Physiotens® 28's 0.4 mg coated tablets

The instruction
for medical use


of Physiotens®® medicine

the Trade name
of Physiotens®®

the International unlicensed


name Moksonidin Lekarstvennaya
the Tablet form, coated, 0.2 mg, 0.4 mg

Structure
One tablet contains
active agent – moksonidin 0.2 mg, or 0.4 mg,
excipients: lactoses monohydrate, K25 povidone, krospovidon, magnesium stearate,
structure of a cover: a gipromelloza of 6 mPas, ethyl cellulose of 30% water dispersion (in terms of dry matter), a macrogoal 6000, talc, iron (III) oxide red (E172), the titan dioxide (E171).

The description
of the Tablet of round shape, with a biconvex surface, film coated light pink color, with an engraving 0.2 on one party (for a dosage of 0.2 mg).
Tablets of round shape, with a biconvex surface, film coated pale red color, with an engraving 0.4 on one party (dosage of 0.4 mg).

Pharmacotherapeutic group
Hypotensive drugs. Adrenostimulyatora central. 2-adrenomimetika alpha central, derivative imidazoline. Moksonidin.
ATX C02AC05 code

Pharmacological

Pharmacokinetics Absorption properties. At intake moksonidin quickly and almost completely (Tmaks about 1 hour) it is soaked up from upper parts of digestive tract. Absolute bioavailability – 88% that indicates lack of primary hepatic metabolism. Meal does not influence pharmacokinetics of a moksonidin. Communication with proteins of blood plasma makes 7.2%.
Biotransformation. In blood only one metabolite of a moksonidin – degidromoksonidin comes to light. Its pharmacological activity is 10 times less, than a moksonidina.
Removal. Within 24 hours more than 78% of a moksonidin are removed by kidneys, and 13% in the form of a degidromoksonidin. Other, less significant metabolites, are found in urine in number of about 8% of the entered dose. Less than 1% of a dose are removed with a stake in the form of metabolites: 4.5 degidromoksonidin and guanidine derivatives. Elimination half-life of a moksonidin and its main metabolite makes 2.5 and 5 hours, respectively.
Pharmacokinetics at patients with arterial hypertension
At patients with arterial hypertension changes of pharmacokinetics are not revealed.
Pharmacokinetics at elderly
At elderly patients the differences in pharmacokinetics of a moksonidin in comparison with persons of younger age generally caused by the lowered metabolic activity and/or increase in bioavailability at elderly are observed. However these distinctions of pharmacokinetics have no clinical importance.
Pharmacokinetics at children and teenagers up to 18 years
of the Research of pharmacokinetics at children and teenagers were not carried out.
The pharmacokinetics in a renal failure
Removal of a moksonidin substantially correlates with the clearance of creatinine (CC). Patients with a renal failure of moderate severity have (glomerular filtration rate (GFR) of 30-60 ml/min.) equilibrium concentration in blood plasma and final elimination half-life, respectively, in 2 and 1.5 times is higher, than at patients with hypertensia with normal function of kidneys (SKF & gt, 90 ml/min.). Moreover, the maximum concentration of a moksonidin in blood plasma are 1.5-2 times higher at patients with a renal failure of moderate severity. At patients with a heavy renal failure (SKF & lt, 30 ml/min.) equilibrium concentration in blood plasma and final elimination half-life is about 3 times higher, than at patients with arterial hypertension with normal function of kidneys. Reception of repeated doses does not lead to cumulation of a moksonidin in an organism of patients of this group. At patients in an end-stage of a renal failure (SKF & lt, 10 ml/min.) on dialysis, the area under curve (AUC) and terminal elimination half-life in 6 and 4 times, respectively, is higher, than at patients with normal function of kidneys. Therefore, the dose of a moksonidin at patients with a renal failure needs to be titrated according to individual requirements. Moksonidin in insignificant degree is brought when carrying out a hemodialysis.
The pharmacodynamics
of Physiotens®® is antihypertensive drug. Available experimental data show that localization of action of a moksonidin is the central nervous system (CNS). It was shown what moksonidin selectively stimulates imidazolinovy receptors in a brain trunk. Imidazoline – sensitive receptors are concentrated in rostral department of a ventrolateralny part of a medulla – the site which is considered the center of regulation of peripheral sympathetic nervous system. At stimulation of imidazolinovy receptors the activity of sympathetic nervous system decreases and blood pressure goes down.
Moksonidin differs from other sympatholytic antihypertensive drugs in low affinity to α2-адренорецепторам in comparison with imidazolinovy receptors. It the low probability of sedation and dryness in a mouth at reception of a moksonidin can speak.
Moksonidin reduces arterial blood pressure as a result of reduction of system vascular resistance that is proved by clinical trials. The antihypertensive effect of a moksonidin was shown in double blind people, placebo - controlled, randomized studies. The published data show that at patients with arterial hypertension and the hypertrophy of a left ventricle (HLV) for a similar lowering of arterial pressure the use of the antagonist of angiotensin II together with moksonidiny allowed to reach improvement of regress of GLZh in comparison with use of a combination of thiazide diuretic and a blocker of calcium channels.
Moksonidin improves sensitivity of fabrics to insulin for 21% in comparison with placebo at patients with obesity and insulin resistance with moderate arterial hypertension.

