Nadolol (Anabet, Corgard) 20 mg & 40 mg is a non-selective beta-adrenergic receptor blocker that is used in the treatment of angina and hypertension. It is also used in the prevention of vascular headaches and for the reduction of portal pressures in patients with esophageal varices and portal hypertension.
Nadolol Uses:
-
Angina:
- Used for treatment of angina pectoris
-
Hypertension:
- Used for management of hypertension (not recommended as first-line treatment).
-
Off Label Use of Nadolol in Adults:
- Atrial fibrillation (rate control)
- Prevention of Catecholaminergic polymorphic ventricular tachycardia
- Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosis
- Migraine prophylaxis
- Supraventricular tachycardia
- Thyrotoxicosis
- Prevention of Ventricular arrhythmias due to congenital long QT syndrome
- Suppression of Ventricular premature beat
- Prevention of Ventricular tachycardia
Nadolol Dose in Adults
Nadolol Dose in the treatment of Angina:
P/O:
- Initial: 40 mg once a day, increase dosage gradually by 40 to 80 mg increments at 3- to 7-day intervals until optimum clinical response is obtained
- usual dose: 40 to 80 mg once a day; doses may be titrated up to 160 or 240 mg once daily
Nadolol Dose in the treatment of Atrial fibrillation for rate control:
- P/O: Usual maintenance dose: 10 to 240 mg once a day.
Nadolol Dose in the prevention of Catecholaminergic polymorphic ventricular tachycardia (off-label):
- P/O: 40 to 320 mg once a day.
Nadolol Dose in the treatment of Gastroesophageal variceal hemorrhage prophylaxis in patients with cirrhosis (off-label):
- P/O:
- Initial: 40 mg once a day.
- Consider starting with 20 mg once daily if concern for hypotension.
- Every two to three days until the maximum acceptable dose is reached or the heart rate reaches 55 to 60 beats per minute.
- Reduce the dose or stop taking the medication if your systolic blood pressure is less than 90 mm Hg.
- For individuals without ascites, some doctors advise a maximum dose of 160 mg/day, and for those with ascites, 80 mg/day.
Note:
May use for primary or secondary prophylaxis. Primary prophylaxis is indicated for patients with cirrhosis and medium/large varices, variceal red wale markings on endoscopy, or decompensation and small varices.
Nadolol Dose as an alternative agent in the treatment of Hypertension:
P/O:
- Initial: 40 mg once a day
- Depending on the patient's response, titrate by increments of 40–80 mg as necessary.
- Usual dosage range: 40 to 120 mg once a day.
- Doses up to 320 mg once daily may be necessary.
Nadolol Dose in the treatment of Supraventricular tachycardia:
P/O:
- 40 mg once daily at first
- Maximum daily maintenance dose: 320 mg.
Nadolol Dose in the treatment of Thyrotoxicosis (off-label):
- P/O: 40 to 160 mg once a day.
Nadolol Dose in the prevention of ventricular arrhythmias due to congenital long QT syndrome (off-label):
- P/O: 40 to 320 mg daily.
Nadolol Dose for the suppression of Ventricular premature beat:
- P/O: 40 to 320 mg daily.
Nadolol Dose for the prevention of Ventricular tachycardia:
- P/O: 40 to 320 mg daily.
Nadolol Dose in Children
Nadolol Dose for Migraine Prophylaxis:
-
Children >6 years and Adolescents:
- P/O: 0.25-1 mg/kg once or twice a day; begin at the low end of the range and slowly titrate upwards every 1-2 weeks.
Nadolol Dose in the treatment of SVT:
-
Infants ≥3 months, Children, and Adolescents:
P/O:
-
- Initial dose: 0.5–1 mg/kg once day; progressively increase to a daily maximum of 2.5 mg/kg
- Using a median dose of 1 mg/kg/day, SVT was well managed in a trial including 26 paediatric patients (aged 3 months to 15 years).
Pregnancy Risk Factor C
- In some studies on animal reproduction, adverse events were reported.
- Nadolol crosses the placenta, and can be measured in infant serum after birth.
- After maternal use of nadolol during childbirth, neonates have experienced hypoglycemia and Bradycardia.
