Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy.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 nadolol administered long term, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1 to 2 weeks and carefully monitor the patient. If angina markedly worsens or acute coronary insufficiency develops, reinstitute nadolol administration promptly, at least temporarily, and take other measures appropriate for the management of unstable angina. Warn patients against interruption or discontinuation of therapy without the health care provider'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.
Angina: Oral: Initial: 40 mg once daily, increase dosage gradually by 40 to 80 mg increments at 3- to 7-day intervals until optimum clinical response is obtained; usual dose: 40 to 80 mg once daily; doses may be titrated up to 160 or 240 mg once daily.
Atrial fibrillation/flutter, maintenance of ventricular rate control (off-label use): Oral: Initial: Start at the lower end of the usual dosage range and increase gradually as tolerated to achieve ventricular rate control; usual dosage range: 10 to 240 mg once daily (AHA/ACC/HRS [January 2014]).
Catecholaminergic polymorphic ventricular tachycardia (prevention) (off-label use): Oral: 40 to 320 mg once daily (AHA/ACC/HRS [Al-Khatib 2017]; Claudio 2018; Hyashi 2009).
Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosis (off-label use): Oral: Initial: 40 mg once daily (de la Peña 2005; Garcia-Tsao 2017; Lo 2004; Lo 2009; Lo 2010; Lo 2012); consider starting with 20 mg once daily if concern for hypotension (Garcia-Tsao 2017; Sanyal 2018); adjust every 2 to 3 days to maximal tolerated dose or until heart rate is ~55 to 60 beats per minute (Garcia-Tsao 2017). If systolic blood pressure is <90 mm Hg, reduce dose or discontinue. Some experts recommend a maximum dose of 160 mg/day in patients without ascites and 80 mg/day in patients with ascites (Garcia-Tsao 2017). Note: May use for primary or secondary prophylaxis. Primary prophylaxis is indicated for patients with cirrhosis and medium/large varices, variceal red wale markings on endoscopy, or decompensation and small varices (Garcia-Tsao 2017).
Hypertension (alternative agent): Oral: Initial: 40 mg once daily; titrate as needed based on patient response by 40 to 80 mg increments; usual dosage range: 40 to 120 mg once daily (ACC/AHA [Whelton 2017]). Doses up to 320 mg once daily may be necessary.
Migraine, prevention (off-label use) :
Note: An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (EHF [Steiner 2019]).
Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability up to 240 mg/day (Schwedt 2022; Silberstein 2015; manufacturer's labeling).
Supraventricular tachycardia (off-label use): Oral: Initial: 40 mg once daily; maximum maintenance dose: 320 mg once daily (ACC/AHA/HRS [Page 2015]).
Thyrotoxicosis (off-label use): Oral: 40 to 160 mg once daily (Ross 2016).
Ventricular arrhythmias due to congenital long QT syndrome (prevention) (off-label use): Oral: 40 to 320 mg daily (AHA/ACC/HRS [Al-Khatib 2017]).
Ventricular premature beat (suppression) (off- label use): Oral: 40 to 320 mg daily (AHA/ACC/HRS [Al-Khatib 2017]).
Ventricular tachycardia (prevention) (off- label use): Oral: 40 to 320 mg daily (AHA/ACC/HRS [Al-Khatib 2017]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >50 mL/minute/1.73 m2: Administer every 24 hours
CrCl 31 to 50 mL/minute/1.73 m2: Administer every 24 to 36 hours
CrCl 10 to 30 mL/minute/1.73 m2: Administer every 24 to 48 hours
CrCl <10 mL/minute/1.73 m2: Administer every 40 to 60 hours
Dosage adjustments for dialysis are not provided in the manufacturer’s labeling; however, the following guidelines have been used by some clinicians (Aronoff 2007):
ESRD requiring hemodialysis: Administer dose postdialysis.
Peritoneal dialysis: Administer every 40 to 60 hours
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Nadolol: Pediatric drug information")
Supraventricular tachycardia (SVT), treatment: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 0.5 to 1 mg/kg/day once daily or in 2 divided doses; increase dose gradually based on clinical response to a maximum of 2.5 mg/kg/day (Mehta 1992a; von Alvensleben 2017). Dosing based on a trial of 26 pediatric patients (age range: 3 months to 15 years) which showed SVT was well controlled with a median dose of 1 mg/kg/day (Mehta 1992a) and a retrospective study of 20 patients with SVT (age range: 10 to 390 days [median age: 30 days]) treated with nadolol 0.5 to 2 mg/kg/day (80% of patients responded to1 mg/kg/day) in 1 to 2 divided doses; 85% of patients were SVT free at 1 year (von Alvensleben 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing. In the management of hypertension, consider lower initial doses (eg, 20 mg daily) and titrate to response (Aronow 2011).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Corgard: 20 mg [contains corn starch, fd&c blue #2 (indigotine)]
Corgard: 20 mg [DSC] [scored; contains fd&c blue #2 (indigotine)]
Corgard: 40 mg [contains corn starch, fd&c blue #2 (indigotine)]
Corgard: 40 mg [DSC], 80 mg [scored; contains fd&c blue #2 (indigotine)]
Generic: 20 mg, 40 mg, 80 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 40 mg, 80 mg, 160 mg
Oral: May be administered without regard to meals.
Oral: May administer without regard to meals.
Angina: Treatment of angina pectoris
Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2017]).
