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  • CLASSES

    Antimalarials

    BOXED WARNING

    Muscle cramps

    Both the FDA and the manufacturer warn against the off-label use of quinine for leg cramps. When used as approved by the FDA in the treatment of chloroquine-resistant malaria, a life-threatening illness, the risks associated with quinine use are justified. However, in the off-label use to prevent or treat nocturnal leg muscle cramps, the risks associated with quinine use, and the absence of evidence regarding its efficacy for such use, outweigh any potential benefit for this benign, self-limiting condition. Quinine has a narrow margin between an effective dose and a toxic dose. The dosing for FDA-approved use is supported by data to maximize the safety and efficacy of the product; the dosing for unapproved drugs and unapproved indications has not been reviewed and approved by FDA. Since 1969, FDA has received 665 reports of adverse events with serious outcomes associated with quinine use, including 93 deaths. Quinine-containing drugs are associated with serious side effects, severe hypersensitivity reactions, and the potential for serious drug interactions (see Contraindications/Precautions, Adverse Reactions, and Drug Interactions).

    DEA CLASS

    Rx

    DESCRIPTION

    Antimalarial; occurs naturally in the bark of the cinchona tree; more toxic and potent antimalarial than quinidine; FDA ruled that it lacked evidence of effectiveness for relief of nocturnal muscle cramps; non-prescription forms are no longer available but prescription forms are still available.

    COMMON BRAND NAMES

    Qualaquin

    HOW SUPPLIED

    Qualaquin/Quinine/Quinine Sulfate Oral Cap: 324mg

    DOSAGE & INDICATIONS

    For the treatment of malaria.
    For the treatment of malaria caused by P. falciparum, including chloroquine-resistant strains.
    Oral dosage
    Adults and Adolescents >= 16 years

    648 mg PO every 8 hours for 7 days is recommended by the manufacturer. The CDC recommends treatment for 3 days (7 days in southeast Asia), with concurrent administration of tetracycline, clindamycin, or doxycycline for 7 days. The CDC recommends for chloroquine-resistant infections and for infections of unknown resistance; may also be used for chloroquine-sensitive infections if necessary. May also be used as step-down therapy from IV quinidine for severe malaria once the parasite density is < 1% and the patient can take oral therapy.

    Children† and Adolescents < 16 years†

       Guidelines suggest 10 mg/kg/dose (Max: 648 mg) every 8 hours, for at least 3 days (7 days in southeast Asia), with concurrent administration of tetracycline (only for children over age 8 years), clindamycin, or doxycycline (only for children over the age of 8 years) for 7 days. The CDC recommends for chloroquine-resistant infections and for infections of unknown resistance; may also be used for chloroquine-sensitive infections if necessary. May also be used as step-down therapy from IV quinidine for severe malaria once the parasite density is < 1% and the patient can take oral therapy.

    For the treatment of malaria caused by chloroquine-resistant strains of P. vivax†.
    Oral dosage
    Adults

    The CDC recommends 648 mg PO every 8 hours for at least 3 days (7 days in southeast Asia) with concurrent administration of primaquine phosphate for 14 days PLUS either tetracycline or doxycycline for 7 days. May also be used as step-down therapy from IV quinidine for severe malaria once the parasite density is < 1% and the patient can take oral therapy.

    Children and Adolescents

    Guidelines suggest 10 mg/kg/dose (Max: 648 mg) every 8 hours, for at least 3 days (7 days in southeast Asia), with concurrent administration of tetracycline (only for children over age 8 years), clindamycin, or doxycycline (only for children over the age of 8 years) for 7 days. The CDC suggests adding primaquine phosphate for 14 days. May also be used as step-down therapy from IV quinidine for severe malaria once the parasite density is < 1% and the patient can take oral therapy.

    For the treatment of babesiosis†.
    Oral dosage
    Adults

    648 mg PO 3—4 times per day with concurrent administration of clindamycin IV for 7—10 days.

    Children†

    Safety and efficacy have not been established. The suggested dosage is 25 mg/kg/day, divided every 8 hours with concurrent administration of clindamycin for 7—10 days. Maximum single dose is 648 mg.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1944 mg/day PO.

