Nadolol is an oral, nonselective, beta-adrenergic receptor antagonist similar to propranolol. Nadolol does not demonstrate appreciable intrinsic sympathomimetic or membrane-stabilizing activities. Unlike propranolol, nadolol is renally eliminated and possesses a low degree of lipid solubility and has the longest plasma half-life of all the beta-blockers. The 2007 AHA guidelines for the management of hypertension state beta-blockers should not be used as first-line therapy for the treatment of hypertension, as several comparative clinical trials have shown beta blockers to be inferior to ACE inhibitors, angiotensin-receptor blockers, or calcium channel blockers for preventing both stroke and coronary artery disease complications. These guidelines do, however, recommend the use of beta-blockers for the treatment of hypertension in patients with angina, prior myocardial infarction, or heart failure. Nadolol was approved by the FDA in December 1989.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer nadolol without regard to meals.
The adverse effects of nadolol are generally mild and temporary; they usually occur at the onset of therapy and diminish over time.
Most adverse reactions of nadolol are manifestations of its therapeutic effect. Because beta-blockers depress myocardial contractility, nadolol may precipitate or exacerbate congestive heart failure, especially in patients with systolic dysfunction. Congestive heart failure was reported in 1% of patients in clinical trials and is more likely to occur in patients with preexisting left ventricular dysfunction and usually will respond to discontinuation of nadolol therapy. In some patients with heart failure, however, beta-blockers have been beneficial. In addition, because beta-blockers slow AV nodal conduction, bradycardia (heart rate < 60 bpm) occurs commonly, but symptomatic bradycardia and/or heart rate < 40 bpm occurs in 2% of patients recieving nadolol). AV block may also occur. Sinus bradycardia and hypotension (1%) are rarely serious and can be reversed with IV atropine, if necessary. AV block, secondary to depressed conduction at the AV node, may necessitate sympathomimetic and/or pressor therapy or use of a temporary pacemaker. Common cardiovascular signs or symptoms associated with overdosage of a beta-blocker include bradycardia, hypotension, congestive heart failure, and heart block. If the hypotensive effects of nadolol are excessive, syncope can occur.
It has been proposed that lipophilic beta-blockers (e.g., propranolol) are more likely to be associated with CNS effects than hydrophilic drugs such as nadolol; however, this theory has been debated based on clinical experience with beta-blockers. The most frequent adverse CNS effects during nadolol therapy include dizziness (2%) and fatigue (2%). Infrequent CNS effects (0.1-0.6%; without regard to causality) reported during nadolol therapy include: behavioral changes, impaired cognition, depression, disorientation, drowsiness or sedation, dysarthria (slurred speech), emotional lability with clouded sensorium, hallucinations, headache, paresthesias, short-term memory loss and visual impairment. Nightmares, vivid dreams, insomnia, and psychosis have also been reported during beta-blocker therapy.
Beta-blockers can cause bronchospasm, dyspnea or wheezing in patients with asthma or pulmonary disease (see Contraindications). Non-selective beta-blockers such as nadolol are more likely than selective agents to precipitate bronchospasm. Patients with preexisting bronchospastic disease are at greater risk. In clinical trials, bronchospasm was reported in 0.1% of patients and cough was reported in 0.1-0.6% of patients.
Beta-blockers have been shown to increase the risk of developing diabetes mellitus in hypertensive patients; however this risk should be evaluated relative to the proven benefits of beta-blockers in reducing cardiovascular events. Nadolol can prolong or enhance hypoglycemia by interfering with glycogenolysis; this effect may be less pronounced with beta1-selective beta-blockers than with nonselective agents. Nadolol can also mask signs of hypoglycemia, especially tachycardia, palpitations, and tremors; in contrast, sweating and the hypertensive response to hypoglycemia are not suppressed with beta-blockade. Beta-blockers can occasionally cause hyperglycemia. This is thought to be due to blockade of beta2-receptors on pancreatic islet cells, which would inhibit insulin secretion.
Hematologic adverse reactions, such as agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and nonthrombocytopenic purpura, have been reported rarely during therapy with nadolol.
Some beta-blockers have been shown to cause hypertriglyceridemia and decrease plasma HDL-cholesterol during therapy. A meta-analysis suggests that these effects are less pronounced with cardioselective agents than non-selective agents such as nadolol, particularly in diabetic patients. The clinical implications of these effects, relative to the cardiovascular benefits of beta-blocker therapy, are not known.
Exacerbation of peripheral vasoconstriction (e.g., Raynaud's phenomenon) was reported in 2% of patients during clinical trials of nadolol.
Sexual dysfunction, specifically impotence (erectile dysfunction) and libido decrease, occurred in 0.1 to 0.6% of nadolol-treated patients in clinical trials. Peyronie's disease (an abnormal curvature of the penis during erection with penile fibrosis) also been reported with various beta-blockers postmarketing.
Dermatologic and allergic reactions with beta-blockers (e.g., nadolol) are usually mild and transient. Some of these reactions include pruritus, skin hyperpigmentation, reversible alopecia, xerosis, and exfoliative dermatitis. Dermatologic reactions reported in 0.1-0.6% of patients during nadolol therapy include: reversible alopecia, pemphigoid rash, diaphoresis, pruritus, rash (unspecified), xerostomia, xerophthalmia, and xerosis. Angioedema (facial swelling), laryngospasm, and respiratory distress also have been rarely reported.
