Tenzotran

General characteristics. Structure:

1 tablet, film coated 0,2 mg contains:
active agent: моксонидин 0,2 mg;
excipients: lactoses monohydrate of 94,5 mg, povidone - K25 2 mg, кросповидон 3 mg, magnesium stearate of 0,3 mg, Opadray of Y-1-7000 3,498 mg (titanium dioxide of 1,093 mg, a gipromelloza of 2,186 mg, a macrogoal-400 of 0,219 mg), dye ferrous oxide of red 0,002 mg.
1 tablet, film coated 0,3 mg contains:
active agent: моксонидин 0,3 mg;
excipients: lactoses monohydrate of 94,4 mg, povidone - K25 2 mg, кросповидон 3 mg, magnesium stearate of 0,3 mg, Opadray of Y-1-7000 3,488 mg (titanium dioxide of 1,090 mg, a gipromelloza of 2,180 mg, a macrogoal-400 of 0,218 mg), dye ferrous oxide of red 0,012 mg.
1 tablet, film coated 0,4 mg contains:
active agent: моксонидин 0,4 mg;
excipients: lactoses monohydrate of 94,3 mg, povidone - K25 2 mg, кросповидон 3 mg, magnesium stearate of 0,3 mg, Opadray of Y-1-7000 3,465 mg (titanium dioxide of 1,083 mg, a gipromelloza of 2,165 mg, a macrogoal-400 of 0,217 mg), dye ferrous oxide of red 0,035 mg.

Description
 Round tablets light pink (tablets of 0,2 mg), pink (tablets of 0,3 mg) or dark pink (tablets of 0,4 mg) colors, film coated.

Pharmacological properties:

Pharmacodynamics. The selection agonist of the imidazolinovy receptors which are responsible for reflex control over a sympathetic nervous system (are localized in ventero-lateral department of a myelencephalon). Has low affinity with the central alfa2-adrenoceptors with which due to interaction sedation and dryness of a mucous membrane of an oral cavity are mediated. Moksonidin improves a sensitivity index to insulin for 21% in comparison with placebo at the patients and insulinrezistentny patients having obesity with moderate degree of arterial hypertension. Influence on a hemodynamics: decrease in the systolic and diastolichgsky arterial pressure (AP) at single and long dose of a moksonidin is connected with reduction of pressor action of sympathetic system by peripheral vessels, decrease in the general peripheric vascular resistance while cordial emission and the heart rate (HR) significantly do not change.

Pharmacokinetics. After intake моксонидин quickly and almost it is completely absorbed from an upper part of the digestive tract (DT). Tmax (time of achievement of the maximum concentration) makes about 1 hour. Absolute bioavailability makes about 88%, metabolism of "the first passing" through a liver insignificant. Meal does not exert impact on drug pharmacokinetics. Communication with proteins of a blood plasma makes 7,2%.
Main metabolite: dehydrogenated моксонидин. Pharmakodinamichesky activity of the dehydrogenated moksonidin - about 1/10 in comparison with moksonidiny. The elimination half-life of a moksonidin and metabolites makes 2,5 and 5 hours, respectively. Within 24 hours more than 90% of a moksonidin are removed by kidneys, about 78% in not changed look and 13% in the form of the dehydrogenated moksonidin. Other metabolites in urine make about 8% of a dose. Less than 1% of a dose are removed through intestines.
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 the final elimination half-life approximately in 2 and 1,5 times is higher, than at patients with arterial hypertension 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 the final elimination half-life is 3 times higher, than at patients with normal function of kidneys. Purpose of repeated doses of a moksonidin does not lead to cumulation in an organism of patients with a moderate and heavy renal failure. At late stages 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 the final elimination half-life respectively in 6 and 4 times is higher, than at patients with normal function of kidneys. At patients with renal failures the dosage has to be selected individually. Moksonidin in insignificant degree is brought when carrying out a hemodialysis. Gets through a blood-brain barrier.

Indications to use:

• Arterial hypertension.

Route of administration and doses:

Inside, irrespective of meal, washing down with enough liquid. In most cases the initial dose of Tenzotran makes 0,2 mg a day at one time, more preferably in the morning. At insufficiency of therapeutic effect the dose can be increased after 3 weeks of therapy to 0,4 mg a day in 2 receptions (in the morning and in the evening) or once (morning). The maximum daily dose which should be divided into 2 receptions (in the morning and in the evening) makes 0,6 mg. The maximum single dose makes 0,4 mg.
Elderly patients with normal function of kidneys have recommendations about a dosage same, as well as for adult patients.
At patients with a renal failure (KK from 30-60 ml/min.) and the patients who are on a hemodialysis, the single dose should not exceed 0,2 mg. The maximum daily dose - 0,4 mg.

Features of use:

In need of cancellation of at the same time accepted beta adrenoblockers and Tenzotran, at first cancel beta adrenoblockers and, only in several days, Tenzotran.
It is not recommended to appoint tricyclic antidepressants along with Tenzotran.
During treatment regular control of the ABP, ChSS and ECG is necessary.
Moksonidin can be appointed with thiazide diuretics, inhibitors of an angiotensin-converting enzyme (APF) and blockers of "slow" calcium channels.
It is necessary to stop Tenzotran's reception gradually.
Patients with rare hereditary pathology of intolerance of a galactose, deficit of lactase or malabsorption of glucose galactose should not accept this drug.

