nebivolol

Nebivolol is a medication used to lower blood pressure in adults with high blood pressure (hypertension), and in addition, heart failure in adults older than 70 years of age. Reducing blood pressure to normal levels reduces the risk for heart attacks and strokes. Nebivolol is a beta-1 selective beta blocker that reduces blood pressure by blocking the activity of beta-1 receptors, protein molecules located in the heart muscles. Beta blockers, including nebivolol, are generally used as a second-line therapy for hypertension.

Normal blood pressure and heart rate are maintained by the autonomic nervous system and various hormones, which regulate heart and blood vessel contraction and relaxation. Two hormones, norepinephrine and epinephrine, produced by adrenal gland and nerve cells, bind to beta-1 receptors on the heart muscle and stimulate their contraction. During times of stress, more hormones are released, which results in more forceful contraction of heart muscles, and consequently a rise in blood pressure and heart rate.

Nebivolol binds to the beta-1 receptors and blocks the effect of these two hormones, and as a result, the heart contracts with less force, arteries dilate, and vascular resistance and blood pressure come down. At doses up to 10 mg, nebivolol acts selectively only on beta-1 receptors, and at higher doses, it also blocks beta-2 receptors which are found in lungs and smooth muscles. Beta blockers, including nebivolol, should not be stopped suddenly, as it can result in heart attack or sudden death.

• Do not use nebivolol to treat hypertension in patients with any of the following conditions:
  • Hypersensitivity to any component of the formulation
  • Heart rhythm disorders including:
    • Severely low heart rate (bradycardia)
    • Sick sinus syndrome (unless a permanent pacemaker is in place)
    • Heart block greater than first degree
  • Cardiogenic shock
  • Decompensated cardiac failure
  • Severe hepatic impairment (higher than Child-Pugh class B)
  • Bronchospastic diseases
• Caution patients that abrupt discontinuation of nebivolol in patients with coronary artery disease can result in exacerbation of chest pain (angina), heart attack (myocardial infarction) and irregular ventricular rhythm (ventricular arrhythmia). Nebivolol should be gradually tapered with minimized physical activity and careful monitoring, and may be restarted, at least temporarily, if the patient develops coronary insufficiency.
• Nebivolol has not been studied for use in patients with angina pectoris or in those who have had a recent myocardial infarction (MI).
• Patients taking nebivolol must continue the treatment during the perioperative period of anesthesia and major surgery, because of the increased risk of angina and MI from withdrawal. Withdrawal of nebivolol can also increase the risks of general anesthesia and surgical procedures. Monitor patients carefully if anesthetic agents that depress myocardial function are used.
• Beta blockers may mask some manifestations of low blood glucose (hypoglycemia), especially rapid heart rate (tachycardia). Nonselective beta blockers may potentiate insulin-induced hypoglycemia and delay normalization of blood glucose levels, however, it is not known if nebivolol has these effects. Caution patients with diabetes taking antidiabetic drugs or insulin and patients prone to spontaneous hypoglycemia, of this possibility.
• Beta blockers may mask signs of hyperthyroidism, such a tachycardia. Abrupt withdrawal may exacerbate hyperthyroidism symptoms or lead to a thyroid storm.
• Beta blockers, including nebivolol, may exacerbate symptoms of arterial insufficiency in patients with peripheral vascular disease.
• If nebivolol is used concurrently with other blood pressure drugs of the class non-dihydropyridine calcium channel blockers such as verapamil or diltiazem, monitor the patient’s blood pressure and ECG.
• Concurrent use with drugs that inhibit the liver enzyme CYP2D6 can increase exposure to nebivolol.
• Metabolism of nebivolol is reduced in patients with moderately impaired liver function. Nebivolol use has not been studied in patients with severe liver function impairment.
• Nebivolol clearance by the kidney is reduced in patients with severe kidney function impairment, but nebivolol has not been studied for use in patients receiving dialysis.
• Patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges, while taking beta blockers. These patients may not respond to the usual doses of epinephrine used to treat allergic reactions.
• Initiate an alpha blocker medication before starting a beta blocker in patients with pheochromocytoma, a rare but usually benign tumor on the adrenal gland.

