METHODS OF INTRAVENOUSLY ADMINISTERING SOTALOL
Methods of administering one or more IV doses of sotalol hydrochloride to a patient in need thereof are described. In embodiments, one or more of the IV doses of sotalol hydrochloride are administered as substitute(s) for one or more oral dose(s) of sotalol hydrochloride, with the substitute IV dosing based on the subject's creatinine clearance and when repeated as a selected interval is capable of providing a sotalol concentration commensurate with the steady state concentration expected from multiple sequential oral doses.
1 . A method of intravenously administering sotalol, comprising:
determining a creatinine clearance of a subject;
selecting an oral sotalol hydrochloride dosing regimen capable of providing a desired effect in the subject as a result of multiple sequential oral doses;
selecting an IV dose comprising an amount of sotalol hydrochloride that when based on the subject's creatinine clearance and repeated at a selected interval is capable of providing a sotalol concentration commensurate with the steady state concentration expected from the multiple sequential oral doses; and
for treatment of a cardiovascular condition and as a substitute for the oral dosing regimen, administering to the subject the IV dose repeated at the selected interval to achieve the sotalol concentration commensurate with the steady state concentration expected from the multiple sequential oral doses.
2 . A method of substituting oral sotalol with intravenous sotalol hydrochloride, comprising:
a. inputting a subject's creatinine clearance into a treatment management application;
b. inputting into the treatment management application an oral sotalol hydrochloride dosing regimen capable of providing a desired effect when administered to the subject as multiple sequential oral doses;
c. the treatment management application providing an output comprising an IV dose comprising an amount of sotalol hydrochloride that when based on the subject's creatinine clearance and repeated at a selected interval is capable of providing a sotalol concentration commensurate with the steady state concentration expected from the multiple sequential oral doses; and
d. for treatment of a cardiovascular condition and as a substitute for the oral dosing regimen, administering to the subject the IV dose repeated at the selected interval to achieve the sotalol concentration commensurate with the steady state concentration expected from the multiple sequential oral doses.
3 . The method of claim 1 , wherein:
the amount of each sotalol hydrochloride IV dose for a first subject with mild renal impairment and a creatinine clearance in the range of 60-89 mL/min is the same as for a second subject with normal renal function and a creatinine clearance in the range of ≥90 mL/min; and
the selected dosing interval is the same for the first and second subjects;
whereby no adjustment as to IV dosing amount or interval is needed to accommodate the subject with mild renal impairment relative to the subject with normal renal function in order to achieve the sotalol concentration commensurate with the steady state concentration associated with and expected from the multiple sequential oral doses;
optionally wherein the oral sotalol hydrochloride dosing regimen comprises oral doses in the amount of 80 mg, or 120 mg, or 160 mg.
4 . The method of claim 1 , wherein the IV dosing protocol is selected from any one or more of the following:
Creatinine
Current/
Dosing
Clearance
Substituted
Interval
(mL/min)
Oral Dose (mg)
IV Dose (mg)
(h)
≥90
80
50-100, e.g., 75
12
60-89
50-100, e.g., 75
12
30-59
42.5-92.5, e.g., 67.5
12 or 24
10-29
42.5-92.5, e.g., 67.5
12, 24 or 48
≥90
120
87.5-137.5, e.g.,
12
112.5
60-89
87.5-137.5, e.g.,
12
112.5
30-59
80-130, e.g., 105
12 or 24
10-29
80-130, e.g., 105
12, 24 or 48
≥90
160
125-175, e.g., 150
12
60-89
125-175, e.g., 150
12
30-59
117.5-167.5, e.g.,
12 or 24
142.5
10-29
110-160, e.g., 135
12, 24 or 48.
