Moxarel, 0.2 mg 30 pcs.

Pharmacodynamics

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

Moxonidine differs from other adrenergic hypotensive agents in its lower affinity for α1-adrenoreceptors, which explains the lower likelihood of sedation and dry mouth.

The administration of moxonidine results in decreased systemic vascular resistance and BP.

Moxonidine improves insulin sensitivity index in patients with obesity, insulin resistance and moderate arterial hypertension.

Pharmacokinetics

Intake. After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. Tmax is about 1 hour. Food intake has no effect on pharmacokinetics of the drug.

Distribution. Binding with blood plasma proteins is 7.2%.

Metabolism. The main metabolite is dehydrated moxonidine. The pharmacodynamic activity of dehydrated moxonidine is about 10% compared to moxonidine.

Excretion. The T1/2 of moxonidine and the metabolite is 2.5 and 5 h, respectively. Within 24 hours more than 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% as dehydromoxonidine, other metabolites in the urine do not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestine.

Particular groups of patients

Patients of advanced age. Clinically insignificant changes in pharmacokinetic parameters of moxonidine have been observed in elderly patients, probably due to decreased intensity of its metabolism and/or slightly higher bioavailability.

Children. Moxonidine is not recommended for use in patients younger than 18 years of age; therefore, no pharmacokinetic studies have been performed in this group.

Kidney function impairment. Excretion of moxonidine correlates significantly with creatinine clearance. In patients with moderate renal impairment (creatinine Cl 30-60 ml/min) plasma Css and final T1/2 are approximately 2 and 1.5 times higher than in patients with normal renal function (creatinine Cl over 90 ml/min). In patients with severe renal impairment (creatinine Cl less than 30 ml/min) plasma Css and final T1/2 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 (creatinine Cl less than 10 ml/min) on hemodialysis, plasma Css and final T1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function.

The maximum plasma concentration of moxonidine is 1.5-2 times higher in all groups. In patients with impaired renal function the dosage should be adjusted individually. Moxonidine is excreted to a small extent during hemodialysis.

Indications

Arterial hypertension.

Pharmacological effect

Pharmacodynamics

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

Moxonidine differs from other adrenergic antihypertensive drugs in its lower affinity for α1-adrenergic receptors, which explains the lower likelihood of developing sedation and dryness of the oral mucosa.

Taking moxonidine leads to a decrease in systemic vascular resistance and blood pressure.

Moxonidine improves the insulin sensitivity index in patients with obesity, insulin resistance and moderate arterial hypertension.

Pharmacokinetics

Suction. After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. Tmax is about 1 hour. Food intake does not affect the pharmacokinetics of the drug.

Distribution. The binding to plasma proteins is 7.2%.

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

Excretion. T1/2 of moxonidine and 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% as dehydromoxonidine, other metabolites in the urine do not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestines.

Special patient groups

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

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

Renal dysfunction. Moxonidine excretion is significantly correlated with creatinine clearance. In patients with moderate renal failure (creatinine clearance 30–60 ml/min), plasma Css and final T1/2 are approximately 2 and 1.5 times higher than in patients with normal renal function (creatinine clearance more than 90 ml/min). In patients with severe renal failure (Cl creatinine less than 30 ml/min), plasma Css 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 accumulation in the body of patients with moderate and severe renal failure. In patients with end-stage renal failure (Cl creatinine less than 10 ml/min) on hemodialysis, plasma Css 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 was 1.5–2 times higher. In patients with impaired renal function, the dosage should be adjusted individually. Moxonidine is excreted to a small extent during hemodialysis.

Special instructions

There is currently no evidence that stopping Moxarel® leads to an increase in blood pressure. However, it is not recommended to stop taking Moxarel® suddenly; instead, you should gradually reduce the dose of the drug over 2 weeks.

If it is necessary to cancel simultaneously taken β-blockers and the drug Moxarel®, first cancel the β-blockers and only after a few days moxonidine.

During treatment, regular monitoring of blood pressure, heart rate and ECG registration is necessary. You should stop taking Moxarel® gradually.

During treatment with Moxarel®, alcohol consumption should be avoided.

Impact on the ability to drive vehicles and operate machinery. The effect of Moxarel® on the ability to drive vehicles or operate machinery has not been studied. However, given the possible occurrence of dizziness and drowsiness, patients should be careful when engaging in potentially hazardous activities that require increased alertness, such as driving or operating machinery.

Active ingredient

Moxonidine

Composition

Active ingredient:

moxonidine;

Excipients:

lactose monohydrate;

MCC;

colloidal silicon dioxide;

povidone K30;

croscarmellose sodium;

magnesium stearate.

Contraindications

severe heart rhythm disturbances;
sick sinus syndrome;
AV block II and III degrees;
severe bradycardia (heart rate less than 50 beats/min);
acute and chronic heart failure (III-IV functional class according to the NYHA classification);
simultaneous use with tricyclic antidepressants;
severe renal failure (creatinine clearance less than 30 ml/min), including patients on hemodialysis;
age over 75 years;
age under 18 years (the effectiveness and safety of moxonidine have not been established);
breastfeeding period;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
hypersensitivity to the active substance or other components of the drug.

With caution

renal dysfunction (creatinine clearance more than 30 ml/min);
severe liver failure (more than 9 points according to the Child-Pugh classification);
AV block of the first degree;
severe diseases of the coronary vessels;
severe ischemic heart disease or unstable angina (insufficient experience);
chronic heart failure.

Side Effects

From the side of the central nervous system: often – headache, dizziness (vertigo), drowsiness; infrequently – fainting.

From the cardiovascular system: infrequently – marked decrease in blood pressure, orthostatic hypotension, bradycardia.

From the gastrointestinal tract: very often – dryness of the oral mucosa; often – nausea, diarrhea, vomiting, dyspepsia.

From the skin and subcutaneous tissues: often – skin rash, itching; infrequently – angioedema.

Mental disorders: often – insomnia; infrequently – nervousness.

From the organ of hearing and labyrinthine disorders: infrequently – ringing in the ears.

From the musculoskeletal and connective tissue side: often – back pain; infrequently – pain in the neck.

General disorders and disorders at the injection site: often – asthenia; infrequently – peripheral edema.

Interaction

The combined use of moxonidine with other antihypertensive drugs leads to an additive effect.

Tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive drugs, and therefore their use together with moxonidine is not recommended.

Moxonidine may enhance the effect of tricyclic antidepressants, tranquilizers, ethanol, sedatives and hypnotics.

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

Prescribing moxonidine together with benzodiazepine derivatives may be accompanied by an increase in the sedative effect of the latter.

The simultaneous use of moxonidine with beta-blockers leads to increased bradycardia, the severity of ino- and dromotropic effects.

When moxonidine is prescribed together with moclobemide, there is no pharmacodynamic interaction. Moxonidine is released by tubular secretion, so its interaction with other drugs released by tubular secretion is possible.

Overdose

Symptoms:

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

Treatment:

There is no specific antidote for the drug. In case of a pronounced decrease in blood pressure, it is recommended to administer fluid to restore blood volume and dopamine. Bradycardia can be relieved with atropine. α-Adrenergic antagonists may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose. In severe cases of overdose, it is recommended to carefully monitor impairment of consciousness and avoid respiratory depression. Moxonidine is excreted to a small extent during hemodialysis.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 °C.

Shelf life

3 years

Manufacturer

Vertex, Russia