Tenzotran (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis Group PTC ehf. (Iceland)

Manufactured By

Merckle, GmbH (Germany)

ATC Code

C02AC05 (Moxonidine)

Active Substance

Moxonidine (Rec.INN registered by WHO)

Dosage Forms

	Tenzotran	Film-coated tablets, 200 mcg: 14, 28, or 42 pcs.
		Film-coated tablets, 400 mcg: 14, 28, or 42 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light pink in color, round, biconvex.

Excipients : lactose monohydrate – 94.5 mg, povidone K25 – 2 mg, crospovidone – 3 mg, magnesium stearate – 0.3 mg.

Shell composition Opadry Y-1-7000 white (titanium dioxide – 1.093 mg, hypromellose – 2.186 mg, macrogol 400 – 0.219 mg) – 3.498 mg, dye iron oxide red 30 (E172) – 0.002 mg.

14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (3) – cardboard packs^×.

Film-coated tablets dark pink in color, round, biconvex.

Excipients : lactose monohydrate – 94.3 mg, povidone K25 – 2 mg, crospovidone – 3 mg, magnesium stearate – 0.3 mg.

Shell composition Opadry Y-1-7000 white (titanium dioxide – 1.083 mg, hypromellose – 2.165 mg, macrogol 400 – 0.217 mg) – 3.465 mg, dye iron oxide red 30 (E172) – 0.035 mg.

14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (3) – cardboard packs^×.

^× protective stickers may additionally be applied.

Clinical-Pharmacological Group

Selective imidazoline receptor agonist. Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive agents; centrally-acting antiadrenergic agents; imidazoline receptor agonists

Pharmacological Action

It is a selective agonist of imidazoline receptors responsible for the reflex regulation of the sympathetic nervous system (located in the ventrolateral part of the medulla oblongata). It has low affinity for central α₂-adrenergic receptors, interaction with which mediates sedative effects and dryness of the oral mucosa.

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

Effect on hemodynamics: the decrease in systolic and diastolic blood pressure with single and prolonged use of moxonidine is associated with a reduction in the pressor effect of the sympathetic nervous system on peripheral vessels, a decrease in total peripheral vascular resistance, while cardiac output and heart rate do not change significantly.

Pharmacokinetics

Absorption and Distribution

After oral administration, Moxonidine is rapidly and almost completely absorbed from the upper gastrointestinal tract. T_max is approximately 1 hour. The absolute bioavailability is approximately 88%. It undergoes minimal metabolism during the first pass through the liver. Food intake does not affect the pharmacokinetics of the drug.

Plasma protein binding is 7.2%. Moxonidine penetrates the blood-brain barrier.

Metabolism

The main metabolite is dehydrogenated Moxonidine, whose pharmacodynamic activity is about 1/10 that of moxonidine.

Elimination

The T_1/2 of moxonidine and metabolites is 2.5 and 5 hours, respectively. Within 24 hours, more than 90% of moxonidine is excreted by the kidneys: approximately 78% unchanged, 13% as dehydrogenated moxonidine. Other metabolites in urine account for approximately 8% of the dose. Less than 1% of the dose is excreted via the intestines.

Pharmacokinetics in Special Patient Groups

The elimination of moxonidine largely correlates with creatinine clearance. In patients with moderate renal impairment (creatinine clearance 30-60 ml/min), the C_ss in plasma and the terminal T_1/2 are approximately 2 and 1.5 times higher, respectively, than in patients with arterial hypertension and normal renal function (creatinine clearance greater than 90 ml/min). In patients with severe renal impairment (creatinine clearance less than 30 ml/min), the C_ss in plasma and the terminal T_1/2 are 3 times higher than in patients with normal renal function. The use of moxonidine in multiple doses does not lead to accumulation in the body of patients with moderate and severe renal impairment. In patients with end-stage renal disease (creatinine clearance less than 10 ml/min) on hemodialysis, the C_ss in plasma and the terminal T_1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function. In patients with impaired renal function, the dose should be adjusted individually. Moxonidine is minimally removed during hemodialysis.

Indications

• Arterial hypertension.

ICD codes

Dosage Regimen

The drug is administered orally, regardless of meals. The tablets should be taken with a sufficient amount of liquid.

In most cases, the initial dose of Tenzotran is 200 mcg/day in a single dose, preferably in the morning. If the therapeutic effect is insufficient, the dose can be increased after 3 weeks of therapy to 400 mcg/day in 2 doses (morning and evening) or in a single dose (in the morning). The maximum daily dose, which should be divided into 2 doses (morning and evening), is 600 mcg. The maximum single dose is 400 mcg.

In elderly patients with normal renal function, the dosing recommendations are the same as for adult patients.

In patients with renal impairment (creatinine clearance 30-60 ml/min) and patients on hemodialysis, a single dose should not exceed 200 mcg. The maximum daily dose is 400 mcg.

Adverse Reactions

The most frequent adverse reactions, especially at the beginning of therapy, were dry mouth, headache, asthenia, and drowsiness. Their intensity and frequency decrease with repeated administration.

The frequency of adverse reactions is defined as follows: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000 and <1/100), very rare (<1/1000, including isolated reports).

From the central nervous system common – increased fatigue, drowsiness, headache, dizziness; uncommon – insomnia, asthenia.

