Sotalol - Betapace AF

Question 1

Antiarrhythmic class

Answer 1

• Class III with Class II activities

Question 2

Mechanism of action

Answer 2

• b-blocker

* Prolongs cardiac action potential

Question 3

Indications

Answer 3

• Maintenance of sinus rhythm in symptomatic AF/AFL in patients who are in sinus rhythm

Question 4

Oral Dosing Strengths

Answer 4

80 mg, 120 mg, 160 mg

Question 5

Dosing

Answer 5

• Must be initiated in a setting that provides continuous ECG and monitored for minimum of 3 days

• Individualize dose: 5-step instructions
1. Assess QTc interval
2. Calculate CrCl
3. Starting dose breakpoints: CrCl >60 mL/min
(80 mg BID), 40-60 mL/min (80 mg QD),
<500 ms, discharge or ↑ dose to
120 mg BID with monitoring (in hospital)

• Reevaluate QTc and CrCl regularly if warranted
• Approved for use in children

Precaution: Adjust dose based on kidney function. Sotalol clearance not affected by hepatic insufficiency

Question 6

Treatment setting

Answer 6

• Start in appropriate facility where HCPs are trained in the management of serious VAs

Question 7

Monitoring requirements at initiation

Answer 7

• Continuous ECG monitoring at initiation (3-day minimum)

Question 8

Pharmacokinetics

Answer 8

• Dose proportional

Question 9

Bioavailability/ absorption

Answer 9

• Oral bioavailability 90%–100%

* Steady-state plasma levels within 2–3 days

Question 10

Half-life

Answer 10

• 12 hours
• Dosing every 12 hours results in trough plasma
concentrations which are approximately one-half of those at peak

Question 11

Protein binding

Answer 11

No protein binding

• Due to lack of protein binding, hemodialysis is used to reduce sotalol plasma concentrations

Question 12

Metabolism

Answer 12

• Not metabolized

Question 13

Major active metabolite

Answer 13

• No metabolite

Question 14

Route of elimination

Answer 14

• Mostly via kidneys

Question 15

Overdosage

Answer 15

• Treat with hemodialysis
• Common signs: bradycardia, CHF, hypotension,
bronchospasm, hypoglycemia
• Discontinue and monitor QT interval and BP
• In addition, for bradycardia: atropine; hypotension:
epinephrine; bronchospasm: aminophylline or b2-stimulant

Question 16

Contraindications

Answer 16

• Sinus bradycardia • SSS
• 2nd- and 3rd-degree AV block (unless a
• pacemaker is present)
• Congenital or acquired long QT syndromes • Baseline QT interval >450 ms
• Cardiogenic shock • Uncontrolled HF • Hypokalemia
• CrCl <40 mL/min • Asthma
Hypersensitivity to drug

Question 17

Boxed Warning

Answer 17

• To minimize risk of arrhythmias, initiate or re-initiate treatment in appropriate facility for 3 days (minimum) in order to provide cardiac resuscitation, continuous electrocardiographic monitoring, and CrCl calculations
• Do not substitute Betapace AF with Betapace because of labeling differences

Question 18

Warnings(except boxed warning—see above)

Answer 18

Bolded Warnings
• Can cause serious VA, primarily TdP
• Prolonged interval is related to ↓ CrCl, gender,
and dose
• Risk of TdP can be reduced by dose adjustment
according to CrCl and monitoring ECG

Warnings
• Proarrhythmia occurred in AF/AFL and other SVAs (TdP=0.6%)
• In patients with a history of sustained VT, the incidence of TdP during sotalol treatment was 4% and worsened VT in about 1%; in patients with other less serious ventricular arrhythmias the incidence of TdP was 1% and new or worsened VT in about 0.7%
• Use with drugs that prolong QT interval is not recommended
• Class IA and Class III AADs not recommended
• Caution in HF or LVD
• Do not use in patients with hypokalemia or
hypomagnesemia
• Can cause bradycardia (13%)
Warnings related to β-blocker activity
• Abrupt withdrawal of sotalol, especially with ischemic
heart disease • Patients with
— Nonallergic bronchospasm (bronchitis, emphysema) — Anaphylaxis history
— Anesthesia
— Diabetes
— SSS
— Thyrotoxicosis (may mask symptoms)
Betapace AF® Flecainide acetate5,a Rythmol® (propafenone HCl)/Rythmol® SR (sotalol HCl)4,a,c (propafenone HCl extended release)6,7,a,d

Question 19

Precautions

Answer 19

• There is a direct relationship between renal
function and elimination rate of Betapace
• See dosing guidance for patients with renal
impairment
• Advise patient to read PPI
— Assess medication history
— Report symptoms of electrolyte imbalance (prolonged diarrhea, sweating, vomiting, loss of appetite) to HCP
— Dosing schedule: If dose is missed, do NOT double next dose

Question 20

Drug interactions

Answer 20

studied and are not recommended (many AADs, some phenothiazines, bepridil, tricyclic antidepressants, certain oral macrolides)
• Class I or III agents should be withheld for
3 half-lives prior to dosing with Betapace AF; Class IA and Class III AADs not recommended; only limited data for Class 1C
• Pharmacodynamic interactions:
— Digoxin
— CCBs
— Catecholamine-depleting agents (reserpine,
guanethidine)
— Insulin and oral antidiabetics
— b-agonists (salbutamol, terbutaline, isoprenaline)
— Clonidine
— Antacids: avoid taking Betapace AF within 2 hours of antacids containing aluminum oxide and magnesium hydroxide
• Not expected to interact with drugs undergoing CYP450 metabolism (eg, CYP3A)
• Drug-laboratory tests:
— Falsely elevates levels of urinary metanephrine

No interaction with hydrochlorothiazide or warfarin

Question 21

Adverse Reactions

Answer 21

• TdP in 0.3% given ≤320 mg/day (n=597)
• Safety evaluated in 275 AF/AFL patients given
Betapace AF; most common AEs (160-240 mg, >240-320 mg, placebo):
— Abnormal ECG (3.3%, 2.5%, 0.4%)
— Bradycardia (13.1%, 12.3%, 2.5%)
— Diarrhea (5.2%, 5.7%, 2.1%)
— Nausea/vomiting (7.8%, 5.7%, 5.3%)
— Fatigue (19.6%, 18.9%, 8.5%)
— Hyperhidrosis (5.2%, 4.9%, 3.2%)
— Weakness (5.2%, 4.9%, 3.2%)
— Dizziness (16.3%, 13.1%, 12.4%)
— Dyspnea (9.2%, 9.8%, 7.4%)
— Upper respiratory infection (2.6%, 3.3%,
1.1%)
— Vision disturbance (2.6%, 0.8%, 0.7%)
• b-blocking effects (bradycardia, dyspnea, fatigue) and Class III effect (QT interval prolongation) are dose-related