Quinine Sulfate
Capsule · Oral
Uses
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. Treatment or prevention of nocturnal leg cramps [see WARNINGS AND PRECAUTIONS ( 5.1 )] .
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 )] . Quinine sulfate capsules USP should be taken with food to minimize gastric upset [see CLINICAL PHARMACOLOGY ( 12.3 )] . 2.2 Renal Impairment In patients with acute uncomplicated malaria and severe chronic renal impairment, the following dosage regimen is recommended: one loading dose of 648 mg quinine sulfate capsules USP followed 12 hours later by maintenance doses of 324 mg every 12 hours. The effects of mild and moderate renal impairment on the safety and pharmacokinetics of quinine sulfate are not known [see USE IN SPECIFIC POPULATIONS ( 8.6 ), CLINICAL PHARMACOLOGY ( 12.3 )] . 2.3 Hepatic Impairment Adjustment of the recommended dose is not required in mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, but patients should be monitored closely for adverse effects of quinine. Quinine should not be administered in patients with severe (Child-Pugh C) hepatic impairment [see USE IN SPECIFIC POPULATIONS ( 8.7 ), CLINICAL PHARMACOLOGY ( 12.3 )] .
Dosage forms and strengths
324 mg size "0" capsules with clear transparent cap and clear transparent body imprinted with "LU" on cap and "Y51" on body in black ink, containing white to off white powder ( 3 ). 324 mg size "0" capsules with clear transparent cap and clear transparent body imprinted with "LU" on cap and "Y51" on body in black ink, containing white to off white powder.
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. falciparum malaria [see WARNINGS AND PRECAUTIONS ( 5.3 )].
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Hemolysis can occur in patients with G6PD deficiency receiving quinine.
• Known hypersensitivity reactions to quinine.
• These include, but are not limited to, the following [see WARNINGS AND PRECAUTIONS ( 5.6 )] :
• Thrombocytopenia
• Idiopathic thrombocytopenia purpura (ITP) and Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic uremic syndrome (HUS)
• Blackwater fever (acute intravascular hemolysis, hemoglobinuria, and hemoglobinemia)
• Known hypersensitivity to mefloquine or quinidine: cross-sensitivity to quinine has been documented [see WARNINGS AND PRECAUTIONS ( 5.6 )].
• Myasthenia gravis. Quinine has neuromuscular blocking activity, and may exacerbate muscle weakness.
• Optic neuritis. Quinine may exacerbate active optic neuritis [see ADVERSE REACTIONS ( 6 )] .
Warnings and precautions
Not indicated for the prevention or treatment of nocturnal leg cramps. Risk of serious and life-threatening adverse reactions ( 1 , 5.1 ). Thrombocytopenia, including ITP and HUS/TTP, has been reported. Discontinue drug ( 5.2 ). QT prolongation and ventricular arrhythmias. Avoid concomitant use with drugs known to prolong QT interval ( 5.3 ). Avoid concomitant use with rifampin. Quinine sulfate treatment failures have been reported ( 5.4 ). Avoid concomitant use with neuromuscular blocking agents. Quinine sulfate may potentiate neuromuscular blockade and cause respiratory depression ( 5.5 ). Serious and life threatening hypersensitivity reactions. Discontinue drug ( 4 , 5.6 ). Atrial fibrillation and flutter. Paradoxical increase in ventricular rate may occur. Closely monitor digoxin levels if used concomitantly ( 5.7 ). Hypoglycemia. Monitor for signs and symptoms ( 5.8 ). 