Quinine
FDA Drug Information • Also known as: Quinine Sulfate
- Brand Names
- Quinine Sulfate
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: HEMATOLOGIC REACTIONS Quinine sulfate 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. The risk associated with quinine sulfate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit [see Indications and Usage (1) and Warnings and Precautions (5.1) ] . WARNING: HEMATOLOGIC REACTIONS See full prescribing information for complete boxed warning Quinine sulfate 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. The risk associated with quinine sulfate use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit. ( 1 , 5.1 )
Description
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
What Is Quinine Used For?
1 INDICATIONS AND USAGE Quinine sulfate 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) ] . Limitations of Use: Quinine sulfate capsules 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) ] . Quinine sulfate is an antimalarial indicated for treatment of uncomplicated Plasmodium falciparum malaria. (1) Limitations of Use: Quinine sulfate capsules are not approved for: Treatment of severe or complicated P. falciparum malaria. Prevention of malaria. Treatment or prevention of nocturnal leg cramps
Dosage and Administration
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) ] . Quinine sulfate capsules 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 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) and 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) and Clinical Pharmacology (12.3) ] .
Side Effects (Adverse Reactions)
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 Amneal Pharmaceuticals at 1-877-835-5472 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
7 DRUG INTERACTIONS Table 1 below presents clinically significant drug interactions with quinine sulfate. Table 1: Clinically Significant Drug Interactions with Quinine Sulfate Drug(s) Clinical Impact Recommendation Effects of Drugs and Other Substances on Quinine Pharmacokinetics 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. If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. Additionally, patients should be monitored closely for adverse reactions associated with these anticonvulsants. Histamine H 2 -receptor blockers [cimetidine, ranitidine (nonspecific CYP450 inhibitors)] 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 [see Clinical Pharmacology (12.3) ] . Patients should be monitored closely for adverse events associated with quinine. Ketoconazole (CYP3A4 inhibitor) No change in the quinine sulfate dosage regimen is necessary with concomitant ketoconazole [see Clinical Pharmacology (12.3) ] . Patients should be monitored closely for adverse reactions associated with quinine. Macrolide antibiotics (erythromycin, troleandomycin) (CYP3A4 inhibitors) Increased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with quinine sulfate should be avoided [see Warnings and Precautions (5.4) ] . Rifampin (CYP3A4 inducer) Decreased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of rifampin with quinine sulfate should be avoided [see Warnings and Precautions (5.5) ] . Ritonavir Increased quinine plasma levels have been observed when used concomitantly [see Clinical Pharmacology (12.3) ] . Concomitant administration of ritonavir with quinine sulfate should be avoided. Tetracycline Tetracycline may be concomitantly administered with quinine sulfate [see Clinical Pharmacology (12.3) ] . Patients should be monitored closely for adverse reactions associated with quinine sulfate. Theophylline or aminophylline No change in the quinine sulfate dosage regimen is necessary with concomitant theophylline or aminophylline [see Clinical Pharmacology (12.3) ] . Patients should be monitored closely for adverse reactions associated with quinine. Urinary alkalizers (acetazolamide, sodium bicarbonate) Urinary alkalinizing agents...
Contraindications
4 CONTRAINDICATIONS Quinine sulfate capsules are 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 (5.4) ] . Known hypersensitivity reactions to quinine. These include, but are not limited to, the following [see Warnings and Precautions (5.7) ] : 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 (5.7) ] . Myasthenia gravis. Quinine has neuromuscular blocking activity, and may exacerbate muscle weakness. Optic neuritis. Quinine may exacerbate active optic neuritis [see Adverse Reactions (6.1) ] . Quinine sulfate capsules are contraindicated in patients with the following: Prolongation of QT interval. (4) Myasthenia gravis. (4) Known hypersensitivity to quinine, mefloquine, or quinidine. (4) Optic neuritis. (4)
Overdosage
10 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...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Quinine Sulfate Capsules USP, 324 mg are clear transparent size ‘0’ hard gelatin capsules filled with white to off-white powder and imprinting ‘AMNEAL’ on the cap and ‘811’ on the body. They are available as follows: Bottles of 30: NDC 65162-811-03 Bottles of 90: NDC 65162-811-09 Bottles of 500: NDC 65162-811-50 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight container as defined in the USP.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.