Tenzotran, 0.4 mg 28 pcs

Pharmacotherapeutic group: hypotensive drug of central action

ATX code: C02AC05

Pharmacological properties

Pharmacodynamics

Moxonidine is a hypotensive agent, the action of which is associated with the effect on the central mechanisms of regulation of sympathetic nervous system activity and blood pressure. In brain stem structures (rostral layer of lateral ventricles) moxonidine selectively stimulates imidazolin-sensitive receptors that participate 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 when using it. Administration of moxonidine is accompanied by a decrease in systemic vascular resistance and BP. The hypotensive effect of moxonidine has been confirmed in double-blind placebo-controlled randomized trials. The results of a clinical trial involving 42 patients with arterial hypertension and left ventricular hypertrophy (LVH) demonstrated that, with similar BP reductions, the combination of angiotensin II receptor antagonists with moxonidine reduces LVH to a greater extent than the combination of a thiazide diuretic and calcium channel blocker (15% versus 11%; p < 0.05).

Moxonidine improves insulin sensitivity index by 21% (compared with placebo) in patients with obesity, insulin resistance, and moderate arterial hypertension.

Pharmacokinetics

absorption

. After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%, indicating no significant “first” pass-through effect.

The 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 a dehydrated moxonidine derivative. The pharmacodynamic activity of the main metabolite is about 10% of the activity of moxonidine.

Elimation

The elimination half-life (T_1/2) of moxonidine and the dehydrated metabolite is 2.5 and 5 hours, respectively. More than 90% of moxonidine is excreted by the kidneys within 24 hours (about 78% – unchanged and 13% – as dehydrimoxonidine, the level of other metabolites in the urine does not exceed 8% of the accepted dose). 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 noted in elderly patients, probably due to a decrease in its metabolic rate and/or slightly higher bioavailability.

Pharmacokinetics in children

Moxonidine is not recommended for use in persons younger than 18 years of age, and therefore no pharmacokinetic studies have been performed in this group.

Pharmacokinetics in renal impairment

The excretion of moxonidine is highly correlated with creatinine clearance (CK). In patients with moderate renal impairment (CK between 30-60 mL/min), equilibrium plasma concentrations and final T_1/2 are approximately 2 and 1.5 times higher than in those with normal renal function (CK greater than 90 mL/min).

In patients with severe renal impairment (CK less than 30 mL/min), equilibrium plasma concentrations and final T_1/2 are 3 times higher than in patients with normal renal function.

The 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 T_1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function. In patients with moderate renal impairment, the maximum plasma concentration of moxonidine is 1.5-2 times higher. In patients with impaired renal function the dosage should be adjusted individually. Moxonidine is slightly excreted during hemodialysis.

Indications

Arterial hypertension.

Pharmacological effect

Pharmacotherapeutic group: centrally acting antihypertensive agent

ATX code: C02AC05

Pharmacological properties

Pharmacodynamics

Moxonidine is an antihypertensive drug, the action of which is associated with an effect on the central mechanisms regulating the activity of the sympathetic nervous system and blood pressure. In the stem structures of the brain (rostral layer of the lateral ventricles), moxonidine selectively stimulates imidazoline-sensitive receptors that take part in the tonic and reflex regulation of the sympathetic nervous system. Stimulation of imidazoline receptors reduces peripheral sympathetic activity and blood pressure (BP).

Moxonidine differs from other sympatholytic antihypertensive drugs in its lower affinity for α2-adrenergic receptors, which explains the lower likelihood of developing sedation and dry mouth when used. Taking moxonidine is accompanied by a decrease in systemic vascular resistance and blood pressure. The hypotensive effect of moxonidine has been confirmed in double-blind, placebo-controlled, randomized studies. The results of a clinical trial involving 42 patients with arterial hypertension and left ventricular hypertrophy (LVH) demonstrated that, with a similar reduction in blood pressure, the use of a combination of angiotensin II receptor antagonists with moxonidine allowed a greater reduction in LVH compared to the combination of a thiazide diuretic and a calcium channel blocker (15% versus 11%; p < 0.05).

