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.

Active ingredient

Composition

1 film-coated tablet contains: dosage 0.2 mg:

the active ingredient:

moxonidine 0.2 mg

excipients (core):

croscarmellose sodium (primellose) – 3.0 mg;

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

Colloidal silica (aerosil) -; 0.5 mg;

sodium stearyl fumarate -; 1.0 mg;

accompanied substances (coating):

Opadray 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;

soya lecithin E 322 -; 0.105 mg;

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

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

Description

Light pink film-coated, round, biconvex tablets. The tablets on the break are white or almost white.

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How to take, the dosage

Ingestion, regardless of meals. In most cases, the initial dose of Moxonidine-SZ is 0.2 mg/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 with moderate to severe renal impairment is 0.2 mg/day.

If necessary and if well tolerated, the daily dose can be increased to a maximum of 0.4 mg.

Interaction

The co-administration of moxonidine with other hypotensive agents leads to additive effects.

Tricyclic antidepressants may decrease the effectiveness of centrally acting hypotensive agents, therefore it is not recommended to take them together with moxonidine.

Moxonidine may increase the effects of tricyclic antidepressants, tranquilizers, ethanol, sedatives and hypnotics.

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

Moxonidine may increase the sedative effect of benzodiazepine derivatives when prescribed concomitantly.

Moxonidine is excreted by tubular secretion. Therefore, its interaction with other drugs excreted by tubular secretion cannot be excluded.

Beta-adrenoblockers increase bradycardia, the severity of negative and dromotropic effects.

Special Instructions

If it is necessary to cancel beta-adrenoblockers and Moxonidine taken simultaneously, the beta-adrenoblockers should be cancelled first and only after several days Moxonidine. There is currently no evidence that discontinuation of Moxonidine leads to an increase in BP. However, it is not recommended to stop Moxonidine abruptly; instead, the dose should be gradually reduced over a period of two weeks. During treatment, avoid alcohol consumption. During treatment it is necessary to monitor heart rate and electrocardiography regularly.

The effect on the ability to drive 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 somnolence patients should be careful when engaging in potentially dangerous activities requiring increased attention, such as driving vehicles or operating machinery requiring increased concentration.

Contraindications

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

– sinus node weakness syndrome;

– pronounced bradycardia (resting heart rate less than 50 beats/min.

– atrioventricular block of II and III degree;

– expressed arrhythmia;

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

– concurrent use with tricyclic antidepressants (see “Interaction with other antidepressants”).

– concomitant use of tricyclic antidepressants (see section “Interaction with other medicinal products”);

– severe renal insufficiency (CKR less than 30 ml/min);

– hemodialysis;

– lactation period;

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

– age older than 75 years;

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

Cautions

Particular caution should be exercised when using moxonidine in patients with atrioventricular block of degree I (risk of bradycardia); severe coronary artery disease, severe coronary heart disease or unstable angina (insufficient experience of use), chronic heart failure, severe hepatic insufficiency, with impaired renal function (CKG greater than 30 ml/min).

Side effects

The frequency of adverse effects listed below was determined accordingly as follows: very frequently (≥1/10); frequently (≥1/100, <1/10); infrequently (≥1/1000, <1/100), including individual reports.

CNS side:often – headache*, dizziness (vertigo), somnolence; infrequent – fainting*.

Systems:infrequent – marked decrease in BP, orthostatic hypotension*, bradycardia.

Gastrointestinal disorders:very often – dry mucous membrane of the mouth; often – diarrhea, nausea, vomiting, dyspepsia.

Skin and subcutaneous tissue:often – skin rash, itching; infrequently – angioedema.

Mental disorders:often – insomnia; infrequently – nervousness.

Hearing organ and labyrinth disorders: infrequently – tinnitus.

Skeletal, muscular and connective tissue disorders:often – back pain; infrequently – neck pain.

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

Overdose

There have been reports of several nonfatal overdoses when doses up to 19.6 mg were used at one time.

Symptoms:Headache, sedation, marked BP decrease, dizziness, asthenia, bradycardia, dry oral mucosa, vomiting, increased fatigue, epigastric pain, respiratory depression and impaired consciousness. In addition, transient BP elevation, tachycardia and hyperglycemia are also possible, as has been shown in several high-dose animal studies.

Treatment:There is no specific antidote to the drug. In cases of marked BP decrease, it may be necessary to restore blood pressure by administration of fluids and dopamine (by injection). Bradycardia may be stopped with atropine (injection). In severe cases of overdose, it is recommended to carefully control impaired consciousness and avoid respiratory depression. Alpha-adrenoceptor antagonists may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose. Moxonidine is slightly excreted by hemodialysis.

Similarities