5 . The method of claim 1 , wherein the subject/patient is currently in sinus rhythm, or is not currently in sinus rhythm, or has been or will be converted to sinus rhythm with sotalol or another antiarrhythmic and/or cardioversion, such as electric cardioversion (e.g., DCCV or direct current cardioversion), and sotalol hydrochloride is administered for the treatment of one or more cardiovascular condition selected from atrial flutter (AFL), atrial fibrillation (AF), persistent atrial fibrillation, paroxysmal atrial fibrillation, paroxysmal or persistent atrial fibrillation or atrial flutter, such as for patients who have experienced a recent AF/AFL episode who are in sinus rhythm or who will be cardioverted, ventricular fibrillation (VF) or ventricular arrhythmias, life-threatening recurrent VF or life-threatening recurrent hemodynamically unstable VT, focal atrial tachycardia, supraventricular tachycardia (SVT), atrioventricular re-entrant tachycardia (AVRT), atrioventricular nodal re-entrant tachycardia (AVNRT), atrial tachycardia, paroxysmal atrial tachycardia, junctional tachycardia, junctional ectopic tachycardia (JET), congenital heart disease (CHD), multifocal atrial tachycardia, atrial ectopic tachycardia, accessory pathway SVT, infantile SVT, post-operative SVT, paroxysmal SVT, treating Wolff-Parkinson-White syndrome, ventricular tachycardia (VT), premature ventricular contractions (PVCs), hemodynamically stable or unstable ventricular tachycardia, heart failure, coronary artery disease, and pulmonary artery hypertension, maintenance of normal sinus rhythm (for example, delay in time to recurrence of atrial fibrillation/atrial flutter (AF/AFL)) for example in patients with symptomatic AF/AFL and/or who are currently in sinus rhythm, and/or indicated for the treatment of life-threatening ventricular tachycardia; and/or treating people, such as hospitalized people, with atrial fibrillation cardioverted to normal sinus rhythm, without ventricular arrhythmias or various forms of blocks, in patients with normal kidney function.
6 . The method of claim 5 , wherein the subject is currently in sinus rhythm and/or has experienced cardioversion to sinus rhythm, for example by way of electrocardioversion, such as DCCV, or chemical cardioversion, such as with sotalol hydrochloride, or combinations thereof.
7 . The method of claim 5 , wherein:
the oral sotalol hydrochloride dosing regimen comprises 80 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min;
the IV dose is administered in an amount of 67.5 mg.
8 . The method of claim 5 , wherein:
the oral sotalol hydrochloride dosing regimen comprises 120 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min;
the IV dose is administered in an amount of 105 mg.
9 . The method of claim 5 , wherein:
the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 30-59 mL/min;
the IV dosage is administered in an amount of 142.5 mg.
10 . The method of claim 5 , wherein:
the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 10-29 mL/min;
the IV dose is administered in an amount of 135 mg.
11 . The method of claim 1 , wherein the selected interval is a 12-hour, 24-hour or 48-hour interval.
12 . The method of claim 1 , wherein the IV dose is a 5-hour intravenous dose.
13 . The method of claim 1 , wherein the sotalol concentration is commensurate with the steady state concentration expected from the multiple sequential oral doses when the sotalol concentration is in the range of ±5% or ±10% or ±15% or ±20% of the expected steady state concentration.
14 . The method of claim 2 , wherein the sotalol concentration is commensurate with the steady state concentration expected from the multiple sequential oral doses when the sotalol concentration is in the range of ±5% or ±10% or ±15% or ±20% of the expected steady state concentration.
15 . The method of claim 2 , wherein the IV dosing protocol is selected from any one or more of the following:
Creatinine
Current/
Dosing
Clearance
Substituted
Interval
(mL/min)
Oral Dose (mg)
IV Dose (mg)
(h)
≥90
80
50-100, e.g., 75
12
60-89
50-100, e.g., 75
12
30-59
42.5-92.5, e.g., 67.5
12 or 24
10-29
42.5-92.5, e.g., 67.5
12, 24 or 48
≥90
120
87.5-137.5, e.g.,
12
112.5
60-89
87.5-137.5, e.g.,
12
112.5
30-59
80-130, e.g., 105
12 or 24
10-29
80-130, e.g., 105
12, 24 or 48
≥90
160
125-175, e.g., 150
12
60-89
125-175, e.g., 150
12
30-59
117.5-167.5, e.g.,
12 or 24
142.5
10-29
110-160, e.g., 135
12, 24 or 48.