- In utero beta-blocker exposure has been linked to a reduction in birth weight.
- It is recommended that infants are monitored at birth in a safe environment.
- Preeclampsia and chronic maternal hypertension that are not treated can also cause adverse events in the infant, mother, and fetus.
- While beta-blockers can be used to treat hypertension during pregnancy, it is better to use other agents than nadolol.
Nadolol use during breastfeeding:
- Breast milk contains Nadolol.
- Six hours is required for peak milk concentration.
- The half-life of nadolol found in breastmilk is the same as that in maternal serum.
- Noradilol can be detected in breastmilk for several days following the last maternal dose.
- The manufacturer recommends that the mother decide whether to stop breastfeeding or discontinue the drug.
- This is in consideration of the risk of serious adverse reactions in breastfed babies.
Nadolol Dose in Kidney Disease:
-
CrCl >50 mL/minute/1.73 m²:
- Administer every 24 hours
-
CrCl 31 to 50 mL/minute/1.73 m²:
- Administer every 24 to 36 hours
-
CrCl 10 to 30 mL/minute/1.73 m²:
- Administer every 24 to 48 hours
-
CrCl <10 mL/minute/1.73 m²:
- Administer every 40 to 60 hours
-
Dosage adjustments for dialysis are not provided in the manufacturer’s labeling; however, the following guidelines have been used by some clinicians (Aronoff 2007):
-
ESRD requiring hemodialysis:
- Administer dose postdialysis.
-
Peritoneal dialysis:
- Administer every 40 to 60 hours
-
Nadolol Dose in Liver disease:
- No dosage adjustments provided in the manufacturer’s labeling.
Common Side Effects of Nadolol (Anabet):
-
Central nervous system:
- Drowsiness
- Insomnia
Less Common Side Effects of Nadolol (Anabet):
-
Cardiovascular:
- Atrioventricular Block
- Bradycardia
- Cardiac Conduction Disturbance
- Cardiac Failure
- Cold Extremities
- Edema
- Hypotension
- Palpitations
- Peripheral Vascular Insufficiency
- Raynaud's Phenomenon
-
Central Nervous System:
- Depression
- Dizziness
- Fatigue
- Sedation
Contraindications to Nadolol (Anabet):
- Bronchial asthma
- Sinus bradycardia
- Heart block of greater than the first degree is possible (except for patients who have a working artificial pacemaker).
- Cardiogenic shock
- Uncompensated cardiac Failure
- There is not much evidence of cross-reactivity between beta-blockers and allergenic beta-blockers.
- Cross-sensitivity is possible due to similarities in chemical structure and/or drugcologic actions. However, this cannot be ruled out.
Canadian labeling: Additional contraindications not in US labeling
- Hypersensitivity to nadolol and any component of the formulation
- Cor pulmonale
- Anesthesia using agents that cause myocardial depression
- Allergy rhinitis, Bronchospasm or severe chronic obstructive lung disease (COPD).
Warnings and precautions
-
Anaphylactic reactions
- Avoid using this product if you have had severe allergic reactions to allergens in the past.
- Beta-blockers can make patients more sensitive to repeated challenges.
- Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
-
Bronchospastic disease
- Patients with bronchospastic diseases should not be given beta-blockers.
- You should use caution if you are going to use it.
-
Conductive abnormality
- Before you start, consider preexisting conditions like sick sinus syndrome.
-
Diabetes:
- Diabetics should be cautious
- Could cause hypoglycemia or mask symptoms.
-
Heart failure (HF):
- Patients with compensated heart disease should be cautious and monitored for any possible complications. Noradrolol's efficacy in HF has not yet been proven to work.
-
Myasthenia gravis:
- Patients with myasthenia gravis should be treated with caution.
-
Raynaud and peripheral vascular disease (PVD).
- It can cause or exacerbate arterial insufficiency symptoms in patients with Raynaud and PVD.
- Be cautious and monitor for arterial obstruction.
-
Untreated Pheochromocytoma
- Before any beta-blocker can be used, it is necessary to have adequate alpha-blockade.
