Nadolol (Rx)

(Corgard)
Category: Beta-blockers

DESCRIPTION:

 Nadolol is an oral, nonselective, beta adrenergic receptor antagonist

related to propranolol.

 The American Heart Association (2007) states that Nadolol should

not be used as first-line treatment for the management of
hypertension in the absence of indications to start beta-blockers.
Nadolol can reduce blood pressure significantly with minimal cardio
depressant effect.

 The drug was approved in December 1989 by the Food and Drug

ROUTE-SPECIFIC ADMINISTRATION:

Oral Administration

 It should have been administered without regard to meals

ADVERSE EFFECTS:

The side effects of the Nadolol are only just mild and temporary. These side effects are
shown within the therapy and will disappear over time.

 myocardial contractility depresses and can result as congestive heart failure, particularly to those who have
systolic dysfunction.

 1% of the patients is shown is CHF in trials which can occur with preexisting left ventricular dysfunction. That’s
why the treatment of Nadolol therapy stop. However, in some cases, using beta-blockers as a treatment is
working and effective. It slows the patient’s heart rate by less than 60 bpm and 2% to those who have a heart rate
of less than 40 bpm that is using it as a treatment. Atrioventricular block might also occur.

 1% of Hypotension and Sinus bradycardia can be sometimes severe but IV atropine serves as the replacement
when needed. With AV block, that is depressed conduction subordinate to the AV node, may needed
sympathomimetic or a pressor therapy. Overdosing of beta-blockers, CHF, bradycardia and blocking of heart can
cause cardiovascular symptoms. Moreover, Syncope might occur if there are hypotensive effects.
 Lipophilic beta-blockers are being connected to effects of CNS aside from hydrophilic medications like Nadolol.
In spite of the theory debated with the trials of beta blockers. The recurrent CNS side effects using Nadolol is
associated with dizziness and fatigue. While on the other hand, the rare effects of CNS are changes in behavior,
depression, drowsiness, dysarthria, confusion, cognitive impairment, hallucinations, short term memory loss,
insomnia, vivid dreams, psychosis, altered sensorium, nightmares and paresthesia.

 Patients with pulmonary dispease or asthma may give rise to bronchospasm and dyspnea with the use of
betablockers.

 There is also a risk of having diabetes mellitus of patients with HTN. This kind of risk must be related with
advantages of using beta-blockers to decrease the cardiovascular complications.

 Sexual dysfunction, specifically impotence (erectile dysfunction) and decrease in libido; Peyronie's disease (0.1-
0.6%% of patients)

 Exacerbation of peripheral vasoconstriction (e.g., Raynaud's phenomenon).- (2% of patients)

 0.1-0.6% of patients have shown with Gastrointestinal effects in clinical trials have abdominal pain, diarrhea,
flatulence, nausea and vomiting, indigestion, anorexia, increasing of weight and
bloating. Moreover, ischemic colitis, mesenteric arterial thrombosis, and elevated hepatic enzymes is also shown

 Nasal congestion and tinnitus

Sudden discontinuation of using beta-blockers with hypertensive patients having experienced

withdrawal symptoms with tremor and sinus tachycardia, headache, diaphoresis, hypertension
and palpitations.

 The sudden changes to stop Nadolol, can result to myocardial infarction, severe HTN especially
to those people who have cardiac disease, the possible growth of myocardial ischemia, and ventricular
arrhythmias.

 Nadolol must be used carefully to patients particularly, to those with thyrotoxicosis and/or hyperthyroidism.
Tachycardia can be mask by beta-blockers, in which can help to monitor the thyroid disease. The sudden
discontinuation of beta-blockers with hyperthyroidism can result to more complications. Moreover, it is overall
useful in the treatment of symptomatic hyperthyroid
diseases like thyrotoxicosis.
OTHER ADVERSE EFFECTS:

Dermatologic and Allergic Reaction

 pruritus, skin hyperpigmentation, reversible alopecia,
Hematologic Adverse Reaction
xerosis, and exfoliative dermatitis. 0.1-0.6% of
 agranulocytosis, thrombotic thrombocytopenic
patients are reported to have reversible alopecia,
purpura (TTP) and non-thrombocytopenic purpura,
pemphigoid rash, diaphoresis, pruritus, rash
have been reported rarely during treatment with
(unspecified), xerostomia, xerophthalmia, and
Nadolol.
xerosis. Angioedema (facial swelling), laryngospasm,
and respiratory distress also have been sometimes
reported.

CONTRAINDCATION

 advanced AV block if there is presence of pacemaker

 sick sinus syndrome if there’s no present of pacemaker
 acute systolic congestive heart failure or cardiogenic shock
 acute pulmonary edema
 asthma/COPD
 diabetes mellitus of patients with HTN
 hypersensitivity
 hypothermia

PREGNANCY CATEGORY:

-C
 ORAL DOSAGE:

 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 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 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.

 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.
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.

 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.

 Alpha-blockers
(Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.

 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.

 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.

 Chlorpromazine
(Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive
effect.

 Dextromethorphan; Promethazine
(Moderate) Concomitant treatment with nadolol and phenothiazines, especially in large doses, can have an additive hypotensive
effect.

 Carbidopa; Levodopa
(Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.

 Chloroprocaine
(Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.