Moksarel

General characteristics. Structure:

Active ingredient: 0,2 mg, 0,3 mg or 0,4 mg of a moksonidin.

Excipients: lactoses monohydrate - 64,00 mg, cellulose microcrystallic - 29,70 mg, silicon dioxide colloid - 1,00 mg, K-30 povidone - 2,00 mg, croscarmellose sodium - 2,00 mg, magnesium stearate - 1,00 mg.

Film cover: [a gipromelloza - 1,80 mg, talc - 0,60 mg, titanium dioxide - 0,31 mg, a macrogoal 4000 (polyethyleneglycol 4000) - 0,27 mg, ferrous oxide red (ferrous oxide) - 0,02 mg] or [the dry mix for a film covering containing a gipromelloza (60%), talc (20%), titanium dioxide (10,33%), a macrogoal 4000 (polyethyleneglycol 4000); dyes.

Pharmacological properties:

Pharmacodynamics. Moksonidin is an antihypertensive with the central mechanism of action. моксонидин selectively stimulates imidazoline in trunk structures of a brain (a rostral layer of side ventricles) - the sensitive receptors which are taking part in tonic and reflex regulation of a sympathetic nervous system. Stimulation of imidazolinovy receptors reduces peripheral sympathetic activity and the arterial pressure (AP).

Moksonidin differs from other sympatholytic antihypertensives in lower affinity to α1-адренорецепторам that explains smaller probability of development of sedation and dryness of a mucous membrane of an oral cavity.

Reception of a moksonidin leads to decrease in system vascular resistance and the ABP.

Moksonidin improves a sensitivity index to insulin at patients with obesity, insulin resistance and moderate degree of arterial hypertension.

Pharmacokinetics. Absorption. After intake моксонидин quickly and almost it is completely absorbed in upper parts of digestive tract. Absolute bioavailability makes about 88%. Time of achievement of the maximum concentration - about 1 hour. Meal does not exert impact on drug pharmacokinetics. 

Distribution. Communication with proteins of a blood plasma makes 7,2%.

Metabolism. The main metabolite - dehydrogenated моксонидин. Pharmakodinamichesky activity of the dehydrogenated moksonidin - about 10% in comparison with moksonidiny.

Removal. The elimination half-life (T1/2) of a moksonidin and a metabolite makes 2,5 and 5 hours respectively. Within 24 hours over 90% of a moksonidin are removed by kidneys (about 78% in not changed look and 13% in the form of a degidromoksonidin, other metabolites in urine do not exceed 8% of the accepted dose). Less than 1% of a dose are removed through intestines.

Pharmacokinetics at patients of advanced age. Clinically insignificant changes of pharmacokinetic indicators of a moksonidin at elderly patients probably caused by decrease in intensity of his metabolism and/or a little higher bioavailability are noted.

Pharmacokinetics at children. Moksonidin is not recommended for use for patients more young than 18 years in this connection in this group pharmacokinetic researches were not conducted.

Pharmacokinetics at a renal failure. Removal of a moksonidin substantially correlates with the clearance of creatinine (CC). At patients with a moderate renal failure (KK in the range of 30-60 ml/min.) equilibrium concentration in a blood plasma and final T1/2 approximately in 2 and 1,5 times is higher, than at patients with normal function of kidneys (KK more than 90 ml/min.).

At patients with a heavy renal failure (KK less than 30 ml/min.) equilibrium concentration in a blood plasma and final T1/2 is 3 times higher, than at patients with normal function of kidneys. Purpose of repeated doses of a moksonidin leads to predictable cumulation in an organism of patients with a moderate and heavy renal failure. At the patients with a terminal renal failure (KK less than 10 ml/min.) who are on a hemodialysis, equilibrium concentration in a blood plasma and final T1/2 respectively in 6 and 4 times is higher, than at patients with normal function of kidneys.

In all groups the maximum concentration of a moksonidin in a blood plasma is 1,5-2 times higher. At patients with a renal failure the dosage has to be selected individually.

Moksonidin in insignificant degree is brought when carrying out a hemodialysis.

Indications to use:

Arterial hypertension.

Route of administration and doses:

Inside, irrespective of meal. In most cases the initial dose of the drug Moksarel® makes 0,2 mg a day. The maximum single dose makes 0,4 mg. The maximum daily dose which should be divided into 2 receptions makes 0,6 mg.

The initial dose for patients with a moderate or heavy renal failure, and also for the patients who are on a hemodialysis makes 0,2 mg/days. In case of need and at good tolerance the daily dose can be increased to 0,4 mg.

Features of use:

Use at pregnancy and during breastfeeding. Clinical data on treatment pregnant with the drug Moksarel® are absent. It is necessary to appoint Moksarel® pregnant with care only after careful assessment of a ratio of risk and advantage when the advantage for mother exceeds potential risk for a fruit. Moksonidin gets into breast milk. The feeding women during treatment are recommended to stop breastfeeding or to cancel drug.

There are no confirmations that the termination of administration of drug of Moksarel® leads to increase in the ABP now. However it is not recommended to stop administration of drug of Moksarel® sharply, instead it is necessary to reduce gradually a drug dose within two weeks.

In need of cancellation of at the same time accepted beta adrenoblockers and the drug Moksarel® at first cancel beta adrenoblockers, and only in several days моксонидин.

During treatment regular control of the ABP, ChSS and registration of an electrocardiography (ECG) is necessary. It is necessary to stop administration of drug of Moksarel® gradually.