GI side effects of nadolol that were reported in 0.1-0.6% of patients in clinical trials include abdominal pain, anorexia, constipation, diarrhea, flatulence, indigestion, nausea, vomiting, indigestion, weight gain, and bloating. Elevated hepatic enzymes, ischemic colitis, and mesenteric arterial thrombosis also have been reported with nadolol.
Tinnitus and nasal congestion have been reported rarely (0.1-0.6%) in patients receiving nadolol.
Withdrawal symptoms, including headache, diaphoresis, palpitations, sinus tachycardia, tremor, and hypertension, have been associated with abrupt discontinuation of beta-blockers in hypertensive patients. Gradual tapering and/or prolonged administration of small doses of nadolol prior to complete cessation may prevent adverse events.
Abrupt discontinuation of any beta-adrenergic-blocking agent, including nadolol, can result in the development of myocardial ischemia, myocardial infarction, ventricular arrhythmias, or severe hypertension, particularly in patients with preexisting cardiac disease.
Nadolol should be used with caution in patients with hyperthyroidism or thyrotoxicosis because beta-blockers can mask tachycardia, which is a useful monitoring parameter in thyroid disease. Abrupt withdrawal of beta-blockers in a patient with hyperthyroidism can precipitate thyroid storm. However, beta-blockers are generally useful in the symptomatic treatment of hyperthyroid-related states, like thyrotoxicosis.
Beta-blockers such as nadolol depress conduction through the AV node, beta-blockers are contraindicated in patients with severe bradycardia, or advanced AV block unless a functioning pacemaker is present. Beta-blockers should also be avoided in patients with sick sinus syndrome unless a functioning pacemaker is present. In general, beta-blockers are contraindicated in patients with cardiogenic shock or acute systolic congestive heart failure, particularly in those with severely compromised left ventricular dysfunction, and should not be used in patients with acute pulmonary edema, because the negative inotropic effect of these drugs can further depress cardiac output. In stable patients with heart failure, however, beta-blockers (e.g., bisoprolol, carvedilol, metoprolol) given in low doses have been documented to be beneficial. Many beta-blockers are used in the treatment of hypertrophic cardiomyopathy. Beta-blocker monotherapy should be used with caution in patients with a pheochromocytoma or vasospastic angina (Prinzmetal's angina) because of the risk of hypertension secondary to unopposed alpha-receptor stimulation. In patients with pheochromocytoma, an alpha-blocking agent should be used prior to the initiation of any beta-blocker. In the treatment of myocardial infarction, beta-blockers are contraindicated in patients with hypotension (SBP < 100 mmHg).
Nadolol should be used with caution in patients with cerebrovascular insufficiency (cerebrovascular disease) or stroke because of potential effects of beta-blockade on blood pressure and pulse. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of beta-blocker, alternative therapy should be considered.
Beta-blockers have been shown to increase the risk of developing diabetes mellitus in hypertensive patients; however this risk should be evaluated relative to the proven benefits of beta-blockers in reducing cardiovascular events. Nadolol should be used with caution in patients with poorly controlled diabetes mellitus, particularly brittle diabetes. Beta-blockers can prolong or enhance hypoglycemia by interfering with glycogenolysis; this effect may be less pronounced with beta1-selective beta-blockers than with nonselective agents. Beta-blockers can also mask signs of hypoglycemia, especially tachycardia, palpitations, and tremors; in contrast, diaphoresis and the hypertensive response to hypoglycemia are not suppressed with beta-blockade. Beta-blockers can occasionally cause hyperglycemia. This is thought to be due to blockade of beta2-receptors on pancreatic islet cells, which would inhibit insulin secretion. Thus, blood glucose levels should be monitored closely if a beta-blocker is used in a patient with diabetes mellitus.
Because beta-blocker therapy reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli, the risks of general anesthesia and surgical procedures may be augmented. Although, gradual withdrawal of beta-blockers is sometimes recommended prior to general anesthesia to limit the potential for hypotension and heart failure, the manufacturer does not recommend withdrawal of chronically-administered nadolol prior to major surgery. The risk of precipitating adverse cardiac events (e.g., myocardial infarction, tachycardia) following preoperative withdrawal of beta-blockers may outweigh the risks of ongoing beta-blocker therapy, particularly in patients with coexisting cardiovascular disease. Patients receiving nadolol before or during surgery involving the use of general anesthetics with negative inotropic effects (e.g., ether, cyclopropane, or trichloroethylene) should be monitored closely for signs of heart failure. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery in patients receiving beta-blockers. Consideration should be given to the type of surgery (e.g., cardiac vs. noncardiac), anesthetic strategy, and coexisting health conditions. The anesthetic technique may be modified to reduce the risk of concurrent beta-blocker therapy. If needed, the negative inotropic effects of beta-blockers may be cautiously reversed by sufficient doses of adrenergic agonists such as isoproterenol, dopamine, dobutamine, or norepinephrine. Vagal dominance, if it occurs, may be corrected with atropine (1-2 mg IV).
Nadolol drug clearance may be reduced by renal disease (e.g., renal failure or renal impairment). Dosage adjustment is recommended for patients with a creatinine clearance <= 50 ml/min. Nadolol is hemodialyzable and may require dosage supplementation in patients undergoing dialysis/hemodialysis (see Dosage).
