Nebivolol stada: Antihypertensive medicine

2021-06-19 08:04 AM

Nebivolol is a selective and competitive beta-receptor blocker, acting by the SRRR-enantiomer (d-enantiomer), which has mild vasodilator properties due to interactions with L-arginine/nitric oxide along the way.

Producer

Stellapharm J.V.

Ingredient

Each tablet: Nebivolol HCl 5mg.

Presentation and packaging

Tablets: box of 3 blisters x 10 tablets, box of 5 blisters x 10 tablets.

Pharmacodynamic

Nebivolol is a racemic mixture of two isomers SRRR-nebivolol (or d-nebivolol) and RSSS-nebivolol (or l-nebivolol). The drug combines both pharmacological actions:

Nebivolol is a selective and competitive beta-receptor blocker: this effect is due to the SRRR-enantiomer (d-enantiomer)

The drug has mild vasodilator properties due to interaction with L-arginine/nitric oxide en route.

Pharmacokinetics

Both nebivolol isomers are rapidly absorbed following oral administration. The absorption of nebivolol is not affected by food, therefore nebivolol can be administered regardless of the meal.

Nebivolol is extensively metabolized, partly to the active hydroxyl metabolite. Nebivolol is metabolized via hydroxylation of the saturated and aromatic rings, dealkylation at N- and glucuronication, in addition to the formation of glucuronides of the hydroxyl metabolites. The metabolism of nebivolol by aromatic hydroxylation is subject to CYP2D6-dependent genetic redox polymorphisms. The mean oral bioavailability of nebivolol is 12% in fast metabolizers and almost completely in slow metabolizers.

Because of the varying degrees of metabolism, the dose of nebivolol should always be adjusted according to individual patient response: low-metabolizers require lower doses. In rapid metabolizers, the mean half-life of the nebivolol isomers is 10 hours. In slow metabolizers, the time is 3 to 5 times longer. In rapid metabolizers, the half-life of the hydroxyl metabolites of both isomers averaged 24 hours and was twice that in slow metabolizers.

Stable plasma levels in most subjects (rapid metabolizers) are achieved within 24 hours for nebivolol and within days for the hydroxyl metabolites. In plasma, both nebivolol isomers are largely bound to albumin. Binding to plasma proteins is 98.1% for the SRRR-nebivolol form and 97.9% for the RSSS-nebivolol form.

One week after dosing, 38% of the dose was excreted in the urine and 48% in the feces. Urinary excretion of nebivolol as an unchanged drug is less than 0.5% of the dose.

Indications and uses

Treatment of hypertension.

Dosage and Administration

Nebivolol stada 5mg is to be taken orally.

Adults

Dosage is one tablet (5 mg)/day, preferably at the same time of day.

The effect of lowering blood pressure is evident after 1-2 weeks of treatment. Sometimes, the optimal effect is achieved only after 4 weeks.

Patients with impaired renal function

The recommended starting dose is 2.5 mg/day. If necessary, the dose can be increased to 5 mg/day.

Elderly

In patients over 65 years of age, the recommended starting dose is 2.5 mg/day. If necessary, the dose can be increased to 5 mg/day.

Warning

Anesthetic drugs

Maintenance of beta-blocker therapy reduces the risk of arrhythmias during induction and endoscopic preparation. If beta-blockers must be discontinued in preparation for surgery, they should be discontinued at least 24 hours in advance. Careful monitoring is required for some anesthetics that can cause myocardial failure. The patient is protected against parasympathetic nervous system reactions by intravenous administration of atropine.

Heart

In general, beta-adrenergic blockers should not be used in patients with untreated congestive heart failure, unless the patient's condition is stable.

In patients with ischemic heart disease, treatment with beta-blockers should be discontinued gradually (1-2 weeks). If necessary, alternative therapy should be initiated at the same time to prevent increased angina.

Beta-adrenergic blockers can cause bradycardia

If the pulse rate falls below 50-55 bpm at rest and/or the patient has signs associated with bradycardia, the dose should be reduced.

Beta-adrenergic blockers should be used with caution

In patients with peripheral circulatory disorders (Raynaud's disease or syndrome, claudication) because of possible exacerbation of these disorders.

In patients with first-degree heart block, due to the negative effect of beta-blockers during conduction.

In patients with Prinzmetal angina due to non-antagonistic alpha receptor indirect coronary vasoconstriction, beta-adrenergic blockers may increase the frequency and duration of angina attacks.

Metabolism/endocrine

Nebivolol has no effect on glucose levels in diabetic patients. However, it should be used with caution because nebivolol may mask some symptoms of hypoglycemia (tachycardia, palpitations).

Respiratory

In patients with the chronic obstructive pulmonary disorder, beta-adrenergic blockers are used with caution because they may further increase airway constriction.

Nebivolol stada 5mg contains lactose

This medicine should not be used in patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Effects on ability to drive and use machinery

The effects on the ability to drive and use machines have not been studied. Pharmacodynamic studies have shown that nebivolol has no effect on psychomotor function. When driving or operating machinery taking medication can sometimes cause dizziness and fatigue.

Overdose

There are no data on overdosage of nebivolol.

