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Pronunciation

(KWYE nine)

Index Terms

  • Quinine Sulfate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as sulfate:

Qualaquin: 324 mg

Generic: 324 mg

Brand Names: U.S.

  • Qualaquin

Pharmacologic Category

  • Antimalarial Agent

Pharmacology

Depresses oxygen uptake and carbohydrate metabolism; intercalates into DNA, disrupting the parasite's replication and transcription; cardiovascular effects similar to quinidine

Absorption

Readily, mainly from upper small intestine

Distribution

Adults: 2.5 to 7.1 L/kg (varies with severity of infection); Children: ~0.9 L/kg (subjects with malaria)

Intraerythrocytic levels are ~30% to 50% of the plasma concentration; distributes poorly to the CSF (~2% to 7% of plasma concentration)

Metabolism

Hepatic via CYP450 enzymes, primarily CYP3A4; forms metabolites; major metabolite, 3-hydroxyquinine, is less active than parent

Excretion

Urine (~20% as unchanged drug); renal excretion is twofold in the presence of acidic urine

Time to Peak

Children: Serum: 2 hours in healthy subjects; 4 hours with malaria

Adults: Serum: 2 to 4 hours in healthy subjects; 1 to 11 hours with malaria

Half-Life Elimination

Children: ~3 hours in healthy subjects; ~12 hours with malaria

Healthy adults: 10 to 13 hours

Healthy elderly subjects: 18 hours

Protein Binding

69% to 92% in healthy subjects; 78% to 95% with malaria (due to increase in alpha1-acid glycoprotein)

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 hours in patients with severe long-term renal impairment; dosage adjustment needed. Negligible amounts are removed by hemodialysis or hemofiltration.

Special Populations: Hepatic Function Impairment

AUC increased 55% without a significant change in Cmax in patients with moderate hepatic impairment. Plasma elimination half-life and volume of distribution are increased in patients with severe hepatic impairment.

Special Populations: Elderly

Mean AUC is ~38% higher in healthy subjects 65-78 years of age compared with subjects 20-35 years of age. Mean Tmax and Cmax are similar in elderly and younger subjects. Mean oral clearance 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.

Use: Labeled Indications

In conjunction with other antimalarial agents, treatment of uncomplicated chloroquine-resistant P. falciparum malaria

Use: Unlabeled

Treatment of Babesia microti infection in conjunction with clindamycin; treatment of uncomplicated chloroquine-resistant P. vivax malaria (in conjunction with other antimalarial agents)

Contraindications

Hypersensitivity to quinine or any component of the formulation; hypersensitivity to mefloquine or quinidine (cross sensitivity reported); history of potential hypersensitivity reactions (including black water fever, thrombotic thrombocytopenia purpura [TTP], hemolytic uremic syndrome [HUS], or thrombocytopenia) associated with prior quinine use; prolonged QT interval; myasthenia gravis; optic neuritis; G6PD deficiency

Dosing: Adult

Note: Actual duration of quinine treatment for malaria may be dependent upon the geographic region or pathogen. Dosage expressed in terms of the salt; 1 capsule Qualaquin = 324 mg of quinine sulfate = 269 mg of base; Canadian products contain 200 mg of quinine sulfate = 167 mg of base or 300 mg of quinine sulfate = 250 mg of base.

Treatment of uncomplicated chloroquine-resistant P. falciparum malaria: Oral:

CDC guidelines: 648 mg every 8 hours for 3 to 7 days. Tetracycline, doxycycline, or clindamycin should also be given.

Canadian product: 600 mg every 8 hours for 3 to 7 days. Note: Use in combination with tetracycline, doxycycline, or clindamycin.

Treatment of uncomplicated chloroquine-resistant P. vivax malaria (off-label use; CDC guidelines): Oral: 648 mg every 8 hours for 3 to 7 days. Tetracycline or doxycycline plus primaquine should also be given.

Babesiosis (off-label use): Oral: 650 mg every 6 to 8 hours for 7 to 10 days with clindamycin (Vannier 2012; Wormser 2006). Note: Relapsing infection may require at least 6 weeks of therapy (Vannier 2012).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Actual duration of quinine treatment for malaria may be dependent upon the geographic region or pathogen. Dosage expressed in terms of the salt; 1 capsule Qualaquin = 324 mg of quinine sulfate = 269 mg of base; Canadian products contain 200 mg of quinine sulfate = 167 mg of base or 300 mg of quinine sulfate = 250 mg of base.

Treatment of uncomplicated chloroquine-resistant P. falciparum malaria: CDC guidelines: Oral: 30 mg/kg/day in divided doses every 8 hours for 3 to 7 days. Tetracycline, doxycycline, or clindamycin (consider risk versus benefit of using tetracycline or doxycycline in children <8 years) should also be given.