Nadolol is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. Neonates whose mothers received nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated symptoms; use caution near the time of labor and obstetric delivery. Both embryotoxicity and fetotoxicity were observed in rabbits that received doses 5 to 10 times the maximum indicated human dose; these effects were not seen in rats or hamsters. According to the manufacturer, nadolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
According to the manufacturer, nadolol should not be used during breast-feeding. Nadolol is excreted into breast milk. Based on the drug's long half-life, low protein binding, and significant urinary excretion, there is risk for accumulation in a nursing infant, particularly neonates. In 12 lactating women taking nadolol 80 mg/day PO for 5 days, the amount of nadolol measured in breast milk was 4.6 times higher than maternal serum levels. Based on this study, it is estimated that a 5 kg infant would have received 2-7% of the maternal dose. Although the American Academy of Pediatrics (AAP) considers nadolol to be usually compatible with breast-feeding, other beta-blockers that are associated with lower exposure via breast-milk that the AAP also regards as usually compatible such as labetalol, metoprolol, and propranolol may represent preferable alternatives for some patients. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Nadolol is contraindicated in patients who have a pulmonary disease such as bronchial asthma, and should not be used in patients with nonallergic bronchospastic disease [e.g., chronic obstructive pulmonary disease (COPD), emphysema, bronchitis], or acute bronchospasm because this drug inhibits bronchodilation via its beta2-blocking activity.
Beta-blockers such as nadolol may be associated with dizziness or drowsiness in some patients. Patients should be cautioned to avoid driving or operating machinery until the drug response is known.
Nadolol is relatively contraindicated in patients with Raynaud's phenomenon or peripheral vascular disease because reduced cardiac output and the relative increase in alpha stimulation can exacerbate symptoms.
The actual relationship between depression and beta-blockers has not been definitively established. Nadolol should be used with caution in patients with major depression.
Because it is a beta-blocker, nadolol may exacerbate conditions such as psoriasis.
Because it is a beta-blocker, nadolol may potentiate muscle weakness and double vision in patients with myasthenia gravis.
Nadolol can be used safely in geriatric patients, however these patients may have unpredictable responses to beta-blockers. The elderly may be less sensitive to the antihypertensive effects of the drug, however, reduced elimination (via renal excretion) may increase the potency of nadolol in this population. The elderly may have age-related peripheral vascular disease and the relative increase in alpha stimulation can exacerbate symptoms. Geriatric patients are at increased risk of beta-blocker-induced hypothermia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. Additionally, beta-blockers are associated with depression, bronchospasm, cardiac decompensation that may require dose adjustments in those with acute heart failure, and they may mask some symptoms of hypoglycemia (e.g., tachycardia). Beta-blockers metabolized in the liver may have an increased effect or accumulate in those with hepatic impairment. There are many drug interactions that can potentiate the effects of antihypertensives. Beta-blockers may cause or exacerbate bradycardia, particularly in patients receiving other medications that affect cardiac conduction. When discontinuing, a gradual taper may be required to avoid adverse consequences caused by abrupt discontinuation.
Nadolol is contraindicated in patients exhibiting hypersensitivity to the drug or any of its excipients. Do not use nadolol in patients with known beta-blocker hypersensitivity. Cross-sensitivity between beta-blockers may occur.
For the long-term management of angina pectoris:
Oral dosage:
Adults: Initially, 40 mg PO once daily, then increase as needed by 40 to 80 mg/day every 3 to 7 days. Usual maintenance dose is 40 to 80 mg/day. Maximum dose is 240 mg/day.
For the treatment of hypertension, either alone or in combination with other antihypertensive agents, especially thiazide diuretics:
Oral dosage:
Adults: Initially, 40 mg PO once daily, increased as needed by 40 to 80 mg/day every 2 to 14 days. Usual maintenance dose is 40 to 80 mg/day. Doses up to 240 to 320 mg may be required.
For ventricular tachycardia prophylaxis*:
Oral dosage:
Adults: Maintenance doses of 40 to 240 mg/day PO given in single or divided doses have been effective in suppressing ventricular ectopy, including episodes of nonsustained ventricular tachycardia. Although larger dosages have been used, in the majority of patients, a dosage of 160 mg/day or less has been effective for arrhythmia suppression.
For heart rate control in patients with atrial fibrillation* or atrial flutter*:
Oral dosage:
Adults: 10 to 240 mg PO daily. Clinical practice guidelines recommend the use of beta-blockers to control the ventricular rate for patients with paroxysmal, persistent, or permanent atrial fibrillation.
For paroxysmal supraventricular tachycardia (PSVT) prophylaxis* in patients with recurrent PSVT due to AV reentry:
Oral dosage:
Adults: Dosages of 80 to 160 mg/day PO have been used.
Adolescents* and Children*: Although the optimal dose is not well established, 0.5 to 2.5 mg/kg PO once daily (median 1 mg/kg once daily) has been effective. Maximum dose is 2.5 mg/kg/day.
For migraine prophylaxis*:
Oral dosage:
Adults: 80 mg PO daily. Doses up to 240 mg/day have been used. Guidelines classify nadolol as probably effective for migraine prophylaxis.
