Moxonidine-SZ, 0.2 mg 60 pcs

Pharmacotherapeutic drug group:

Hypotensive drug of central action.

ATC code: [C02AC05]

Pharmacodynamics

Moxonidine is a hypotensive drug with a central mechanism of action. In brain stem structures (rostral layer of lateral ventricles) moxonidine selectively stimulates imidazoline-sensitive receptors involved 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 sedative effects and dry mouth. Administration of moxonidine results in reduction of systemic vascular resistance and BP. Moxonidine improves insulin sensitivity index (compared to placebo) by 21 % 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%. 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; dehydrated moxonidine. The pharmacodynamic activity of dehydrated moxonidine is; about 10% compared to moxonidine. Excretion The elimination 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 (approximately 78% unchanged and 13% as dehydri-romoxonidine, other metabolites in the urine do not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestine.

Pharmacokinetics in patients with arterial hypertension:

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

Pharmacokinetics in the elderly

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

Pharmacokinetics in children

Moxonidine is not recommended for use in patients younger than 18 years, and therefore no pharmacokinetic studies have been performed in this group. Pharmacokinetics in renal failure

The excretion of moxonidine is highly correlated with creatinine clearance (CK). In patients with moderate renal insufficiency (CK between 30-60 ml/min), equilibrium plasma concentrations and final T1/2 are approximately 2 and l.5 times higher than in patients with normal renal function (CK greater than 90 ml/min). In patients with severe renal impairment (CKD less than 30 ml/min), equilibrium plasma concentrations and final T1/2 are 3 times higher than in patients with normal renal function. Administration of repeated doses of moxonidine results in predictable cumulation in patients with moderate to severe renal impairment. In patients with terminal renal failure (CKD less than 10 ml/min) on hemodialysis, 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 plasma concentration of moxonidine is 1.5 to 2 times higher. 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

Pharmacotherapeutic group of the drug:

Centrally acting antihypertensive agent.

ATX code: [C02AC05]

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 (BP). Moxonidine differs from other sympatholytic antihypertensive drugs in its lower affinity for α2-adrenergic receptors, which explains the lower likelihood of developing sedation and dry mouth. Taking moxonidine leads to a decrease in systemic vascular resistance and blood pressure. Moxonidine improves the insulin sensitivity index by 21% (compared to placebo) in patients with obesity, insulin resistance and moderate hypertension. Pharmacokinetics

Suction:

After oral administration, moxonidine is rapidly and almost completely absorbed from the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. Time to reach maximum concentration -; about 1 hour. Food intake does not affect the pharmacokinetics of the drug.

Distribution

The connection with blood plasma proteins is 7.2%.

Metabolism

The main metabolite is; dehydrogenated moxonidine. Pharmacodynamic activity of dehydrogenated moxonidine -; about 10% compared to moxonidine. Elimination The half-life (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 dehydriroxonidine, other metabolites in the urine do not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestines.

Pharmacokinetics in patients with arterial hypertension:

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

Pharmacokinetics in old age

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.

Pharmacokinetics in 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. Pharmacokinetics in renal failure

Moxonidine excretion is significantly correlated with creatinine clearance (CC). In patients with moderate renal failure (creatinine clearance in the range of 30-60 ml/min.), steady-state plasma concentrations and final T1/2 are approximately 2 and l.5 times higher than in patients with normal renal function (creatinine clearance more than 90 ml/min.). In patients with severe renal failure (creatinine clearance less than 30 ml/min.), steady-state 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 accumulation in the body of patients with moderate and severe renal failure. In patients with end-stage renal failure (creatinine clearance less than 10 ml/min) on hemodialysis, steady-state 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 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

If it is necessary to cancel beta-blockers and the drug Moxonidine taken simultaneously, first cancel the beta-blockers and only after a few days Moxonidine. There is currently no evidence that stopping Moxonidine leads to an increase in blood pressure. However, it is not recommended to stop taking Moxonidine suddenly; instead, you should gradually reduce the dose of the drug over two weeks. Avoid drinking alcohol during treatment. During treatment, regular monitoring of heart rate and electrocardiography is necessary.