Moxonidine improves the insulin sensitivity index by 21% (compared to placebo) in patients with obesity, insulin resistance and moderate arterial hypertension.

Pharmacokinetics

Suction

After oral administration, moxonidine is rapidly and almost completely absorbed from the upper gastrointestinal tract. Absolute bioavailability is approximately 88%, indicating no significant first-pass effect.

The time to reach maximum concentration is about 1 hour. Food intake does not affect the pharmacokinetics of the drug.

Distribution

The connection with blood plasma proteins is 7.2%.

Metabolism

The main metabolite is a dehydrogenated derivative of moxonidine. The pharmacodynamic activity of the main metabolite is about 10% of the activity of moxonidine.

Removal

The half-life (T1/2) of moxonidine and the dehydrogenated metabolite is 2.5 and 5 hours, respectively. Within 24 hours, over 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% as dehydriromoxonidine, the level of other metabolites in the urine does not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestines.

Pharmacokinetics in patients with arterial hypertension

Compared with healthy volunteers, patients with arterial hypertension show no changes in the pharmacokinetics of moxonidine.

Pharmacokinetics in old age

Clinically insignificant changes in the pharmacokinetic parameters of moxonidine were noted in elderly patients, probably due to a decrease in the intensity of its metabolism and/or slightly higher bioavailability.

Pharmacokinetics in children

Moxonidine is not recommended for use in persons under 18 years of age, and therefore no pharmacokinetic studies have been conducted in this group.

Pharmacokinetics in renal failure

Moxonidine excretion is significantly correlated with creatinine clearance (CC). In patients with moderate renal failure (creatinine clearance in the range of 30-60 ml/min), steady-state plasma concentrations and final T1/2 are approximately 2 and 1.5 times higher than in individuals with normal renal function (creatinine clearance more than 90 ml/min).

In patients with severe renal failure (creatinine clearance less than 30 ml/min), steady-state plasma concentrations and final T1/2 are 3 times higher than in patients with normal renal function.

The administration of multiple doses of moxonidine leads to predictable accumulation in the body of patients with moderate and severe renal failure.

In patients with end-stage renal failure (creatinine clearance less than 10 ml/min) on hemodialysis, steady-state plasma concentrations and final T1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function. In patients with moderate renal failure, the maximum concentration of moxonidine in the blood plasma is 1.5–2 times higher. In patients with impaired renal function, the dosage should be adjusted individually. Moxonidine is excreted to a small extent during hemodialysis.

Special instructions

During treatment, regular monitoring of blood pressure is necessary.

During post-marketing surveillance, cases of atrioventricular block of varying severity have been recorded in patients taking moxonidine. An association between moxonidine and atrioventricular conduction slowing cannot be completely excluded. Therefore, caution is recommended when treating patients with a possible predisposition to developing atrioventricular block.

If it is necessary to cancel beta-blockers taken simultaneously with the drug Tenzotran, first cancel the beta blockers and only after a few days the drug Tenzotran.

There is currently no evidence that stopping Tenzotran leads to an increase in blood pressure.

However, it is not recommended to stop taking Tenzotran abruptly; in these cases, the dose of the drug should be gradually reduced over two weeks.

Elderly patients may have an increased risk of developing cardiovascular complications due to the use of antihypertensive drugs, therefore therapy with Tenzotran should be started with a minimum dose.

Impact on the ability to drive vehicles and machinery

Studies of the effect of the drug on the ability to drive a car and other mechanisms have not been conducted.

There are reports of drowsiness and dizziness during treatment with moxonidine. This should be taken into account when performing the above steps.

Active ingredient

Moxonidine

Composition

1 tablet (0.4 mg) contains: active ingredient moxonidine 0.40 mg; excipients: lactose monohydrate 94.30 mg, povidone K25 2.00 mg, crospovidone 3.00 mg, magnesium stearate 0.30 mg; shell – Opadry Y-1-7000 white (titanium dioxide 1.083 mg; hypromellose 2.165 mg; macrogol 400 0.217 mg) 3.465 mg; iron dye red oxide 30 (E172) 0.035 mg.

Pregnancy

Pregnancy

There are no clinical data on the use of the drug Tenzotran in pregnant women.

