Your activity: 203 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Quinine: Drug information

Quinine: Drug information
(For additional information see "Quinine: Patient drug information" and see "Quinine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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 (TTP). Chronic renal impairment associated with the development of TTP 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.

Brand Names: US
  • Qualaquin
Brand Names: Canada
  • APO-QuiNINE;
  • JAMP-QuiNINE;
  • PRO-QuiNINE-200;
  • QuiNINE-Odan;
  • TEVA-QuiNINE
Pharmacologic Category
  • Antimalarial Agent
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.

Babesiosis

Babesiosis (alternative agent) (off-label use): Oral: 650 mg every 6 to 8 hours in combination with clindamycin for 7 to 10 days; a longer duration of ≥6 weeks, including 2 weeks after resolution of parasitemia, may be necessary for patients at high risk of relapse (eg, highly immunocompromised patients) (IDSA [Krause 2021]; Krause 2008; Sanchez 2016). Note: US manufactured quinine sulfate capsule is 324 mg; 2 capsules (648 mg quinine sulfate) should be sufficient for adult dosing.

Malaria, treatment

Malaria, treatment: Oral:

Note: If used for Plasmodium vivax or Plasmodium ovale, use in combination with primaquine. If used for severe malaria (after completion of IV therapy), use full 3- or 7-day schedule (duration depends on area infection was acquired) (CDC 2020).

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 2020).

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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: Adult

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

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

Dosing: Pediatric

(For additional information see "Quinine: Pediatric drug information")

Note: Dosage expressed in terms of the quinine sulfate salt; 324 mg capsule quinine sulfate = 269 mg of base. Canadian products: 200 mg capsule of quinine sulfate = 167 mg of base or 300 mg capsule of quinine sulfate = 250 mg of base.

Malaria

Malaria: Children and Adolescents; regardless of HIV status (HHS [OI pediatric 2013]): Limited data available in ages <16 years: Note: Duration of quinine treatment for malaria dependent upon the geographic region or pathogen. Lack of an appropriate quinine dosage form may restrict use in some smaller patients.

P. falciparum (chloroquine resistant), uncomplicated; treatment: Oral: 10 mg/kg/dose quinine sulfate every 8 hours for 3 to 7 days depending on region; maximum dose: 650 mg/dose; use in combination with tetracycline, doxycycline, or clindamycin (dependent upon patient age) (CDC 2013)

P. vivax (chloroquine resistant), uncomplicated; treatment: Oral: 10 mg/kg/dose quinine sulfate every 8 hours for 3 to 7 days depending on region; maximum dose: 650 mg/dose; use in combination with primaquine and tetracycline or doxycycline (dependent upon patient age) (CDC 2013)

Severe malaria: Oral quinine, using the regimens previously described (dose and duration), may be used following IV quinidine including antimicrobial regimen once parasite density is <1% and patient is able to tolerate oral medications (CDC 2013)

Babesiosis

Babesiosis: Limited data available: Children and Adolescents: Oral: 10 mg/kg/dose quinine sulfate every 8 hours for 7 to 10 days; maximum dose: 650 mg/dose (Red Book [AAP 2015]; Wittner 1982); use in combination with clindamycin as a first-line treatment option (IDSA [Wormser 2006])

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Adolescents ≥16 years:

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

Severe chronic renal failure not on dialysis: Initial dose: 648 mg quinine sulfate followed by 324 mg quinine sulfate every 12 hours

Dosing: Hepatic Impairment: Pediatric

Adolescents ≥16 years:

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

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

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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

Capsule, Oral, as sulfate:

Qualaquin: 324 mg

Generic: 324 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Capsule, Oral:

Generic: 200 mg, 300 mg

Tablet, Oral:

Generic: 300 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021799s029lbl.pdf#page=26, must be dispensed with this medication.

Administration: Adult

Oral: 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.

Administration: Pediatric

Oral: Swallow dose whole to avoid bitter taste. Administer with food to minimize upset stomach.

Use: Labeled Indications

Malaria, treatment: Treatment of uncomplicated, chloroquine-resistant Plasmodium falciparum malaria, in combination with other antimalarial agents. Note: Centers for Disease Control and Prevention guidelines also recommend quinine, in combination with other antimalarial agents, as an alternative agent for treatment of malaria due to other chloroquine-sensitive or chloroquine-resistant Plasmodium species, and as oral treatment for severe malaria after completion of IV therapy or as interim oral therapy pending IV therapy (CDC 2020).