Impact on the ability to drive vehicles and operate machinery

The effect of Moxonidine on the ability to drive vehicles or operate machinery has not been studied. However, taking into account the possibility of dizziness and drowsiness, patients should be careful when engaging in potentially hazardous activities that require increased attention, such as driving a vehicle or operating equipment that requires increased concentration.

Active ingredient

Moxonidine

Composition

1 film-coated tablet contains: dosage 0.2 mg:

active substance:

moxonidine 0.2 mg

excipients (core):

croscarmellose sodium (primellose) – 3.0 mg;

lactose monohydrate (lactopress) (milk sugar) -; 95.3 mg;

colloidal silicon dioxide (aerosil) -; 0.5 mg;

sodium stearyl fumarate -; 1.0 mg;

excipients (shell):

Opadry II (polyvinyl alcohol, partially hydrolyzed -; 1.32 mg;

titanium dioxide E 171 -; 0.6027 mg;

talc -; 0.6 mg;

macrogol (polyethylene glycol 3350) -; 0.3705 mg;

soy lecithin E 322 -; 0.105 mg;

dye iron oxide (II) yellow -; 0.0003 mg;

dye iron oxide (II) red -; 0.0015 mg).

Description

Light pink, film-coated tablets, round, biconvex. The tablets are white or almost white when broken.

Contraindications

– hypersensitivity to the active substance and other components of the drug;

– sick sinus syndrome;

– severe bradycardia (resting heart rate less than 50 beats/min);

– atrioventricular block II and III degrees;

– severe heart rhythm disturbances; – acute and chronic heart failure (III-IV functional class according to the NYHA classification);

– simultaneous use with tricyclic antidepressants (see section “Interaction with other drugs”);

– severe renal failure (creatinine clearance less than 30 ml/min);

– hemodialysis;

– lactation period;

– hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

– age over 75 years;

– age under 18 years (due to the lack of data on safety and effectiveness).

With caution

Particular care must be taken when using moxonidine in patients with first degree atrioventricular block (risk of developing bradycardia); severe coronary artery disease, severe coronary heart disease or unstable angina (insufficient experience), chronic heart failure, severe liver failure, with impaired renal function (creatinine clearance more than 30 ml/min).

Side Effects

The frequency of side effects listed below was determined according to the following: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100), including isolated reports.

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 – diarrhea, nausea, 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.

Moxonidine may enhance the sedative effect of benzodiazepine derivatives when administered simultaneously.

Moxonidine is released by tubular secretion. Therefore, its interaction with other drugs released by tubular secretion is not excluded.

Beta-blockers increase bradycardia and the severity of negative ino- and dromotropic effects.

Overdose

There have been reports of several cases of non-fatal overdose when doses up to 19.6 mg were used simultaneously.

Symptoms: headache, sedation, marked decrease in blood pressure, dizziness, asthenia, bradycardia, dry oral mucosa, vomiting, fatigue, pain in the epigastric region, respiratory depression and impaired consciousness. In addition, short-term increases in blood pressure, tachycardia and hyperglycemia are also possible, as shown in several high-dose animal studies.

Treatment: There is no specific antidote for the drug. In the case of a pronounced decrease in blood pressure, it may be necessary to restore bcc through the administration of fluid and dopamine (injection). Bradycardia can be stopped with atropine (injection). In severe cases of overdose, it is recommended to carefully monitor impairment of consciousness and avoid respiratory depression. Alpha-adrenergic antagonists may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose. Moxonidine is excreted to a small extent during hemodialysis.

Storage conditions

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

Shelf life

3 years. Do not use after the expiration date stated on the package.

Manufacturer

North Star NAO, Russia