Description
Release form
Tablets, film-coated, dark pink, round, biconvex at a break – white or almost white.
Pharmacological action
Pharmacodynamics
Moxonidine is a hypotensive drug with a central mechanism of action. In the brain stem structures (the rostral layer of the lateral ventricles), moxonidine selectively stimulates imidazoline-sensitive receptors involved in the tonic and reflex regulation of the sympathetic nervous system. Stimulation of imidazoline receptors reduces peripheral sympathetic activity and blood pressure. Moxonidine differs from other central antihypertensive agents in lower affinity for 2 adrenoreceptors, which explains the lower likelihood of developing a sedative effect and dry mouth. The use of moxonidine leads to a decrease in systemic vascular resistance and blood pressure. Moxonidine improves the insulin sensitivity index (compared with placebo) by 21% in patients with obesity, insulin resistance and moderate arterial hypertension.
Pharmacokinetics
Suctionianie. After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. Tmax – about 1 hour. Eating does not affect the pharmacokinetics of the drug.
distribution. Communication with plasma proteins is 7.2%.
Metabolism. The main metabolite is dehydrogenated moxonidine. The pharmacodynamic activity of dehydrogenated moxonidine is about 10% of that of moxonidine.
Withdrawal. T1 / 2 of moxonidine and metabolite are 2.5 and 5 hours, respectively. Within 24 hours, over 90% of moxonidine is excreted by the kidneys (about 78% unchanged and 13% in the form of dehydromoxonidine, other metabolites in the urine do not exceed 8% of the dose). Less than 1% of the dose is excreted through the intestines.
Special patient groups
Arterial hypertension. Compared with healthy volunteers, patients with arterial hypertension did not show a change in the pharmacokinetics of moxonidine.
Old age. Clinically insignificant changes in the pharmacokinetic parameters of moxonidine in elderly patients were noted, probably due to a decrease in the intensity of its metabolism and / or a slightly higher bioavailability.
Children. Moxonidine is not recommended for use in patients under 18 years of age, and therefore pharmacokinetic studies have not been conducted in this group.
Renal failure. Excretion of moxonidine is largely correlated with creatinine clearance. In patients with moderate renal failure (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 greater than 90 ml / min). In patients with severe renal failure (creatinine Cl less than 30 ml / min), plasma Css 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 cumulation in the body of patients with moderate and severe renal failure. In patients with terminal renal failure (Cl creatinine less than 10 ml / min) undergoing hemodialysis, plasma Css and final T1 / 2 are respectively 6 and 4 times higher than in patients with normal renal function. In all groups, Cmaxmoxonidine in blood plasma is 1.5 2 times higher. In patients with impaired renal function, the dosage should be selected individually. Moxonidine is slightly excreted during hemodialysis.
Indications
Arterial hypertension.
Contraindications
hypersensitivity to the active substance and other components of the drug
sine sinus syndrome
severe bradycardia (resting heart rate less than 50 beats / min)
atrioventricular blockade II and III degree srdlkrp acute and severe heart failure III IV functional class according to NYHA classification)
simultaneous use with tricyclic antidepressants (see Interaction )
severe renal failure (creatinine Cl less than 30 ml / Ying)
hemodialysis
hereditary lactose intolerance, lactase deficiency or malabsorption of glucose-galactose
lactation period
patients older than 75 years old
patients under 18 years of age (due to lack of safety and efficacy data).
Precautions: I degree atrioventricular block (risk of developing bradycardia) severe coronary artery disease severe coronary heart disease or unstable angina (insufficient experience) chronic heart failure severe liver failure impaired renal function (creatinine Cl more than 30 ml / min).
Use during pregnancy and lactation
Clinical data on the use of moxonidine in pregnant women are not available. In animal studies, the embryotoxic effect of the drug was established. Moxonidine-SZ 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.
Moxonidine passes into breast milk and therefore should not be prescribed during breast-feeding. If it is necessary to use the drug Moxonidine-SZ during lactation, breastfeeding must be stopped.
