Overview
11 DESCRIPTION Quinine sulfate is a cinchona alkaloid chemically described as cinchonan-9-ol, 6'-methoxy-, (8α, 9R)-, sulfate (2:1) (salt), dihydrate with a molecular formula of (C 20 H 24 N 2 O 2 ) 2 •H 2 SO 4 •2H 2 O and a molecular weight of 782.94. The structural formula of quinine sulfate is: Quinine sulfate occurs as a white, crystalline powder that darkens on exposure to light.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Quinine is an antimalarial agent [see CLINICAL PHARMACOLOGY ( 12.4 )] . 12.2 Pharmacodynamics QTc interval prolongation was studied in a double-blind, multiple dose, placebo- and positive-controlled crossover study in young (N=13, 20 to 39 years) and elderly (N=13, 65 to 78 years) subjects. After 7 days of dosing with quinine sulfate 648 mg three times daily, the maximum mean (95% upper confidence bound) differences in QTcI from placebo after baseline correction was 27.7 (32.2) ms. Prolongation of the PR and QRS interval was also noted in subjects receiving quinine sulfate. The maximum mean (95% upper confidence bound) difference in PR from placebo after baseline-correction was 14.5 (18.0) ms.
Indications
- 1 INDICATIONS AND USAGE Quinine sulfate capsule USP is a cinchona alkaloid indicated for treatment of uncomplicated Plasmodium falciparum malaria ( 1 ). Quinine sulfate capsule USP is an antimalarial drug indicated only for treatment of uncomplicated Plasmodium falciparum malaria. Quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented [see CLINICAL STUDIES ( 14 )] . Quinine sulfate capsules USP are not approved for: Treatment of severe or complicated P. falciparum malaria. Prevention of malaria.
Common Doses
- 648 mg
- 324 mg
Dosage
2 DOSAGE AND ADMINISTRATION Adults (≥ 16 years of age): 648 mg (two capsules) every 8 hours for 7 days ( 2.1 ). Patients with severe chronic renal impairment: one loading dose of 648 mg (two capsules) followed 12 hours later by 324 mg (one capsule) every 12 hours for 7 days ( 2.2 ). 2.1 Treatment of Uncomplicated P. falciparum Malaria For treatment of uncomplicated P. falciparum malaria in adults: Orally, 648 mg (two capsules) every 8 hours for 7 days [see CLINICAL STUDIES ( 14 )] .
Black Box Warning
WARNING: HEMATOLOGIC REACTIONS [see FULL PRESCRIBING INFORMATION for complete boxed warning] Quinine sulfate capsules use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported.
Contraindications
- 4 CONTRAINDICATIONS Quinine sulfate is contraindicated in patients with the following: Prolongation of QT interval ( 4 ) Glucose-6-phosphate dehydrogenase (G6PD) deficiency ( 4 ) Myasthenia gravis ( 4 ) Known hypersensitivity to quinine, mefloquine, or quinidine ( 4 ) Optic neuritis ( 4 ) Quinine sulfate is contraindicated in patients with the following: • Prolonged QT interval. One case of a fatal ventricular arrhythmia was reported in an elderly patient with a prolonged QT interval at baseline, who received quinine sulfate intravenously for P.
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions are a cluster of symptoms called "cinchonism", which occurs to some degree in almost all patients taking quinine: headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, disturbance in color perception, vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or www.lupinpharmaceuticals.com. or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Interactions
- 7 DRUG INTERACTIONS Interacting Drug Interaction Drugs known to prolong QT interval (e.g., Class IA and Class III antiarrhythmic agents). Quinine sulfate prolongs QT interval, ECG abnormalities including QT prolongation and Torsades de Pointes. Avoid concomitant use ( 5.3 ). Other antimalarials (e.g., halofantrine, mefloquine). ECG abnormalities including QT prolongation Avoid concomitant use ( 5.3 , 7.2 ). CYP3A4 inducers or inhibitors Alteration in plasma quinine concentration. Monitor for lack of efficacy or increased adverse events of quinine ( 7.1 ).