1 門診處方討論 Nadolol 用於 Gastrointestinal tract bleeding 的治療 報告者：蔡岱利

2 Nadolol (80mg/tab) 0.5#QD Esophageal varices with bleeding

3 Isosorbide dinitrate (10mg/tab) 1#TID Nadolol (80mg/tab) 0.5#QD Hemorrhage of gastrointestinal tract

4 FDA labeled indications Angina pectoris Hypertension Non-FDA labeled indications Arrhythmias Gastrointestinal bleeding Hyperthyroidism Migraine headache Indications

5 Mechanism of Nadolol  Nadolol is a nonselective beta-adrenergic receptor blocking agent.  Dilatory tone of the mesenteric arterioles resulting in unopposed α-adrenergic- mediated vasoconstriction,and a decrease in portal inflow and portal pressure.

6 MONOTHERAPY  Long-term NADOLOL reduces the risk of recurrent and first episodes of gastrointestinal bleeding  May reduce the mortality rate in patients with cirrhosis and variceal 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 tolerated, because bleeding can occur when β-blocker therapy is abruptly discontinued. Clinical application Dosage  Gastrointestinal (GI) bleeding: mg ORALLY once daily; titrate dose to reduce resting heart rate by 20%-25% or 55 beats/min

7 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

8 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

9 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.

10 References  MICROMEDEX  PHARMACOTHERAPY