Description of Nebivolol Tablet
Nebivolol Hydrochloride is a medicine used for the treatment of essential hypertension. It comes in different strengths which include 2.5mg, 5mg, 10mg, and 20mg.
Nebivolol is pharmacologically categorised as a Hypotensive agent, hence its indication as an antihypertensive.
Pharmacology
Nebivolol tablet is a competitive and selective B1-receptor antagonist which is attributable to the d-enantiomer.
It has mild vasodilating properties, possible due to an interaction with the L-arginine/nitric oxide pathway.
The medicine reduces heart rate & blood pressure at rest & during exercise. In healthy volunteers, it has no significant effect on maximal exercise or endurance:
An in-vitro and in vivo experiment in animals showed that nebivolol has no intrinsic sympathicomimetic activity and at pharmacological doses, has no membrane stabilising effect.
It is also devoid of alpha-adrenergic antagonism at therapeutic doses.
Pharmacokinetics
Nebivolol can be given with or without meals with peak plasma concentrations occurring within 2-6 hours after dosing.
It is extensively metabolised partly to active hydroxy metabolites. The bioavailability of nebivolol averages 12% in extensive metabolisers (EM’s) and is virtually complete in poor metabolisers (PM’s), but the mean bioavailability of the separate enantiomers and hydroxylated metabolites was fairly similar between EM’s & PM’s and no differences were found in the pharmacodynamic effects.
Steady-state plasma levels for nebivolol are reached within 24 hours in most subjects (EM’s).
The elimination half lives of the hydroxy-metabolites of both enantiomers average 24 hours in EM’s and are twice as long in PM’s.
Plasma concentrations are dose proportional and the pharmacokinetics of nebivolol are unaffected by age.
Nebivolol is highly protein bound, d-nebivolol being 98.1% and l- nebivolol 97,9% bound to albumin.
About 52% of the dose is excreted in urine and about 15% in the faeces in PM’s one week after administration.
Indications and uses of Nebivolol Tablet
It is used for the treatment of mild to moderate essential hypertension.
Contraindications
- Nebivolol Tablet should not be used in individual who are hypersensitive to it.
- It should not be used also in individuals with Liver insufficiency or liver function impairment,
- It should not be used in pregnancy and lactation.
- It is also contra-indicated in:
- Cardiogenic shock
- Uncontrolled heart failure
- Sick sinus syndrome, including sino-atrial block-
- 2nd & 3rd degree heart block
- History of bronchospasm & bronchial asthma
Use in pregnancy
Insufficient data exist on the use of Nebivolol in human pregnancy to determine its potential harmfulness.
Animal studies have not shown any indication of harmful effects, other than on the basis of its pharmacological properties.
Beta-blockers reduce placental perfusion, which may result in intrauterine fetal death and in immature and premature delivery.
In addition, adverse effects (hypoglycaemia and bradycardia) may occur in the fetus and the neonate. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Therefore, Nebivolol should not be used during pregnancy
Use in lactation
Most beta-blockers, particularly lipophilic compounds like nebivolol and its active metabolites, pass into breast milk although to a variable extent.
Since it is not known whether nebivolol is excreted into human milk, the use of Nebivolol when breast feeding is contra-indicated.
Animal studies have shown that nebivolol is excreted in breast milk
Side effects of Nebivolol Tablet
The most common side effects (incidence between-1-10%) are headache, dizziness, tiredness & paraesthesia.
Other side-effects reported in 1% of patients are diarrhoea, constipation, nausea, dyspnoea & oedema.
Typical beta adrenergic antagonist side-effects reported in less than 1% of patients are; bradycardia, slowed AV conduction/AV-block, hypotension, heart failure, increase of intermittent claudication, impaired vision, impotence, depression, nightmare, dyspepsia, flatulence, vomiting, bronchospasm and rash
The following side-effects have also been reported with some beta adrenergic antagonists: hallucinations, psychoses, confusion, cold/cyanotic extremities, Raynaud phenomenon, dry eyes and mucocutaneous toxicity of the practolol-type, sleep disturbances and abdominal cramping.
