June, 2000, Vol 2

Formulary Additions

Sotalol Hydrochloride (Betapace AF™)

80 mg, 120 mg, and 160 mg tablets

Berlex Laboratories

Restricted to Cardiology Use Only

Sotalol hydrochloride is a nonselective beta-adrenergic blocking agent with Class II (beta-adrenoreceptor blocking) and Class III (cardiac action potential duration prolongation) antiarrhythmic properties. The beta-blocking effect of sotalol is non-cardioselective, half-maximal at approximately 80 mg/day and maximal at doses between 320 and 640 mg/d. At oral doses of 160 to 640 mg/d, a dose related mean in QT increases 40-100 msec and 10-40 msec in QTc. Betapace AF™ is indicated for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation/atrial flutter who are currently in sinus rhythm.

The appropriate dose of sotalol should be individualized based on calculated creatinine clearance and QT interval. Patients should be anticoagulated according to standard of practice for atrial fibrillation and hypokalemia corrected prior to initiation of sotalol.  The maximum daily dose for BETAPACE AF™ is 160 mg BID.  Higher doses have been associated with increased risk of torsade de pointes.

Sotalol is contraindicated in patients with sinus bradycardia, sick sinus syndrome or second and third degree AV block, congenital or acquired long-QT syndromes, baseline QT interval >450 msec, cardiogenic shock, uncontrolled heart failure, hypokalemia (<4 mEq/L), creatinine clearance <40 mL/min, bronchial asthma and hypersensitivity to sotalol.  Sotalol can cause serious ventricular arrhythmias, primarily torsade de pointes, associated with QT interval prolongation, which is directly related to the dose of sotalol.  Factors such as reduced creatinine clearance, gender (female), and larger doses increase the risk of torsade de pointes.  Adjusting the dose according to creatinine clearance and monitoring ECG for excessive increases in QT interval can decrease this risk. 

            Other warnings and precautions for the use of sotalol include patients with proarrhythmia in atrial fibrillation/atrial flutter or ventricular arrhythmia, congestive heart failure, electrolyte disturbances (hypokalemia or hypomagnesemia), bradycardia/heart block, recent acute MI, abrupt withdrawal of sotalol therapy, non-allergic bronchospasm, anaphylaxis with prior beta-blocker therapy, anesthesia, diabetes, thryotoxicosis, and renal impairment.

            Sotalol is primary eliminated by renal excretion, therefore, drugs that are metabolized by cytochrome P450 isoenzymes are not expected to alter the pharmacokinetics of sotalol.  The following medications should be given with caution in patients receiving sotalol: antiarrhythmics, drugs that prolong the QT interval digoxin, calcium channel blocking agents, catecholamine-depleting agents (i.e. reserpine), insulin and oral antidiabetics, beta-2-receptors agonists (i.e. terbutaline), clonidine, and antacids.

The most common adverse effects with sotalol are dose related and typical of antiarrhythmic activities, including bradycardia (13%), fatigue (20%), dizziness (16%), subjective rhythm disturbance (10%), dyspnea (9%), weakness (5%), non-anginal chest pain (5%), and abnormal ECG (3%) at doses of 160 to 240 mg.

Sotalol is classified as a FDA Pregnancy Category B rating. Sotalol crosses the placenta and has been found in amniotic fluid.  Subnormal birth weights have been reported with sotalol. Sotalol should only be used during pregnancy if the potential benefit outweighs the potential risk. Sotalol excretion has been reported in human milk.  Due to potential adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue sotalol, taking into consideration the importance of the drug to the mother.

Ursodiol (URSO250^®)

250mg tablet

Axcan Pharma U.S., Inc.

Ursodiol, also known as ursodeoxycholic acid, is a naturally occurring bile acid present in small quantities in human bile. It dissolves cholesterol gallstones by altering bile composition to become unsaturated and promotes enhanced removal of the cholesterol from the gallbladder into the intestine. Additionally, ursodiol is believed to protect bile ducts against injury by replacing hydrophobic bile acids and other hepatotoxins with the gentler, hydrophilic ursodeoxycholic acid. Ursodiol is used in the dissolution of gallstones in chronic cholestasis associated with cystic fibrosis and the prevention of gallstones in rapid weight loss.  Urso® is indicated for the treatment of primary biliary cirrhosis (PBC).

For the treatment of non-calcified gallstone dissolution less than 20mm in diameter, the recommended oral dosage of ursodiol is 8 to 10 mg/kg/day in 2 to 3 divided doses with food over 9 months to 2 years.  The recommended dose of ursodiol for the treatment of PBC is 13 to 15 mg/kg/day in four divided doses with food. Axacan Pharma U.S. Inc. has a reimbursement support program, URSOurce, to ensure third-party coverage of long-term ursodiol therapy.  Hepatic enzymes should be monitored upon the initiation of therapy and thereafter as indicated by the particular clinical circumstances or at 1 and 3 months and then every 6 months.

Ursodiol is contraindicated in patients with calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones and hypersensitivity to bile acids.  Patients with compelling reasons for a cholecystectomy, including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula, are not candidates for ursodiol therapy. Cholestyramine, colestipol, other bile acid sequestering agents, and aluminum-containing antacids may reduce the absorption of ursodiol.  Estrogens, oral contraceptives, clofibrate, and potentially other lipid lowering medications may counteract the effectiveness of ursodiol by increasing hepatic cholesterol secretion and encouraging cholesterol gallstone formation.

Adverse reactions reported in clinical trials with ursodiol, included abdominal pain, cholecystitis, constipation, gastrointestinal disorder, nausea and vomiting.  These reactions were also reported in placebo-treated patients and may be attributed to the underlying illness.   

Ursodiol is classified as a FDA Pregnancy Category B.  It is unknown if ursodiol is excreted in human milk.  Use caution if ursodiol is administered to a nursing mother. 

Desenex®

Novartis Consumer/ OTC Division

Active Ingredient Change

The formulation for Desenex^®, an over-the-counter antifungal preparation, has changed. Undecylenic acid is no longer the active ingredient. The currently available Desenex^® products contain miconazole 2% in the spray and powder and clotrimazole 1% in the cream. Both miconazole and clotrimazole creams are currently available on the KU formulary, therefore, Desenex^® cream will no longer be available. Desenex^® powder, which now contains miconazole 2%, will remain on KU formulary.

FORMULARY BOOK 1999-2000 UPDATES

Formulary Deletions Not Listed in 1999-2000 Formulary Book (as of 5/23/00)

Formulary Additions Not Listed in 1999-2000 Formulary Book (as of 5/23/00)

Formulary Additions Not Listed in 1999-2000 Formulary Book (as of 5/23/00) Cont.

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