Vazotaim (Tablets) Instructions for Use

Marketing Authorization Holder

Xantis Pharma, Limited (Cyprus)

Manufactured By

Alsi Pharma, JSC (Russia)

ATC Code

C02AC05 (Moxonidine)

Active Substance

Moxonidine (Rec.INN registered by WHO)

Dosage Forms

	Vazotaim	Film-coated tablets 0.2 mg: 30, 60, or 90 pcs.
		Film-coated tablets 0.4 mg: 30, 60, or 90 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from light pink to pink in color, round, biconvex; the cross-section shows an inner layer of white or almost white color.

Excipients: lactose monohydrate, crospovidone, magnesium stearate, ready-made mixture for pink film coating (polyvinyl alcohol, titanium dioxide, macrogol (polyethylene glycol), talc, dye carmine red (E120)).

10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.

Film-coated tablets from light pink to pink in color, round, biconvex; the cross-section shows an inner layer of white or almost white color.

Excipients: lactose monohydrate, crospovidone, magnesium stearate, ready-made mixture for pink film coating (polyvinyl alcohol, titanium dioxide, macrogol (polyethylene glycol), talc, dye carmine red (E120)).

10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.

Clinical-Pharmacological Group

Selective imidazoline receptor agonist. Antihypertensive drug

Pharmacotherapeutic Group

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

Pharmacological Action

Antihypertensive agent. The mechanism of action of moxonidine is primarily associated with its effect on the central regulatory components of blood pressure. Moxonidine is predominantly an agonist of imidazoline receptors.

By stimulating these receptors on neurons of the solitary tract, Moxonidine, via a system of inhibitory interneurons, contributes to the suppression of the vasomotor center activity and thus to a reduction in descending sympathetic influences on the cardiovascular system. Blood pressure (systolic and diastolic) decreases gradually. Moxonidine differs from other sympatholytic antihypertensive drugs by its lower affinity for α₂-adrenoceptors, which explains the lower likelihood of developing sedative effects and dry mouth.

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

Pharmacokinetics

After oral administration, Moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. The absolute bioavailability is approximately 88%. The time to reach C_max is about 1 hour. Food intake does not affect the pharmacokinetics of moxonidine. Plasma protein binding is 7.2%. The main metabolite of moxonidine is dehydrogenated Moxonidine and guanidine derivatives. The pharmacodynamic activity of dehydrogenated moxonidine is about 10% compared to moxonidine.

The T_1/2 of moxonidine and the metabolite is 2.5 and 5 hours, respectively. Within 24 hours, more than 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% as dehydrogenated moxonidine, other metabolites in urine do not exceed 8% of the administered dose). Less than 1% of the dose is excreted via the intestines.

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

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

The excretion of moxonidine significantly 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 individuals with 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. Administration of moxonidine in multiple doses leads to predictable accumulation in the body in patients with moderate and severe renal impairment. In patients with end-stage renal disease (creatinine clearance less than 10 ml/min) undergoing 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 all groups, the C_max of moxonidine in plasma is 1.5-2 times higher. In patients with impaired renal function, the dose should be adjusted individually. Moxonidine is insignificantly removed during hemodialysis.

Indications

Arterial hypertension.

ICD codes

Dosage Regimen

Administered orally. The initial dose is on average 200 mcg orally once a day. Maximum single dose – 400 mcg. Individual adjustment of the daily dose is necessary depending on therapy tolerance. Maximum daily dose – 600 mcg in 2 divided doses.

For patients with moderate and severe renal impairment, as well as those undergoing hemodialysis, the initial dose is 200 mcg/day. If necessary and well tolerated, the daily dose can be increased to a maximum of 400 mcg.

Adverse Reactions

From the central nervous system: frequently – headache, dizziness (vertigo), drowsiness; infrequently – fainting.

From the cardiovascular system infrequently – pronounced decrease in blood pressure, orthostatic hypotension, bradycardia.

From the digestive system very frequently – dry mouth; frequently – diarrhea, nausea, vomiting, dyspepsia.

From the skin and subcutaneous tissues: frequently – skin rash, itching; infrequently – angioedema.

From the psyche: frequently – insomnia; infrequently – nervousness.

From the hearing organ and labyrinthine disorders: infrequently – ringing in the ears.

From the musculoskeletal system: frequently – back pain; infrequently – neck pain.

General disorders: frequently – asthenia; infrequently – peripheral edema.

Contraindications

Severe bradycardia (less than 50 beats/min), sick sinus syndrome, second and third-degree AV block, acute and chronic heart failure, lactation period (breastfeeding), children and adolescents under 18 years of age, hypersensitivity to moxonidine.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of moxonidine during pregnancy have not been conducted, therefore it should not be used in this category of patients.

Should not be used during lactation, as Moxonidine is excreted in breast milk. If it is necessary to use moxonidine during lactation, breastfeeding should be discontinued.

During experimental studies in animals, an embryotoxic effect of the drug was established.

Use in Hepatic Impairment

Contraindicated in severe liver function impairment.

Use in Renal Impairment

Contraindicated in severe renal function impairment.

Moxonidine should be used with caution in patients with impaired renal function; in such cases, dosage regimen adjustment is required based on creatinine clearance values.

During treatment of patients with impaired renal function, careful monitoring of their condition is necessary.

Pediatric Use

Due to the lack of clinical experience, Moxonidine should not be used in children and adolescents under 16 years of age.

Special Precautions

Special caution is necessary when using moxonidine in patients with first-degree AV block (risk of bradycardia); severe coronary artery disease and unstable angina (insufficient experience of use); renal failure.

If it is necessary to discontinue concurrently taken beta-blockers and moxonidine, the beta-blockers should be discontinued first and only after several days – Moxonidine.

Currently, there is no confirmation that discontinuation of moxonidine leads to an increase in blood pressure. However, abrupt discontinuation of moxonidine is not recommended; the dose should be reduced gradually over 2 weeks.

Effect on the ability to drive vehicles and operate machinery

During treatment, patients should exercise caution when engaging in potentially hazardous activities that require concentration and high speed of psychomotor reactions.

Drug Interactions

Concomitant use of moxonidine with other antihypertensive agents leads to an additive effect.

Tricyclic antidepressants may reduce the effectiveness of centrally acting antihypertensive agents, therefore their concurrent use with moxonidine is not recommended.

Moxonidine may enhance the effect of tricyclic antidepressants, tranquilizers, ethanol, sedatives, and hypnotics.

Moxonidine is capable of moderately improving impaired cognitive functions in patients receiving lorazepam.

Moxonidine may enhance the sedative effect of benzodiazepine derivatives when co-administered.

Moxonidine is excreted by tubular secretion. Therefore, interaction with other drugs excreted by tubular secretion cannot be excluded.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.