Nadolol (tablet)

Nadolol (tablet)
	Black Box Warning
	Adult Indications & Dosage
	Pediatric Indications & Dosage
	Contraindications
	Warnings & Precautions
	Adverse Reactions
	Drug Interactions
	Use in Specific Populations
	Administration & Monitoring
	Overdosage
	Pharmacology
	Clinical Studies
	How Supplied
	Images
	Patient Counseling Information
	Precautions with Alcohol
	Brand Names
	Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

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Black Box Warning

WARNING

See full prescribing information for complete Boxed Warning.

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered nadolol, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of one to two weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, nadolol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue nadolol therapy abruptly even in patients treated only for hypertension.

Overview

Nadolol (tablet) is a beta-adrenergic blocker that is FDA approved for the {{{indicationType}}} of agina pectoris, hypertension. There is a Black Box Warning for this drug as shown here. Common adverse reactions include bradyarrhythmia, dizziness, fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Angina Pectoris

Dosing infromation

The usual initial dose is 40 mg nadolol once daily. Dosage may be gradually increased in 40 to 80 mg increments at 3 to 7 day intervals until optimum clinical response is obtained or there is pronounced slowing of the heart rate. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 160 or 240 mg administered once daily may be needed.
The usefulness and safety in angina pectoris of dosage exceeding 240 mg per day have not been established. If treatment is to be discontinued, reduce the dosage gradually over a period of one to two weeks

Hypertension

Dosing infromation

The usual initial dose is 40 mg nadolol once daily, whether it is used alone or in addition to diuretic therapy. Dosage may be gradually increased in 40 to 80 mg increments until optimum blood pressure reduction is achieved. The usual maintenance dose is 40 or 80 mg administered once daily. Doses up to 240 or 320 mg administered once daily may be needed.

Dosage Adjustment in Renal Failure

Absorbed nadolol is excreted principally by the kidneys and, although nonrenal elimination does occur, dosage adjustments are necessary in patients with renal impairment. The following dose intervals are recommended:

This image is provided by the National Library of Medicine.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Atrial Fibrillation, Heart Rate Control

Developed by: AHA/ACC

Class of Recommendation: Class I

Strength of Evidence: Level B

Dosing Information/Recommendation

10 to 240 mg PO daily^[1]

Non–Guideline-Supported Use

Supraventricular Tachycardia

Dosing information

Initial dose of 0.01 followed by 0.02 and then 0.04 mg/kg administered every 10 minutes until achieving a positive response or the maximum dose of 0.07 mg/kg is reached. Do not exceed 10 mg.^[2]

Gastrointestinal Hemorrhage

Dosing Information

40 to 160 mg/day^[3]

Hyperthyroidism

Dosing Information

80 to 160 mg/day^[4]

Migraine Prophylaxis

Dosing Information

Combined therapy: nadolol 40 to 80 mg + tipiramate 50 to 200 mg^[5]
Monotherapy: 80 to 240 mg daily^[6]

Tremor

Dosing information

80 to 240 mg/day^[7]^[8]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Nadolol (tablet) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Nadolol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Nadolol in pediatric patients.

Contraindications

Warnings

WARNING

See full prescribing information for complete Boxed Warning.

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered nadolol, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of one to two weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, nadolol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue nadolol therapy abruptly even in patients treated only for hypertension.

Cardiac Failure

Sympathetic stimulation may be a vital component supporting circulatory function in patients with congestive heart failure, and its inhibition by beta-blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, they can be used with caution in patients with a history of failure who are well-compensated, usually with digitalis and diuretics. Beta-blockers do not abolish the inotropic action of digitalis on heart muscle.

In patients without a history of heart failure, continued use of beta-blockers can, in some cases, lead to cardiac failure. Therefore, at the first sign or symptom of heart failure, the patient should be digitalized and/or treated with diuretics, and the response observed closely, or nadolol should be discontinued (gradually, if possible).

Nonallergic Bronchospasm (e.g., chronic bronchitis, emphysema)

Patients with bronchoespastic disease should in general not receive beta-blockers. Nadolol should be administered with caution since it may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors.

Major Surgery

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes and Hypoglycemia

Beta-blockers may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia and blood pressure changes) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of antidiabetic drugs.