-
Angina Prinzmetal version:
- Patients with Prinzmetal variant Angina should avoid beta-blockers that do not block alpha1adrenergic receptor activity. Unopposed alpha1adrenergic receivers mediate the coronary vasoconstriction, which can lead to worsening of anginal symptoms.
-
Psoriasis:
- Although beta-blocker usage has been linked to psoriasis exacerbation or induction, cause and effect are not clear.
-
Renal impairment
- Patients with impaired renal function should be cautious.
- Dosage adjustments may be required.
-
Thyroid disease:
- Hyperthyroidism may be disguised (eg, Tachycardia).
- Hyperthyroidism should be suspected and treated accordingly.
- Rapid withdrawal can worsen hyperthyroidism symptoms or cause a thyroid storm.
Nadolol: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Acetylcholinesterase Inhibitors |
May enhance the bradycardic effect of Beta-Blockers. |
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Alpha1-Blockers |
Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1Blockers. The risk associated with ophthalmic products is probably less than systemic products. |
|
Amiodarone |
May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. |
|
Amphetamines |
May lessen the effectiveness of antihypertensive agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
|
Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Bradycardia-Causing Agents |
May intensify other bradycardia-causing agents' bradycardic effects. |
|
Bretylium |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. In patients taking AV blocking medications, bretylium may also strengthen atrioventricular (AV) blockade. |
|
Brigatinib |
May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. |
|
Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bupivacaine |
Beta-Blockers may increase the serum concentration of Bupivacaine. |
|
Calcium Channel Blockers (Nondihydropyridine) |
May enhance the hypotensive effect of BetaBlockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. |
|
Cardiac Glycosides |
Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. |
|
Cholinergic Agonists |
Beta-Blockers may make Cholinergic Agonists' harmful or toxic effects worse. The possibilities for bronchoconstriction and aberrant cardiac conduction are of special concern. Management: Use cautious while combining these drugs, and keep an eye out for conduction issues. Because methacholine may cause further bronchoconstriction when used with any beta blocker, avoid using it. |
|
Dexmethylphenidate |
Can lessen an antihypertensive drug's therapeutic impact. |
|
Diazoxide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Dipyridamole |
Could make beta-blockers' bradycardic impact stronger. |
|
Disopyramide |
Could make beta-blockers' bradycardic impact stronger. Beta-blockers might make Disopyramide's adverse inotropic impact worse. |
|
DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
|
EPINEPHrine (Nasal) |
The hypertensive impact of EPINEPHRINE may be enhanced by beta-blockers like Nonselective (Nasal). |
|
EPINEPHrine (Oral Inhalation) |
The hypertensive impact of EPINEPHRINE may be enhanced by beta-blockers like Nonselective (Oral Inhalation). |
|
Epinephrine (Racemic) |
Epinephrine's hypertensive action may be enhanced by beta-blockers like Nonselective (Racemic). |
|
EPINEPHrine (Systemic) |
The hypertensive impact of EPINEPHRINE may be enhanced by beta-blockers like Nonselective (Systemic). |
|
Erdafitinib |
P-glycoprotein/ABCB1 Substrates serum levels can rise. |
|
Herbs (Hypertensive Properties) |
May lessen the effectiveness of antihypertensive agents. |
|
Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Hypotension-Associated Agents |
Blood pressure drugs may intensify the hypotensive effects of hypotension-associated substances. |
|
Insulins |
Beta-Blockers might improve insulin's ability to lower blood sugar. |
|
Ivabradine |
Bradycardia-Causing Agents may intensify Ivabradine's bradycardic impact. |
|
Lacosamide |
Bradycardia-Causing Substances may intensify Lacosamide's AV-blocking effects. |
|
Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
|
Lidocaine (Systemic) |
Beta-blockers might boost the level of lidocaine in the blood (Systemic). |
|
Lidocaine (Topical) |
Beta-blockers might boost the level of lidocaine in the blood (Topical). |
|
Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Lumacaftor |
May lower the level of P-glycoprotein/ABCB1 Substrates in the serum. The serum concentration of P-glycoprotein/ABCB1 Substrates may rise when using lumacaftor. |
|
Mepivacaine |
Mepivacaine's serum levels may rise after taking beta-blockers. |
|
Methoxyflurane |
May enhance the hypotensive effect of Beta-Blockers. |
|