    Elderly

    1944 mg/day PO.

    Adolescents

    >= 16 years: 1944 mg/day PO.
    < 16 years: Safety and efficacy have not been established; AAP recommends doses up to 30 mg/kg/day PO (max 1944 mg).

    Children

    Safety and efficacy have not been established; AAP recommends doses up to 30 mg/kg/day PO (max 1944 mg).

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Avoid use in patients with severe hepatic impairment (Child-Pugh C). Dosage adjustments are not required for mild to moderate hepatic impairment (Child-Pugh A and B); however, these patients should be closely monitored for quinine associated adverse effects.

    Renal Impairment

    CrCl > 50 ml/min: no dosage adjustment needed.
    CrCl 10—50 ml/min: reduce recommended dose by 25% and extend dosing interval to every 8—12 hours.
    CrCl < 10 ml/min: reduce recommended dose by 30—50% and extend dosing interval to every 24 hours.

    ADMINISTRATION

     
    NOTE: A MedGuide is available for quinine and is to be dispensed with every prescription and prescription refill. The MedGuide discusses side effects for quinine and details that quinine is not approved for the treatment of leg cramps due to serious side effects.

    Oral Administration

    Administer orally.

    Oral Solid Formulations

    Do not crush tablets prior to administration to avoid bitter taste.

    STORAGE

    Generic:
    - Do not freeze
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Qualaquin:
    - Do not freeze
    - Do not refrigerate
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Muscle cramps

    Both the FDA and the manufacturer warn against the off-label use of quinine for leg cramps. When used as approved by the FDA in the treatment of chloroquine-resistant malaria, a life-threatening illness, the risks associated with quinine use are justified. However, in the off-label use to prevent or treat nocturnal leg muscle cramps, the risks associated with quinine use, and the absence of evidence regarding its efficacy for such use, outweigh any potential benefit for this benign, self-limiting condition. Quinine has a narrow margin between an effective dose and a toxic dose. The dosing for FDA-approved use is supported by data to maximize the safety and efficacy of the product; the dosing for unapproved drugs and unapproved indications has not been reviewed and approved by FDA. Since 1969, FDA has received 665 reports of adverse events with serious outcomes associated with quinine use, including 93 deaths. Quinine-containing drugs are associated with serious side effects, severe hypersensitivity reactions, and the potential for serious drug interactions (see Contraindications/Precautions, Adverse Reactions, and Drug Interactions).

    Children, infants, neonates

    The safe and effective use of quinine in neonates, infants, children, and adolescents less than 16 years of age has not been established.

    Geriatric

    Clinical studies of quinine did not include sufficient numbers of geriatric patients (age >= 65 years) to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

    Pregnancy

    Quinine is classified as pregnancy category C by the manufacturer. Adequate and well-controlled studies of quinine during pregnancy are not available. Quinine crosses the placenta and results in measurable fetal blood concentrations; however, fetal blood concentrations may not be therapeutic. Rare and isolated case reports have included deafness and optic nerve hypoplasia in children exposed in utero to maternal ingestion of high doses of quinine. Based on clinical data and epidemiological surveys, quinine does not cause congenital malformation and is not associated with an increased risk of stillbirth. Quinine does not cause uterine contractions at recommended therapeutic doses, however, large doses may be oxytocic. Historically, quinine has been used as an abortifacient. Apart from effects on the fetus, quinine is also more likely to induce low blood sugars in pregnant women. Other less toxic drugs are available to treat malaria during pregnancy and should be considered. If quinine is used during pregnancy, or if the patient becomes pregnant while taking quinine, the patient should be apprised of the potential hazards to the fetus.

    Breast-feeding

    Quinine is excreted into breast milk. However, the manufacturer and the American Academy of Pediatrics (AAP) consider quinine to be compatible with breast-feeding. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1—10 days) was administered to 25 lactating women. In one study, quinine concentrations in placental cord blood and breast milk were approximately 32% and 31%, respectively, of concentrations in maternal plasma. It is estimated from this study that the breast-fed infant would receive less than 2—3 mg per day of quinine base (< 0.4% of the maternal dose) via breast milk. Both the mother and the infant should be ruled out for Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, an infant who requires chemoprophylaxis must receive the recommended dosages of antimalarial drugs. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Hypoglycemia

    Quinine stimulates the release of insulin and should be used with caution in patients with hypoglycemia. P. falciparum malarial attacks also can induce hypoglycemia, and pregnant women and children are more susceptible.

