Trade Names:Qualaquin- Capsules 324 mg
Trade Names:Quinine sulfate- Capsules 200 mg- Capsules 260 mg- Capsules 325 mg- Tablets 260 mgApo-Quinine (Canada)Quinine-Odan (Canada)
Causes pH elevation in intracellular organelles of parasites; also has skeletal muscle relaxant effects and CV effects similar to those of quinidine.
Exposure is higher in patients with malaria than in healthy subjects. T max in healthy subjects or patient with malaria is 2.8 h and 5.9 h, respectively. C max in healthy subjects or patients with malaria is 3.2 and 8.4 mcg/mL, respectively.
In healthy subjects, the Vd ranged 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 subjects 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. Half-life is 4 to 5 h. Elimination is twice as rapid in an acid urine compared with an 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.
The effects of mild and moderate renal impairment on pharmacokinetics and efficacy of quinine are not known. Because the plasma half-life is prolonged from 26 h in patients with severe chronic renal impairment compared with 9.7 h in healthy controls, dosage adjustments are needed in patients with severe chronic renal failure. Negligible amounts are removed by hemodialysis or hemofiltration.Hepatic Function Impairment
In patients with mild to moderate hepatic impairment, dosage adjustment is not needed; however, monitor patient for adverse reactions.Elderly
Mean AUC is approximately 38% higher in healthy subjects 65 to 78 yr of age compared with subjects 20 to 35 yr 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 patients. Despite these pharmacokinetic differences, no alteration in dosage is needed.Children
Pharmacokinetics are similar in children 1.5 to 12 yr of age compared with adults with uncomplicated malaria. Mean total Cl and Vd are reduced in children with malaria compared with healthy pediatric controls.
Treatment of uncomplicated Plasmodium falciparum malaria.
Prevention and treatment of nocturnal recumbency leg cramps.
Blackwater fever; pregnancy (except Qualaquin ); hypersensitivity to any component of the product; G-6-PD deficiency; history of thrombocytopenia; optic neuritis; tinnitus.Qualaquin
Prolonged QT interval; myasthenia gravis.
PO 260 to 975 mg 3 times daily for 6 to 12 days.Qualaquin
648 mg every 8 h for 7 days. In patients with acute uncomplicated malaria and severe chronic renal failure, administer a 648 mg loading dose followed 12 h later by maintenance dosages of 324 mg every 12 h.
Store at 59° to 86°F. Protect from moisture. Protect from light.Qualaquin capsules
Store at 77° to 86°F.
Causes delayed or decreased quinine absorption.Anticoagulants, oral (eg, warfarin)
May cause depression of hepatic enzyme system that synthesizes vitamin K–dependent clotting factors and may enhance action of oral anticoagulants.Carbamazepine, phenobarbital
Plasma concentrations of these drugs may be elevated, increasing the pharmacologic effects and risk of adverse reactions.Cimetidine, ranitidine
May reduce quinine's Cl and prolong its half-life.CYP1A2 substrates (aminophylline, theophylline)
Plasma concentrations of these agents may be reduced, decreasing the efficacy.CYP2D6 (eg, debrisoquine, desipramine, dextromethorphan, flecainide, metoprolol, mexiletine, tolterodine) and CYP3A4 (eg, atorvastatin, zolpidem) substrates
Quinine may inhibit the metabolism of these substrates, increasing the pharmacologic effects and risk of adverse reactions.Digoxin
May cause increased digoxin serum concentration.Erythromycin, ketoconazole
Quinine metabolism may be inhibited, increasing the risk of adverse reactions.Mefloquine
May cause ECG abnormalities or cardiac arrest and may increase risk of convulsions. Do not use concurrently. Delay administration 12 h after last dose of quinine.Neuromuscular blocking agents
May potentiate neuromuscular blockade and may result in respiratory difficulties.Phenobarbital, phenytoin, rifampin
Quinine metabolism may be increased, reducing plasma concentrations and decreasing the efficacy.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.Tetracycline
Quinine plasma concentrations may be elevated, increasing the risk of adverse reactions.Urinary alkalinizers
May increase quinine serum concentrations and potentiate toxicity.
Urinary 17-ketogenic steroids may have elevated values with Zimmerman method.
Angina, atrioventricular 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, unifocal premature ventricular contractions, U waves, vasodilation, ventricular tachycardia.
Acute dystonic reaction, aphasia, apprehension, ataxia, altered mental status, asthenia, coma, confusion, disorientation, dizziness, headache, restlessness, seizures, suicide, tremor, vertigo.
Acrinal necrosis, allergic contact dermatitis, bullous dermatitis, cutaneous rash (including popular, scarlatinal, or urticarial rashes), cutaneous vasculitis, erythema multiforme, exfoliative dermatitis, facial edema, fixed drug eruption, photosensitivity reactions, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), urticaria.
Blindness, burred vision, deafness, diminished visual fields, diplopia, disturbances in color perception, fixed papillary dilatation, hearing impairment, night blindness, optic neuritis, photophobia, sudden loss of vision, tinnitus, visual impairment (including blurred vision with scotomata).
Abdominal pain, diarrhea, epigastric pain, esophagitis, gastric irritation, nausea, vomiting.
Acute interstitial nephritis, hemoglobinuria, renal failure, renal impairment.
Acute hemolysis, agranulocytosis, aplastic anemia, blackwater fever, coagulopathy, DIS, 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.
Myalgia, muscle weakness.
Asthma, dyspnea, pulmonary edema.
Chills, fever, flushing, lupus-like syndrome, sweating.
Monitor patients with hepatic impairment for adverse reactions.
Category X .Qualaquin
Category C .
Excreted in breast milk.
Safety and efficacy not established in children younger than 16 yr of age.
Studies did not include sufficient numbers of subjects older than 65 yr of age to determine if they respond differently from younger subjects.
Serious hypersensitivity reactions, including anaphylactic and anaphylactoid reactions, angioedema, Stevens-Johnson syndrome, and TEN, have been reported.
Adjust dose in patients with severe chronic renal failure. Effects of mild and moderate renal impairment are not known.
Use with caution.
Use with caution.
Patients with cardiac arrhythmias may have exacerbation of symptoms with quinine, which acts similarly to quinidine. May cause cardiotoxicity. In patients with atrial fibrillation, quinine requires the same precautions as for quinidine.
Has been associated with G-6-PD deficiency. Discontinue immediately if hemolysis appears.
Release of insulin from the pancreas may be stimulated, increasing the risk of hypoglycemia, especially in pregnant women.
May predispose patients to serious complications of blackwater fever, including anemia, RBC destruction, and renal failure.
Muscle weakness may be exacerbated.
Unpredictable, serious, and life-threatening hypersensitivity reactions may occur. Potentially fatal cardiac arrhythmias, including torsades de pointes and ventricular fibrillation. Avoid use in patients with known QT interval prolongation or conditions know to prolong the QT interval (eg, bradycardia, certain cardiac conditions, uncorrected hypokalemia).
Adult respiratory distress syndrome, 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, hypoglycemia, 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, hypoglycemia, hypotension, pulmonary edema, ventricular arrhythmias (including AV block, bradycardia, idioventricular rhythm, torsades de pointes, ventricular fibrillation, ventricular tachycardia,), visual impairment (including blurred vision, effective color perception, visual field constriction and permanent blindness).
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