QUININE DOSAGE FORMS AND METHODS OF USE THEREOF
Disclosed herein are quinine formulations and methods of using quinine formulations. Specifically disclosed are methods of using quinine and informing a user of information, including potential adverse effects, the effect of food on quinine's pharmacokinetics, effect of dosing various strengths of quinine, effect of maximum plasma concentrations of quinine in a patient as it relates to adverse events, effects of deviating from the prescribed dosage, etc.
1 . A method of using quinine comprising:
providing a patient with quinine; and
informing the patient:
QTc interval prolongation was evaluated in a pharmacokinetic study in healthy patients who received single oral doses of quinine sulfate (324 mg and 648 mg) wherein the mean±SD maximum QTc change from baseline around the quinine T max was 10±19 msec for 324 mg and 12±18 msec for 648 mg doses;
there were no subjects who had a QTc interval greater than 500 msec, and
there were no subjects who had a maximum QTc change from baseline of greater than 60 msec.
2 . The method of claim 1 , wherein the patient is a patient with uncomplicated Plasmodium falciparum malaria, malaria caused by Plasmodium species, severe or complicated Plasmodium falciparum malaria, leg cramps, or babesiosis.
3 . The method of claim 1 , wherein the patient is a patient with uncomplicated Plasmodium falciparum malaria.
4 . The method of claim 1 , wherein the patient is a patient receiving quinine therapy for the prophylaxis of malaria or leg cramps.
5 . The method of claim 1 , wherein the informing is provided by a product insert or a printed label.
6 . The method of claim 1 , wherein the quinine is quinine free base, quinine sulfate, or quinine hydrochloride.
7 . The method of claim 1 , wherein the quinine is quinine sulfate.
8 . The method of claim 1 , further comprising informing the patient
a) that the oral administration of quinine under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions;
b) that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions;
c) that the oral administration of quinine under fed conditions increases T max of quinine when compared to fasted conditions; or
d) that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions increases T max of quinine when compared to fasted conditions.
9 . The method of claim 8 , wherein the patient is informed that the oral administration of quinine under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions.
10 . The method of claim 8 , wherein the patient is informed that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions.
11 . The method of claim 8 , wherein the patient is informed that the oral administration of quinine under fed conditions increases T max of quinine when compared to fasted conditions.
12 . The method of claim 8 , wherein the patient is informed that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions increases T max of quinine when compared to fasted conditions.
13 . The method of claim 8 , further comprising informing the patient that the quinine can be taken with or without food.
14 . The method of claim 8 , further comprising informing the patient that it is recommended to take quinine with food to minimize gastric upset.
15 . The method of claim 8 , further comprising informing the patient that quinine taken with food extends the time to achieve T max by about 15 minutes to about 4.0 hours compared to a T max achieved under fasted conditions.
16 . The method of claim 1 , further comprising informing the patient that quinine taken with food extends the time to achieve T max by about 1.0 hour to about 2.0 hours greater than a T max achieved under fasted conditions.
17 . The method of claim 1 , wherein the patient is provided with quinine as a capsule formulation.
18 . A method of using quinine comprising:
providing a patient with quinine; and
informing the patient:
QTc interval prolongation was evaluated in a pharmacokinetic study in healthy patients who received single oral doses of quinine sulfate (324 mg and 648 mg) wherein the mean±SD maximum QTc change from baseline around the quinine T max was 10±19 msec for 324 mg and 12±18 msec for 648 mg doses;
there were no subjects who had a QTc interval greater than 500 msec, and
there were no subjects who had a maximum QTc change from baseline of greater than 60 msec; and
a) that the oral administration of quinine under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions;
b) that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions does not substantially affect C max or AUC of quinine when compared to fasted conditions;
c) that the oral administration of quinine under fed conditions increases T max of quinine when compared to fasted conditions; or
d) that the oral administration of about 324 or about 648 mg of quinine sulfate under fed conditions increases T max of quinine when compared to fasted conditions.
19 . The method of claim 18 , further comprising informing the patient that quinine taken with food extends the time to achieve T max by about 15 minutes to about 4.0 hours compared to a T max achieved under fasted conditions.
20 . The method of claim 18 , further comprising informing the patient that quinine taken with food extends the time to achieve T max by about 1.0 hour to about 2.0 hours greater than a T max achieved under fasted conditions.