Atrial fibrillation/flutter, maintenance of ventricular rate control; Catecholaminergic polymorphic ventricular tachycardia (prevention); Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosis; Migraine, prevention; Supraventricular tachycardia (atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, atrial flutter, focal atrial tachycardia); Thyrotoxicosis; Ventricular arrhythmias due to congenital long QT syndrome (prevention); Ventricular premature beat (suppression); Ventricular tachycardia (prevention)
Corgard may be confused with Cognex, Coreg
Nadolol may be confused with Mandol brand name for cefamandole [Belgium, Netherlands, New Zealand, Russia]
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Central nervous system: Drowsiness, insomnia
1% to 10%:
Cardiovascular: Atrioventricular block, bradycardia, cardiac conduction disturbance, cardiac failure, cold extremities, edema, hypotension, palpitations, peripheral vascular insufficiency, Raynaud's phenomenon
Central nervous system: Depression, dizziness, fatigue, sedation
<1%, postmarketing, and/or case reports: Abdominal distress, anorexia, behavioral changes, bloating, blurred vision, bronchospasm, cardiac arrhythmia, chest pain, confusion (especially in the elderly), constipation, cough, decreased libido, diaphoresis, diarrhea, dyspepsia, dyspnea, facial edema, flatulence, hallucination, headache, impotence, nasal congestion, nausea, nervousness, paresthesia, pruritus, psoriasis (Song 2021), skin rash, slurred speech, thrombocytopenia, tinnitus, transient alopecia, vomiting, weight gain, xeroderma, xerophthalmia, xerostomia
Bronchial asthma; sinus bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure
Documentation of allergenic cross-reactivity for beta-blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to nadolol or any component of the formulation; cor pulmonale; anesthesia with agents that produce myocardial depression; allergic rhinitis, bronchospasm, or severe chronic obstructive pulmonary disease (COPD)
Concerns related to adverse events:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Conduction abnormality: Consider preexisting conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition (efficacy of nadolol in HF has not been demonstrated).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease. Use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Prinzmetal variant angina: Beta-blockers without alpha1-adrenergic receptor blocking activity should be avoided in patients with Prinzmetal variant angina since unopposed alpha1-adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer 1998).
• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustments are required.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Special populations:
• Older adults: Bradycardia may be observed more frequently in patients >65 years of age; dosage reductions may be necessary.
Other warnings/precautions:
• Abrupt withdrawal: [US Boxed Warning]: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
Substrate of OCT1, OCT2, P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk C: Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antidiabetic Agents: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Cannabis: Beta-Blockers may enhance the adverse/toxic effect of Cannabis. Specifically, the risk of hypoglycemia may be increased. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy
DOBUTamine: Beta-Blockers may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Increase monitoring for clinical response and adverse effects. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
EPHEDrine (Systemic): Beta-Blockers may diminish the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
EPINEPHrine (Nasal): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). Risk C: Monitor therapy
EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy
Epinephrine (Racemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy
EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Etilefrine: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may diminish the therapeutic effect of Etilefrine. Risk C: Monitor therapy
Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider therapy modification
Green Tea: May decrease the serum concentration of Nadolol. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Insulins: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Isoproterenol: Beta-Blockers may diminish the therapeutic effect of Isoproterenol. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapy
Mavacamten: Beta-Blockers may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk C: Monitor therapy
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Mivacurium: Beta-Blockers may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Nadolol. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Beta-Blockers may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy
Tasimelteon: Beta-Blockers may diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
White Birch Allergen Extract: Beta-Blockers may enhance the adverse/toxic effect of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid combination
Exposure to beta-blockers during pregnancy may increase the risk for adverse events in the neonate. If maternal use of a beta-blocker is needed, fetal growth should be monitored during pregnancy and the newborn should be monitored for 48 hours after delivery for bradycardia, hypoglycemia, and respiratory depression (ESC [Regitz-Zagrosek 2018]).
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 203 2019).
When treatment of chronic hypertension in pregnancy is indicated, agents other than nadolol are preferred (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]; Magee 2014). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018])
Nadolol is present in breast milk.
Nadolol 80 mg/day was administered for 5 days to 12 normotensive breastfeeding women who had been breastfeeding for ≥1 month. The time to peak milk concentration was 6 hours after the oral dose, the half-life of nadolol in breast milk and maternal serum were similar, and nadolol was detected in breast milk for several days after the last maternal dose (Devlin 1981).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or the drug, considering the importance of treatment to the mother. Use of a beta-blocker other than nadolol may be preferred in breastfeeding females (Anderson 2017; Ito 2000).
Heart rate, blood pressure, signs/symptom of angina exacerbation when discontinued
Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):
Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended.
Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable.
Competitively blocks response to beta1- and beta2-adrenergic stimulation; does not exhibit any membrane stabilizing or intrinsic sympathomimetic activity. Nonselective beta-adrenergic blockers (propranolol, nadolol) reduce portal pressure by producing splanchnic vasoconstriction (beta2 effect) thereby reducing portal blood flow.
Duration: 17 to 24 hours
Absorption: ~30%
Distribution: Vd: ~2 L/kg
Protein binding: 30%
Metabolism: Not metabolized
Half-life elimination:
Infants 3 to 22 months (n=3): 3.2 to 4.3 hours (Mehta 1992)
Children 10 years (n=1): 15.7 hours (Mehta 1992)
Children ~15 years (n=1): 7.3 hours (Mehta 1992)
Adults: 20 to 24 hours; prolonged with renal impairment; (up to 45 hours in severe impairment) (Herrera 1979)
Time to peak, serum: 3 to 4 hours
Excretion: Urine (as unchanged drug)
Tablets (Corgard Oral)
20 mg (per each): $5.18
40 mg (per each): $6.06
80 mg (per each): $8.33
Tablets (Nadolol Oral)
20 mg (per each): $0.07 - $6.19
40 mg (per each): $0.12 - $4.97
80 mg (per each): $0.26 - $5.51
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