Thyrotoxicosis

Beta-blockers may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blockade which might precipitate a thyroid storm.

Adverse Reactions

Clinical Trials Experience

Cardiovascular

Bradycardia with heart rates of less than 60 beats per minute occurs commonly, and heart rates below 40 beats per minute and/or symptomatic bradycardia were seen in about 2 of 100 patients. Symptoms of peripheral vascular insufficiency, usually of the Raynaud type, have occurred in approximately 2 of 100 patients.
Cardiac failure, hypotension, and rhythm/conduction disturbances have each occurred in about 1 of 100 patients.
Single instances of first degree heart block and third degree heart block have been reported; intensification of AV block is a known effect of beta-blockers.

=Central Nervous System

Dizziness or fatigue has been reported in approximately 2 of 100 patients.
Paresthesias, sedation, change in behavior have each been reported in approximately 6 of 1000 patients.

Respiratory

Bronchospasm has been reported in approximately 1 of 1000 patients.

Gastrointestinal

Nausea, diarrhea, abdominal discomfort, constipation, vomiting, indigestion, anorexia, bloating, and flatulence have been reported in 1 to 5 of 1000 patients.

Miscellaneous

Each of the following has been reported in 1 to 5 of 1000 patients:

Rash
Pruritus
Headache
Dry mouth, eyes, or skin
Impotence or decreased libido
Facial swelling
Weight gain
Slurred speech
Cough
Nasal stuffiness
Sweating
Tinnitus
Blurred vision
Reversible alopecia has been reported infrequently.

The following adverse reactions have been reported in patients taking nadolol and/or other beta-adrenergic blocking agents, but no causal relationship to nadolol has been established.

Central Nervous System

Reversible mental depression progressing to catatonia
Visual disturbances
Hallucinations
An acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability with slightly clouded sensorium, and decreased performance on neuropsychometrics.

=Gastrointestinal

Hematologic

Allergic

Fever combined with aching and sore throat
Laryngospasm
Respiratory distress

Miscellaneous

Pemphigoid rash
Hypertensive reaction in patients with pheochromocytoma
Sleep disorders
Peyronie's disease
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with nadolol.

Postmarketing Experience

There is limited information regarding Nadolol (tablet) Postmarketing Experience in the drug label.

Drug Interactions

When administered concurrently, the following drugs may interact with beta-adrenergic receptor blocking agents:

General anesthetics: Exaggeration of the hypotension induced by general anesthetics.
Antidiabetic drugs (oral agents and insulin): Hypoglycemia or hyperglycemia; adjust dosage of antidiabetic drug accordingly.
Catecholamine-depleting drugs (e.g., reserpine): Additive effect; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g., vertigo, syncope, orthostatic hypotension).
Digitalis glycosides: Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Response to Treatment for Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

In animal reproduction studies with nadolol, evidence of embryo- and fetotoxicity was found in rabbits, but not in rats or hamsters, at doses 5 to 10 times greater (on a mg/kg basis) than the maximum indicated human dose. No teratogenic potential was observed in any of these species.
There are no adequate and well-controlled studies in pregnant women. Nadolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates whose mothers are receiving nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated symptoms.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Nadolol (tablet) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Nadolol (tablet) during labor and delivery.

Nursing Mothers

Nadolol is excreted in human milk. Because of the potential for adverse effects in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of nadolol to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatic Use

There is no FDA guidance on the use of Nadolol (tablet) in geriatric settings.

Gender

There is no FDA guidance on the use of Nadolol (tablet) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Nadolol (tablet) with respect to specific racial populations.

Renal Impairment

Nadolol should be used with caution in patients with impaired renal function.

Hepatic Impairment

There is no FDA guidance on the use of Nadolol (tablet) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Nadolol (tablet) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Nadolol (tablet) in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral/Intravenous

Monitoring

There is limited information regarding Nadolol (tablet) Monitoring in the drug label.