Methylphenidate |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Midodrine |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
NIFEdipine |
May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Nonsteroidal Anti-Inflammatory Agents |
May diminish the antihypertensive effect of BetaBlockers. |
|
Opioids (Anilidopiperidine) |
May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
P-glycoprotein/ABCB1 Inducers |
May lower the level of Pglycoprotein/ABCB1 Substrates in the serum. P-glycoprotein inducers may also further restrict the distribution of p-glycoprotein substrates to particular cells, tissues, and organs that have high levels of p-glycoprotein (e.g., brain, T-lymphocytes, testes, etc.). |
|
P-glycoprotein/ABCB1 Inhibitors |
Pglycoprotein/ABCB1 Substrates serum levels can rise. Additionally, p-glycoprotein inhibitors may improve the distribution of pglycoprotein substrates to particular cells, tissues, and organs where high levels of p-glycoprotein are present (e.g., brain, T-lymphocytes, testes, etc.). |
|
Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
|
Phosphodiesterase 5 Inhibitors |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Prostacyclin Analogues |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Quinagolide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Ranolazine |
P-glycoprotein/ABCB1 Substrates serum levels can rise. |
|
Regorafenib |
Could make beta-blockers' bradycardic impact stronger. |
|
Reserpine |
May strengthen beta-blockers' hypotensive effects. |
|
Ruxolitinib |
May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. |
|
Sulfonylureas |
Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. |
|
Terlipressin |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Tofacitinib |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Yohimbine |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Alpha2-Agonists |
May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. |
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Ceritinib |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. |
|
Dronedarone |
May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in betablocker dose. |
|
Ergot Derivatives |
Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. |
|
Fingolimod |
Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. |
|
Grass Pollen Allergen Extract (5 Grass Extract) |
Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. |
|
Green Tea |
May decrease the serum concentration of Nadolol. Management: Advise patients to minimize green tea consumption during nadolol treatment. The impact of separating nadolol doses from green tea consumption has not been investigated. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Siponimod |
Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. |
|
Theophylline Derivatives |
Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. |
|
Risk Factor X (Avoid combination) |
|
|
Beta2-Agonists |
Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2Agonists. |
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Floctafenine |
May enhance the adverse/toxic effect of Beta-Blockers. |
|
Methacholine |
Beta-Blockers may enhance the adverse/toxic effect of Methacholine. |
|
Rivastigmine |
May enhance the bradycardic effect of Beta-Blockers. |
Monitoring parameters:
- Heart rate
- Blood pressure
- Signs/symptom of angina exacerbation when discontinued
Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):
-
Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
- Target blood pressure <130/80 mm Hg is recommended.
-
Confirmed hypertension without markers of increased ASCVD risk:
- Target blood pressure <130/80 mm Hg may be reasonable.
How to administer Nadolol (Anabet)?
P/O:
- May be administered without regard to meals.
Mechanism of action of Nadolol (Anabet):
- Competitively blocks the beta-1 and beta-2 adrenergic stimulation responses
- It doesn't exhibit any intrinsic sympathomimetic or membrane stabilizing activity.
- Non-selective beta adrenergic blocking drugs (propranolol and nadolol), reduce portal pressure by producing splanchnic vascular constriction (beta effect), which in turn reduces portal blood flow.
Duration:
- 17 to 24 hours
Absorption:
- ~30%
Protein binding:
- 30%
Metabolism:
- Not metabolized
Half-life elimination:
- Infants 3 to 22 months: 3.2 to 4.3 hours.
- Children 10 years: 15.7 hours
- Children ~15 years: 7.3 hours
- Adults: 20 to 24 hours;
- prolonged with renal impairment; (up to 45 hours in severe impairment).
Time to peak serum concentration:
- 3 to 4 hours
Excretion:
- Urine (as unchanged drug)
International Brand Names of Nadolol:
- Corgard
- TEVA-Nadolol
- Anabet
- Apo-Nadolol
- Corgard
- Farmagard
- Solgol
Nadolol Brand Names in Pakistan:
No Brands Available in Pakistan.
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