Use: Off-Label: Adult

Babesiosis

Medication Safety Issues
Sound-alike/look-alike issues:

QuiNINE may be confused with quiNIDine

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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, vasodilation, 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 (blackwater 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

Contraindications

Hypersensitivity to quinine or any component of the formulation; hypersensitivity to mefloquine or quinidine (cross sensitivity reported); history of potential hypersensitivity reactions (including blackwater fever, immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura), thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], or thrombocytopenia) associated with prior quinine use; prolonged QT interval; myasthenia gravis; optic neuritis.

Warnings/Precautions

Concerns related to adverse effects:

• Hemolytic anemia: Acute hemolytic anemia has been reported, including in patients with G6PD deficiency; causal relationship has not been established. Monitor hemoglobin and hematocrit during use; discontinue therapy if hemolytic anemia develops.

• 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.

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.

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification

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

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

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amiodarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Antacids: May decrease the serum concentration of QuiNINE. Risk X: Avoid combination

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

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

Arsenic Trioxide: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Artemether and Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider therapy modification

Astemizole: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Astemizole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Bedaquiline: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Bedaquiline. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

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

CarBAMazepine: May decrease the serum concentration of QuiNINE. QuiNINE may increase the serum concentration of CarBAMazepine. Management: Consider alternatives to this combination when possible. If coadministration of carbamazepine and quinine cannot be avoided, monitor for reduced quinine efficacy and for increased carbamazepine serum concentrations and toxicities. Risk D: Consider therapy modification

Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ChlorproMAZINE: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of ChlorproMAZINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Cimetidine: May increase the serum concentration of QuiNINE. Management: Consider using an alternative H2-receptor antagonist (eg, ranitidine) instead of cimetidine due to a lower interaction risk. If combined, monitor patients closely for signs and symptoms of quinine toxicity. Risk D: Consider therapy modification

Cisapride: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Cisapride. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: 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-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of QuiNINE. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced quinine efficacy and treatment failure. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of QuiNINE. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of QuiNINE. Risk C: Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy

Dabrafenib: May enhance the QTc-prolonging effect of QuiNINE. Dabrafenib may decrease the serum concentration of QuiNINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and reduced quinine efficacy. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Delamanid: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Delamanid. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

Dronedarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

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

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy

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

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

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

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy

Halofantrine: May enhance the QTc-prolonging effect of QuiNINE. Risk X: Avoid combination

Haloperidol: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

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

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

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

Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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

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

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination

Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Loperamide-Loperamide Oxide: QuiNINE may enhance the QTc-prolonging effect of Loperamide-Loperamide Oxide. QuiNINE may increase the serum concentration of Loperamide-Loperamide Oxide. Risk C: 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. Risk X: Avoid combination

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinine. Risk X: Avoid combination

Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methadone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

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

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

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

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

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

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

Nirmatrelvir and Ritonavir: QuiNINE may increase the serum concentration of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may decrease the serum concentration of QuiNINE. This effect has been seen with lopinavir/ritonavir. The effects of nirmatrelvir and ritonavir on quinine are unclear. Risk X: 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. Risk C: Monitor therapy

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

PAZOPanib: QuiNINE may enhance the QTc-prolonging effect of PAZOPanib. QuiNINE may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

PHENobarbital: QuiNINE may increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If coadministration of phenobarbital and quinine cannot be avoided, monitor for reduced quinine efficacy and for increased phenobarbital serum concentrations and toxicities. Risk D: Consider therapy modification

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination

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. Risk C: Monitor therapy

Primidone: QuiNINE may increase the serum concentration of Primidone. Primidone may decrease the serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If coadministration of primidone and quinine cannot be avoided, monitor for reduced quinine efficacy and for increased phenobarbital (active metabolite) serum concentrations and toxicities. Risk D: Consider therapy modification

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Miscellaneous Agents (Highest Risk): May enhance the QTc-prolonging effect of QuiNINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for increased toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Risk X: Avoid combination

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Quinidine (Non-Therapeutic): May enhance the adverse/toxic effect of QuiNINE. Risk X: Avoid combination

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

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

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

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

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

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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. Ritonavir may increase the serum concentration of QuiNINE. Risk X: Avoid combination

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

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

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

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

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

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

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. Risk C: Monitor therapy

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

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

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

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

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

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

Theophylline Derivatives: May increase the serum concentration of QuiNINE. QuiNINE may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Tobacco (Smoked): May decrease the serum concentration of QuiNINE. Risk C: Monitor therapy

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

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

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

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

Reproductive Considerations

A decrease in sperm motility and an increase in abnormal sperm morphology was observed in men receiving quinine.