IV Compatibility

Solution

Compatible

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Not Tested

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Variable

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Incompatible

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Y-Site

Compatible

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Not Tested

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Variable

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Incompatible

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Admixture

Compatible

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Not Tested

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Variable

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Incompatible

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Syringe

Compatible

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Not Tested

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Variable

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Incompatible

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TPN/TNA

Compatible

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Not Tested

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Variable

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Incompatible

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Overdosage

Nadolol can be removed from the general circulation by hemodialysis.
In addition to gastric lavage, the following measures should be employed, as appropriate. In determining the duration of corrective therapy, note must be taken of the long duration of the effect of nadolol:

Excessive Bradycardia: Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.
Cardiac Failure: Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.
Hypotension: Administer vasopressors, e.g., epinephrine or levarterenol. (There is evidence that epinephrine may be the drug of choice.)
Bronchospasm: Administer a beta2-stimulating agent and/or a theophylline derivative.

Pharmacology

Template:Px
Nadolol (tablet)
Systematic (IUPAC) name
* rel-(2R,3S)-5-{[(2R)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol (2R,3S)-5-{[(2R)-3-(tert*-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol
Identifiers
CAS number	42200-33-9
ATC code	C07AA12
PubChem	39147
DrugBank	DB01203
Chemical data
Formula	Template:OrganicBox atom Template:OrganicBox atom Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox atom Template:OrganicBox Template:OrganicBox atom Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox Template:OrganicBox
Mol. mass	309.401 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	?
Protein binding	30%
Metabolism	Nil
Half life	14-24 hours
Excretion	Renal and fecal (unchanged)
Therapeutic considerations
Pregnancy cat.	C(US)
Legal status	POM(UK) [[Prescription drug\|Template:Unicode-only]](US)
Routes	Oral

Mechanism of Action

The mechanism of the antihypertensive effects of beta-adrenergic receptor blocking agents has not been established; however, factors that may be involved include (1) competitive antagonism of catecholamines at peripheral (non-CNS) adrenergic neuron sites (especially cardiac) leading to decreased cardiac output, (2) a central effect leading to reduced tonic-sympathetic nerve outflow to the periphery, and (3) suppression of renin secretion by blockade of the beta-adrenergic receptors responsible for renin release from the kidneys.

While cardiac output and arterial pressure are reduced by nadolol therapy, renal hemodynamics are stable, with preservation of renal blood flow and glomerular filtration rate.

By blocking catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and blood pressure, nadolol generally reduces the oxygen requirements of the heart at any given level of effort, making it useful for many patients in the long-term management of angina pectoris. On the other hand, nadolol can increase oxygen requirements by increasing left ventricular fiber length and end diastolic pressure, particularly in patients with heart failure.

Although beta-adrenergic receptor blockade is useful in treatment of angina and hypertension, there are also situations in which sympathetic stimulation is vital. For example, in patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. Beta-adrenergic blockade may worsen AV block by preventing the necessary facilitating effects of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.

Structure

Nadolol is a synthetic nonselective beta-adrenergic receptor blocking agent designated chemically as 1-(tert-butylamino)-3-[(5,6,7,8-tetrahydro-cis-6,7-dihydroxy-1-naphthyl)oxy]-2-propanol. Structural formula:

Nadolol is a white crystalline powder. It is freely soluble in ethanol, soluble in hydrochloric acid, slightly soluble in water and in chloroform, and very slightly soluble in sodium hydroxide.

Nadolol is available for oral administration as 20 mg, 40 mg, and 80 mg tablets. Inactive ingredients: microcrystalline cellulose, colorant (FD&C Blue No. 2), corn starch, magnesium stearate, povidone (except 20 mg and 40 mg), and other ingredients.

Pharmacodynamics

(Description)

Pharmacokinetics

(Description)

Nonclinical Toxicology

Carcinogenesis
Mutagenesis
Impairment of Fertility

In chronic oral toxicologic studies (one to two years) in mice, rats, and dogs, nadolol did not produce any significant toxic effects. In two-year oral carcinogenic studies in rats and mice, nadolol did not produce any neoplastic, preneoplastic, or non-neoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, nadolol caused no adverse effects.