5.1 Use of Quinine Sulfate for Treatment or Prevention of Nocturnal Leg Cramps Quinine sulfate may cause unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in addition to hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization. Chronic renal impairment associated with the development of TTP, and fatalities have also been reported. The risk associated with the use of quinine sulfate in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition [see BOXED WARNING and CONTRAINDICATIONS ( 4 )] . 5.2 Thrombocytopenia Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode. 5.3 QT Prolongation and Ventricular Arrhythmias QT interval prolongation has been a consistent finding in studies which evaluated electrocardiographic changes with oral or parenteral quinine administration, regardless of age, clinical status, or severity of disease. The maximum increase in QT interval has been shown to correspond with peak quinine plasma concentration [see CLINICAL PHARMACOLOGY ( 12.2 )] . Quinine sulfate has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation. Quinine sulfate has been shown to cause concentration-dependent prolongation of the PR and QRS interval. At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (e.g. verapamil) or QRS interval (e.g. flecainide or quinidine) [see CLINICAL PHARMACOLOGY ( 12.2 )] . Quinine sulfate is not recommended for use with other drugs known to cause QT prolongation, including Class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), and Class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide). The use of macrolide antibiotics such as erythromycin should be avoided in patients receiving quinine sulfate. Fatal torsades de pointes was reported in an elderly patient who received concomitant quinine, erythromycin, and dopamine. Although a causal relationship between a specific drug and the arrhythmia was not established in this case, erythromycin is a CYP3A4 inhibitor and has been shown to increase quinine plasma levels when used concomitantly. A related macrolide antibiotic, troleandomycin, has also been shown to increase quinine exposure in a pharmacokinetic study [see DRUG INTERACTIONS ( 7.1 )] . Quinine may inhibit the metabolism of certain drugs that are CYP3A4 substrates and are known to cause QT prolongation, e.g., astemizole, cisapride, terfenadine, pimozide, halofantrine and quinidine. Torsades de pointes has been reported in patients who received concomitant quinine and astemizole. Therefore, concurrent use of quinine sulfate with these medications, or drugs with similar properties, should be avoided [see DRUG INTERACTIONS ( 7.2 )] . Concomitant administration of quinine sulfate with the antimalarial drugs, mefloquine or halofantrine, may result in electrocardiographic abnormalities, including QT prolongation, and increase the risk for torsades de pointes or other serious ventricular arrhythmias. Concurrent use of quinine sulfate and mefloquine may also increase the risk of seizures [see DRUG INTERACTIONS ( 7.2 )] . Quinine sulfate should also be avoided in patients with known prolongation of QT interval and in patients with clinical conditions known to prolong the QT interval, such as uncorrected hypokalemia, bradycardia, and certain cardiac conditions [see CONTRAINDICATIONS ( 4 )] . 5.4 Concomitant Use of Rifampin Treatment failures may result from the concurrent use of rifampin with quinine sulfate, due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided [see DRUG INTERACTIONS ( 7.1 )] . 5.5 Concomitant Use of Neuromuscular Blocking Agents The use of neuromuscular blocking agents should be avoided in patients receiving quinine sulfate.