Congestive heart failure or heart block may be precipitated in patients with underlying cardiac disorders. Pneumonitis, pleurisy, paraesthesia, peripheral neuropathy, overt psychosis, myopathies, skin rash, pruritis, and reversible alopecia have been reported.
Ocular symptoms include decreased tear production, blurred vision and soreness.
Haematological reactions include nonthrombocytopenic purpura, thrombocytopenia, and less frequently agranulocytosis. Transient eosinophilia can occur.
Precautions & warnings
Beta-adrenergic antagonists may increase the sensitivity to allergens and the severity of anaphylactic reactions
Special precautions
Cardiovascular: Beta-adrenergic antagonists should not be used in patients with untreated congestive heart failure, unless their condition has been stabilized. One of the pharmacological actions of beta blockers is to reduce the heart rate.
Abrupt discontinuation of therapy may cause exacerbation of angina pectoris in patients suffering from ischaemic heart disease.
Discontinuation of therapy should be gradual (over a period of 1-2 weeks) and patients should be advised to limit the extent of their physical activity during the period that their medicine may be discontinued.
If the pulse rate drops below 50-55 beats per minute at rest and/or the patient experiences symptoms suggestive of bradycardia, the dosage should be reduced.
Drug interactions
Calcium Antagonists: Caution should be exercised when administering beta-blockers with calcium antagonists of the verapamil or diltiazem type because of their negative effect on contractility and atrio-ventricular conduction.
Exaggeration of these effects can occur particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities.
Neither medicine should therefore be administered intravenously within 48 hours of discontinuing the other.
Anti-arrhythmics: Caution should be exercised when administering beta-blockers with Class I anti-arrhythmic drugs and amiodarone as their effect on atrial conduction time and their negative inotropic effect may be potentiated. Such interactions can have life threatening consequences.
Clonidine: Beta-blockers increase the risk of rebound hypertension after sudden withdrawal of chronic clonidine treatment.
Digitalis: Digitalis glycosides associated with beta-blockers may increase atrio-ventricular conduction times. Nebivolol does not influence the kinetics of digoxin & clinical trials have not shown any evidence of an Interaction
Dosage of Nebivolol Tablet
The dosage of Nebivolol Tablet is 5 mg per day orally; the dose may be increased every 2 weeks. However, it should not to exceed 40 mg/day
Nebivolol dosage in Adults: Take one 5 mg tablet daily, preferable at the same time of the day, with or without meals
Combination with other antihypertensive agents: An additional antihypertensive effect has been observed only when Nebivolol tablets 5mg is combined with hydrochlorothiazide 12.5-25 mg
Dosage in Patients with renal insufficiency: The recommended starting dose is 2.5 mg daily. The daily dose may be increased to 5 mg if needed.
Dosage in Patients with hepatic insufficiency: There is no data in patients with hepatic or impaired liver function. Therefore, the use of Nebivolol tablets 5mg is contra-indicated in these patients.
Nebivolol dosage in the Elderly: In patients over 65 years, the recommended starting dose is 2.5 mg daily. The dose may be increased to 5 mg daily if needed.
Due to limited experience in patients above 75 years, caution must be exercised and these patients monitored closely.
Overdosage: Symptoms and antidote
1. Symptoms of Nebivolol Tablet overdose
The following are the symptoms of Nebivolol overdose:
- Bradycardia
- Hypotension
- Bronchospasm and
- Acute cardiac insufficiency.
Treatment of Nebivolol Tablet overdose
Blood glucose levels should be checked and symptomatic and supportive therapy given
How to store Nebivolol Tablet
Store below 30°C. Keep out from the reach of children.
Reference
Nebivolol. Pub Chem.
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