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Quinine Sulfate

Pronunciation: KWYE-nine SUL-fate
Class: Cinchona alkaloid

Trade Names

- Capsules, oral 324 mg

Apo-Quinine (Canada)
Quinine-Odan (Canada)


Inhibits nucleic acid synthesis, protein synthesis, and glycolysis in Plasmodium falciparum and can bind with hemozoin in parasitized erythrocytes.



Bioavailability is 76% to 88% in healthy adults; exposure is higher in patients with malaria. T max in healthy patients and patients with malaria is 2.8 h and 5.9 h, respectively. C max in healthy patients and patients with malaria is 3.2 and 8.4 mcg/mL, respectively. T max was prolonged to approximately 4 h when taken with a high-fat meal, but C max and AUC were not affected.


In healthy patients, the Vd ranges from 2.5 to 7.1 L/kg. In patients with malaria, the Vd decreases in proportion to the severity of the infection. Protein binding ranges from 69% to 92% in healthy patients and 78% to 95% in patients with malaria. Penetration into the CSF is relatively poor in patients with cerebral malaria, reaching approximately 2% to 7% of plasma concentrations. Concentrations in placental cord blood and breast milk are approximately 32% and 31%, respectively, of concentrations in maternal plasma. Less than 2 to 3 mg/day of quinine is secreted into breast milk.


Metabolism is almost exclusively via CYP pathways, primarily CYP3A4; other isozymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, are less influential in quinine metabolism.


Elimination is primarily by hepatic biotransformation. Approximately 20% is excreted unchanged in the urine. Elimination is twice as rapid in acidic urine compared with alkaline urine. In healthy subjects, the mean plasma Cl ranges from 0.08 to 0.47 L/h/kg, with a mean plasma elimination half-life of 9.7 to 12.5 h.

Special Populations

Renal Function Impairment

The effects of mild and moderate renal impairment on the pharmacokinetics and efficacy of quinine are not known. The plasma half-life is prolonged to 26 h in patients with severe long-term renal impairment; dosage adjustment needed. Negligible amounts are removed by hemodialysis or hemofiltration.

Hepatic Function Impairment

AUC increased 55% without a significant change in C max in patients with moderate hepatic impairment. In patients with mild to moderate hepatic impairment, dosage adjustment is not needed; however, monitor patients for adverse reactions. No pharmacokinetic data are available for patients with severe hepatic impairment.


Mean AUC is approximately 38% higher in healthy subjects 65 to 78 y of age compared with subjects 20 to 35 y of age. Mean T max and C max are similar in elderly and younger subjects. Mean oral Cl is decreased and mean elimination half-life is increased in elderly compared with younger subjects. The proportion of quinine excreted unchanged in the urine is larger in elderly compared with younger subjects. Despite these pharmacokinetic differences, no alteration in dosage is needed.


Pharmacokinetics are similar in children 1.5 to 12 y of age compared with adults with uncomplicated malaria. Mean total Cl and Vd are reduced in children with malaria compared with healthy pediatric controls.


AUC is decreased 25% and C max is decreased 16.5% in malaria patients who are smokers. No dosage adjustment is necessary.

Indications and Usage

Treatment of uncomplicated P. falciparum malaria.

Unlabeled Uses

Prevention and treatment of nocturnal recumbency leg cramps. Because of reports of serious and life-threatening adverse reactions, the risk associated with quinine use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit.


Prolonged QT interval; G6PD deficiency; myasthenia gravis; optic neuritis; known hypersensitivity to quinine, mefloquine, or quinidine; potential hypersensitivity reactions with previous quinine use (eg, hemolytic uremic syndrome, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, thrombocytopenia, blackwater fever [acute intravascular hemolysis, hemoglobinuria, hemoglobinemia]).

Dosage and Administration

Adults and Children 16 y and older

PO 648 mg every 8 h for 7 days.

Renal function impairment

PO In patients with severe long-term renal failure, administer a 648 mg loading dose followed 12 h later by maintenance dosage of 324 mg every 12 h.

General Advice

  • Administer with food to minimize GI upset.


Store between 68° and 77°F.

Drug Interactions

Aluminum- and/or magnesium-containing antacids

Causes delayed or decreased quinine absorption. Avoid coadministration.

Anticholinesterases (eg, neostigmine)

Beneficial effects of anticholinesterases in the treatment of myasthenia gravis may be reversed by quinine. Avoid coadministration in patients receiving anticholinesterases for myasthenia gravis.

Anticoagulants (eg, warfarin)

May cause depression of hepatic enzyme system that synthesizes vitamin K–dependent clotting factors and may enhance action of anticoagulants. Closely monitor PT, PTT, and INR during coadministration. Adjust the anticoagulant dose as needed.