Side effects
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. 6.1 Overall Quinine can adversely affect almost every body system. The most common adverse events associated with quinine use are a cluster of symptoms called "cinchonism", which occurs to some degree in almost all patients taking quinine. Symptoms of mild cinchonism include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception. More severe symptoms of cinchonism are vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction. Most symptoms of cinchonism are reversible and resolve with discontinuation of quinine. The following ADVERSE REACTIONS have been reported with quinine sulfate. Because these reactions have been reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General Fever, chills, sweating, flushing, asthenia, lupus-like syndrome, and hypersensitivity reactions. Hematologic Agranulocytosis, hypoprothrombinemia, thrombocytopenia, disseminated intravascular coagulation, hemolytic anemia; hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, petechiae, ecchymosis, hemorrhage, coagulopathy, blackwater fever, leukopenia, neutropenia, pancytopenia, aplastic anemia, and lupus anticoagulant. Neuropsychiatric Headache, diplopia, confusion, altered mental status, seizures, coma, disorientation, tremors, restlessness, ataxia, acute dystonic reaction, aphasia, and suicide. Dermatologic Cutaneous rashes, including urticarial, papular, or scarlatinal rashes, pruritus, bullous dermatitis, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, photosensitivity reactions, allergic contact dermatitis, acral necrosis, and cutaneous vasculitis. Respiratory Asthma, dyspnea, pulmonary edema. Cardiovascular Chest pain, vasodilatation, hypotension, postural hypotension, tachycardia, bradycardia, palpitations, syncope, atrioventricular block, atrial fibrillation, irregular rhythm, unifocal premature ventricular contractions, nodal escape beats, U waves, QT prolongation, ventricular fibrillation, ventricular tachycardia, torsades de pointes, and cardiac arrest. Gastrointestinal Nausea, vomiting, diarrhea, abdominal pain, gastric irritation, and esophagitis. Hepatobiliary Granulomatous hepatitis, hepatitis, jaundice, and abnormal liver function tests. Metabolic Hypoglycemia and anorexia. Musculoskeletal Myalgias and muscle weakness. Renal Hemoglobinuria, renal failure, renal impairment, and acute interstitial nephritis. Special Senses Visual disturbances, including blurred vision with scotomata, sudden loss of vision, photophobia, diplopia, night blindness, diminished visual fields, fixed pupillary dilatation, disturbed color vision, optic neuritis, blindness, vertigo, tinnitus, hearing impairment, and deafness.
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 ). CYP3A4 and CYP2D6 substrates Quinine is an inhibitor of CYP3A4 and CYP2D6. Monitor for lack of efficacy or increased adverse events of the co-administered drug ( 7.2 ). Digoxin Increased digoxin plasma concentration ( 5.8 , 7.1 ). See full prescribing information for a complete list of reported and potential interactions. 7.1 Effects of Drugs and Other Substances on Quinine Pharmacokinetics Quinine is a P-gp substrate and is primarily metabolized by CYP3A4. Other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 may contribute to the metabolism of quinine [see CLINICAL PHARMACOLOGY ( 12.3 )] . Antacids Antacids containing aluminum and/or magnesium may delay or decrease absorption of quinine. Concomitant administration of these antacids with quinine sulfate should be avoided. Antiepileptics (AEDs) (Carbamazepine, Phenobarbital, and Phenytoin) Carbamazepine, phenobarbital, and phenytoin are CYP3A4 inducers and may decrease quinine plasma concentrations if used concurrently with quinine sulfate. Cholestyramine In 8 healthy subjects who received quinine sulfate 600 mg with or without 8 grams of cholestyramine resin, no significant difference in quinine pharmacokinetic parameters was seen. Cigarette Smoking (CYP1A2 Inducer) In healthy male heavy smokers, the mean quinine AUC following a single 600 mg dose was 44% lower, the mean C max was 18% lower, and the elimination half-life was shorter (7.5 hours versus 12 hours) than in their non-smoking counterparts. However, in malaria patients who received the full 7-day course of quinine therapy, cigarette smoking produced only a 25% decrease in median