Treatment of uncomplicated chloroquine-resistant P. vivax malaria (off-label use): CDC guidelines: Oral: 30 mg/kg/day in divided doses every 8 hours for 3 to 7 days. Tetracycline, doxycycline, or clindamycin (consider risk versus benefit of using tetracycline or doxycycline in children <8 years) should also be given. Oral: 30 mg/kg/day in divided doses every 8 hours for 3 to 7 days. Tetracycline or doxycycline (consider risk versus benefit of using tetracycline or doxycycline in children <8 years) plus primaquine should also be given.

Dosing: Renal Impairment

Mild or moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use caution.

Severe chronic impairment:

US labeling: Patients not on dialysis: Initial dose: 648 mg followed by 324 mg every 12 hours

Canadian product: Initial dose: 600 mg followed by 300 mg every 12 hours for 7 days

Alternative recommendations (Aronoff 2007): Note: Dosage adjustments are not recommended in cases of severe malaria

GFR >50 mL/minute: No dosage adjustment necessary.

GFR 10 to 50 mL/minute: Administer every 8 to 12 hours

GFR <10 mL/minute: Administer every 24 hours

Intermittent hemodialysis: Administer dose after dialysis. Note: Clearance of ~6.5% achieved within 1 hour of hemodialysis.

Peritoneal dialysis: Dose as for GFR <10 mL/minute

CRRT: Dose as for GFR 10 to 50 mL/minute

Dosing: Hepatic Impairment

Mild to moderate impairment (Child-Pugh classes A and B): No dosing adjustment required; monitor closely.

Severe impairment (Child-Pugh class C): Avoid use.

Administration

Avoid use of aluminum- or magnesium-containing antacids because of drug absorption problems. Swallow dose whole to avoid bitter taste. May be administered with food.

Dietary Considerations

Take with food to decrease incidence of gastric upset.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Alkalinizing Agents: May increase the serum concentration of QuiNINE. Monitor therapy

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antacids: May decrease the serum concentration of QuiNINE. Exceptions: Calcium Carbonate; Sodium Bicarbonate. Avoid combination

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of QuiNINE. Avoid combination

Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Blood Pressure Lowering Agents: Herbs (Hypotensive Properties) may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

CarBAMazepine: May decrease the serum concentration of QuiNINE. QuiNINE may increase the serum concentration of CarBAMazepine. Consider therapy modification

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cimetidine: May increase the serum concentration of QuiNINE. Consider therapy modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. Monitor therapy

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy

CYP2D6 Substrates: QuiNINE may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapsone (Systemic): May enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Digoxin: QuiNINE may increase the serum concentration of Digoxin. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May decrease the serum concentration of QuiNINE. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Halofantrine: QuiNINE may enhance the adverse/toxic effect of Halofantrine. QuiNINE may increase the serum concentration of Halofantrine. Avoid combination

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the adverse/toxic effect of other Herbs (Hypotensive Properties). Excessive blood pressure lowering may manifest. Monitor therapy

Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination

HMG-CoA Reductase Inhibitors: QuiNINE may increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Exceptions: Fluvastatin; Pitavastatin; Pravastatin; Red Yeast Rice; Rosuvastatin. Consider therapy modification

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Indapamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Consider therapy modification

Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Lopinavir: May decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. Avoid combination

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Macrolide Antibiotics: May increase the serum concentration of QuiNINE. Exceptions: Fidaxomicin; Roxithromycin. Avoid combination

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Mefloquine: QuiNINE may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of QuiNINE. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinine when possible. Avoid combination

MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents: QuiNINE may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Avoid combination

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

PHENobarbital: QuiNINE may increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of QuiNINE. Consider therapy modification

Phenytoin: May decrease the serum concentration of QuiNINE. Consider therapy modification

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

RifAMPin: May decrease the serum concentration of QuiNINE. Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Ritonavir: May decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. QuiNINE may increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of QuiNINE. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Tetracycline: May increase the serum concentration of QuiNINE. Monitor therapy

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Theophylline Derivatives: QuiNINE may increase the serum concentration of Theophylline Derivatives. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Vitamin K Antagonists (eg, warfarin): QuiNINE may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

May interfere with urine detection of opioids (false-positive); positive Coombs' [direct]; false elevation of urinary steroids (when assayed by Zimmerman method) and catecholamines; qualitative and quantitative urine dipstick protein assays

Adverse Reactions

Frequency not defined.

Cardiovascular: Atrial fibrillation, atrioventricular block, bradycardia, cardiac arrest, chest pain, hypotension, irregular rhythm, nodal escape beats, orthostatic hypotension, palpitation, QT prolongation, syncope, tachycardia, torsade de pointes, unifocal premature ventricular contractions, U waves, vasodilation, ventricular fibrillation, ventricular tachycardia

Central nervous system: Aphasia, ataxia, chills, coma, confusion, disorientation, dizziness, dystonic reaction, fever, flushing, headache, mental status altered, restlessness, seizure, suicide, vertigo

Dermatologic: Acral necrosis, allergic contact dermatitis, bullous dermatitis, bruising, cutaneous rash (urticaria, papular, scarlatinal), cutaneous vasculitis, exfoliative dermatitis, erythema multiforme, petechiae, photosensitivity, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Hypoglycemia