For the treatment of portal hypertension* and/or variceal bleeding prophylaxis* in patients with esophageal varices*:
-to prevent first variceal bleed (primary prophylaxis):
Oral dosage:
Adults: Nonselective beta-blockers adjusted to the maximal tolerated dose are recommended for patients with medium or large varices regardless of Child-Pugh class or presence of red wale marks and are preferred for patients with class A and no red signs. For small varices, nonselective beta-blockers are recommended for patients regardless of Child-Pugh class in the presence of red wale marks and for patients with Child-Pugh class B or C without red wale marks. Nonselective beta-blockers may be used for patients with Child-Pugh class A and small varices without red wale marks, but their long-term benefit has not been established. Gastroesophageal variceal bleeding occurred in 13 of 50 patients with moderate or large varices associated with any red color sign who received nadolol 40 mg/day PO (initial dose) titrated to a resting HR reduction of 25% or to 55 bpm.
-to prevent recurrence of variceal bleed (secondary prophylaxis):
Oral dosage:
Adults: Nonselective beta-blockers adjusted to the maximal tolerated dose plus a nitrate and endoscopic variceal ligation are recommended for patients without shunt surgery/TIPS and no evidence of hemorrhage for at least 24 hours. Significantly fewer patients who got nadolol, isosorbide mononitrate, and endoscopic band ligation had variceal re-bleeding (14 of 80 patients) as compared with those who just got pharmacologic therapy (25 of 78 patients). Nadolol was titrated (a common initial dose is 40 mg PO once daily) every 2 to 3 days to a maximum tolerated dose or up to 240 mg/day PO before initiating isosorbide mononitrate (ISMN, 10 mg PO at night titrated to the maximal tolerated dose or 20 mg PO twice daily).
For the treatment of tremor*:
-for the treatment of essential tremor*:
Oral dosage:
Adults: In one placebo-controlled study, doses of 120 to 240 mg/day PO reduced essential tremor in patients who had previously responded to propranolol.
-for the treatment of lithium-induced tremor*:
Oral dosage:
Adults: Doses of 20 to 40 mg PO once daily have been used.
For the treatment of anxiety*:
Oral dosage:
Adults: Doses of 20 to 40 mg PO, given 2 hours prior to the anxiety-producing event have been successful.
For the treatment of thyrotoxicosis*:
Oral dosage:
Adults: 40 to 160 mg PO once daily.
Maximum Dosage Limits:
-Adults
320 mg/day PO for hypertension; 240 mg/day PO for angina.
-Elderly
320 mg/day PO for hypertension; 240 mg/day PO for angina.
-Adolescents
No specific maximum dosage information is available.
-Children
2.5 mg/kg/day PO for paroxysmal supraventricular tachycardia (PSVT) prophylaxis.
Patients with Hepatic Impairment Dosing
No dosage adjustments are necessary.
Patients with Renal Impairment Dosing
CrCl > 50 ml/min: no dosage adjustment needed.
CrCl 31 to 50 ml/min: extend dosage interval to 24 to 36 hours.
CrCl 10 to 30 ml/min: extend dosage interval to 24 to 48 hours.
CrCl < 10 ml/min: extend dosage interval to 40 to 60 hours.
Intermittent hemodialysis
Nadolol is hemodialyzable. A supplemental dose of up to 40 mg may be given following hemodialysis.
*non-FDA-approved indication
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Acetaminophen; Aspirin: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Adenosine: (Moderate) Use adenosine with caution in the presence of beta blockers due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes.
Albiglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Aldesleukin, IL-2: (Moderate) Beta blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Moderate) Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving beta-blockers.
Alfuzosin: (Moderate) The manufacturer warns that the combination of alfuzosin with antihypertensive agents has the potential to cause hypotension in some patients. Alfuzosin (2.5 mg, immediate-release) potentiated the hypotensive effects of atenolol (100 mg) in eight healthy young male volunteers. The Cmax and AUC of alfuzosin was increased by 28% and 21%, respectively. Alfuzosin increased the Cmax and AUC of atenolol by 26% and 14%, respectively. Significant reductions in mean blood pressure and in mean heart rate were reported with the combination.
Aliskiren; Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Alogliptin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Alpha-blockers: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Alpha-glucosidase Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as beta-clockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving beta-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amiodarone: (Moderate) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Atorvastatin: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Benazepril: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Celecoxib: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Olmesartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Valsartan: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Amobarbital: (Moderate) Although concurrent use of amobarbital with antihypertensive agents may lead to hypotension, barbiturates, as a class, can enhance the hepatic metabolism of beta-blockers that are significantly metabolized by the liver. Beta-blockers that may be affected include betaxolol, labetalol, metoprolol, pindolol, propranolol, and timolol. Clinicians should closely monitor patients blood pressure during times of coadministration.
Amyl Nitrite: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Antithyroid agents: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Apomorphine: (Moderate) Use of beta blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Theoretically, additive blood pressure reductions could occur when apraclonidine is combined with antihypertensive agents.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Articaine; Epinephrine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of nadolol. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known; the nadolol dosage may need to be adjusted.
Aspirin, ASA: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Caffeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Carisoprodol: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Dipyridamole: (Major) Beta-blockers should generally be withheld before dipyridamole-stress testing. Monitor the heart rate carefully following the dipyridamole injection. (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Omeprazole: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Aspirin, ASA; Pravastatin: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Atazanavir: (Moderate) Atazanavir can prolong the PR interval. Coadministration with other agents that prolong the PR interval, like beta blockers, may result in elevated risk of conduction disturbances and atrioventricular block.