Symptom

Symptoms of beta-blocker overdose are bradycardia, hypotension, bronchospasm, and acute heart failure.

Treatment

In case of overdose or hypersensitivity to the drug, the patient should be closely monitored and treated under special care. Blood glucose levels should be checked. Absorption of drug residues still present in the gastrointestinal tract can be prevented by gastric lavage, activated charcoal, and a laxative. Need artificial respiration. Bradycardia or an exaggerated parasympathetic reaction should be treated with atropine or methylatropin. Hypotension and shock should be treated with plasma/plasma substitutes and, if necessary, catecholamines. The effects of beta-blockers can be reduced by slow intravenous injection of isoprenaline hydrochloride, starting at approximately 5 mcg/min, or dobutamine starting at 2.5 mcg/min until the desired effect is achieved. In persistent cases, isoprenaline can be combined with dopamine. If the desired effect is still not achieved, glucagon 50-100 mcg/kg may be given intravenously. If necessary, the intravenous injection should be repeated within one hour, followed, if necessary, by an infusion of glucagon 70 mcg/kg/hour. In cases of bradycardia that is excessively resistant to treatment, additional pacemakers may be used.

Contraindications

Hypersensitivity to the active substance or to any of the excipients of the drug.

Deficiency of liver function or impaired liver function.

Acute heart failure, cardiogenic shock, or episodes of decompensated heart failure require intravenous inotropic drugs.

Sinus node failure syndrome includes a sinus-atrial block.

Second- or third-degree heart block (without pacemaker).

History of bronchospasm or bronchial asthma.

Adrenal myeloma is not treated.

Metabolic acidosis.

Bradycardia (heart rate < 60 beats/min before starting treatment).

Hypotension (systolic blood pressure < 90 mmHg).

Severe peripheral circulatory disorders.

Use in pregnant and lactating women

Pregnant

Nebivolol has pharmacological effects that may be harmful to pregnant women and/or fetuses/newborns. Nebivolol should not be used during pregnancy unless its use is essential. If treatment with nebivolol is necessary, control of placental blood flow and fetal growth should be considered.

Breastfeeding Women

Animal studies have shown that nebivolol is excreted in milk. It is not known whether this drug is excreted in breast milk. Therefore, nebivolol should not be used while breastfeeding.

Pharmacodynamic interactions

Shouldn't coordinate

Class I antiarrhythmic drugs (quinidine, hydroquinidine, cibenzolin, flecainide, disopyramide, lidocaine, mexiletin, propafenon): increase the effect on atrioventricular conduction time and increase the negative myotropic effect.

Calcium channel blockers of the verapamil/diltiazem class: negative effect on atrioventricular contractility and conduction. Intravenous administration of verapamil to patients on beta-blocker therapy may lead to cardiac arrest and atrioventricular block.

Centrally acting antihypertensives (clonidine, guanfacin, moxonidine, methyldopa, rilmenidin): Concomitant use with centrally acting antihypertensives may worsen heart failure by reducing nerve tone. CNS (decreased heart rate and cardiac output, vasodilation). Abrupt discontinuation, especially if a beta-blocker was previously discontinued, may increase the risk of "rebound hypertension".

Use caution when coordinating

Class III antiarrhythmic drugs (amiodarone): increase the effect on atrioventricular conduction time.

Halogenated volatile anesthetics: Concomitant use of beta-blockers and anesthetics may decrease the tachycardia reflex and increase the risk of hypotension. As a general rule, abrupt discontinuation of beta-blockers should be avoided. Notify the anesthesiologist when the patient is taking nebivolol.

Note when coordinating

Digitalis glycosides: Concomitant use may increase atrioventricular conduction time.

Dihydropyridine calcium blockers (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine): Concomitant use may increase the risk of hypotension and does not exclude an increase in the risk of impaired pump function. of the ventricles in patients with heart failure.

Sedatives, antidepressants (3-cyclics, barbiturates, and phenothiazines): Concomitant use may enhance the hypotensive effect of beta-blockers (synergistic effect).

Sympathomimetics: Concomitant administration may neutralize the effects of beta-adrenergic blocking agents. Beta-adrenergic blocking agents may not counteract the alpha-adrenergic activity of sympathomimetic agents with both alpha and beta-adrenergic effects (risk of hypertension, severe bradycardia, and heart block).

Pharmacokinetic interactions

Because the mechanism of nebivolol metabolism involves the CYP2D6 isoenzyme, co-administration of these enzyme inhibitors, especially paroxetine, fluoxetine, thioridazine, and quinidine may lead to increased plasma concentrations of nebivolol in combination with increased risk of excessive slowing of the heart rate and other side effects.

Co-administration with cimetidine increased plasma concentrations of nebivolol but did not alter the clinical effect.

Co-administration of nebivolol and nicardipine resulted in a slight increase in plasma concentrations of both drugs but no change in clinical effects.

Incompatibility

Due to the absence of incompatibility studies, this drug should not be mixed with other medicinal products.

Side effects

Common side effects that have been reported include headache, dizziness, paresthesia, dyspnea, constipation, nausea, diarrhea, fatigue, and edema.

Preservation

In a tightly closed container, in a dry place, at a temperature not exceeding 30oC.