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門診處方討論Nadolol 用於 Gastrointestinal

tract bleeding 的治療

報告者：蔡岱利 94.06.17

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Nadolol (80mg/tab) 0.5#QD

Esophageal varices with bleeding

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Isosorbide dinitrate (10mg/tab) 1#TIDNadolol (80mg/tab) 0.5#QD

Hemorrhage of gastrointestinal tract

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FDA labeled indications

•Angina pectoris

•Hypertension

Non-FDA labeled indications

•Arrhythmias

•Gastrointestinal bleeding

•Hyperthyroidism

•Migraine headache

Indications

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Mechanism of NadololNadolol is a nonselective beta-adrenergic re

ceptor blocking agent. Dilatory tone of the mesenteric arterioles re

sulting in unopposed α-adrenergic-mediated vasoconstriction,and a decrease in portal inflow and portal pressure.

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MONOTHERAPY Long-term NADOLOL reduces the risk of recurrent and first epis

odes of gastrointestinal bleeding May reduce the mortality rate in patients with cirrhosis and varice

al bleeding episodes NADOLOL and PROPRANOLOL appear to be equally effective

at preventing gastrointestinal bleeding β-adrenergic blocker therapy should be lifelong, unless it is not tol

erated, because bleeding can occur when β-blocker therapy is abruptly discontinued.

Clinical application

DosageGastrointestinal (GI) bleeding: 40-160 mg ORALLY once daily; titrate dose to reduce resting heart rate by 20%-25% or 55 beats/min

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A. Nadolol is not significantly metabolized in the liver (Prod Info Corgard(R), 2001; Dreyfuss et al, 1977) and dosing adjustments in hepatic insufficiency do not appear warranted.

B. It was reported that therapy with nadolol for 6 months at doses to reduce the resting heart rate by 25% did not further impair liver function in cirrhotic patients with portal hypertension (Merkel et al, 1988).

DOSAGE IN HEPATIC INSUFFICIENCY

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Combination therapy

The combination of nadolol and isosorbide mononitrate is superior to nadolol monotherapy in prevention of variceal bleeding but does not significantly affect survival

Use of nadolol and isosorbide mononitrate is significantly more effective than sclerotherapy for the prevention of recurrent variceal bleeding and is associated with a lower rate of major complications

Studies comparing ligation with nadolol- isosorbide mononitrate therapy have not shown consistent results as to which treatment modality has greater efficacy

The combination of ligation, nadolol, and sucralfate is more effective than ligation alone for preventing variceal recurrence and rebleeding

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Combination therapy Dosage

The initial oral dose of nadolol is 80 milligrams (mg) once daily then the dose is adjusted to reduce the resting heart rate by 20% to 25% or to 55 beats per minute.

The dose of isosorbide mononitrate is progressively increased from an oral dose of 20 mg once daily up to a dose of 40 mg twice daily, unless adverse effects appear, in which case the maximum dose tolerated is given.

The combination of nadolol and isosorbide mononitrate does not impair renal function or increase the risk of ascites.

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ReferencesMICROMEDEX

PHARMACOTHERAPY