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Nadolol

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
CAS Number: 42200-33-9
Brands: Corgard

Medically reviewed by Drugs.com on Jan 18, 2021. Written by ASHP.

Introduction

Nonselective β-adrenergic blocking agent (β-blocker).

Uses for Nadolol

Hypertension

Management of hypertension, alone or in combination with other antihypertensive agents.

β-Blockers generally not preferred for first-line therapy of hypertension according to current evidence-based hypertension guidelines, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics). Nadolol is one of several β-blockers (including bisoprolol, carvedilol, metoprolol succinate, metoprolol tartrate, propranolol, and timolol) recommended by a 2017 ACC/AHA multidisciplinary hypertension guideline as first-line therapy for hypertension in patients with stable ischemic heart disease/angina.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

The 2017 ACC/AHA hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potentials harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg) and average BP >20/10 mm Hg above BP goal.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers. However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.

Chronic Stable Angina

Long-term management of chronic stable angina.

β-Blockers are recommended as first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.

Supraventricular Tachyarrhythmias

Has been used for management of frequent VPCs, paroxysmal atrial tachycardia, and sinus tachycardia and to decrease heart rate in patients with atrial flutter or fibrillation.

Vascular Headache

Prophylaxis of migraine headache.

US Headache Consortium states there is evidence of efficacy, and clinical experience suggests clinically important improvement in most patients.

Nadolol Dosage and Administration

General

  • Individualize dosage according to patient response.

  • If long-term therapy is discontinued, reduce dosage gradually over 1–2 weeks. (See Abrupt Withdrawal of Therapy under Cautions.)

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic). Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Administration

Oral Administration

Administer orally once daily without regard to meals.

Dosage

Adults

Hypertension
Nadolol Therapy
Oral

Initially, 20–40 mg daily, either alone or in combination with a diuretic.

May gradually increase by 40–80 mg daily at 2- to 14-day intervals until optimum BP response is achieved.

Manufacturers recommend usual maintenance dosage of 40–80 mg daily; dosages up to 240 or 320 mg daily may be needed.

Some experts state usual dosage range is 40–120 mg once daily; may be preferable to add another antihypertensive agent to the regimen rather than to continue increasing nadolol dosage.

Nadolol/Bendroflumethiazide Fixed-combination Therapy
Oral

Initially 40 mg of nadolol and 5 mg of bendroflumethiazide once daily. If needed, increase to 80 mg of nadolol and 5 mg of bendroflumethiazide once daily.

If BP is not adequately controlled with the fixed combination alone, may gradually add another nondiuretic hypotensive agent, starting with 50% of the usual recommended starting dosage to avoid excessive reduction in BP.

Manufacturers state fixed-combination preparations should not be used for initial antihypertensive therapy.

Chronic Stable Angina
Oral

Initially, 40 mg daily. Gradually increase by 40–80 mg daily at 3- to 7-day intervals until optimum control of angina is obtained or there is pronounced slowing of the heart rate (i.e., <55 bpm).

Usual maintenance dosage is 40 or 80 mg daily. Up to 160 or 240 mg daily may be needed.

Periodically evaluate chronic therapy for angina to determine need for dosage alteration or continued therapy.

Supraventricular Tachyarrhythmias†
Various Cardiac Arrhythmias†
Oral

Maintenance dose: 60–160 mg daily in single or divided doses has been used.

Vascular Headache†
Prevention of Migraine†
Oral

Usual effective dosage: 80–240 mg daily.

Prescribing Limits

Adults

Chronic Stable Angina
Oral

Safety and efficacy of dosages >240 mg daily not established.

Special Populations

Renal Impairment

Adjust intervals for usual dosage of nadolol alone or in fixed combination with bendroflumethiazide:

Clcr (mL/minute per 1.73 m2)

Dosage Interval

>50

24 h

31–50

24–36 h

10–30

24–48 h

<10

40–60 h

Cautions for Nadolol

Contraindications

  • Bronchial asthma.

  • Sinus bradycardia and heart block greater than first degree.

  • Cardiogenic shock.

  • Overt heart failure.

Warnings/Precautions

Warnings

Heart Failure

Possible precipitation of heart failure. Avoid use in patients with overt heart failure; may use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending heart failure occur; if heart failure continues, discontinue therapy, gradually if possible.

Abrupt Withdrawal of Therapy

Abrupt withdrawal of nadolol not recommended as it may exacerbate angina symptoms or precipitate MI in patients with angina pectoris and/or CAD. Avoid abrupt discontinuance, even when used only for hypertension. Abrupt withdrawal may cause transient symptoms (e.g., tremulousness, sweating, palpitation, headache, malaise) in patients without CAD.

Discontinue long-term therapy gradually (particularly in patients with myocardial ischemia); decrease dosage over 1–2 weeks and monitor carefully. If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for the management of unstable angina.

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous or exogenous catecholamines; use not recommended in patients with bronchial asthma. (See Contraindications under Cautions.)

Generally, β-blockers should not be used in patients with bronchospastic disease. Use with caution in patients with a history of nonallergic bronchospasm (e.g., chronic bronchitis, emphysema).

Major Surgery

Possible increased risks associated with general anesthesia and surgical procedures due to decreased ability of the heart to respond to reflex β-adrenergic stimuli. Use with caution in major surgery involving general anesthesia. Manufacturer states that chronically administered β-blocking therapy should not be routinely withdrawn prior to major surgery. If nadolol is continued during surgery, inform the anesthesiologist.