In animal studies, the embryotoxic effect of the drug was established.

Tenzotran should be prescribed to pregnant women only after a careful assessment of the risk-benefit ratio, when the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

Moxonidine passes into breast milk and should therefore not be given during breastfeeding. If it is necessary to use the drug Tenzotran during lactation, breastfeeding should be stopped.

Contraindications

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

– history of angioedema;

– sick sinus syndrome or sinoatrial block;

– severe liver failure;

– severe renal failure;

– severe bradycardia (resting heart rate (HR) less than 50 beats/min);

– atrioventricular block II or III degree;

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

– breastfeeding period;

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

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

With caution

First degree atrioventricular block (risk of developing bradycardia); diseases of the coronary arteries (including coronary heart disease, unstable angina, early post-infarction period); peripheral circulatory diseases (including intermittent claudication, Raynaud’s syndrome); epilepsy; Parkinson’s disease; depression; glaucoma; moderate renal failure (creatinine clearance 30–60 ml/min, serum creatinine 105–160 µmol/l); liver failure; pregnancy.

Side Effects

The most common adverse reactions (ARs) in patients taking moxonidine are dry mouth, dizziness, asthenia and drowsiness. These symptoms usually decrease after the first weeks of therapy.

The following side effects were observed in patients participating in placebo-controlled clinical trials of moxonidine.

The incidence of HP development is given in accordance with the classification of the World Health Organization: very common ≥ 10%; often ≥ 1% and < 10%; uncommon ≥ 0.1% and < 1%; rarely ≥ 0.01% and < 0.1%; very rare <0.01%; frequency unknown (it is impossible to estimate the frequency based on the available data).

Nervous system disorders

Common: headache*, dizziness (vertigo), drowsiness, insomnia. Uncommon: fainting*, increased excitability.

Cardiovascular disorders

Uncommon: marked decrease in blood pressure, orthostatic hypotension*, bradycardia.

Gastrointestinal disorders

Very common: dry mouth. Common: diarrhea, nausea, vomiting, dyspepsia.

Skin and subcutaneous tissue disorders

Common: skin rash, itching. Uncommon: angioedema.

Hearing and labyrinth disorders

Uncommon: ringing in the ears.

Musculoskeletal and connective tissue disorders

Common: back pain. Uncommon: neck pain.

General disorders and changes at the injection site

Often: asthenia. Uncommon: peripheral edema.

(* – frequency comparable to placebo).

Interaction

The combined use of moxonidine with other antihypertensive drugs is accompanied by an additive effect.
Tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive drugs, and therefore their use together with moxonidine is not recommended.
Moxonidine may enhance the sedative effect of tricyclic antidepressants (co-administration should be avoided), tranquilizers, ethanol, sedatives and hypnotics.
Moxonidine may moderately improve impaired cognitive function in patients receiving lorazepam.
The drug may enhance the sedative effect of benzodiazepine derivatives when administered simultaneously.
Moxonidine is excreted by the kidneys by tubular secretion. Therefore, its interaction with other drugs released by tubular secretion is not excluded.

Overdose

There have been reports of several cases of non-fatal overdose when doses of moxonidine up to 19.6 mg were used simultaneously.

Symptoms: headache, sedation, drowsiness, marked decrease in blood pressure, dizziness, asthenia, bradycardia, dry mouth, vomiting, fatigue, epigastric pain, respiratory depression and impaired consciousness.

In addition, short-term increases in blood pressure, tachycardia and hyperglycemia are also possible, as has been shown in several high-dose animal studies.

Treatment: There is no specific antidote. In the case of a pronounced decrease in blood pressure, it may be necessary to restore the volume of circulating blood by introducing fluid and dopamine (injection).

Bradycardia can be stopped with atropine (injection).

In severe cases of overdose, it is recommended to carefully monitor disturbances of consciousness and avoid respiratory depression.

Alpha-adrenergic receptor blockers (antagonists) may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose.

Storage conditions

Store at a temperature not exceeding 30°C, in the original packaging.
Keep out of the reach of children!

Shelf life

3 years

Manufacturer

Merkle GmbH, Germany