Indications
- arterial hypertension


accept the Route of administration and doses of the Tablet inside, washing down with enough water, irrespective of meal.
In most cases the initial dose of Physiotens®a® makes 0.2 mg a day, the maximum daily dose which should be divided into 2 receptions makes 0.6 mg. The maximum single dose makes 0.4 mg. The dose and a course of treatment are selected individually, depending on the clinical answer.
At patients with a moderate or heavy renal failure the initial dose of a moksonidin makes 0.2 mg a day. If necessary and good tolerance at patients with a moderate renal failure the dose of a moksonidin can be increased up to 0.4 mg a day, at patients with a heavy renal failure – up to 0.3 mg a day. At the patients who are on a hemodialysis, the initial dose makes 0.2 mg a day. If necessary and good tolerance the dose can be increased up to 0.4 mg a day.
Use of a moksonidin for children and teenagers is younger than 18 years it is not recommended due to the lack of data on safety and efficiency.

Side effects
Very often
- dryness in a mouth
it is frequent
- dizziness, a headache, drowsiness, insomnia, an asthenia
- diarrhea, nausea/vomiting, dyspepsia
- rash, an itching
- a dorsodynia
Infrequently
- bradycardia, hypotension, including orthostatic hypotension
- a Quincke's disease, peripheral hypostases
- pain in a neck
- tinnit
- nervousness,

the Contraindication syncope
- hypersensitivity to drug components
- a sick sinus syndrome
- bradycardia (heart rate at rest less than 50 in a minute)
- atrioventricular block of II or III degree
- heart failure
- children's and teenage age up to 18 years
- pregnancy and the period of a lactation

Medicinal interactions
At combined use of Physiotens®a® happens to other antihypertensives mutual strengthening of action.
As tricyclic antidepressants can reduce efficiency of antihypertensive drugs of the central action, the concomitant use of Physiotens®a® with drugs of this group is not recommended.
Физиотенз® can strengthen sedative effect of tricyclic antidepressants (it is necessary to avoid their joint appointment), tranquilizers, alcohol, sedative and sleeping medicines.

Физиотенз® moderately improves reduced cognitive ability at the patients accepting lorazepam. Физиотенз® enhances sedation of benzodiazepines at joint reception.
As Physiotens®® is removed by means of tubular excretion, interaction with the drugs having the same way of removal is not excluded.

Special
instructions C care are appointed by Physiotens®® at patients with possible predisposition to development of atrioventricular block and the patient with atrioventricular block of the 1st degree in order to avoid bradycardia.
Patients with a serious ischemic disease or unstable stenocardia need careful observation as experience of use of Physiotens®a® for this group of patients is limited.
It is necessary to observe extra care at use of a moksonidin for patients with heavy coronary heart disease or unstable stenocardia as experience of use of drug for this category of patients is limited.
It is recommended to observe precautionary measures when assigning Physiotens®a® the patient with a renal failure as moksonidin it is removed by kidneys. These patients need careful selection of a dose, especially at the beginning of therapy. The initial dose of a moksonidin has to make 0.2 mg a day and, on condition of clinical indications and good tolerance, can be increased at most up to 0.4 mg a day at patients with a moderate renal failure (SKF & gt, 30 ml/min., but & lt, 60 ml/min.) and at most up to 0.3 mg a day at patients with a heavy renal failure (SKF & lt, 30 ml/min.). If Physiotens®® accept in a combination with drug from group of beta blockers, then in need of cancellation of both drugs at first cancel beta blocker and only in several days - Physiotens®®. The withdrawal at the termination of reception of Physiotens® is not observed. However it is not necessary to interrupt sharply treatment, it is recommended gradually, to reduce a dose within two weeks. Patients with congenital intolerance of a galactose, deficiency of Lappa lactase or disturbance of absorption of glucose galactose should not accept Physiotens®®.
The feature of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
during treatment needs to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Overdose
Symptoms: a headache, sedation, drowsiness, hypotension, dizziness, an asthenia, bradycardia, dryness in a mouth, vomiting, fatigue and a stomach ache. In cases of serious overdose disorders of consciousness and respiratory depression are possible. Also short-term increase in the ABP, tachycardia, a hyperglycemia are potentially possible.
Treatment: specific antidotes do not exist. In hypotension the introduction of a dopamine and measure for circulation maintenance, including infusion of solutions can be required. It is possible to apply atropine to elimination of bradycardia. Antagonists of alpha adrenoceptors can reduce or eliminate paradoxical arterial hypertension.

The form of release and packing
On 14 or 28 tablets place in blister strip packaging from a film of polyvinylchloride and aluminum foil.
1 blister strip packaging together with the instruction for medical use in the state and Russian languages is put in a pack cardboard.


To Store storage conditions at a temperature not above 25 °C (for 0.2 mg).
To store at a temperature not above 30 °C (for 0.4 mg).
To store out of children's reach!


2 years
3 years (for a dosage of 0.4 mg)
not to apply a period of storage (to a dosage of 0.2 mg) after the expiration date specified on packing.

Prescription status
According to

Naimenovaniye's prescription and the manufacturing organization country
Abbott Helscare of SAS, France
Ruth de Belvill, Mayar 01400,

Shatiyon-sur-Shalaron Naimenovaniye and the country of the owner of the registration certificate
of Abbott Laboratories GmbH, Hanover, Germany

Naimenovaniye and the country of the organization packer
Abbott Helscare of SAS, France
Ruth de Belvill, Mayar 01400,

Shatiyon-sur-Shalaron Adres of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products
of Abbott Kazakhstan LLP
050059, Almaty, Dostyk Ave. 117/6, Business center Khan Tengri-2.
ph.: +7 727 244 75 44, fax: +7 727 244 76 44.
E-mail:

To Develop pv.kazakhstan@abbott.com