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

Active ingredient

Composition

How to take, the dosage

Ingestion, regardless of meals.

In most cases, the starting dose of the drug 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 (moxonidine in 0.3 mg tablets from other manufacturers should be used for this dosing regimen). Individual adjustment of the daily dose is necessary depending on the patient’s tolerance to the therapy. No dose adjustment is required for patients with hepatic insufficiency.

The starting dose for patients on hemodialysis is 0.2 mg per day. If necessary and if well tolerated, the daily dose can be increased to a maximum of 0.4 mg per day.

Patients with renal insufficiency are recommended to choose the dose cautiously, especially at the beginning of treatment. The initial dose should be 0.2 mg per day. If necessary and if well tolerated, daily dose of the drug can be increased to maximum 0.4 mg for patients with moderate renal insufficiency (CKD more than 30 ml/min but less than 60 ml/min) and 0.3 mg for patients with severe renal insufficiency (CKD less than 30 ml/min)

Patients with mild renal insufficiency should use the daily dose.

Interaction

Special Instructions

Regular BP monitoring is necessary during treatment.

In post-marketing surveillance, cases of atrioventricular block of varying severity have been reported in patients taking moxonidine. The association between moxonidine administration and delayed atrioventricular conduction cannot be completely excluded. Thus, caution is advised when treating patients with a probable predisposition to develop atrioventricular block.

If it is necessary to cancel beta-adrenoblockers taken simultaneously with Tenzotran, the beta-adrenoblockers should be cancelled first and only after several days with Tenzotran.

There is currently no evidence that discontinuing Tensotran causes an increase in BP.

Tenzotran should not be stopped abruptly, however, and the dose should be reduced gradually over a period of two weeks.

In elderly patients there may be an increased risk of cardiovascular complications from the use of hypotensive drugs, so therapy with Tenzotran should be started with the lowest dose.

Influence on the ability to drive vehicles, machinery

There have been no studies of the effect of the drug on the ability to drive vehicles and other mechanisms.

There have been reports of drowsiness and dizziness during treatment with moxonidine. This should be considered when performing the above actions.

Synopsis

Contraindications

– hypersensitivity to the active ingredient and other ingredients of the drug;

– history of angioedema;

– sinus node weakness syndrome or sinoatrial block;

– severe hepatic insufficiency;

– severe renal insufficiency;

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

– atrioventricular block of II or III degree;

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

– breastfeeding period;

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

– age under 18 years (due to lack of efficacy and safety data).

With caution

Atrioventricular block of degree I (risk of bradycardia); coronary artery disease (including coronary artery disease).coronary artery disease (including coronary artery disease, unstable angina, and early postinfarction period); peripheral circulatory disease (including intermittent claudication).including intermittent claudication, Raynaud’s syndrome); epilepsy; Parkinson’s disease; depression; glaucoma; moderate renal insufficiency (CK 30-60 ml/min, serum creatinine 105-160 μmol/l); hepatic insufficiency; pregnancy.

Side effects

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

The following side effects have been reported in patients who have participated in placebo-controlled clinical trials of moxonidine.

The incidence of HF is given according to the World Health Organization classification: very common ≥10%; common ≥1% and < 10%; infrequent ≥0.1% and < 1%; rare ≥0.01% and < 0.1%; very rare < 0.01%; frequency unknown (no data available to estimate frequency).

Nervous system disorders

Frequently:headache*, dizziness (vertigo), somnolence, insomnia. Infrequent:fainting*, increased excitability.

Disorders of the cardiovascular system

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

Disorders on the side .gastrointestinal tract

very often: dry mouth. often:diarrhea, nausea, vomiting, dyspepsia.

Skin and subcutaneous tissue disorders

Frequently:skin rash, skin itching. Infrequent: angioedema.

Hearing organ and labyrinth disorders

Infrequent: ringing in the ears.

Musculoskeletal and connective tissue disorders

Frequently:back pain. Infrequent:neck pain.

General disorders and changes at the site of administration

Frequently:asthenia. Infrequent:peripheral edema.

(* – frequency is comparable to placebo).

Overdose

There have been reports of several non-fatal overdoses when doses of up to 19.6 mg of moxonidine were used at one time.

Symptoms: headache, sedation, somnolence, marked BP decrease, dizziness, asthenia, bradycardia, dry mouth, vomiting, 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 cases 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.

The alpha-adrenoreceptor blockers (antagonists) may reduce or eliminate the paradoxical hypertensive effects of moxonidine overdose.

Pregnancy use

Pregnancy

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

In animal studies an embryotoxic effect of the drug was found.

The drug Tenzotran should be administered to pregnant women only after careful assessment of the risk-benefit ratio when the benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding

Moxonidine penetrates into breast milk and therefore should not be administered during breastfeeding. If it is necessary to use the drug Tensotran during lactation, breastfeeding should be stopped.

Similarities