Carbamazepine, phenobarbital

Plasma concentrations of these drugs may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If concomitant use cannot be avoided, frequently monitor the concentration of these agents. In addition, quinine metabolism may be increased, reducing plasma concentrations and decreasing the efficacy. Adjust the quinine dose as needed.

Cigarette smoking

Quinine AUC and C max may be reduced and the half-life shortened. However, dosage adjustment does not appear to be necessary in treating acute malaria.

Cimetidine, ranitidine

May reduce quinine's Cl and prolong its half-life. Closely monitor for quinine adverse reactions and adjust the quinine dose as needed.

CYP1A2 substrates (eg, aminophylline, theophylline)

Plasma concentrations of these agents may be reduced, decreasing the efficacy. Monitor theophylline concentrations and adjust the dose as needed. In addition, quinine plasma concentrations may be elevated, increasing the risk of adverse reactions. Closely monitor for quinine adverse reactions and adjust the quinine dose as needed.

CYP2D6 (eg, debrisoquine, desipramine, dextromethorphan, flecainide, metoprolol, mexiletine, paroxetine, tolterodine) and CYP3A4 (eg, zolpidem) substrates

Quinine may inhibit the metabolism of these substrates, increasing the pharmacologic effects and risk of adverse reactions. Monitor patient for adverse reactions and adjust treatment as needed.


May cause increased digoxin serum concentration. Closely monitor digoxin serum concentrations and adjust the digoxin dose as needed.

Erythromycin, ketoconazole, ritonavir

Quinine metabolism may be inhibited, increasing the risk of adverse reactions. Closely monitor for quinine adverse reactions and adjust the quinine dose as needed. Avoid coadministration of erythromycin or ritonavir.

HMG-CoA reductase inhibitors (eg, atorvastatin, lovastatin, simvastatin)

Quinine may increase plasma concentration of HMG-CoA reductase inhibitors, thereby increasing the risk of myopathy or rhabdomyolysis. Consider lower initial and maintenance doses of the HMG-CoA reductase inhibitors. Closely monitor patients for signs or symptoms of muscle pain, tenderness, or weakness. If symptoms occur in conjunction with elevated CPK, discontinue the HMG-CoA reductase inhibitor.


In addition to QT prolongation, the risk of seizures may be increased. Avoid coadministration.

Neuromuscular blocking agents (eg, pancuronium)

May potentiate neuromuscular blockade and may result in respiratory difficulties (eg, apnea, respiratory depression). Avoid use of quinine during administration of and for several hours after recovery from nondepolarizing muscle relaxants. If this combination is required, closely monitor neuromuscular function, titrate the dose of neuromuscular blocking agent, and provide mechanical respiratory support as needed.


Quinine metabolism may be increased, reducing plasma concentrations and decreasing the efficacy. Observe the clinical response of the patient and adjust the quinine dose as needed.

QT-prolonging drugs (eg, amiodarone, cisapride, disopyramide, dofetilide, halofantrine, levofloxacin, macrolide antibiotics [eg, clarithromycin, erythromycin], mefloquine, paroxetine, pimozide, procainamide, propafenone, quinidine, sotalol)

Risk of life-threatening arrhythmias, including torsades de pointes, may be increased; coadministration of quinine is not recommended.

Rifamycins (eg, rifampin)

Avoid concurrent use because of decreased plasma concentrations of quinine; treatment failures may result.


Quinine plasma concentrations may be elevated, increasing the risk of adverse reactions. Monitor patient for adverse reactions associated with quinine and adjust treatment as needed.

Urinary alkalinizers

May increase quinine serum concentrations and potentiate toxicity. Monitor the clinical response of the patient. If an interaction is suspected, adjust the quinine dose as needed.

Laboratory Test Interactions

Urinary 17-ketogenic steroids may have elevated values with Zimmerman method.

Adverse Reactions


Atrial fibrillation, AV block, bradycardia, cardiac arrest, chest pain, disturbances in cardiac rhythm or conduction, hypotension, irregular rhythm, nodal escape beats, palpitations, postural hypotension, QT prolongation, syncope, tachycardia, torsades de pointes, U waves, unifocal premature ventricular contractions, vasodilation, ventricular fibrillation, ventricular tachycardia.


Acute dystonic reaction, altered mental status, aphasia, asthenia, ataxia, coma, confusion, disorientation, dizziness, headache, restlessness, seizures, suicide, tremor, vertigo.


Acral necrosis, allergic contact dermatitis, bullous dermatitis, cutaneous rash (including papular, scarlatinal, or urticarial rashes), cutaneous vasculitis, erythema multiforme, exfoliative dermatitis, fixed drug eruption, photosensitivity reactions, pruritus, Stevens-Johnson syndrome, sweating, TEN.