From the cardiovascular system common – vasodilation; uncommon – excessive decrease in blood pressure, orthostatic hypotension, paresthesia, Raynaud’s syndrome, peripheral microcirculation disorders.

From the gastrointestinal tract very common – dry oral mucosa; common – nausea, constipation and other gastrointestinal function disorders; very rare – hepatitis, cholestasis.

From the genitourinary system uncommon – urinary retention or incontinence, impotence, decreased libido.

Allergic reactions: uncommon – skin manifestations, angioedema.

From the organ of vision uncommon – dry eyes causing itching or burning sensation.

Other uncommon – edema of various localization, weakness in the legs, fainting, fluid retention, anorexia, pain in the parotid gland area, gynecomastia.

Contraindications

• Sick sinus syndrome;
• Sinoatrial block;
• Second and third degree AV block;
• Severe bradycardia (heart rate less than 50 beats/min);
• Chronic heart failure of functional class III and IV according to the NYHA classification;
• Unstable angina pectoris;
• History of angioedema;
• Severe hepatic impairment (more than 9 points on the Child-Pugh scale);
• Chronic renal failure (creatinine clearance <30 ml/min, serum creatinine content >160 µmol/l);
• Age under 18 years (efficacy and safety not established);
• Lactation period;
• Galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome;
• Hypersensitivity to moxonidine and other components of the drug.

With caution the drug should be used in Parkinson’s disease (severe form), epilepsy, glaucoma, depression, intermittent claudication, Raynaud’s disease, first degree AV block, chronic renal failure (creatinine clearance >30 ml/min but <60 ml/min), severe cerebrovascular disorders, after myocardial infarction, chronic heart failure of functional class I and II, impaired liver function, hemodialysis, pregnancy.

Use in Pregnancy and Lactation

There are no clinical data on negative effects on the course of pregnancy. However, Tenzotran should be prescribed to pregnant women only if the intended benefit to the mother outweighs the potential risk to the fetus.

Moxonidine is excreted in breast milk. It is recommended to discontinue breastfeeding or discontinue the drug during treatment.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment (more than 9 points on the Child-Pugh scale).

With caution the drug should be used in impaired liver function.

Use in Renal Impairment

Contraindicated in chronic renal failure (creatinine clearance <30 ml/min, serum creatinine content >160 µmol/l).

With caution the drug should be used in chronic renal failure (creatinine clearance >30 ml/min but <60 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age (efficacy and safety not established).

Geriatric Use

In elderly patients with normal renal function, the dosing recommendations are the same as for adult patients.

Special Precautions

If it is necessary to discontinue concurrently taken beta-blockers and Tenzotran, the beta-blockers should be discontinued first and only after a few days – Tenzotran.

Discontinuation of Tenzotran should be gradual.

It is not recommended to prescribe tricyclic antidepressants concurrently with Tenzotran.

During treatment, regular monitoring of blood pressure, heart rate, and ECG is necessary.

Moxonidine can be prescribed with thiazide diuretics, ACE inhibitors, and slow calcium channel blockers.

Patients with rare hereditary conditions of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome should not take Tenzotran.

Effect on the ability to drive vehicles and operate machinery

There are no data on the adverse effect of moxonidine on the ability to drive vehicles and operate machinery. There are reports of drowsiness and dizziness during treatment with moxonidine. This should be taken into account when prescribing the drug to patients engaged in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Overdose

There are reports of several cases of overdose without fatal outcome when doses up to 19.6 mg were taken at one time.

Symptoms: headache, sedative effect, drowsiness, marked decrease in blood pressure, dizziness, asthenia, bradycardia, dry mouth, vomiting and stomach pain, increased fatigue. A transient increase in blood pressure, tachycardia, hyperglycemia are potentially possible.

Treatment: there is no specific antidote. Gastric lavage, administration of activated charcoal and laxatives, symptomatic therapy. In case of marked decrease in blood pressure, fluid administration to restore circulating blood volume and dopamine administration are recommended. Bradycardia can be controlled with atropine. α-adrenergic receptor antagonists can reduce or eliminate transient arterial hypertension in case of moxonidine overdose.

Drug Interactions

Moxonidine can be prescribed with thiazide diuretics, slow calcium channel blockers, and other antihypertensive agents. Concomitant use of moxonidine with these and other antihypertensive agents leads to an additive effect and enhancement of the hypotensive effect.

There is no pharmacokinetic interaction when moxonidine is prescribed with hydrochlorothiazide, glibenclamide (glyburide), or digoxin.

Tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive agents, therefore it is not recommended to prescribe tricyclic antidepressants concurrently with moxonidine.

Moxonidine moderately enhances the reduced cognitive ability in patients taking lorazepam.

Prescribing moxonidine together with benzodiazepines may be accompanied by an enhancement of the sedative effect of the latter.

Moxonidine is able to potentiate the effect of ethanol when used concomitantly.

There is no pharmacodynamic interaction when moxonidine is prescribed together with moclobemide.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life for 200 mcg tablets is 2 years; for 400 mcg tablets is 3 years.

Dispensing Status

The drug is dispensed by prescription.

TENO-RU-00003-DOC-PHARM

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.