quinine AUC and a 16.5% decrease in median C max , suggesting that the already reduced clearance of quinine in acute malaria could have diminished the metabolic induction effect of smoking. Because smoking did not appear to influence the therapeutic outcome in malaria patients, it is not necessary to increase the dose of quinine in the treatment of acute malaria in heavy cigarette smokers. Grapefruit Juice (P-gp/CYP3A4 Inhibitor) In a pharmacokinetic study involving 10 healthy subjects, the administration of a single 600 mg dose of quinine sulfate with grapefruit juice (full-strength or half-strength) did not significantly alter the pharmacokinetic parameters of quinine. Quinine sulfate may be taken with grapefruit juice. Histamine H 2 -Receptor Blockers [Cimetidine, Ranitidine (Nonspecific CYP450 Inhibitors)] In healthy subjects who were given a single oral 600 mg dose of quinine sulfate after pretreatment with cimetidine (200 mg three times daily and 400 mg at bedtime for 7 days) or ranitidine (150 mg twice daily for 7 days), the apparent oral clearance of quinine decreased and the mean elimination half-life increased significantly when given with cimetidine but not with ranitidine. Compared to untreated controls, the mean AUC of quinine increased by 20% with ranitidine and by 42% with cimetidine (p<0.05) without a significant change in mean quinine C max . When quinine is to be given concomitantly with a histamine H 2 -receptor blocker, the use of ranitidine is preferred over cimetidine. Although cimetidine and ranitidine may be used concomitantly with quinine sulfate, patients should be monitored closely for adverse events associated with quinine. Isoniazid Isoniazid 300 mg/day pretreatment for 1 week did not significantly alter the pharmacokinetic parameter values of quinine. Adjustment of quinine sulfate dosage is not necessary when isoniazid is given concomitantly. Ketoconazole (CYP3A4 Inhibitor) In a crossover study, healthy subjects (N=9) who received a single oral dose of quinine hydrochloride (500 mg) concomitantly with ketoconazole (100 mg twice daily for 3 days) had a mean quinine AUC that was higher by 45% and a mean oral clearance of quinine that was 31% lower than after receiving quinine alone. Although no change in the quinine sulfate dosage regimen is necessary with concomitant ketoconazole, patients should be monitored closely for adverse reactions associated with quinine. Macrolide Antibiotics (Erythromycin, Troleandomycin) (CYP3A4 Inhibitors) In a crossover study (N=10), healthy subjects who received a single oral 600 mg dose of quinine sulfate with the macrolide antibiotic, troleandomycin (500 mg every 8 hours) exhibited a 87% higher mean quinine AUC, a 45% lower mean oral clearance of quinine, and a 81% lower formation clearance of the main metabolite, 3-hydroxyquinine, than when quinine was given alone. Erythromycin was shown to inhibit the in vitro metabolism of quinine in human liver microsomes, an observation confirmed by an in vivo interaction study. In a crossover study (N=10), healthy subjects who received a single oral 500 mg dose of quinine sulfate with erythromycin (600 mg every 8 hours for four days) showed a decrease in quinine oral clearance (CL/F), an increase in half-life, and a decreased metabolite (3-hydroxyquinine) to quinine AUC ratio, as compared to when quinine was given with placebo. Therefore, concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with quinine sulfate should be avoided [see WARNINGS AND PRECAUTIONS ( 5.3 )] .
Use in specific populations
Renal impairment: Reduce dose and dosing frequency for patients with severe chronic renal impairment ( 2.2 , 8.6 , 12.3 ). Hepatic impairment: Closely monitor for adverse events. Quinine should not be administered in patients with severe (Child-Pugh C) hepatic impairment ( 2.3 , 8.7 , 12.3 ). Pregnancy: Based on animal data may cause fetal harm. Use only if the potential benefit justifies the risk ( 8.1 ). Nursing Mothers: Exercise caution when administering to a nursing woman ( 8.3 ). 8.1 Pregnancy Pregnancy Category C There are extensive published data but few well-controlled studies of quinine sulfate in pregnant women. Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester. In developmental and reproductive toxicity studies, central nervous system (CNS) and ear abnormalities and increased fetal deaths occurred in some species when pregnant animals received quinine at doses about 1 to 4 times the human clinical dose. Quinine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. P. falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population. Pregnant women with P. falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death. Therefore, treatment of malaria in pregnancy is important. Hypoglycemia, due to increased pancreatic secretion of insulin, has been associated with quinine use, particularly in pregnant women. Quinine crosses the placenta with measurable blood concentrations in the fetus. In 8 women who delivered live infants 1 to 6 days after starting quinine therapy, umbilical cord plasma quinine concentrations were between 1.0 and 4.6 mg/L (mean 2.4 mg/L) and the mean (±SD) ratio of cord plasma to maternal plasma quinine concentrations was 0.32 ± 0.14. Quinine levels in the fetus may not be therapeutic. If congenital malaria is suspected after delivery, the infant should be evaluated and treated appropriately. A study from Thailand (1999) of women with P. falciparum malaria who were treated with oral quinine sulfate 10 mg/kg 3 times daily for 7 days at anytime in pregnancy reported no significant difference in the rate of stillbirths at >28 weeks of gestation in women treated with quinine (10 of 633 women [1.6%]) as compared with a control group without malaria or exposure to antimalarial drugs during pregnancy (40 of 2201 women [1.8%]). The overall rate of congenital malformations (9 of 633 offspring [1.4%]) was not different for women who were treated with quinine sulfate compared with the control group (38 of 2201 offspring [1.7%]). The spontaneous abortion rate was higher in the control group (10.9%) than in women treated with quinine sulfate (3.5%) [OR = 3.1; 95% CI 2.1 to 4.7]. An epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy, found no increased risk of structural birth defects was seen (2 fetal malformations [1.9%]). Rare and isolated case reports describe deafness and optic nerve hypoplasia in children exposed in utero due to maternal ingestion of high doses of quinine. In animal developmental studies conducted in multiple animal species, pregnant animals received quinine by the subcutaneous or intramuscular route at dose levels similar to the maximum recommended human dose (MRHD; 32 mg/kg/day) based on body surface area (BSA) comparisons. There were increases in fetal death in utero in rabbits at maternal doses ≥ 100 mg/kg/day and in dogs at ≥ 15 mg/kg/day corresponding to dose levels approximately 0.5 and 0.25 times the MRHD respectively based on BSA comparisons. Rabbit offspring had increased rates of degenerated auditory nerve and spiral ganglion and increased rates of CNS anomalies such as anencephaly and microcephaly at a dose of 130 mg/kg/day corresponding to a maternal dose approximately 1.3 times the MRHD based on BSA comparison. Guinea pig offspring had increased rates of hemorrhage and mitochondrial change in the cochlea at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the MRHD based on BSA comparison. There were no teratogenic findings in rats at maternal doses up to 300 mg/kg/day and in monkeys at doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the MRHD respectively based on BSA comparisons. In a pre- postnatal study in rats, an estimated oral dose of quinine sulfate of 20 mg/kg/day corresponding to approximately 0.1 times the MRHD based on BSA comparison resulted in offspring with impaired growth, lower body weights at birth and during the lactation period, and delayed physical development of teeth eruption and eye opening during the lactation period. 8.2 Labor and Delivery There is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. In doses several-times higher than those used to treat malaria, quinine may stimulate the pregnant uterus. 8.3 Nursing Mothers There is limited information on the safety of quinine in breastfed infants. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. It is estimated from this study that breastfed infants would receive less than 2 to 3 mg per day of quinine base (< 0.4% of the maternal dose) via breast milk [see CLINICAL PHARMACOLOGY ( 12.3 )] . Although quinine is generally considered compatible with breastfeeding, the risks and benefits to infant and mother should be assessed. Caution should be exercised when administered to a nursing woman.