Atazanavir; Cobicistat: (Moderate) Atazanavir can prolong the PR interval. Coadministration with other agents that prolong the PR interval, like beta blockers, may result in elevated risk of conduction disturbances and atrioventricular block.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Beta-agonists: (Moderate) Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Bismuth Subsalicylate: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concurrent use of beta-blockers with bismuth subsalicylate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Bretylium: (Moderate) Bretylium and beta-blockers may have an additive effect when used concomitantly; monitor for hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Bupivacaine Liposomal: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Bupivacaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Bupivacaine; Epinephrine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Bupivacaine; Lidocaine: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers. (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Bupivacaine; Meloxicam: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including beta-blockers. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Canagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Carbidopa; Levodopa: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Ceritinib: (Major) Avoid concomitant use of ceritinib with nadolol if possible due to the risk of additive bradycardia. Both ceritinib and nadolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Cevimeline: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Charcoal: (Major) Charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal. While the reduction in absorption is beneficial in treating overdoses of drugs and toxins, activated charcoal dietary supplements used for flatulence or other purposes may reduce the effectiveness of certain beta-blocking agents (e.g., atenolol, sotalol, nadolol, pindolol). Use of activated charcoal is best limited to situations of drug overdose. Activated charcoal (single dose, 50-gram) reduced the absorption of therapeutic doses of atenolol, pindolol, and sotalol by > 90%. Repeat charcoal doses may decrease the entero-hepatic recycling of some of these agents. Repeated doses increased the elimination of sotalol and nadolol.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpromazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Chlorthalidone; Clonidine: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Clevidipine: (Moderate) Use clevidipine and nadolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Clonidine: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Although beta-blockers are indicated to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias, concomitant use of cocaine and non-selective beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. In addition, cocaine can reduce the therapeutic effects of beta-blockers.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Codeine; Promethazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
Colesevelam: (Moderate) Colesevelam may decrease the absorption of nadolol. To minimize potential for interactions, consider administering nadolol at least 1 hour before or at least 4 hours after colesevelam.
Crizotinib: (Major) Avoid coadministration of crizotinib with agents known to cause bradycardia, such as beta-blockers, to the extent possible due to the risk of additive bradycardia. If concomitant use is unavoidable, monitor heart rate and blood pressure regularly. An interruption of crizotinib therapy or dose adjustment may be necessary if bradycardia occurs.
Dapagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Cardiac and neurologic events have been reported when ritonavir was concurrently administered with beta-blockers.
Dasiglucagon: (Minor) A temporary increase in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure. Glucagon exerts positive inotropic and chronotropic effects and may, therefore, cause tachycardia and hypertension in some patients. The increase in blood pressure and pulse rate may require therapy in some patients with coronary artery disease.
Desflurane: (Moderate) Concurrent use of beta-blockers with desflurane may result in exaggerated cardiovascular effects (e.g., hypotension and negative inotropic effects). Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects. Withdrawal of a beta-blocker perioperatively may be detrimental to the patient's clinical status and is not recommended. Caution is advised if these drugs are administered together.
Dexmedetomidine: (Major) In general, the concomitant administration of dexmedetomidine with antihypertensive agents could lead to additive hypotensive effects. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that lower the heart rate such as beta-blockers.
Dextromethorphan; Quinidine: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agent. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers.
Digoxin: (Moderate) Because the pharmacologic effects of nadolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Dihydroergotamine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
Diltiazem: (Moderate) Use diltiazem and nadolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Dipyridamole: (Major) Beta-blockers should generally be withheld before dipyridamole-stress testing. Monitor the heart rate carefully following the dipyridamole injection.
Disopyramide: (Major) Disopyramide and beta-blockers, like nadolol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects. In general, patients receiving combined therapy with disopyramide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Donepezil: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as beta-blockers. These interactions are pharmacodynamic in nature rather than pharmacokinetic.
Donepezil; Memantine: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as beta-blockers. These interactions are pharmacodynamic in nature rather than pharmacokinetic.
Doxazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Dronedarone: (Major) In dronedarone clinical trials, bradycardia was seen more frequently in patients also receiving beta blockers. If coadministration of dronedarone and a beta blocker is unavoidable, administer a low dose of the beta blocker initially and increase the dosage only after ECG verification of tolerability. Concomitant administration may decreased AV and sinus node conduction. Furthermore, dronedarone is an inhibitor of CYP2D6, and some beta blockers are substrates for CYP2D6 (e.g., metoprolol, propranolol, nebivolol, carvedilol). Coadministration of dronedarone with a single dose of propranolol and multiple doses of metoprolol increased propranolol and metoprolol exposure by 1.3- and 1.6-fold, respectively.
Dulaglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of nadolol and duloxetine may increase the risk of hypotension. It is advisable to monitor blood pressure if the combination is necessary.
Dutasteride; Tamsulosin: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
Empagliflozin; Linagliptin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Empagliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Enalapril; Felodipine: (Moderate) Coadministration of felodipine and nadolol can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Encainide: (Major) Pharmacologically, beta-blockers, like nadolol, cause AV nodal conduction depression and additive effects are possible when used in combination with encainide. When used together, AV block can occur. Patients should be monitored closely and the dose should be adjusted according to clinical response.
