Description
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 the 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 (BP).
Moxonidine differs from other sympatholytic antihypertensive agents in its lower affinity for 2-adrenergic receptors, which explains the lower likelihood of developing a sedative effect and dry mouth.
Taking 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:
Absorption: After oral administration, moxonidine is rapidly and almost completely absorbed in the upper gastrointestinal tract. Absolute bioavailability is approximately 88%. The time to reach maximum concentration is about 1 hour. Eating does not affect the pharmacokinetics of the drug.
Distribution of
Communication with plasma proteins is 7.2%.
Metabolism
The main metabolite is dehydrogenated moxonidine. The pharmacodynamic activity of dehydrogenated moxonidine is about 10% compared with moxonidine.
Excretion
The elimination half-life (T1 / 2) of moxonidine and the metabolite is 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 dehydri-romoxonidine, other metabolites in the urine do not exceed 8% of the dose). Less than 1% of the dose is excreted through the intestines.
Pharmacokinetics in patients with arterial hypertension:
Compared with healthy volunteers, patients with arterial hypertension did not show changes in the pharmacokinetics of moxonidine.
Pharmacokinetics in the elderly
Clinically insignificant changes in the pharmacokinetic parameters of moxonidine in elderly patients have been noted, probably due to a decrease in the intensity of its metabolism and / or slightly higher bioavailability.
Pharmacokinetics in 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.
Pharmacokinetics for renal failure
Excretion of moxonidine is significantly correlated with creatinine clearance (CC). In patients with moderate renal failure (CC in the range of 30-60 ml / min), the equilibrium plasma concentrations and final T1 / 2 are approximately 2 and l, 5 times higher than in patients with normal renal function (CC more than 90 ml / min.).
In patients with severe renal failure (CC less than 30 ml / min.), equilibrium plasma concentrations 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 (CC less than 10 ml / min) undergoing hemodialysis, the equilibrium plasma concentrations and final T1 / 2 are 6 and 4 times higher, respectively, than in patients with normal renal function. In all groups, the maximum concentration of moxonidine in blood plasma is 1.5 to 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 block II and III degree cardiac srdlk acute heart disease insufficiency (III-IV functional class according to NYHA classification)
simultaneous use with tricyclic antidepressants (see section “Interaction with other medicinal products Rathy “)
severe renal failure (CC less than 30 ml / min)
hemodialysis
lactation period
hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption
age over 75 years old
age up to 18 years (due to lack of safety and efficacy data).
Caution: special care must be taken when using moxonidine in patients with grade I 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, with impaired renal function (CC more than 30 ml / min).
Use during pregnancy and lactation
Pregnancy
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 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.
Lactation
Moxonidine passes into breast milk and therefore should not be prescribed during breast-feeding. If it is necessary to use Moxonidine during lactation, breastfeeding should be stopped.
Composition
Composition (1 tablet, dosage 0.4 mg): active substance: moxonidine 0.4 mg
excipients (core): croscarmellose sodium (primellose) –
3.0 mg lactose monohydrate (lactopress) (milk sugar) – 95.1 mg silicon colloidal dioxide (aerosil) – 0.5 mg sodium stearyl fumarate – 1.0 mg
excipients (shell): Opadry II (polyvinyl alcohol, partially hydrolyzed – 1.32 mg of titanium dioxide E 171 – 0.5751 mg talc – 0.6 mg macrogol (polyethylene glycol 3350) – 0.3705 mg soy lecithin E 322 – 0.105 mg indigo carmine aluminum varnish – 0.0018 mg aluminum varnish based on dye azorubine – 0.0153 mg aluminum varnish based on dye crimson [Ponceau 4R] – 0.0123 g).
Dosage and administration
Inside, regardless of food intake. In most cases, the initial dose of Moxonidine is 0.2 mg per day. The maximum single dose is 0.4 mg. The maximum daily dose, which should be divided into 2 doses, is 0.6 mg. An individual correction of the daily dose is necessary depending on the patient’s tolerance of the therapy. Dose adjustment for patients with liver failure 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 / 1000,
From the central nervous system:
Often: headache *, dizziness (vertigo), drowsiness.
Infrequently: fainting *.
From the cardiovascular system:
Infrequently: vyra woman’s decreased blood pressure, orthostatic hypotension *, bradycardia.
From the gastrointestinal tract:
Very often: dry mucous membrane of the oral cavity.
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.
(* – frequency is comparable to placebo).
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, and 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, epigastric pain, respiratory depression and impaired consciousness. In addition, a short-term increase in blood pressure, tachycardia and hyperglycemia are also possible, as shown in several studies on the study of high doses in animals.
Treatment:
There is no specific antidote. In the case of a marked decrease in blood pressure, it may be necessary to restore the volume of circulating blood 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 place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.
The Expiration of
is 3 years.
Deystvuyuschee substances
Moksonydyn
Dosage form
tablet
Northern Star, Russia
