Moxonidine-SZ, 0.4 mg 60 pcs

Pharmacotherapeutic drug group:

Hypotensive drug of central action.

ATC code: [C02AC05]

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 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. 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: Compared with healthy volunteers, patients with arterial hypertension show no changes in the 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 (CKR 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 multiple doses of moxonidine results in predictable cumulation in patients with moderate to severe renal impairment.

In patients with terminal renal failure (KC 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 slightly excreted during hemodialysis.

Indications

Hypertension (high blood pressure)

Arterial hypertension.

Active ingredient

Moxonidine

Composition

Active substance:

moxonidine 0.4 mg

auxiliary substances(core):

croscarmellose sodium (primellose) -; 3.0 mg;

lactose monohydrate (lactopress) (milk sugar) -; 95.1 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; E 171 titanium dioxide -; 0.5751 mg; talc -; 0.6 mg; macrogol (polyethylene glycol 3350) -; 0.3705 mg; E 322 soy lecithin -; 0.105 mg; aluminum varnish based on indigo carmine -; 0.0018 mg; aluminum varnish based on azorubin dye -; 0.0153 mg; aluminum varnish based on crimson dye [Ponceau 4R] -; 0.0123 mg).

Description:

The film-coated tablets are dark pink, round, biconvex. Tablets on the fracture are white or almost white.

How to take, the dosage

Ingestion, regardless of meals. In most cases, the initial dose of Moxonidine 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. Individual adjustment of the daily dose is necessary depending on the patient’s tolerance to the therapy.

Dose adjustment for patients with hepatic insufficiency is not required.

The starting dose for patients with moderate to severe renal insufficiency is 0.2 mg/day. If necessary and if well tolerated, the daily dose may be increased to a maximum of 0.4 mg.

Interaction

The co-administration of moxonidine with other hypotensive agents leads to an additive effect. Tricyclic antidepressants may decrease the effectiveness of central hypotensive agents, and therefore it is not recommended to take them together with moxonidine.

Moxonidine may increase the effect 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. Currently, there is no evidence that stopping Moxonidine causes an increase in BP.

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 hazardous 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 impairment, with impaired renal function (CKG greater than 30 ml/min).

Side effects

The frequency of side 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.

Anxiety to the central nervous system:

Often: headache*, dizziness (vertigo), drowsiness.

Infrequent: fainting*.

Cardiovascular system disorders:

Infrequent: marked decrease in BP, orthostatic hypotension*, bradycardia.

Gastrointestinal tract disorders:

very often: dryness of the oral mucosa.

Often: diarrhea, nausea, vomiting, dyspepsia.

Skin and subcutaneous tissue:

Often: skin rash, itching.

Infrequent: angioedema.

Mental disorders:

Often: insomnia.

Infrequent: nervousness.

Hearing organ and labyrinth disorders:

Infrequent: tinnitus.

Skeletal, muscular and connective tissue disorders:

Often: back pain.

Infrequent: pain in the neck area.

General disorders and disorders at the site of administration:

Often: asthenia.

Infrequent: peripheral edema.

(* – frequency is comparable to placebo).

Overdose

There have been reports of several non-fatal overdoses in which doses up to 19.6 mg were administered 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. In case of marked BP decrease it may be necessary to restore circulating blood volume by administration of fluids and dopamine (by injection).

Bradycardia may be controlled with atropine (injection).

In severe cases of overdose, it is recommended that impaired consciousness be carefully controlled and respiratory depression avoided.

Alpha-adrenoreceptor antagonists may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose.

Moxonidine is slightly excreted by hemodialysis.

Similarities

Moxonidine, Moxonitex, Tensotran, Physiotensis, Moxarel