Clinical Studies

Condition 1

(Description)

Condition 2

(Description)

Condition 3

(Description)

How Supplied

Nadolol tablets USP for oral administration are available as:

20 mg:White, round, uncoated tablets stamped SZ above and 465 below the bisect line on one side and plain on the other side and supplied as (NDC 68001-221-00 bottles of 100)
40 mg: White, round, uncoated tablets stamped SZ above and 466 below the bisect line on one side and plain on the other side and supplied as (NDC 68001-220-00 bottles of 100), (NDC 68001-220-08 bottles of 1000).
80 mg: White, round, uncoated tablets stamped SZ above and 467 below the bisect line on one side and plain on the other side and supplied as (NDC 68001-219-00 bottles of 100)

Storage

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].
Protect from moisture, freezing and excessive heat.
Dispense in a tight container as defined in the USP.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

(Patient Counseling Information)

Precautions with Alcohol

Alcohol-Nadolol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Nadolol (tablet) Brand Names in the drug label.

Look-Alike Drug Names

(Paired Confused Name 1a) — (Paired Confused Name 1b)
(Paired Confused Name 2a) — (Paired Confused Name 2b)
(Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

↑ January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE; et al. (2014). "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol. doi:10.1016/j.jacc.2014.03.022. PMID 24685669.
↑ Olukotun AY, Klein GJ (1987). "Efficacy and safety of intravenous nadolol for supraventricular tachycardia". Am J Cardiol. 60 (6): 59D–62D. PMID 3630923.
↑ Gatta A, Merkel C, Sacerdoti D, Bolognesi M, Caregaro L, Zuin R; et al. (1987). "Nadolol for prevention of variceal rebleeding in cirrhosis: a controlled clinical trial". Digestion. 37 (1): 22–8. PMID 3301478.
↑ Lazarus JH, Kingswood JC, John R (1987). "The effect of nadolol on heart rate in hyperthyroidism. A controlled trial". Acta Endocrinol (Copenh). 114 (1): 102–6. PMID 3544631.
↑ Pascual J, Rivas MT, Leira R (2007). "Testing the combination beta-blocker plus topiramate in refractory migraine". Acta Neurol Scand. 115 (2): 81–3. doi:10.1111/j.1600-0404.2006.00772.x. PMID 17212609.
↑ Ryan RE, Ryan RE, Sudilovsky A (1983). "Nadolol: its use in the prophylactic treatment of migraine". Headache. 23 (1): 26–31. PMID 6131052.
↑ Edwards RV (1982). "Nadolol use for cerebellar tremor". Am J Psychiatry. 139 (11): 1522. PMID 6127958.
↑ Koller WC (1983). "Nadolol in essential tremor". Neurology. 33 (8): 1076–7. PMID 6348587.

[pmid24685669-1] January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE; et al. (2014). "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol. doi:10.1016/j.jacc.2014.03.022. PMID 24685669.

[pmid3630923-2] Olukotun AY, Klein GJ (1987). "Efficacy and safety of intravenous nadolol for supraventricular tachycardia". Am J Cardiol. 60 (6): 59D–62D. PMID 3630923.

[pmid3301478-3] Gatta A, Merkel C, Sacerdoti D, Bolognesi M, Caregaro L, Zuin R; et al. (1987). "Nadolol for prevention of variceal rebleeding in cirrhosis: a controlled clinical trial". Digestion. 37 (1): 22–8. PMID 3301478.

[pmid3544631-4] Lazarus JH, Kingswood JC, John R (1987). "The effect of nadolol on heart rate in hyperthyroidism. A controlled trial". Acta Endocrinol (Copenh). 114 (1): 102–6. PMID 3544631.

[pmid17212609-5] Pascual J, Rivas MT, Leira R (2007). "Testing the combination beta-blocker plus topiramate in refractory migraine". Acta Neurol Scand. 115 (2): 81–3. doi:10.1111/j.1600-0404.2006.00772.x. PMID 17212609.

[pmid6131052-6] Ryan RE, Ryan RE, Sudilovsky A (1983). "Nadolol: its use in the prophylactic treatment of migraine". Headache. 23 (1): 26–31. PMID 6131052.

[pmid6127958-7] Edwards RV (1982). "Nadolol use for cerebellar tremor". Am J Psychiatry. 139 (11): 1522. PMID 6127958.

[pmid6348587-8] Koller WC (1983). "Nadolol in essential tremor". Neurology. 33 (8): 1076–7. PMID 6348587.

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