Epoprostenol: (Moderate) Epoprostenol can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Ergonovine: (Major) Whenever possible, concomitant use of beta-blockers and ergot alkaloids should be avoided, since propranolol has been reported to potentiate the vasoconstrictive action of ergotamine. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergot alkaloids are coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
Ergotamine: (Moderate) Monitor blood pressure during concomitant beta-blocker and ergotamine use. Beta-blockers may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.
Ergotamine; Caffeine: (Moderate) Monitor blood pressure during concomitant beta-blocker and ergotamine use. Beta-blockers may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.
Ertugliflozin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored for antihypertensive effectiveness.
Etomidate: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Exenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Felodipine: (Moderate) Coadministration of felodipine and nadolol can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Fenoldopam: (Major) Avoid concomitant use of fenoldopam with beta-blockers due to the risk of hypotension. If used together, monitor blood pressure frequently. Beta-blockers may inhibit the sympathetic reflex response to fenoldopam.
Fingolimod: (Major) If possible, do not start fingolimod in a patient who is taking a drug that slows the heart rate or atrioventricular conduction such as beta-blockers. Use of these drugs during fingolimod initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating fingolimod. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients who cannot stop taking drugs that slow the heart rate or atrioventricular conduction. Experience with fingolimod in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction is limited.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Flecainide: (Moderate) Pharmacologically, beta-blockers, like nadolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Fluorescein: (Moderate) Patients on beta-blockers are at an increased risk of adverse reaction when administered fluorescein injection. It is thought that beta-blockers may worsen anaphylaxis severity by exacerbating bronchospasm or by increasing the release of anaphylaxis mediators; alternately, beta-blocker therapy may make the patient more pharmacodynamically resistance to epinephrine rescue treatment.
Fluphenazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Galantamine: (Moderate) The increase in vagal tone induced by cholinesterase inhibitors, such as galantamine, may produce bradycardia or syncope. The vagotonic effect of galantamine may theoretically be increased when given with beta-blockers.
General anesthetics: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
Glipizide; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Glucagon: (Minor) A temporary increase in both blood pressure and pulse rate may occur following the administration of glucagon. Patients taking beta-blockers might be expected to have a greater increase in both pulse and blood pressure. Glucagon exerts positive inotropic and chronotropic effects and may, therefore, cause tachycardia and hypertension in some patients. The increase in blood pressure and pulse rate may require therapy in some patients with coronary artery disease.
Glyburide; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Guanabenz: (Moderate) Guanabenz can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Guanfacine: (Moderate) Guanfacine can have additive effects when administered with other antihypertensive agents, including beta-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Haloperidol: (Moderate) Haloperidol should be used cautiously with nadolol due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Icosapent ethyl: (Moderate) Beta-blockers may exacerbate hypertriglyceridemia and should be discontinued or changed to alternate therapy, if possible, prior to initiation of icosapent ethyl.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Additive reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Incretin Mimetics: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Insulin Degludec; Liraglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Insulin Glargine; Lixisenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Insulins: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Iobenguane I 131: (Major) Discontinue nadolol for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart nadolol until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as nadolol, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Isosorbide Mononitrate: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Isradipine: (Moderate) Although concomitant therapy with beta-blockers and isradipine is generally well tolerated and can even be beneficial in some cases, coadministration of these agents can induce excessive bradycardia or hypotension. Isradipine when used in combination with beta-blockers, especially in heart failure patients, can result in additive negative inotropic effects. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly when isradipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of isradipine therapy can minimize or eliminate this potential interaction. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension when these drugs are given together. In general, these reactions are more likely to occur with other non-dihydropyridine calcium channel blockers than with isradipine.
Itraconazole: (Moderate) Careful monitoring is recommended when itraconazole is coadministered with nadolol. If these drugs are administered together, monitor patient for signs or symptoms of increased or prolonged nadolol-related side effects.
Ivabradine: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like beta-blockers. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Ketamine: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Ketoconazole: (Moderate) Careful monitoring is recommended when ketoconazole is coadministered with nadolol. If these drugs are administered together, monitor patient for signs or symptoms of increased or prolonged nadolol-related side effects.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as beta-blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.
Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Levamlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Levodopa: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Levoketoconazole: (Moderate) Careful monitoring is recommended when ketoconazole is coadministered with nadolol. If these drugs are administered together, monitor patient for signs or symptoms of increased or prolonged nadolol-related side effects.
Levothyroxine: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Levothyroxine; Liothyronine (Porcine): (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Levothyroxine; Liothyronine (Synthetic): (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Lidocaine: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Lidocaine; Epinephrine: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Lidocaine; Prilocaine: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers. (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Linagliptin; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Linezolid: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
Liothyronine: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Liraglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Lixisenatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Lofexidine: (Major) Because both lofexidine and nadolol can cause hypotension and bradycardia, concurrent use should be avoided if possible. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Lopinavir; Ritonavir: (Moderate) Cardiac and neurologic events have been reported when ritonavir was concurrently administered with beta-blockers.
Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Magnesium Salicylate: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Mavacamten: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Mefloquine: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Meglitinides: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Meperidine; Promethazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Mepivacaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Peripheral vasodilation may occur after use of mepivacaine. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance. Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Mestranol; Norethindrone: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Metformin; Repaglinide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Metformin; Rosiglitazone: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Metformin; Saxagliptin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Metformin; Sitagliptin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Methacholine: (Moderate) Beta-blockers may impair reversal of methacholine-induced bronchoconstriction with an inhaled rapid-acting beta-agonist.
