Method of administering sotalol IV/switch
Embodiments of the invention are broadly drawn to methods for determining an optimum dose of an antiarrhythmic drug, for example sotalol. In particular, the method involves titrating the dose of the drug gradually to determine the optimum plasma concentration for a patient, whether the patient has normal or abnormal renal function.
1 . A method comprising, in the following order:
(a) detecting a baseline QTc of a subject;
(b) administering a dose of a class III antiarrhythmic drug to the subject via a first intravenous infusion for a first duration of time;
(c) detecting a second QTc of the subject and determining a delta QTc from the difference between the second QTc measured after the first intravenous infusion and the baseline QTc; and
(d) determining whether the delta QTc is or is not within a specified range;
wherein if the delta QTc is within the specified range then (e) administering a further dose of the class III antiarrhythmic drug to the subject via a second intravenous infusion for a second duration of time, or administering at least one oral dose of the class III antiarrhythmic drug to the subject; or
wherein if the delta QTc is not within the specified range then (e) discontinuing the first intravenous administration and administering any further doses of the class III antiarrhythmic drug to the subject as an oral dose or doses, or administering a reduced second intravenous dose or doses to the subject.
2 . The method of claim 1 , wherein the class III antiarrhythmic drug is sotalol.
3 . The method of claim 1 , wherein the class III antiarrhythmic drug is dofetilide.
4 . The method of claim 2 , wherein the class III antiarrhythmic drug is amiodarone.
5 . The method of claim 1 , wherein the duration of time is 0.5 hour-2 hours.
6 . The method of claim 1 , wherein the subject has normal or abnormal renal function and the dose of class III antiarrhythmic drug administered via the intravenous infusion is 10 mg-80 mg.
7 . The method of claim 1 , wherein the subject has normal or abnormal renal function, and wherein the at least one oral dose of the class III antiarrhythmic drug comprises 80 mg, 120 mg, or 160 mg.
8 . The method of claim 1 , wherein the subject has normal renal function and at least one of the oral dose(s) of the class III antiarrhythmic drug is administered at a 12-hour interval from a previous oral dose.
9 . The method of claim 1 , wherein the subject has abnormal renal function and at least one of the oral dose(s) of the class III antiarrhythmic drug is administered at a 24-hour interval from a previous oral dose.
10 . A method comprising, in the following order:
(a) detecting a baseline QTc of a subject;
(b) administering a dose of a class III antiarrhythmic drug to the subject via a first intravenous infusion for a first duration of time;
(c) detecting a second QTc of the subject;
wherein if the second QTc of the subject prolongs to >500 msec, then (d) discontinuing the first intravenous administration and administering any further doses of the class III antiarrhythmic drug to the subject as an oral dose or doses, or administering a reduced second intravenous dose or doses to the subject; or
wherein if the further QTc does not prolong to >500 msec, then (d) administering at least one oral dose of the class III antiarrhythmic drug to the subject, or administering a second intravenous infusion to the subject for a second duration of time.
11 . The method of claim 10 , wherein the class III antiarrhythmic drug is sotalol.
12 . The method of claim 10 , wherein the class III antiarrhythmic is dofetilide.
13 . The method of claim 10 , wherein the class III antiarrhythmic is amiodarone.
14 . The method of claim 10 , wherein the subject has normal or abnormal renal function and the dose of class III antiarrhythmic drug administered via the intravenous infusion is 10 mg-80 mg.
15 . The method of claim 10 , wherein the subject has normal renal function and at least one of the oral dose(s) of the class III antiarrhythmic drug comprises 80 mg, 120 mg, or 160 mg.
16 . The method of claim 10 , wherein the subject has abnormal renal function and at least one of the oral dose(s) of the class III antiarrhythmic drug comprises 80 mg, 120 mg, or 160 mg.
17 . A method comprising, in the following order:
(a) detecting a QTc of a subject;
(b) administering a dose of a class III antiarrhythmic drug to the subject via a first intravenous infusion for a first duration of time;
(c) detecting a second QTc of the subject;
wherein if the further QTc of the subject prolongs to >500 msec, then (d) discontinuing the first intravenous administration and administering any further doses of the class III antiarrhythmic drug to the subject as an oral dose or doses or administering a reduced second intravenous dose or doses to the subject; or
wherein if the further QTc does not prolong to >500 msec, then (d) administering at least one oral dose of the class III antiarrhythmic drug to the subject or administering a second intravenous infusion to the subject for a second duration of time, wherein the subject achieves steady-state maximum plasma concentration within about 24 hours after initiation of administering the first intravenous infusion.
18 . The method of claim 17 , wherein the class III antiarrhythmic drug is sotalol.
19 . The method of claim 17 , wherein the class III antiarrhythmic drug is dofetilide.
20 . The method of claim 17 , wherein the class III antiarrhythmic drug is amiodarone.
21 . The method of claim 17 , wherein the dose of class III antiarrhythmic drug administered via the intravenous infusion is 10 mg-80 mg.
22 . The method of claim 17 , wherein the at least one oral dose of the class III antiarrhythmic drug is in an amount of 80 mg, 120 mg, or 160 mg.
23 . The method of claim 22 , wherein the at least one oral dose is administered at a 12-hour interval or at a 24-hour interval from a previous oral dose.