Diabetes and Hypoglycemia

Possible masked signs and symptoms of acute hypoglycemia (e.g., tachycardia and BP changes but not sweating), impaired glucose tolerance, delayed rate of recovery of blood glucose concentration following drug-induced hypoglycemia, altered hemodynamic response to hypoglycemia (possibly resulting in an exaggerated hypertensive response), and impaired peripheral circulation.

Use with caution in patients with diabetes mellitus (especially those with labile diabetes or those prone to hypoglycemia). If used with hypoglycemic agents, may need to adjust hypoglycemic agent dosage.

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked. Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.

General Precautions

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens; patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.

Other Precautions

Shares the toxic potentials of β-blockers; observe usual precautions of these agents. In addition, when used in fixed-combination with bendroflumethiazide, consider the cautions, precautions, and contraindications associated with thiazide diuretics.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

Clearance may be decreased; dosage adjustments necessary depending on degree of renal impairment. (See Renal Impairment under Dosage and Administration)

Common Adverse Effects

Bradycardia (heart rate <60 bpm), peripheral vascular insufficiency (usually Raynaud’s type), dizziness, fatigue.

Interactions for Nadolol

Specific Drugs

Drug

Interaction

Comments

Antidiabetic agents

Potential for altered antidiabetic response

Adjust antidiabetic agent dosage if needed

Cardiovascular drugs (e.g., cardiac glycosides, nondihydropyridine calcium-channel blocking agents)

Possible additive negative effects on SA or AV nodal conduction

Catecholamine-depleting drugs (e.g., reserpine)

Potential for additive effects (increased hypotension and marked bradycardia)

Monitor closely for symptoms (e.g., vertigo, syncope, postural hypotension)

Diuretics

Possible increased hypotensive effect

Careful dosage adjustments recommended

Drugs with anticholinergic effects

Potential for antagonism of cardiac β-adrenergic blocking effects

Hypotensive agents

Possible increased hypotensive effect

Careful dosage adjustments recommended

Mibefradil (no longer commercially available in the US)

Slowing or complete suppression of SA node activity with development of slow ventricular rates

Reported principally in geriatric patients with concomitant β-adrenergic blocker therapy

Myocardial depressant general anesthetics

Increased risk of hypotension, myocardial depression, and heart failure

See Major Surgery under Cautions

Neuromuscular blocking agents (e.g., tubocurarine chloride)

High doses of nadolol may increase effects of neuromuscular blocking agents

Phenothiazines

Possible additive hypotensive effect, especially when large phenothiazine doses are used

Sympathomimetic agents (e.g., isoproterenol, epinephrine)

Possible antagonism of β-adrenergic stimulating effects

Administer epinephrine with caution; decreased pulse rate with first- and second-degree heart block and hypertension may occur

Very large doses of isoproterenol may be needed to overcome β-adrenergic blocking effects

Nadolol Pharmacokinetics

Absorption

Bioavailability

Following oral administration, absorption is variable; averages about 30–40%.

Duration

Following doses of 40–320 mg daily, duration of antihypertensive and antianginal effects is ≥24 hours.

Food

Food does not affect the rate or extent of absorption.

Distribution

Extent

Widely distributed; minimal amounts detected in the brain of dogs. Distributed into bile.

Nadolol crosses the placenta in rats and is distributed into human milk.

Plasma Protein Binding

About 30%.

Elimination

Metabolism

Not metabolized.

Elimination Route

Excreted principally unchanged in feces (about 76.9%) and urine (about 24.6%) in 4 days.

Half-life

10–24 hours.

Special Populations

Increased half-life in patients with renal impairment. Removed by hemodialysis.

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at room temperature.

Actions

  • Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium and β2-adrenergic receptors within bronchial and vascular smooth muscle.

  • Decreases resting heart rate, inhibits exercise-induced increases in heart rate, and decreases cardiac output at rest and during exercise.

  • Decreases AV node conduction velocity and decreases myocardial automaticity.

  • No intrinsic sympathomimetic activity, little direct myocardial depressant activity, and no membrane-stabilizing effect on the heart.

  • Reduces BP by blocking peripheral (especially cardiac) adrenergic receptors (decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and/or by suppressing renin release.

  • Decreases BP in both supine and standing positions.

  • In patients with angina, blocks catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and BP resulting in a net decrease in myocardial oxygen consumption.

  • May increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure in patients with heart failure.

  • Increases airway resistance (especially in asthmatic patients) and inhibits the release of free fatty acids and insulin.

Advice to Patients

  • Importance of taking exactly as prescribed.

  • Importance of not interrupting or discontinuing therapy without consulting clinician.

  • Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure or if any difficulty in breathing occurs.

  • Importance of patient informing anesthesiologist or dentist about nadolol therapy before undergoing major surgery.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Nadolol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

20 mg*

Corgard (scored)

Pfizer

Nadolol Tablets

40 mg*

Corgard (scored)

Pfizer

Nadolol Tablets

80 mg*

Corgard (scored)

Pfizer

Nadolol Tablets

Nadolol Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

40 mg with Bendroflumethiazide 5 mg

Corzide (scored)

Pfizer

Nadolol and Bendroflumethiazide Tablets

80 mg with Bendroflumethiazide 5 mg

Corzide (scored)

Pfizer

Nadolol and Bendroflumethiazide Tablets

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 28, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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