Composition
1 tab.
moxonidine 0.4 mg
Excipients: croscarmellose sodium (primellose) – 3 mg, lactose monohydrate (lactopress) (milk sugar) – 95.1 mg, colloidal silicon dioxide (aerosil) – 0.5 mg, sodium stearyl fumarate – 1 mg.
Shell composition: Opadry II (polyvinyl alcohol, partially hydrolyzed – 1.32 mg, titanium dioxide (E171) – 0.5751 mg, talc – 0.6 mg, macrogol (polyethylene glycol 3350) – 0.3705 mg, soy lecithin (E322) – 0.105 mg, aluminum varnish based on indigo carmine – 0.0018 mg, aluminum varnish based on the dye azorubine – 0.0153 mg, aluminum varnish based on the dye crimson [Ponceau 4R] – 0.0123 mg).
Dosage and Administration
Inside, regardless of food intake. In most cases, the initial dose of Moxonidine-SZ is 0.2 mg / day. The maximum single dose is 0.4 mg. The maximum daily dose, which should be divided into 2 doses, is 0.6 mg.
Individual adjustment of the daily dose is required depending on the patient’s tolerance of the therapy.
Dose adjustment for patients with hepatic insufficiency is not required.
The initial dose for patients with moderate or severe renal failure is 0.2 mg / day.
If necessary and with good tolerance, the daily dose can be increased to a maximum of 0.4 mg.
Side effects
The frequency of side effects described below was determined according to the following: very often (? 1/10) often (? 1/100, <1/10) infrequently (? 1/1000, <1/100), including individual messages. From the side of the central nervous system: often – headache *, dizziness (vertigo), drowsiness infrequently – fainting *. From the CCC side: infrequently – marked decrease in blood pressure, orthostatic hypotension *, bradycardia. From the gastrointestinal tract: very often – dryness of the oral mucosa often – diarrhea, nausea, vomiting, dyspepsia. From the skin and subcutaneous tissues: often – skin rash, itching infrequently – angioedema. Mental disorders: often – insomnia infrequently – nervousness. On the part of the hearing organ and labyrinth disorders: infrequently – ringing in the ears. From the side of musculoskeletal and connective tissue: often – back pain infrequently – pain in the neck. General disorders and disorders at the injection site: often – asthenia infrequently – peripheral edema. Drug Interactions The combined use of moxonidine with other antihypertensive agents leads to an additive effect. Tricyclic antidepressants can reduce the effectiveness of central antihypertensive drugs, therefore, it is not recommended to take them together with moxonidine. Moxonidine may enhance the effects of tricyclic antidepressants, tranquilizers, ethanol, sedatives and hypnotics. Moxonidine is able to moderately improve impaired cognitive function in patients receiving lorazepam. Moxonidine may enhance the sedative effect of benzodiazepine derivatives when given concomitantly. Moxonidine is secreted by tubular secretion. Therefore, its interaction with other drugs released by tubular secretion is not ruled out. Beta-blockers increase bradycardia, the severity of the negative foreign and dromotropic effects. Overdose There are reports of several cases of overdose without fatal outcome, when doses up to 19.6 mg were used simultaneously. Symptoms: headache, sedation, marked decrease in blood pressure, dizziness, asthenia, bradycardia, dry oral mucosa, vomiting, fatigue, pain in the epigastric region, respiratory depression and impaired consciousness. In addition, a short-term increase in blood pressure, tachycardia, and hyperglycemia are also possible, as has been shown in several studies on high-dose animals. Treatment: a specific antidote to the drug does not exist. In the case of a marked decrease in blood pressure, it may be necessary to restore the BCC due to the introduction of fluid and dopamine (injection). Bradycardia can be stopped with atropine (injection). In severe cases of overdose, it is recommended to carefully monitor impaired consciousness and prevent respiratory depression. Alpha-adrenergic antagonists can reduce or eliminate the paradoxical hypertensive effects of an overdose of moxonidine. Moxonidine is slightly excreted during hemodialysis. Storage Conditions In a dry, dark placeand a temperature not exceeding 25 ° C. Term hodnosty 3 years Pharmacy conditions Prescription lekarstvennaja form tablets North Star, Russia