Pregnancy Considerations

Quinine crosses the placenta.

Cord plasma to maternal plasma quinine ratios have been reported as 0.18 to 0.46 and should not be considered therapeutic to the infant. Based on available data, therapeutic doses used for malaria are not associated with an increased risk of adverse fetal events.

Quinine may cause significant maternal hypoglycemia and an increased risk of other adverse maternal events, including dizziness, nausea, tinnitus, and vomiting. Pregnant women may also be at risk for a rare triad of complications which includes massive hemolysis, hemoglobinemia, and hemoglobinuria.

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020; CDC Yellow Book 2020).

Quinine may be used to treat chloroquine-resistant uncomplicated malaria during all trimesters of pregnancy. In pregnant patients with severe malaria, quinine may be used as interim oral therapy when the preferred IV agent is not readily available (discontinue once IV treatment is initiated) (CDC 2020; WHO 2015); consult current CDC guidelines.

Breastfeeding Considerations

Quinine is present in breast milk.

Based on limited data, it is estimated that breastfed infants would receive <0.4% of the maternal dose from breastfeeding. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. The World Health Organization considers quinine to be compatible with breastfeeding. Infants should be monitored for hemolysis and jaundice, especially if they are premature or <1 month of age. Breastfeeding should be avoided during maternal therapy in infants with G6PD deficiency (WHO 2002).

Dietary Considerations

Take with food to decrease incidence of gastric upset.

Monitoring Parameters

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

Mechanism of Action

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

Pharmacokinetics

Absorption: Readily, mainly from upper small intestine

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

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

Protein binding: 69% to 92% in healthy subjects; 78% to 95% with malaria (due to increase in alpha 1-acid glycoprotein)

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

Bioavailability: 76% to 88% in healthy subjects; increased 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

Time to peak, serum:

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

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

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

Pharmacokinetics: Additional Considerations

Altered kidney function: 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.

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.

Older adult: 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.

Pricing: US

Capsules (Qualaquin Oral)

324 mg (per each): $7.86

Capsules (quiNINE Sulfate Oral)

324 mg (per each): $7.07 - $7.33

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Albiquin (BD);
  • Alquinn (TH);
  • Circonyl (AR);
  • Euchinin (ID);
  • Genin (TH);
  • Jasoquin (BD);
  • Kanaquine (BD);
  • Kinin (DK, SE);
  • Limptar N (DE);
  • Malaquin (BD);
  • Q200 (HK);
  • Q300 (HK, NZ);
  • Quinate (AU);
  • Quinbisu (AU);
  • Quinimax (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW);
  • Quininga (IN)