Deafness, diminished visual fields, diplopia, disturbances in color perception, fixed pupillary dilatation, hearing impairment, night blindness, optic neuritis, photophobia, sudden loss of vision, tinnitus, visual disturbances (including blindness, blurred vision with scotomata).


Abdominal pain, diarrhea, esophagitis, gastric irritation, nausea, vomiting.


Acute interstitial nephritis, hemoglobinuria, renal failure, renal impairment.


Agranulocytosis, aplastic anemia, blackwater fever, coagulopathy, DIC, ecchymosis, hemolytic anemia, hemolytic uremic syndrome, hemorrhage, hypoprothrombinemia, idiopathic thrombocytopenic purpura, leukopenia, lupus anticoagulant, neutropenia, pancytopenia, petechiae, thrombocytopenia, thrombotic thrombocytopenic purpura.


Abnormal LFTs, granulomatous hepatitis, hepatitis, jaundice.


Hypersensitivity reactions.


Anorexia, hypoglycemia.


Muscle weakness, myalgia.


Asthma, dyspnea, pulmonary edema.


Chills, fever, flushing, lupus-like syndrome, sweating.



Quinine use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Chronic renal impairment associated with the development of thrombotic thrombocytopenic purpura has been reported. The risk associated with quinine use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit.


Monitor patients with renal or hepatic impairment and elderly patients for adverse reactions.


Category C .


Excreted in breast milk. American Academy of Pediatrics classifies quinine as compatible with breast-feeding.


Safety and efficacy not established in children younger than 16 y.


Serious hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, urticaria, serious skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, and pruritus, have been reported. Other serious reactions, including acute interstitial nephritis, blackwater fever, DIC, granulomatous hepatitis, immune thrombocytopenic purpura, leukopenia, neutropenia, thrombocytopenia, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, may also be caused by hypersensitivity reactions.

Renal Function

Adjust dose in patients with severe long-term renal failure.

Hepatic Function

Use with caution.

Atrial fibrillation/flutter

Use with caution; a paradoxical increase in ventricular response may occur.


Has been associated with G6PD deficiency. Discontinue immediately if hemolysis appears.


Release of insulin from the pancreas may be stimulated, increasing the risk of hypoglycemia, especially in pregnant women.

Myasthenia gravis

Muscle weakness may be exacerbated.

Optic neuritis

May exacerbate active optic neuritis.

QT prolongation

Potentially fatal cardiac arrhythmias, including torsades de pointes and ventricular fibrillation, may occur. Avoid use in patients with known QT-interval prolongation, patients taking other drugs known to prolong the QT interval, or those with conditions known to prolong the QT interval (eg, bradycardia, certain cardiac conditions, uncorrected hypokalemia).


Immune-mediated and severe cases that are fatal or life-threatening have been reported, including cases of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Usually resolves within a week of discontinuation of quinine; if therapy is not discontinued, there is a risk of fatal hemorrhage. Upon reexposure to quinine, patients with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.



ARDS, cardiogenic shock, cardiotoxicity (including bundle branch block, increased QT interval, PR prolongation, sinus tachycardia, T-wave inversion, widening of the QRS complex), cinchonism (symptoms may include abdominal pain, blindness, blurred vision, cardiac arrhythmias, circulatory collapse, deafness, diarrhea, flushing, headache, hearing impairment, nausea, sweating, tinnitus, vertigo, vomiting), CNS toxicity (eg, ataxia, coma, convulsions, disturbed consciousness, drowsiness, respiratory depression), death, exacerbation of myocardial depression caused by decreased coronary perfusion, hypotension, pulmonary edema, ventricular arrhythmias (including AV block, bradycardia, idioventricular rhythm, torsades de pointes, ventricular fibrillation, ventricular tachycardia), visual impairment (including blurred vision, defective color perception, visual field constriction and permanent blindness).

Patient Information

  • Advise patient to take all of the medication as directed and not to take more than the amount prescribed.
  • Instruct patient to consult health care provider before combining any new medications with this drug.
  • Advise patient to take medication with or after meals or a snack to minimize GI upset.
  • Instruct patient to report the following symptoms to the health care provider: diarrhea, difficulty breathing, fever, flushing, itching, nausea/vomiting, rash, ringing in ears, vertigo, vision problems.
  • Advise patient that drug may cause dizziness and vision problems, and to use caution while driving or performing other tasks requiring mental alertness.
  • Instruct patient that if a dose is missed, not to double the next dose. If it has been more than 4 h since the missed dose, advise the patient to wait and take the regular dose at the next scheduled time. Instruct patient to contact their health care provider if not sure what to do.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.