Moxarel, 0.2 mg 30 pcs.

Pharmacodynamics

Moxonidine is a hypotensive agent with a central mechanism of action. In brain stem structures (rostral layer of lateral ventricles) moxonidine selectively stimulates imidazolin-sensitive receptors involved in tonic and reflex regulation of sympathetic nervous system. Stimulation of imidazoline receptors reduces peripheral sympathetic activity and BP.

Moxonidine differs from other adrenergic hypotensive agents in its lower affinity for α1-adrenoreceptors, which explains the lower likelihood of sedation and dry mouth.

The administration of moxonidine results in decreased systemic vascular resistance and BP.

Moxonidine improves insulin sensitivity index in patients with obesity, insulin resistance and moderate arterial hypertension.

Pharmacokinetics

Intake. After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. Tmax is about 1 hour. Food intake has no effect on pharmacokinetics of the drug.

Distribution. Binding with blood plasma proteins is 7.2%.

Metabolism. The main metabolite is dehydrated moxonidine. The pharmacodynamic activity of dehydrated moxonidine is about 10% compared to moxonidine.

Excretion. The T1/2 of moxonidine and the metabolite is 2.5 and 5 h, respectively. Within 24 hours more than 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% as dehydromoxonidine, other metabolites in the urine do not exceed 8% of the dose taken). Less than 1% of the dose is excreted through the intestine.

Particular groups of patients

Patients of advanced age. Clinically insignificant changes in pharmacokinetic parameters of moxonidine have been observed in elderly patients, probably due to decreased intensity of its metabolism and/or slightly higher bioavailability.

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

Kidney function impairment. Excretion of moxonidine correlates significantly with creatinine clearance. In patients with moderate renal impairment (creatinine Cl 30-60 ml/min) plasma Css and final T1/2 are approximately 2 and 1.5 times higher than in patients with normal renal function (creatinine Cl over 90 ml/min). In patients with severe renal impairment (creatinine Cl less than 30 ml/min) plasma Css and final T1/2 are 3 times higher than in patients with normal renal function. Administration of multiple doses of moxonidine results in predictable cumulation in patients with moderate to severe renal impairment. In patients with terminal renal failure (creatinine Cl less than 10 ml/min) on hemodialysis, plasma Css and final T1/2 are 6 and 4 times higher, respectively, than in patients with normal renal function.

The maximum plasma concentration of moxonidine is 1.5-2 times higher in all groups. In patients with impaired renal function the dosage should be adjusted individually. Moxonidine is excreted to a small extent during hemodialysis.

Indications

Hypertension (high blood pressure)

Arterial hypertension.

Active ingredient

Moxonidine

Composition

Active ingredient:

moxonidine;

Excipients:

lactose monohydrate;

MCC;

colloidal silica;

povidone K30;

croscarmellose sodium;

magnesium stearate.

How to take, the dosage

Orally, regardless of meals.

In most cases, the starting dose of Moxarel® is 0.2 mg/day. The maximum single dose is 0.4 mg. The maximum daily dose to be divided into 2 doses is 0.6 mg. The initial dose for patients with moderate or severe renal insufficiency and for patients on hemodialysis is 0.2 mg/day. If necessary and if well tolerated, the daily dose may be increased to 0.4 mg.

Interaction

The co-administration of moxonidine with other hypotensive agents leads to additive effects.

Tricyclic antidepressants may decrease the effectiveness of centrally acting hypotensive agents, therefore it is not recommended to take them together with moxonidine.

Moxonidine may increase the effects of tricyclic antidepressants, tranquilizers, ethanol, sedatives and hypnotics.

Moxonidine may moderately improve impaired cognitive function in patients receiving lorazepam.

The administration of moxonidine together with benzodiazepine derivatives may be accompanied by an increased sedative effect of the latter.

The concomitant use of moxonidine with β-adrenoblockers leads to increased bradycardia and increased ino- and dromotropic effects.

There is no pharmacodynamic interaction when prescribing moxonidine together with moclobemide. Moxonidine is excreted by tubular secretion, therefore interactions with other drugs excreted by tubular secretion cannot be excluded.

.

Special Instructions

There is currently no evidence that stopping Moxarel® causes an increase in BP. However, it is not recommended to stop Moxarel® abruptly; instead, the dose of Moxarel® should be gradually reduced over 2 weeks.

If it is necessary to stop simultaneously taking β-adrenoblockers and Moxarel®, the β-adrenoblockers should be stopped first and only after several days with moxonidine.

Monitoring of BP and HR and ECG recordings at regular intervals is necessary during treatment. Moxarel® should be discontinued gradually.

At the time of treatment with Moxarel® , alcohol consumption should be avoided.

Impact on the ability to drive vehicles and operate machinery. The effect of Moxarel® preparation on the ability to drive vehicles or operate machinery has not been studied. However, taking into account the possible dizziness and somnolence, patients should be careful when carrying out potentially dangerous activities, requiring increased attention, such as driving vehicles or operating machinery.

.

Contraindications

• severe heart rhythm disorders;
• syndrome of weak sinus node;
• AV block of degree II and III;
• severe bradycardia (heart rate less than 50 bpm);

.

• acute and chronic heart failure (NYHA functional class III-IV);
• simultaneous use with tricyclic antidepressants;
• Age over 75 years old;
• Age under 18 years of age (effectiveness and safety of moxonidine have not been established);
• period of breastfeeding;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• high sensitivity to the active substance, other components of the drug.

With caution

• renal dysfunction (CK more than 30 ml/min);
• severe hepatic impairment (greater than 9 points on the Child-Pugh classification;
• Grade I AV blockade;
• severe coronary vascular disease;
• severe CHD or unstable angina pectoris (insufficient experience of use);
• chronic heart failure.

.

Side effects

CNS disorders: often – headache, dizziness (vertigo), somnolence; rarely – fainting.

CRC: infrequent – marked BP decrease, orthostatic hypotension, bradycardia.

Gastrointestinal disorders: very common – dry mouth; common – nausea, diarrhea, vomiting, dyspepsia.

Skin and subcutaneous tissue: often – skin rash, itching; infrequent – angioedema.

Psychiatric disorders: frequently – insomnia; infrequently – nervousness.

Hearing organ and labyrinth disorders: infrequent – tinnitus.

Skeletal, muscular and connective tissue: often – back pain; infrequent – pain in the neck.

General disorders and disorders at the site of administration: often – asthenia; infrequently – peripheral edema.

.

Overdose

Symptoms:

Headache, sedation, somnolence, marked decrease in BP, dizziness, increased fatigue, asthenia, bradycardia, dry oral mucosa, vomiting and epigastric pain, respiratory depression, impaired consciousness. Short-term elevation of BP, tachycardia, and hyperglycemia are also possible.

Treatment:

There is no specific antidote to the drug. In case of pronounced BP decrease, administration of fluids to restore the BCC and dopamine is recommended. Bradycardia may be controlled with atropine. α-adrenoreceptor antagonists may reduce or eliminate paradoxical hypertensive effects of moxonidine overdose. In severe cases of overdose, it is recommended that impaired consciousness and respiratory depression be carefully controlled. Moxonidine is slightly excreted by hemodialysis.

.

Similarities

Moxonidine, Moxonitex, Tensotran, Physiotensis, Moxarel