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QuiNINE

Medically reviewed on Sep 10, 2018

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.

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 to 78 years of age compared with subjects 20 to 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

Malaria, uncomplicated, due to Plasmodium falciparum (treatment): Treatment of uncomplicated chloroquine-resistant P. falciparum malaria, in combination with other antimalarial agents

Off Label Uses

Babesiosis

Clinical experience suggests the utility of quinine (in combination with clindamycin) for the treatment of Babesia microti infection [Vannier 2012].

Based on the Infectious Diseases Society of America (IDSA) guidelines for the Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis, quinine (in combination with clindamycin) is an effective and recommended initial therapy in the treatment of babesiosis.

Malaria, uncomplicated, due to Plasmodium vivax (treatment)

Based on the Centers for Disease Control and Prevention (CDC) Guidelines for Treatment of Malaria in the United States, quinine (in combination with other antimalarial agents) is effective and recommended in the treatment of uncomplicated chloroquine-resistant P. vivax malaria.

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: 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.

Malaria, uncomplicated, due to chloroquine-resistant P. falciparum (treatment): Oral:

CDC guidelines: 648 mg every 8 hours, in combination with doxycycline, tetracycline, or clindamycin (preferred in pregnancy). Note: Administer quinine for 3 days unless the infection was acquired in Southeast Asia, in which case quinine duration of therapy is 7 days. Duration of concomitant agent is 7 days, regardless of geographic region (CDC 2013).

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

Malaria, uncomplicated, due to chloroquine-resistant P. vivax (treatment) (off-label use): Oral: 648 mg every 8 hours, in combination with doxycycline or tetracycline plus primaquine. Note: Quinine in combination with clindamycin is an alternative regimen for pregnant patients. Administer quinine for 3 days unless the infection was acquired in Southeast Asia, in which case quinine duration of therapy is 7 days. Duration of concomitant agent is 7 days (doxycycline, tetracycline, clindamycin) or 14 days (primaquine), regardless of geographic region (CDC 2013).

Babesiosis (off-label use): Oral: 650 mg every 6 to 8 hours for at least 7 to 10 days with clindamycin (Vannier 2012; Wormser 2006). Relapsing infection may require at least 6 weeks of therapy (Vannier 2012). Note: US manufactured quinine sulfate capsule is 324 mg; 2 capsules (648 mg quinine sulfate) should be sufficient for adult dosing.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 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.

Malaria, uncomplicated, due to chloroquine-resistant P. falciparum (treatment): 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.

Malaria, uncomplicated, due to chloroquine-resistant P. vivax (treatment) (off-label use): CDC guidelines: 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

Amifampridine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). 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; Potassium Bicarbonate; 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 (High risk with Inhibitors). 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

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

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 (High risk with Inducers). Monitor therapy

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

Buprenorphine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Monitor therapy

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

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. 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. See full monograph for details. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP2D6 Substrates (High risk with Inhibitors): QuiNINE may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inducers). 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): 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. 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. 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 (High risk with Inducers). 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

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 (High risk with Inducers). 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. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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

HMG-CoA Reductase Inhibitors (Statins): QuiNINE may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). 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

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

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

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

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

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

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

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 QTc-Prolonging Agents (Highest Risk). Avoid combination

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

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

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

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

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

Nevirapine: May decrease the serum concentration of QuiNINE. Monitor therapy

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 (High risk with Inhibitors). Monitor therapy

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

Pefloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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.). Exceptions: Loperamide. 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

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. 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

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

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

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

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

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

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). 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

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

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones 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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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 (High risk with Inducers). 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 (High risk with Inhibitors). 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

Teneligliptin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Monitor therapy

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

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

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 QTc-Prolonging Agents (Highest Risk). Avoid combination

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

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). 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: Appearance of U waves on ECG, atrial fibrillation, atrioventricular block, bradycardia, cardiac arrhythmia, chest pain, flushing, hypersensitivity angiitis, hypotension, nodal rhythm disorder (nodal escape beats), orthostatic hypotension, palpitations, prolonged QT interval on ECG, syncope, tachycardia, torsades de pointes, unifocal premature ventricular contractions, vasodilatation, ventricular fibrillation, ventricular tachycardia

Central nervous system: Altered mental status, aphasia, ataxia, chills, coma, confusion, disorientation, dizziness, dystonic reaction, headache, restlessness, seizure, vertigo

Dermatologic: Allergic contact dermatitis, bullous dermatitis, diaphoresis, exfoliative dermatitis, erythema multiforme, pruritus, skin necrosis (acral), skin photosensitivity, skin rash (papular rash, scarlatiniform rash, urticaria), Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Hypoglycemia

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

Genitourinary: Hemoglobinuria

Hematologic & oncologic: Agranulocytosis, aplastic anemia, blood coagulation disorder, bruise, disseminated intravascular coagulation, hemolysis (black water fever), hemolytic anemia, hemolytic-uremic syndrome, hemorrhage, hypoprothrombinemia, immune thrombocytopenia (ITP), leukopenia, neutropenia, pancytopenia, petechia, thrombocytopenia, thrombotic thrombocytopenic purpura

Hepatic: Abnormal hepatic function tests, granulomatous hepatitis, hepatitis, jaundice

Hypersensitivity: Hypersensitivity reaction

Immunologic: Antibody development (lupus anticoagulant syndrome)

Neuromuscular & skeletal: Lupus-like syndrome, myalgia, tremor, weakness

Ophthalmic: Blindness, blurred vision (with or without scotomata), diplopia, mydriasis, nocturnal amblyopia, optic neuritis, photophobia, vision color changes, vision loss (sudden), visual field loss

Otic: Auditory impairment, deafness, tinnitus

Renal: Acute interstitial nephritis, renal failure, renal insufficiency

Respiratory: Asthma, dyspnea, pulmonary edema

Miscellaneous: Fever

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 immune thrombocytopenia. 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 immune thrombocytopenia, 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 dizziness, headache, tinnitus, change in hearing, or flushing. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), abnormal heartbeat, angina, deafness, passing out, vision changes, color blindness, blindness, pinpoint red spots on skin, abdominal pain, severe nausea, vomiting, severe diarrhea, anxiety, chills, muscle weakness, sweating a lot, or signs of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (bruising or bleeding; severe loss of strength and energy; dark urine or jaundice; pale skin; change in amount of urine passed; vision changes; change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance; or fever) (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.

Further information

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

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