Overdosage
Quinine overdose can be associated with serious complications, including visual impairment, hypoglycemia, cardiac arrhythmias, and death. Visual impairment can range from blurred vision and defective color perception, to visual field constriction and permanent blindness. Cinchonism occurs in virtually all patients with quinine overdose. Symptoms range from headache, nausea, vomiting, abdominal pain, diarrhea, tinnitus, vertigo, hearing impairment, sweating, flushing, and blurred vision, to deafness, blindness, serious cardiac arrhythmias, hypotension, and circulatory collapse. Central nervous system toxicity (drowsiness, disturbances of consciousness, ataxia, convulsions, respiratory depression and coma) has also been reported with quinine overdose, as well as pulmonary edema and adult respiratory distress syndrome. Most toxic reactions are dose-related; however, some reactions may be idiosyncratic because of the variable sensitivity of patients to the toxic effects of quinine. A lethal dose of quinine has not been clearly defined, but fatalities have been reported after the ingestion of 2 to 8 grams in adults. Quinine, like quinidine, has Class I antiarrhythmic properties. The cardiotoxicity of quinine is due to its negative inotropic action, and to its effect on cardiac conduction, resulting in decreased rates of depolarization and conduction, and increased action potential and effective refractory period. ECG changes observed with quinine overdose include sinus tachycardia, PR prolongation, T wave inversion, bundle branch block, an increased QT interval, and a widening of the QRS complex. Quinine's alpha-blocking properties may result in hypotension and further exacerbate myocardial depression by decreasing coronary perfusion. Quinine overdose has been also associated with hypotension, cardiogenic shock, and circulatory collapse, ventricular arrhythmias, including ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, and torsades de pointes, as well as bradycardia, and atrioventricular block [see WARNINGS AND PRECAUTIONS ( 5 ), CLINICAL PHARMACOLOGY ( 12.3 )] . Quinine is rapidly absorbed, and attempts to remove residual quinine sulfate from the stomach by gastric lavage may not be effective. Multiple-dose activated charcoal has been shown to decrease plasma quinine concentrations [see CLINICAL PHARMACOLOGY ( 12.3 )] . Forced acid diuresis, hemodialysis, charcoal column hemoperfusion, and plasma exchange were not found to be effective in significantly increasing quinine elimination in a series of 16 patients.
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. It is odorless and has a persistent very bitter taste. It is only slightly soluble in water, alcohol, chloroform, and ether. Quinine sulfate capsules USP are supplied for oral administration as capsules containing 324 mg of the active ingredient quinine sulfate USP, equivalent to 269 mg free base. Inactive ingredients: black iron oxide, corn starch, gelatin, magnesium stearate, potassium hydroxide, propylene glycol shellac, sodium lauryl sulfate, and talc. 1
How supplied
16.1 How Supplied Quinine sulfate capsules USP, 324 mg are available as size "0" capsules with clear transparent cap and clear transparent body imprinted with "LU" on cap and "Y51" on body in black ink, containing white to off white powder: Bottles of 30 NDC 68180-560-06 16.2 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature] Dispense in a tight container as defined in the USP.
Patient information
See FDA-approved patient labelling (Medication Guide) 17.1 Dosing Instructions Patients should be instructed to: Take all of the medication as directed. Take no more of the medication than the amount prescribed. Take with food to minimize possible gastrointestinal irritation. If a dose is missed, patients should also be instructed not to double the next dose. If more than 4 hours has elapsed since the missed dose, the patient should wait and take the next dose as previously scheduled. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States. Manufactured by: Lupin Limited Goa 403 722 INDIA. September 2024 ID#: 277504 Image
Label text from the FDA structured product label by Lupin Pharmaceuticals, Inc. (revised Oct 31, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Quinine Sulfate in 4 products
Quinine Sulfate NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 65162-811 | Quinine Sulfate 324 mg/1 Capsule | Amneal Pharmaceuticals LLC | ANDA |
| 50742-238 | Quinine Sulfate 324 mg/1 Capsule | Ingenus Pharmaceuticals, LLC | ANDA |
| 68180-560 | Quinine Sulfate 324 mg/1 Capsule | Lupin Pharmaceuticals, Inc. | ANDA |
| 0093-3002 | Quinine Sulfate 324 mg/1 Capsule | Teva Pharmaceuticals USA, Inc. | ANDA |
Frequently asked questions
What is Quinine Sulfate used for?
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…
What are the side effects of Quinine Sulfate?
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 (… See the full label for the complete list.
Who makes Quinine Sulfate?
Quinine Sulfate is listed by 4 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Ingenus Pharmaceuticals, LLC, Lupin Pharmaceuticals, Inc., Teva Pharmaceuticals USA, Inc..