Methohexital: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
Methylergonovine: (Moderate) Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide. The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis. However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and beta-blockers may prolong neuromuscular blockade.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nicardipine: (Moderate) Use nicardipine and nadolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Nifedipine: (Moderate) In general, concomitant therapy of nifedipine with beta-blockers is well tolerated and can even be beneficial in some cases (i.e., inhibition of nifedipine-induced reflex tachycardia by beta-blockade). Negative inotropic and/or chronotropic effects can be additive when these drugs are used in combination. Finally, angina has been reported when beta-adrenergic blocking agents are withdrawn abruptly and nifedipine therapy is initiated. A gradual downward titration of the beta-adrenergic blocking agent dosage during initiation of nifedipine therapy may minimize or eliminate this potential interaction. Hypotension and impaired cardiac performance can occur during coadministration of nifedipine with beta-blockers, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis. Monitor clinical response during coadministration; adjustment of nifedipine dosage may be needed during concurrent beta-blocker therapy.
Nimodipine: (Moderate) Nimodipine, a selective calcium-channel blocker, can enhance the antihypertensive effects of beta-blockers. Although often used together, concurrent use of calcium-channel blockers and beta-blockers may result in additive hypotensive, negative inotropic, and/or bradycardic effects in some patients.
Nirmatrelvir; Ritonavir: (Moderate) Cardiac and neurologic events have been reported when ritonavir was concurrently administered with beta-blockers.
Nisoldipine: (Moderate) Concurrent use of nisoldipine with nadolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Nitrates: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Non-Ionic Contrast Media: (Moderate) Use caution when administering non-ionic contrast media to patients taking beta-blockers. Beta-blockers lower the threshold for and increase the severity of contrast reactions and reduce the responsiveness of treatment of hypersensitivity reactions with epinephrine.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs.
Octreotide: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Cardiac and neurologic events have been reported when ritonavir was concurrently administered with beta-blockers.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by beta-blockers. If these drugs are used together, closely monitor for changes in blood pressure.
Ozanimod: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and beta-adrenergic blockers who are susceptible to hypotension.
Pasireotide: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as beta-blockers. Dose adjustments of beta-blockers may be necessary.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perindopril; Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Perphenazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Perphenazine; Amitriptyline: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Phenelzine: (Moderate) Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Additive hypotensive effects may be seen when phenelzine is combined with antihypertensives. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Phenothiazines: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Phenoxybenzamine: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Phentolamine: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Pilocarpine: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
Pioglitazone; Metformin: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Ponesimod: (Moderate) Monitor for decreases in heart rate if concomitant use of ponesimod and beta-blockers is necessary. Consider a temporary interruption in beta-blocker therapy before initiating ponesimod in patients with a resting heart rate less than or equal to 55 bpm. Beta-blocker treatment can be initiated in patients receiving stable doses of ponesimod. Concomitant use of another beta-blocker with ponesimod resulted in a mean decrease in heart rate of 12.4 bpm after the first dose of ponesimod and 7.4 bpm after beginning maintenance ponesimod.
Pramlintide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Prazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Prilocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Prilocaine; Epinephrine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Procainamide: (Major) High or toxic concentrations of procainamide may prolong AV nodal conduction time or induce AV block; these effects could be additive with the pharmacologic actions of beta-blockers, like nadolol. In general, patients receiving combined therapy with procainamide and beta-blockers should be monitored for potential bradycardia, AV block, and/or hypotension.
Procaine: (Minor) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Prochlorperazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Promethazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Promethazine; Dextromethorphan: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Promethazine; Phenylephrine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Propafenone: (Major) Pharmacologically, beta-blockers, like nadolol, cause AV nodal conduction depression and additive effects are possible when used in combination with propafenone. When used together, AV block can occur. Patients should be monitored closely and the dose should be adjusted according to clinical response.
Propofol: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
Quinidine: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving beta-blockers or calcium-channel blockers due to additive hypotensive effects.
Reserpine: (Moderate) Reserpine may have additive orthostatic hypotensive effects when used with beta-blockers due to catecholamine depletion. Beta-blockers may also interfere with reflex tachycardia, worsening the orthostasis. Patients treated concurrently with a beta-blocker and reserpine should be monitored closely for evidence of hypotension or marked bradycardia and associated symptoms (e.g., vertigo, syncope, postural hypotension).
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of nadolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nadolol concomitantly.
Ritonavir: (Moderate) Cardiac and neurologic events have been reported when ritonavir was concurrently administered with beta-blockers.
Rivastigmine: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may theoretically be increased when given with other medications known to cause bradycardia such as beta-blockers.
Ropivacaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Salsalate: (Moderate) Concurrent use of beta-blockers with salsalate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Semaglutide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Sevoflurane: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
SGLT2 Inhibitors: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
Siponimod: (Moderate) Monitor for significant bradycardia with coadministration of siponimod and beta-blockers, as additive lowering effects on heart rate may occur; temporary interruption of beta-blocker treatment may be necessary prior to siponimod initiation. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.
Sufentanil: (Moderate) The incidence and degree of bradycardia and hypotension during induction with sufentanil may be increased in patients receiving beta-blockers.
