No

Beta Blocker, Nonselective

Treatment of hypertension and angina pectoris; prophylaxis of migraine headaches

C

Clinical effects on the fetus: No data available on crossing the placenta. Bradycardia, hypotension, hypoglycemia, respiratory depression, hypothermia, IUGR reported. IUGR probably related to maternal hypertension. Alternative beta-blockers are preferred for use during pregnancy due to limited data. Monitor breast-fed infant for symptoms of beta-blockade.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to nadolol or any component; bronchial asthma; sinus bradycardia; sinus node dysfunction; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure

Administer only with extreme caution in patients with compensated heart failure, monitor for a worsening of the condition. Efficacy in heart failure has not been established for nadolol. Avoid abrupt discontinuation in patients with a history of CAD; slowly wean while monitoring for signs and symptoms of ischemia. Use caution with concurrent use of beta-blockers and either verapamil or diltiazem; bradycardia or heart block can occur. In general, patients with bronchospastic disease should not receive beta-blockers. Nadolol, if used at all, should be used cautiously in bronchospastic disease with close monitoring. Use cautiously in diabetics because it can mask prominent hypoglycemic symptoms. Can mask signs of thyrotoxicosis. Can cause fetal harm when administered in pregnancy. Use cautiously in the renally impaired (dosage adjustments are required). Use care with anesthetic agents which decrease myocardial function.

>10%:

Central nervous system: Drowsiness, insomnia

Endocrine & metabolic: Decreased sexual ability

1% to 10%:

Cardiovascular: Bradycardia, palpitations, edema, congestive heart failure, reduced peripheral circulation

Central nervous system: Mental depression

Gastrointestinal: Diarrhea or constipation, nausea, vomiting, stomach discomfort

Respiratory: Bronchospasm

Miscellaneous: Cold extremities

<1% (Limited to important or life-threatening symptoms): Chest pain, arrhythmias, orthostatic hypotension, nervousness, headache, depression, hallucinations, confusion (especially in the elderly), thrombocytopenia, leukopenia, shortness of breath

Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia; atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol); CNS effects include convulsions, coma, and respiratory arrest (commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs).

Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia, and hypoglycemia; bradycardia and hypotension resistant to atropine, isoproterenol, or pacing may respond to glucagon; wide QRS defects caused by the membrane-depressant poisoning may respond to hypertonic sodium bicarbonate; repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful in removal of only those beta-blockers with a small V_d, long half-life, or low intrinsic clearance (acebutolol, atenolol, nadolol, sotalol)

Albuterol (and other beta₂ agonists): Effects may be blunted by nonspecific beta-blockers.

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.

Epinephrine (including local anesthetics with epinephrine): Propranolol may cause hypertension.

Glucagon: Nadolol may blunt the hyperglycemic action of glucagon.

Insulin and oral hypoglycemics: Nadolol may mask symptoms of hypoglycemia.

Nadolol increases antipyrine's half-life.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.

Competitively blocks response to beta₁- and beta₂-adrenergic stimulation; does not exhibit any membrane stabilizing or intrinsic sympathomimetic activity

Duration of effect: 24 hours

Absorption: Oral: 30% to 40%

Time to peak serum concentration: Within 2-4 hours persisting for 17-24 hours

Distribution: Concentration in human breast milk is 4.6 times higher than serum

Protein binding: 28%

Half-life: Adults: 10-24 hours; increased half-life with decreased renal function

End-stage renal disease: 45 hours

Elimination: Renally unchanged

Oral:

Elderly: Initial: 20 mg/day; increase doses by 20 mg increments at 3- to 7-day intervals; usual dosage range: 20-240 mg/day.

Dosing adjustment in renal impairment:

Cl_cr 31-40 mL/minute: Administer every 24-36 hours or administer 50% of normal dose.

Cl_cr 10-30 mL/minute: Administer every 24-48 hours or administer 50% of normal dose.

Cl_cr <10 mL/minute: Administer every 40-60 hours or administer 25% of normal dose.

Hemodialysis: Moderately dialyzable (20% to 50%); administer dose postdialysis or administer 40 mg supplemental dose.

Peritoneal dialysis: Supplemental dose is not necessary.

Dosing adjustment/comments in hepatic disease: Reduced dose probably necessary.

May be administered without regard to meals; avoid natural licorice (causes sodium and water retention and increases potassium loss)

Nadolol is a nonspecific beta-1 and beta-2 blocker.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

May cause drowsiness, dizziness, depression, insomnia, or confusion

Barbiturates may decrease the effects of beta-blockers; has been used to treat akathisia; propranolol preferred; concurrent use with antipsychotics may potentiate antihypertensive effect or antipsychotic blood levels; use with MAOIs may cause bradycardia; effects of benzodiazepines may be increased by beta-blockers; monitor for clinical changes

Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia

Noncardioselective beta-blockers (ie, propranolol, nadolol) may enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. Many nonsteroidal anti-inflammatory drugs such as ibuprofen and indomethacin can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

Check pulse daily prior to taking medication. If pulse is <50, hold medication and consult prescriber. Do not adjust dosage without consulting prescriber. May cause dizziness, fatigue, blurred vision; change position slowly (lying/sitting to standing) and use caution when driving or engaging in tasks that require alertness until response to drug is known. Exercise and increasing bulk or fiber in diet may help resolve constipation. If diabetic, monitor serum glucose closely (the drug may mask symptoms of hypoglycemia). Report swelling in feet or legs, difficulty breathing or persistent cough, unresolved fatigue, unusual weight gain >5 lb/week, or unresolved constipation. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Patient's therapeutic response may be evaluated by looking at blood pressure, apical and radial pulses

Tablet: 20 mg, 40 mg, 80 mg, 120 mg, 160 mg

Devlin RG and Duchin KL, "Nadolol in Human Serum and Breast Milk," Br J Clin Pharmacol, 1981, 12(3):393-6.

Hitzenberger G, "Initial Experience With a New Long-Acting Beta-Blocker, Nadolol, In Hypertensive Patients," J Int Med Res, 1979, 7(1):33-8.

Levy MB, Fink JN, and Guzzetta PA, "Nadolol and Hypersensitivity Pneumonitis," Ann Intern Med, 1986, 105(5):806-7.

Mehta AV and Chidambaram B, "Efficacy and Safety of Intravenous and Oral Nadolol for Supraventricular Tachycardia in Children," J Am Coll Cardiol, 1992, 19(3):630-5.

Mehta AV, Chidambaram B, and Rice PJ, "Pharmacokinetics of Nadolol in Children With Supraventricular Tachycardia," J Clin Pharmacol, 1992, 32(11):1023-7.