Gastrointestinal: Abdominal pain, anorexia, diarrhea, esophagitis, gastric irritation, nausea, vomiting

Hematologic: Agranulocytosis, aplastic anemia, coagulopathy, disseminated intravascular coagulation, hemolytic anemia, hemolytic uremic syndrome, hemorrhage, hypoprothrombinemia, immune thrombocytopenia (ITP), leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura

Hepatic: Granulomatous hepatitis, hepatitis, jaundice, liver function test abnormalities

Neuromuscular & skeletal: Myalgia, tremor, weakness

Ocular: Blindness, blurred vision (with or without scotomata), color vision disturbance, diminished visual fields, diplopia, night blindness, optic neuritis, photophobia, pupillary dilation, vision loss (sudden)

Otic: Deafness, hearing impaired, tinnitus

Renal: Acute interstitial nephritis, hemoglobinuria, renal failure, renal impairment

Respiratory: Asthma, dyspnea, pulmonary edema

Miscellaneous: Black water fever, diaphoresis, hypersensitivity reaction, lupus anticoagulant, lupus-like syndrome

ALERT: U.S. Boxed Warning

Nocturnal leg cramps:

Quinine 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. 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.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Severe hypersensitivity reactions (eg, Stevens-Johnson syndrome, anaphylactic shock) have occurred; discontinue following any signs of sensitivity. Other events (including acute interstitial nephritis, neutropenia, and granulomatous hepatitis) may also be attributed to hypersensitivity reactions.

• Hypoglycemia: Use may cause significant hypoglycemia due to quinine-induced insulin release.

• Thrombocytopenia: Immune-mediated thrombocytopenia, including life-threatening cases and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), has occurred with use. Chronic renal failure associated with TTP has also been reported. Thrombocytopenia generally resolves within a week upon discontinuation. Re-exposure may result in increased severity of thrombocytopenia and faster onset.

Disease-related concerns:

• Altered cardiac conduction: Use with caution in patients with atrial fibrillation or flutter (paradoxical increase in heart rate may occur). Use with caution in patients with clinical conditions which may prolong the QT interval or cause cardiac arrhythmias. Quinine may cause QT-interval prolongation, with maximum increase corresponding to maximum plasma concentration. Fatal torsade de pointes and ventricular fibrillation has been reported. Use contraindicated in patients with QT prolongation. Concurrent use of Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, dofetilide, sotalol) antiarrhythmic agents or with other drugs known to prolong the QT interval is not recommended. Quinine may also cause concentration-dependent prolongation of the PR and QRS intervals. Risk of prolonged PR and/or QRS intervals is higher in patients with underlying structural heart disease, myocardial ischemia, preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response and concomitant use of drugs known to prolong the PR interval (eg, verapamil) or QRS interval (eg, flecainide or quinidine).

• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment. Avoid in patients with severe hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended in severe chronic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Other warnings/precautions:

• Appropriate use: Quinine should not be used for the prevention of malaria or in the treatment of complicated or severe P. falciparum malaria (oral antimalarial agents are not appropriate for initial therapy of severe malaria).

• Nocturnal leg cramps: [US Boxed Warning]: Quinine is not recommended for the prevention/treatment of nocturnal leg cramps due to the potential for severe and/or life-threatening side effects (eg, cardiac arrhythmias, thrombocytopenia, and HUS/TTP, severe hypersensitivity reactions). These risks, as well as the absence of clinical effectiveness, do not justify its use in the unapproved/off-label prevention and/or treatment of leg cramps.

Monitoring Parameters

Monitor CBC with platelet count, liver function tests, blood glucose; ECG; ophthalmologic examination

Pregnancy Risk Factor

C

Pregnancy Considerations

Teratogenic effects have been reported in some animal studies. Quinine crosses the human placenta. Cord plasma to maternal plasma quinine ratios have been reported as 0.18-0.46 and should not be considered therapeutic to the infant. Teratogenic effects, optic nerve hypoplasia, and deafness have been reported in the infant following maternal use of very high doses; however, therapeutic doses used for malaria are generally considered safe. Quinine may also cause significant hypoglycemia when used during pregnancy. Malaria infection in pregnant women may be more severe than in nonpregnant women. Because P. falciparum malaria can cause maternal death and fetal loss, pregnant women traveling to malaria-endemic areas must use personal protection against mosquito bites. Quinine may be used for the treatment of malaria in pregnant women; consult current CDC guidelines. Pregnant women should be advised not to travel to areas of P. falciparum resistance to chloroquine.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache or flushing. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), arrhythmia, angina, severe dizziness, passing out, hearing impairment, tinnitus, sudden vision changes, color blindness, blindness, pinpoint red spots on skin, abdominal pain, severe nausea, vomiting, severe diarrhea, illogical thinking, seizures, anxiety, chills, mood changes, muscle weakness, loss of strength and energy, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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