Common side effects of nebivolol include:

• Headache
• Dizziness
• Fatigue
• Weakness (asthenia)
• Swelling of extremities (peripheral edema)
• Chest pain
• Nausea
• Diarrhea
• Abdominal pain
• Shortness of breath (dyspnea)
• Slow heart rate (bradycardia)
• Insomnia
• Rash
• Abnormal skin sensations (paresthesia)
• High cholesterol level in blood (hypercholesterolemia)
• Reduced HDL cholesterol
• Increase in triglycerides levels
• Reduced platelet count
• Increase in blood urea nitrogen (BUN)
• Increase in uric acid

Less common side effects of nebivolol include:

• Increase in liver enzymes ALT and AST
• Increase in bilirubin
• Fluid in lungs (pulmonary edema)
• Acute kidney failure
• Atrioventricular block
• Heart attack (myocardial infarction)
• Bronchospasm
• Hypersensitivity reactions including:
  • Hives (urticaria)
  • Allergic inflammation of blood vessels (vasculitis)
  • Swelling of tissue beneath the skin and mucous membranes (angioedema)
• Itching (pruritus)
• Rashes and other skin disorders
• Psoriasis, a skin disease
• Reduced blood flow to extremities (peripheral ischemia) and associated pain (claudication)
• Raynaud’s phenomenon, a condition caused by reduced blood supply to extremities
• Drowsiness (somnolence)
• Loss of consciousness (syncope)
• Vertigo
• Vomiting
• Low platelet levels (thrombocytopenia)
• Erectile dysfunction

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 2.5 mg
• 5 mg
• 10 mg
• 20 mg

Adult:

Hypertension

• 5 mg/day orally; may be increased every 2 weeks; not to exceed 40 mg/day

Dosing Modifications

Renal impairment

• Creatinine clearance (CrCl) above 30-80 mL/minute: Dose adjustment not listed by the manufacturer
• CrCl below 30 mL/minute: 2.5 mg/day orally initially; increased cautiously

Hepatic impairment

• Mild impairment (Child-Pugh A): Dose adjustment not listed by the manufacturer
• Moderate Impairment (Child-Pugh Class B): 2.5 mg orally once daily; increase cautiously if initial response inadequate
• Severe impairment (Child-Pugh Class C): Contraindicated

Geriatric:

Hypertension

• 5 mg/day orally; may be increased every 2 weeks; not to exceed 40 mg/day

Heart Failure

• Below 70 years: Not established
• Above 70 years: 1.25 mg/day orally; may be increased by 2.5 mg/day every 1 or 2 weeks; not to exceed 10 mg/day

Pediatric:

• Safety and efficacy not established

Overdose

• Nebivolol overdose can lower heart rate (bradycardia) and blood pressure (hypotension), and can cause dizziness, low blood sugar (hypoglycemia), fatigue, vomiting, bronchospasm, heart block and congestive heart failure.
• Overdose is treated with supportive measures until the patient stabilizes, and symptomatic therapy including:
  • Bradycardia: Administration of atropine, and if inadequate, isoproterenol or similar drugs to normalize heart rate, or placement of pacemaker in some cases
  • Hypotension: Intravenous (IV) fluids and vasopressors to increase blood pressure
  • Congestive heart failure: Treatment with digitalis glycoside and diuretics
  • Heart block: Isoproterenol infusion, or pacemaker placement under some circumstances
  • Hypoglycemia: Administration of IV glucose
  • Bronchospasm: Administration of bronchodilators

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Nebivolol has no known severe interactions with other drugs.
• Nebivolol has serious interactions with at least 30 different drugs.
• Nebivolol has moderate interactions with at least 201 different drugs.
• Nebivolol has mild interactions with at least 29 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Animal reproductive studies indicate nebivolol use during pregnancy may result in pregnancy and delivery complications and fetal harm, however, untreated maternal hypertension may increase the risk of adverse maternal and fetal outcomes.
• There are no studies of nebivolol use in pregnant women. Nebivolol should be used in pregnant women with caution only if potential benefits outweigh potential risks.
• It is not known if nebivolol is excreted in breastmilk. Nursing mothers taking nebivolol should avoid breastfeeding, because of the potential for serious adverse reactions in the breastfed infant, particularly bradycardia. Agents other than nebivolol are preferred for the treatment of hypertension in nursing mothers.

• Take nebivolol exactly as directed, regularly and continuously. If you miss a dose, continue taking the next scheduled regular dose.
• Do not stop taking nebivolol abruptly, it can lead to chest pain and/or heart attack. It must be gradually withdrawn under your physician’s supervision.
• Consult with your physician if you develop:
  • Breathing difficulty
  • Signs and symptoms of worsening heart failure such as increasing shortness of breath, weight gain or excessively slow heart rate
• Nebivolol may mask some symptoms of low blood sugar, particularly rapid heart rate. Exercise caution to monitor your blood sugar levels, if you are prone to spontaneous hypoglycemia, or if you are diabetic and taking anti-diabetic drugs or insulin.
• Avoid hazardous tasks that require mental and physical alertness such as driving and operating heavy machinery until the effects of nebivolol can be determined.
• Store nebivolol safely out of reach of children.
• In case of overdose, immediately seek medical help or contact Poison Control.