For country code abbreviations (show table)
  1. American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
  2. Apo-Quinine (quinine) [product monograph]. Toronto, Ontario, Canada: Apotex Inc; September 2018.
  3. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. 4th ed. Philadelphia, PA: American College of Physicians; 2007, p 74.
  4. Bateman DN, Blain PG, Woodhouse KW, et al, “Pharmacokinetics and Clinical Toxicity of Quinine Overdosage: Lack of Efficacy of Techniques Intended to Enhance Elimination,” Q J Med, 1985, 54(214):125-31. [PubMed 3983356]
  5. Boland ME, Roper SM, and Henry JA, “Complications of Quinine Poisoning,” Lancet, 1985, 1(8425):384-5.
  6. Buckingham SC. Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies. Paediatr Drugs. 2005;7(3):163-176. [PubMed 15977962]
  7. Centers for Disease Control and Prevention (CDC). CDC Yellow Book 2020: Health Information for International Travel. Oxford University Press; 2019.
  8. Centers for Disease Control (CDC). Clindamycin and quinine treatment for Babesia microti infections. MMWR Morb Mortal Wkly Rep. 1983;32(5):65-66, 72. [PubMed 6405180]
  9. Centers for Disease Control and Prevention (CDC). Guidelines for treatment of malaria in the United States. http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf. Updated September 23, 2011. Accessed May 6, 2013.
  10. Centers for Disease Control and Prevention (CDC). Treatment of malaria: guidelines for clinicians (United States). https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html. Updated May 29, 2020. Accessed June 8, 2020.
  11. “Drugs for Parasitic Infections,” Treatment Guidelines From the Medical Letter, 2004, 50(Suppl):e1-14.
  12. Dyson EH, Proudfoot AT, and Bateman DN, “Quinine Amblyopia: Is Current Management Appropriate?” J Toxicol Clin Toxicol, 1985-6, 23(7-8):571-8.
  13. HHS. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. November 6, 2013. Available at http://aidsinfo.nih.gov
  14. Jaeger A, Sauder P, Kopferschmitt J, et al, “Clinical Features and Management of Poisoning Due to Antimalarial Drugs,” Med Toxicol Adverse Drug Exp, 1987, 2(4):242-73. [PubMed 3306266]
  15. Krause PJ, Auwaerter PG, Bannuru RR, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA): 2020 guideline on diagnosis and management of babesiosis. Clin Infect Dis. 2021;72(2):185-189. doi:10.1093/cid/ciab050 [PubMed 33501959]
  16. Krause PJ, Gewurz BE, Hill D, et al. Persistent and relapsing babesiosis in immunocompromised patients. Clin Infect Dis. 2008;46(3):370-376. doi:10.1086/525852 [PubMed 18181735]
  17. Lockey D and Bateman DN, “Effect of Oral Activated Charcoal on Quinine Elimination,” Br J Clin Pharmacol, 1989, 27(1):92-4. [PubMed 2706191]
  18. Miller LH, Glew RH, Wyler DJ, et al. Evaluation of clindamycin in combination with quinine against multidrug-resistant strains of Plasmodium falciparum. Am J Trop Med Hyg. 1974;23(4):565-569. [PubMed 4603135]
  19. Newman RD, Parise ME, Slutsker L, et al, “Safety, Efficacy and Determinants of Effectiveness of Antimalarial Drugs During Pregnancy: Implications for Prevention Programmes in Plasmodium falciparum-Endemic Sub-Saharan Africa,” Trop Med Int Health, 2003, 8(6):488-506. [PubMed 12791054]
  20. Panisko DM and Keystone JS, “Treatment of Malaria - 1990,” Drugs, 1990, 39(2):160-89. [PubMed 2183998]
  21. Qualaquin (quinine sulfate) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; August 2019.
  22. “Recommendations for the Prevention of Malaria Among Travelers,” MMWR Recomm Rep, 1990, 39(RR-3):1-10.
  23. Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315(16):1767-1777. doi:10.1001/jama.2016.2884 [PubMed 27115378]
  24. Schulbe DE, “Quinine Ban Signals Change for Pharmacists, APhA,” Pharmacy Today, 1995, 1(12):6.
  25. White NJ, “The Treatment of Malaria,” N Engl J Med, 1996, 335(11):800-6. [PubMed 8703186]
  26. Winek CL, Schweighardt FK, Fochtman FW, et al, “Quinine in Urinalysis for Heroin,” JAMA, 1971, 217(9):1243-4. [PubMed 5109466]
  27. Wittner M, Rowin KS, Tanowitz HB, et al. Successful chemotherapy of transfusion babesiosis. Ann Intern Med. 1982;96(5):601-604. [PubMed 7200341]
  28. World Health Organization (WHO); UNICEF. Breastfeeding and maternal medication: recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. Available at http://www.who.int/maternal_child_adolescent/documents/55732/en.
  29. World Health Organization (WHO). Guidelines for the Treatment of Malaria. 3rd edition. WHO Press; 2015.
  30. Wyler DJ, “Malaria Chemoprophylaxis for the Traveler,” N Engl J Med, 1993, 329(1):31-7. [PubMed 8505942]
  31. Wyler DJ, “Malaria: Overview and Update,” Clin Infect Dis, 1993, 16(4):449-56. [PubMed 8513046]
Topic 9847 Version 320.0