Sulfonylureas: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Sympathomimetics: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Tamsulosin: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
Tasimelteon: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Telmisartan; Amlodipine: (Moderate) Coadministration of amlodipine and beta-blockers can reduce angina and improve exercise tolerance. When these drugs are given together, however, hypotension and impaired cardiac performance can occur, especially in patients with left ventricular dysfunction, cardiac arrhythmias, or aortic stenosis.
Terazosin: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use caution with the concomitant use of tetracaine and antihypertensive agents.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as beta-blockers should be used cautiously due to the potential for additive bradycardia.
Thiazolidinediones: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Thiethylperazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Thioridazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Thyroid hormones: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
Tirzepatide: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Trandolapril; Verapamil: (Moderate) Use verapamil and nadolol with caution and close monitoring due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility. There have been reports of excess bradycardia and AV block, including complete heart block, when beta-blockers and verapamil have been used for the treatment of hypertension.
Tranylcypromine: (Major) Avoid concomitant use of beta-blockers and tranylcypromine due to the risk of additive hypotension and/or severe bradycardia. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the beta-blocker). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure and heart rate closely.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Trifluoperazine: (Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive effect.
Verapamil: (Moderate) Use verapamil and nadolol with caution and close monitoring due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility. There have been reports of excess bradycardia and AV block, including complete heart block, when beta-blockers and verapamil have been used for the treatment of hypertension.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
Like other beta-adrenergic antagonists, nadolol competes with adrenergic neurotransmitters (e.g., catecholamines) for binding at sympathetic receptor sites. Similar to propranolol and timolol, nadolol blocks sympathetic stimulation mediated by beta1-adrenergic receptors in the heart and vascular smooth muscle. Pharmacodynamic consequences of beta1-receptor blockade include a decrease in both resting and exercise heart rate and cardiac output, and a decrease in both systolic and diastolic blood pressure. Nadolol may reduce reflex orthostatic hypotension. In addition, nadolol also may competitively block beta2-adrenergic responses in the bronchial smooth muscle, potentially inducing bronchospasm.
Actions that make nadolol useful in treating hypertension include a negative chronotropic effect that decreases heart rate at rest and after exercise; a negative inotropic effect that decreases cardiac output; reduction of sympathetic outflow from the CNS; and suppression of renin release from the kidneys. The fall in cardiac output induced by beta1 effects is often countered by a moderate reflex increase in peripheral vascular resistance that can be magnified by beta2 blockade (unmasked alpha stimulation). As a result, nonselective beta-blocking agents may produce a more modest decrease in (diastolic) blood pressure compared with selective beta1-antagonists. Thus, nadolol, like other beta-blockers, affects blood pressure via multiple mechanisms. In general, beta-blockers without intrinsic sympathomimetic activity (ISA) exert detrimental effects on LVH and the lipid profile, and cause sexual dysfunction.
Pharmacodynamic actions that make nadolol useful in treating hypertension also apply to the management of chronic stable angina. The reduction in myocardial oxygen demand induced by nadolol decreases the frequency of anginal attacks and requirements of nitrate, and increases exercise tolerance. Another postulated anti-anginal activity of nadolol includes an increase in oxygen delivery to the myocardial tissue.
Nadolol has been used to treat portal hypertension and to prevent bleeding of esophageal varices. Nonselective beta-blockers decrease portal venous pressure, decrease blood flow in the superior portosystemic collateral circulation, and decrease blood flow in the splanchnic region. Beta-blockade decreases cardiac output reducing hepatic arterial and portal venous perfusion. Activation of unopposed alpha-receptors lead to splanchnic vasoconstriction, thus decreasing portal perfusion.
Nadolol possesses numerous mechanisms that may contribute to its efficacy to prevent migraine headaches. Beta-blockade can prevent arterial dilation, inhibit renin secretion, and block catecholamine-induced lipolysis. Blocking lipolysis, decreases arachidonic acid synthesis and subsequent prostaglandin production. Inhibition of platelet aggregation is due to this decrease in prostaglandins and blockade of catecholamine-induced platelet adhesion. Other actions include increased oxygen delivery to tissues and prevention of coagulation during epinephrine release.
Nadolol has been used in the management of hereditary or familial essential tremor. Beta-blockade controls the involuntary, rhythmic and oscillatory movements of essential tremor. Tremor amplitude is reduced, but not the frequency of tremor.
Nadolol can dampen the peripheral physiologic symptoms of anxiety. Beta-blockade can attenuate somatic symptoms of anxiety such as palpitations and tremor, but it is less effective in controlling psychologic components, such as intense fear.
Nadolol is administered orally. Nadolol is widely distributed throughout the body, crosses the placenta, and is distributed into both bile and breast milk. The drug is only about 30% bound to plasma proteins. Unlike many other beta-blockers, nadolol is not metabolized by the liver and is primarily eliminated renally as unchanged drug. The half-life in subjects with normal renal function is 10-24 hours, which allows for once-daily dosing of the drug.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration, nadolol is variably and incompletely (30-40%) absorbed from the GI tract. Food does not affect the rate or the extent of nadolol absorption. Following an oral dose, the onset of therapeutic effect occurs within 1 hour, peaks within 3-4 hours, and is sustained for at least 24 hours.
-Special Populations
Renal Impairment
The plasma half-life of nadolol is significantly affected by impairment of renal function. Adjustment of dosing intervals is required in individuals with renal impairment. Nadolol is removed by hemodialysis.
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