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 (atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, atrial flutter, focal atrial 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.
- Adjust every 2 to 3 days to maximally tolerated dose or until heart rate is ~55 to 60 beats per minute.
- If systolic blood pressure is less than 90 mm Hg, reduce the dose or discontinue.
- Some experts recommend a maximum dose of 160 mg/day in patients without ascites and 80 mg/day in patients with ascites.
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
- Titrate as needed based on the patient response by 40 to 80 mg increments
- 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:
- Initial: 40 mg once daily
- Maximum maintenance dose: 320 mg once daily.
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 Childrens
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: 0.5-1 mg/kg once daily; increase dose gradually to a maximum of 2.5 mg/kg/day
- Dosing based on a trial of 26 pediatric patients (age range: 3 months to 15 years) which showed SVT was well controlled with a median dose of 1 mg/kg/day.
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 diminish the antihypertensive effect of Antihypertensive Agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Barbiturates |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Bradycardia-Causing Agents |
May enhance the bradycardic effect of other Bradycardia-Causing Agents. |
|
Bretylium |
May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. |
|
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 enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. |
|
Dexmethylphenidate |
May diminish the therapeutic effect of Antihypertensive Agents. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dipyridamole |
May enhance the bradycardic effect of Beta-Blockers. |
|
Disopyramide |
May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
EPINEPHrine (Nasal) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). |
|
EPINEPHrine (Oral Inhalation) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). |
|
Epinephrine (Racemic) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). |
|
EPINEPHrine (Systemic) |
Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). |
|
Erdafitinib |
May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
Herbs (Hypertensive Properties) |
May diminish the antihypertensive effect of Antihypertensive Agents. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Insulins |
Beta-Blockers may enhance the hypoglycemic effect of Insulins. |
|
Ivabradine |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. |
|
Lacosamide |
Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Lidocaine (Systemic) |
Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). |
|
Lidocaine (Topical) |
Beta-Blockers may increase the serum concentration of Lidocaine (Topical). |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Lumacaftor |
May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
Mepivacaine |
Beta-Blockers may increase the serum concentration of Mepivacaine. |
|
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 decrease the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). |
|
P-glycoprotein/ABCB1 Inhibitors |
May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Ranolazine |
May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
Regorafenib |
May enhance the bradycardic effect of Beta-Blockers. |
|
Reserpine |
May enhance the hypotensive effect of Beta-Blockers. |
|
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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