16 . The method of claim 15 , wherein:
a. the oral sotalol hydrochloride dosing regimen comprises 80 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min; and
the IV dose is administered in an amount of 67.5 mg; or
b. the oral sotalol hydrochloride dosing regimen comprises 120 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min; and
the IV dose is administered in an amount of 105 mg; or
c. the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 30-59 mL/min; and
the IV dosage is administered in an amount of 142.5 mg; or
d. the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 10-29 mL/min; and
the IV dose is administered in an amount of 135 mg.
17 . The method of claim 16 , wherein the subject/patient is currently in sinus rhythm, or is not currently in sinus rhythm, or has been or will be converted to sinus rhythm with sotalol or another antiarrhythmic and/or cardioversion, such as electric cardioversion (e.g., DCCV or direct current cardioversion), and sotalol hydrochloride is administered for the treatment of one or more cardiovascular condition selected from atrial flutter (AFL), atrial fibrillation (AF), persistent atrial fibrillation, paroxysmal atrial fibrillation, paroxysmal or persistent atrial fibrillation or atrial flutter, such as for patients who have experienced a recent AF/AFL episode who are in sinus rhythm or who will be cardioverted, ventricular fibrillation (VF) or ventricular arrhythmias, life-threatening recurrent VF or life-threatening recurrent hemodynamically unstable VT, focal atrial tachycardia, supraventricular tachycardia (SVT), atrioventricular re-entrant tachycardia (AVRT), atrioventricular nodal re-entrant tachycardia (AVNRT), atrial tachycardia, paroxysmal atrial tachycardia, junctional tachycardia, junctional ectopic tachycardia (JET), congenital heart disease (CHD), multifocal atrial tachycardia, atrial ectopic tachycardia, accessory pathway SVT, infantile SVT, post-operative SVT, paroxysmal SVT, treating Wolff-Parkinson-White syndrome, ventricular tachycardia (VT), premature ventricular contractions (PVCs), hemodynamically stable or unstable ventricular tachycardia, heart failure, coronary artery disease, and pulmonary artery hypertension, maintenance of normal sinus rhythm (for example, delay in time to recurrence of atrial fibrillation/atrial flutter (AF/AFL)) for example in patients with symptomatic AF/AFL and/or who are currently in sinus rhythm, and/or indicated for the treatment of life-threatening ventricular tachycardia; and/or treating people, such as hospitalized people, with atrial fibrillation cardioverted to normal sinus rhythm, without ventricular arrhythmias or various forms of blocks, in patients with normal kidney function.
18 . The method of claim 17 , wherein:
a. the oral sotalol hydrochloride dosing regimen comprises 80 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min; and
the IV dose is administered in an amount of 67.5 mg; or
b. the oral sotalol hydrochloride dosing regimen comprises 120 mg oral doses;
the creatinine clearance of the subject is in the range of 10-59 mL/min; and
the IV dose is administered in an amount of 105 mg; or
c. the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 30-59 mL/min; and
the IV dosage is administered in an amount of 142.5 mg; or
d. the oral sotalol hydrochloride dosing regimen comprises 160 mg oral doses;
the creatinine clearance of the subject is in the range of 10-29 mL/min; and
the IV dose is administered in an amount of 135 mg.
19 . The method of claim 18 , wherein the subject is currently in sinus rhythm and/or has experienced cardioversion to sinus rhythm, for example by way of electrocardioversion, such as DCCV, or chemical cardioversion, such as with sotalol hydrochloride, or combinations thereof.
20 . The method of claim 19 , wherein the selected interval is a 12-hour, 24-hour or 48-hour interval and the IV dose is a 5-hour intravenous dose.