia.

Skin and subcutaneous tissue disorders:

often – skin rash, itching;

infrequently – angioedema.

Muscular, skeletal and connective tissue disorders:

often – back pain;

infrequently – neck pain.

General disorders and reactions at the site of administration:

often – asthenia;

infrequently – peripheral edema.

*frequency is comparable to placebo

Overdose

There have been reports of several non-fatal overdoses when doses up to 19.6 mg were used simultaneously.
Symptoms
Headache, sedation, drowsiness, marked BP decrease, dizziness, fatigue, asthenia, bradycardia, dry mouth, vomiting and epigastric pain, respiratory depression, impaired consciousness. In addition, short-term BP elevation, tachycardia, hyperglycemia are possible, as shown in several studies on the study of high doses of the drug on animals.
Treatment
There is no specific antidote. In cases of marked BP decrease, administration of fluids to restore circulating blood volume and dopamine (by injection) is recommended. Bradycardia may be stopped by atropine (injection). Alpha-adrenoceptor antagonists may reduce or eliminate paradoxical hypertensive effects in moxonidine overdose.
In severe cases of overdose, it is recommended that impaired consciousness and respiratory depression be carefully controlled.

Pregnancy use

Pregnancy

There are no clinical data on the treatment of pregnant women with Moxarel®.

An animal study found embryotoxic effects of the drug at doses above therapeutic. The potential risk to humans is unknown.

Prescribing Moxarel® to pregnant women should be used with caution only after careful evaluation by a physician of the risk/benefit ratio when the benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding

Moxonidine penetrates into breast milk and therefore should not be administered during breastfeeding. Breastfeeding should be discontinued if it is necessary to use the drug.

Similarities