Chemical formula: C₂₂H₂₅F₂NO₄ Molecular mass: 405.435 g/mol PubChem compound: 71301
Nebivolol interacts in the following cases:
Concomitant use of sympathicomimetic agents may counteract the effect of beta-adrenergic antagonists. Beta-adrenergic agents may lead to unopposed alpha-adrenergic activity of sympathicomimetic agents with both alpha- and beta-adrenergic effects (risk of hypertension, severe bradycardia and heart block).
As nebivolol metabolism involves the CYP2D6 isoenzyme, co-administration with substances inhibiting this enzyme, especially paroxetine, fluoxetine, thioridazine and quinidine may lead to increased plasma levels of nebivolol associated with an increased risk of excessive bradycardia and adverse events.
In patients with renal insufficiency, the recommended starting dose is 2.5 mg daily. If needed, the daily dose may be increased to 5 mg.
Concomitant use of antipsychotics, antidepressants (tricyclics, barbiturates and phenothiazines) may enhance the hypothensive effect of the beta-blockers (additive effect).
Although nebivolol does not affect glucose level, concomitant use may mask certain symptoms of hypoglycaemia (palpitations, tachycardia).
Concomitant use of digitalis glycosides with nebivolol may increase atrio-ventricular conduction time. Clinical trials with nebivolol have not shown any clinical evidence of an interaction. Nebivolol does not influence the kinetics of digoxin.
Concomitant use of beta-adrenergic antagonists and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension. As a general rule, avoid sudden withdrawal of beta-blocker treatment. The anaesthesiologist should be informed when the patient is receiving nebivolol.
Co-administration of mebivolol with class III antiarrhythmic drugs (amiodarone) should be performed with caution as an effect on atrio-ventricular conduction time may be potentiated.
Concomitant use of calcium antagonists of the dihydropyridine type (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine) with nebivolol may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
Concomitant use of baclofen (antispastic agent), amifostine (antineoplastic adjunct) with antihypertensives is likely to increase the fall in blood pressure, therefore the dosage of the antihypertensive medication should be adjusted accordingly.
Η συγχορήγηση σιμετιδίνης αύξησε τα επίπεδα νεμπιβολόλης στο πλάσμα, χωρίς να αλλάζει το κλινικό αποτέλεσμα.
Co-administration of nebivolol with centrally acting antihypertensives (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine) is not recommended as concomitant use of centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of “rebound hypertension”.
Theoretically, co-administration of mefloquine with beta-adrenergic blocking agents could contribute to the prolongation of the QTc interval.
Combining nebivolol with nicardipine slightly increased the plasma levels of both drugs, without changing the clinical effect.
Co-administration of nebivolol with Class I antiarrhythmic drugs (quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone) is not recommended due to the effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.
Co-administration of nebivolol with verapamil/diltiazem calcium channel antagonists is not recommended as it may cause a negative negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients with β-blocker treatment may lead to profound hypotension and atrio-ventricular block.
In patients with chronic obstructive pulmonary disorders, beta-adrenergic antagonists should be used with caution as airway constriction may be aggravated.
Beta-adrenergic blocking agents may mask tachycardic symptoms in hyperthyroidism. Abrupt withdrawal may intensify symptoms.
Beta-adrenergic antagonists may increase the sensitivity to allergens and the severity of anaphylactic reactions.
Continuation of beta-blockade reduces the risk of arrhythmias during induction and intubation. If beta-blockade is interrupted in preparation for surgery, the beta-adrenergic antagonist should be discontinued at least 24 hours beforehand.
Caution should be observed with certain anaesthetics that cause myocardial depression. The patient can be protected against vagal reactions by intravenous administration of atropine.
Patients with a history of psoriasis should take beta-adrenergic antagonists only after careful consideration.
Nebivolol has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. In general, beta-adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the foetus and newborn infant. If treatment with beta-adrenoceptor blockers is necessary, beta-1 selective adrenoceptor blockers are preferable.
Nebivolol should not be used during pregnancy unless clearly necessary. If treatment with nebivolol is considered necessary, the uteroplacental blood flow and the foetal growth should be monitored. In case of harmful effects on pregnancy or the foetus alternative treatment should be considered. The newborn infant must be closely monitored. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days.
Animal studies have shown that nebivolol is excreted in breast milk. It is not known whether this drug is excreted in human milk. Most beta-blockers, particularly lipophilic compounds like nebivolol and its active metabolites, pass into breast milk although to a variable extent. Therefore, breastfeeding is not recommended during administration of nebivolol.
No studies on the effects on the ability to drive and use machines have been performed. Pharmacodynamic studies have shown that nebivolol does not affect psychomotor function. When driving vehicles or operating machines it should be taken into account that dizziness and fatigue may occasionally occur.
Adverse events are listed separately for hypertension and CHF because of differences in the background diseases.
The adverse reactions reported, which are in most of the cases of mild to moderate intensity, are listed below, classified by system organ class and ordered by frequency.
Not Known: Angioneurotic oedema, hypersensitivity
Uncommon: Nightmares; depression
Common: Headache, dizziness, paraesthesia
Very Rare: Syncope
Uncommon: Impaired vision
Uncommon: Bradycardia, heart failure, slowed AV conduction/AV-block
Uncommon: Hypotension, (increase of) intermittent claudication
Common: Dyspnoea
Uncommon: Bronchospasm
Common: Constipation, nausea, diarrhoea
Uncommon: Dyspepsia, flatulence, vomiting
Uncommon: Pruritus, rash erythematous
Very Rare: Psoriasis aggravated
Not Known: Urticaria
Uncommon: Impotence
Common: Tiredness, oedema
The following adverse reactions have also been reported with some beta adrenergic antagonists: hallucinations, psychoses, confusion, cold/cyanotic extremities, Raynaud phenomenon, dry eyes, and oculo-mucocutaneous toxicity of the practolol-type.
Data on adverse reactions in CHF patients are available from one placebo-controlled clinical trial involving 1,067 patients taking nebivolol and 1,061 patients taking placebo. In this study, a total of 449 nebivolol patients (42.1%) reported at least possibly causally related adverse reactions compared to 334 placebo patients (31.5%). The most commonly reported adverse reactions in nebivolol patients were bradycardia and dizziness, both occurring in approximately 11% of patients. The corresponding frequencies among placebo patients were approximately 2% and 7%, respectively.
The following incidences were reported for adverse reactions (at least possibly drug-related) which are considered specifically relevant in the treatment of chronic heart failure:
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