Influence on ability to driving of the car and to control of cars and mechanisms
 Data on adverse influence of a moksonidin on ability to driving of the car and to control of cars and mechanisms are absent. There are messages on drowsiness and dizziness during treatment moksonidiny. It should be considered when performing the above-stated actions.

Side effects:

Especially at the beginning of therapy the most frequent collateral reactions were: dryness in a mouth, a headache, an adynamy and drowsiness. Intensity of their manifestation and frequency decrease at repeated reception. Development frequency: very often (more than 1/10), it is frequent (more than 1/100, less than 1/10), sometimes (more than 1/1000 and less than 1/100), is very rare (less than 1/1000, including separate messages).
From cardiovascular system: often - a vazodilatation; sometimes – the expressed decrease in the ABP, orthostatic hypotension, paresthesias, Reynaud's syndrome, disturbances of peripheral circulation;
From the central nervous system: often - increased fatigue, drowsiness, a headache, dizziness; sometimes - sleeplessness, an adynamy;
From a digestive tract: dryness of a mucous membrane of an oral cavity; often - nausea, a lock and other dysfunctions of a GIT; very seldom - hepatitis, a cholestasia;
From skin and integuments: sometimes - allergic reactions;
From urinogenital system: sometimes - an ischuria or an incontience, impotence, decrease in a libido;
From an organ of sight: sometimes - the xerophthalmus causing an itch or a burning sensation;
Others: sometimes - hypostases of various localization, weakness in legs, a Quincke's disease, a syncope, a liquid delay, anorexia, pain in the field of parotid glands, a gynecomastia.

Interaction with other medicines:

Moksonidin can be appointed with thiazide diuretics, blockers of "slow" calcium channels and other antihypertensives.
Combined use of a moksonidin with these and other anti-hypertensive means results in the additive effect and strengthening of hypotensive effect.
At purpose of a moksonidin with a hydrochlorothiazide, Glibenclamidum (Glyburidum) or digoxin pharmacokinetic interaction is absent.
Tricyclic antidepressants can reduce efficiency of anti-hypertensive central acting agents therefore it is not recommended to appoint tricyclic antidepressants along with moksonidiny.
Moksonidin moderately increases reduced cognitive ability at the patients accepting lorazepam.
Purpose of a moksonidin together with benzodiazepines can be followed by strengthening of sedation of the last.
Moksonidin can exponentiate effect of ethanol at combined use.
At purpose of a moksonidin together with a moklobemidy pharmakodinamichesko interaction is absent.

Contraindications:

Hypersensitivity to a moksonidin and other components of drug, a sick sinus syndrome, a sinuatrial and atrioventricular block of II and III degrees, the expressed bradycardia (ChSS less than 50 beats/min.), chronic heart failure of III and IV functional classes on NYHA classifications, a Quincke's disease in the anamnesis, unstable stenocardia, the expressed liver failure (more than 9 points on a scale of Chayld-Pyyu), a chronic renal failure (KK less than 30 ml/min., creatinine more than 160 µmol/l), age up to 18 years (efficiency and safety are not established), the lactation period; intolerance of a galactose, deficit of lactase or sprue of glucose galactose.

With care: Parkinson's disease (severe form), epilepsy, glaucoma, a depression, the "alternating" lameness, a Raynaud's disease, an atrioventricular block of the I degree, a chronic renal failure (KK more than 30, but less than 60 ml/min.), the expressed cerebrovascular disturbances, after the postponed myocardial infarction, chronic heart failure of I and II functional classes, abnormal liver function, a hemodialysis, pregnancy.

Pregnancy and period of a lactation
 There are no clinical data on a negative impact on the course of pregnancy. However it is necessary to appoint Tenzotran pregnant only if the potential advantage for mother exceeds possible risk for a fruit.
Moksonidin gets into breast milk, women during treatment are recommended to stop breastfeeding or to cancel drug.

Overdose:

There are messages on several cases of overdose without a lethal outcome when doses to 19,6 mg for 1 reception were applied.
Symptoms: a headache, sedation, drowsiness, the expressed decrease in the ABP, dizziness, an adynamy, bradycardia, dryness of a mucous membrane of an oral cavity, vomiting and a stomach ache, increased fatigue. Are potentially possible also: short-term increase in the ABP, tachycardia, hyperglycemia.
Treatment: there is no specific antidote. Gastric lavage, reception of absorbent carbon and purgatives, symptomatic therapy.
In case of the expressed decrease in the ABP recovery of volume of the circulating blood due to administration of liquid and introduction of a dopamine is recommended. Bradycardia can be stopped by atropine.
Antagonists of alpha adrenoceptors can reduce or eliminate passing arterial hypertension at overdose moksonidiny.

Storage conditions:

List B. At a temperature not above 30 °C. To store in the place, unavailable to children!

Period of validity For a dosage of 0,2 mg - 2 years.
For dosages of 0,3 and 0,4 mg - 3 years.
Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 0,2 mg; 0,3 mg; 0,4 mg.
On 14 tablets in the blister from PVC/PVDH / Aluminum foil.
On 1, 2 or 3 blisters together with the application instruction in a cardboard pack.