|•||Chloroquine-resistant falciparum malaria (alone or with pyrimethamine and a sulfonamide or with a tetracycline; has also be used with clindamycin and mefloquine depending on origin of illness).|
|•||Leg cramps (not recommended due to cardiac side effects.|
Adults and Children 16 y of age and older: 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 dosage of 324 mg every 12 h.
|•||Administer with food to minimize GI upset.|
Causes pH elevation in intracellular organelles of parasites; also has skeletal muscle relaxant effects and CV effects similar to those of quinidine.
Use Cautiously in:
|•||Recurrent or interrupted malaria therapy.|
|•||History of arrhythmias, especially QTc prolongation.|
|•||Atrial fibrillation/flutter (may cause paradoxical increase in ventricular response).|
|•||History of thrombocytopenic purpura.|
|•||Pedi: Safety not established for children <16 yr.|
CV: CARDIAC ARRHYTHMIAS .
Endo: hypoglycemia ( in pregnancy).
Hemat: bleeding, blood dyscrasias, thrombotic thrombocytopenic pupura, thrombocytopenia.
Misc: cinchonism, hypersensitivity reactions including fever andanaphylaxis, hemolytic uremic syndrome, stevens-johnson syndrome.
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, oral (eg, warfarin)
May cause depression of hepatic enzyme system that synthesizes vitamin K–dependent clotting factors and may enhance action of oral anticoagulants. Closely monitor PT, PTT, and INR during coadministration. Adjust the anticoagulant dose as needed.
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.
Quinine AUC and Cmax may be reduced and the half-life shortened. However, dosage adjustment does not appear to be necessary in treating acute malaria.
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, 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.
When quinine was administered to healthy volunteers with a standardized high-fat breakfast, the mean Tmax of quinine was prolonged, but the mean Cmax and AUC were similar to those achieved when quinine was given under fasting conditions. Quinine may be administered without regard to meals. Administer with food to minimize possible GI irritation.
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.
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.
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.
Therapeutic Classification: antimalarials
Absorption: Exposure is higher in patients with malaria than in healthy patients. Tmax in healthy patients and patients with malaria is 2.8 h and 5.9 h, respectively. Cmax in healthy patients and patients with malaria is 3.2 and 8.4 mcg/mL, respectively.
Distribution: 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: 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.
Excretion: 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 acid 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.
Renal Function Impairment: The effects of mild and moderate renal impairment on the pharmacokinetics and efficacy of quinine are not known. Because the plasma half-life is prolonged to 26 h in patients with severe chronic renal impairment compared with 9.7 h in healthy control subjects, 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 y of age compared with subjects 20 to 35 y of age. Mean Tmax and Cmax 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 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.
|ORAL||UNKNOWN||3.2-5.9 HOUR||8 HOUR|