During treatment by the drug Moksarel® it is necessary to exclude alcohol intake.

Influence on ability to control of vehicles and mechanisms. Influence of the drug Moksarel® on ability to driving by vehicles or to control of the equipment was not studied. However, in view of possible developing of dizziness and drowsiness, patients should be careful at occupation potentially dangerous types of activity requiring special attention, such as driving of motor transport or control of the equipment demanding the increased concentration of attention.

Side effects:

Frequency of development of the side effects given below was defined according to the following: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01% (including isolated cases).

From the central nervous system: often  - a headache, dizziness (вертиго), drowsiness; infrequently - a syncope.

From cardiovascular system: infrequently - the expressed decrease in the ABP, orthostatic hypotension, bradycardia.

From digestive tract: very often - dryness of a mucous membrane of an oral cavity; often - nausea, diarrhea, vomiting, dyspepsia.

From skin and hypodermic fabrics: often - skin rash, an itch; infrequently - a Quincke's disease.

Disturbances of mentality: often - sleeplessness; infrequently - nervousness.

From an acoustic organ and labyrinth disturbances: infrequently - a ring in ears.

From skeletal and muscular and connecting fabric: often - a dorsodynia; infrequently - pain in a neck.

The general frustration and disturbances in an injection site: often - an adynamy; infrequently - peripheral hypostases.

Frequency of development of the side effects given below was defined according to the following: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01% (including isolated cases).

From the central nervous system: often - a headache, dizziness (вертиго), drowsiness; infrequently - a syncope.

From cardiovascular system: infrequently - the expressed decrease in the ABP, orthostatic hypotension, bradycardia.

From digestive tract: very often - dryness of a mucous membrane of an oral cavity; often - nausea, diarrhea, vomiting, dyspepsia.

From skin and hypodermic fabrics: often - skin rash, an itch; infrequently - a Quincke's disease.

Disturbances of mentality: often - sleeplessness; infrequently - nervousness.

From an acoustic organ and labyrinth disturbances: infrequently - a ring in ears.

From skeletal and muscular and connecting fabric: often - a dorsodynia; infrequently - pain in a neck.

The general frustration and disturbances in an injection site: often - an adynamy; infrequently - peripheral hypostases.

Interaction with other medicines:

Combined use of a moksonidin with other antihypertensives results in the additive effect.

Tricyclic antidepressants can reduce efficiency of antihypertensives of the central action in this connection their reception together with moksonidiny is not recommended.

Moksonidin can strengthen effect of tricyclic antidepressants, tranquilizers, ethanol, sedative and hypnagogues.

Moksonidin is capable to improve moderately weakened cognitive functions at the patients receiving lorazepam.

Purpose of a moksonidin together with derivatives of benzodiazepine can be followed by strengthening of sedation of the last.

Simultaneous use of a moksonidin with beta adrenoblockers leads to strengthening of bradycardia, expressiveness of other and dromotropic action.

At purpose of a moksonidin together with a moklobemidy pharmakodinamichesko interaction is absent.

Moksonidin is allocated by canalicular secretion therefore his interaction with other drugs which are emitted by canalicular secretion is not excluded.

Contraindications:

- hypersensitivity to active agent, other components of drug;
- the expressed disturbances of a heart rhythm;
- sick sinus syndrome;
- atrioventricular block of II and III degrees;
- the expressed bradycardia (heart rate (HR) less than 50 beats/min);
- acute and chronic heart failure (the III-IV functional class on NYHA classification);
- simultaneous use with tricyclic antidepressants (see the section "Interaction with Other Medicines"); 
- a heavy renal failure (KK less than 30 ml/min.), including the patients who are on a hemodialysis;
- the age is more senior than 75 years;
- age up to 18 years (efficiency and safety of a moksonidin are not established);
- breastfeeding period; 
- lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption.

With care:
- renal failures (KK more than 30 ml/min.); 
- a heavy liver failure (more than 9 points on classification of Chayld-Pyyu);
- atrioventricular block of the I degree;
- serious illness of coronary vessels;
- heavy coronary heart disease or unstable stenocardia (experience of use is insufficient);
- chronic heart failure.

Overdose:

Symptoms. A headache, sedation, drowsiness, the expressed decrease in the ABP, dizziness, increased fatigue, an adynamy, bradycardia, dryness of a mucous membrane of an oral cavity, vomiting and pain in epigastric area, respiratory depression, consciousness disturbance. Also short-term increase in the ABP, tachycardia, a hyperglycemia are potentially possible.

Treatment. The specific antidote does not exist. In case of the expressed decrease in the ABP administration of liquid for recovery of volume of the circulating blood and a dopamine is recommended. Bradycardia can be stopped by atropine. Antagonists of alpha adrenoceptors can reduce or eliminate paradoxical hypertensive effects at overdose moksonidiny.

In hard cases of overdose it is recommended to control carefully disturbances of consciousness and not to allow respiratory depression.

Moksonidin in insignificant degree is brought when carrying out a hemodialysis.

Storage conditions:

In the place protected from light at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 0,2 mg, 0,3 mg or 0,4 mg. 10, 14, 15 or 30 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. 1, 2 or 3 blister strip packagings on 10 tablets, 1, 2 or 4 blister strip packagings on 14 tablets, 1, 2 or 4 blister strip packagings on 15 tablets, 1 or 2 blister strip packagings on 30 tablets together with the application instruction in a pack from a cardboard.