    Optic neuritis, tinnitus

    Quinine should not be used in patients with optic neuritis or tinnitus because it can exacerbate these conditions. The drug can affect the retina and optic nerve as part of an induced syndrome called cinchonism, which also can affect hearing.

    G6PD deficiency

    Quinine is contraindicated in patients with G6PD deficiency as it can induce hemolytic anemia in these patients. Normal doses have been used without adverse effects, but the drug should be used with extreme caution.

    Hemolytic-uremic syndrome, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP)

    Quinine is contraindicated in patients with a history of potential hypersensitivity reactions associated with previous quinine use, including, but not limited to, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and hemolytic-uremic syndrome (HUS). Quinine-induced thrombocytopenia is an immune-mediated disorder and several cases of fatal or life-threatening thrombocytopenia have been reported, including cases of HUS and TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine; however, if therapy is not stopped, there is risk of fatal hemorrhage. Re-exposure to quinine in patients with quinine-dependent antibodies could cause a more rapid onset and more severe symptoms of thrombocytopenia than with the original episode.

    Intramuscular injections

    Intramuscular injections should be administered cautiously to patients receiving quinine. IM injections may cause bleeding, bruising, or hematomas due to platelet effects secondary to quinine therapy.

    Blackwater fever

    Quinine is contraindicated in patients with blackwater fever, which can follow chronic infection of falciparum malaria, because they may be predisposed to complications including hemoglobinuria, and hemoglobinemia, anemia and acute intravascular hemolysis with renal failure.

    Mefloquine hypersensitivity, quinidine hypersensitivity, quinine hypersensitivity

    Quinine is contraindicated in patients with a known allergy to mefloquine, quinidine, or who have experienced quinine hypersensitivity. Patients with mefloquine hypersensitivity or quinidine hypersensitivity may have cross sensitivity to quinine.

    Myasthenia gravis

    Quinine is contraindicated in patients with myasthenia gravis. Quinine produces neuromuscular blockade exacerbating muscular weakness and can cause respiratory distress and dysphagia in myasthenic patients.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Quinine prolongs the QT, QRS, and PR intervals and has been associated with rare cases of potentially fatal cardiac arrhythmias, including torsade de pointes and ventricular fibrillation; therefore, use of the drug is contraindicated in patients with preexisting QT prolongation including congenital long QT syndrome. Use quinine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. Quinine has been prescribed off-label by some clinicians for treating nocturnal leg cramps. However, the manufacturer warns that use of the drug for this indication may cause unpredictable serious and life-threatening hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsade de pointes, and other serious adverse reactions requiring medical intervention and hospitalization. According to the manufacturer, the risk associated with use of quinine outweighs any potential benefit in treating and/or preventing nocturnal leg cramps.

    Hepatic disease

    Due to an increased risk for adverse events, administration of quinine to patients with severe hepatic disease (Child-Pugh C) should be avoided. Use of an alternative therapy is recommended. Patients with mild to moderate hepatic dysfunction (Child-Pugh A and B) may receive quinine without dose adjustment; however, health care providers are advised to closely monitor these patients for adverse effects.

    ADVERSE REACTIONS

    Severe

    torsade de pointes / Rapid / 0-1.0
    ventricular fibrillation / Early / 0-1.0
    hearing loss / Delayed / 10.0
    seizures / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    coma / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    night blindness / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic atrophy / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    coagulopathy / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    AV block / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known

    Moderate

    blurred vision / Early / 10.0
    peripheral vasodilation / Rapid / 10.0
    confusion / Early / Incidence not known
    aphasia / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    scotomata / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    erythema / Early / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    hypoprothrombinemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    dyspnea / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known

    Mild

    vertigo / Early / 10.0
    vomiting / Early / 10.0
    dizziness / Early / 10.0
    tinnitus / Delayed / 10.0
    abdominal pain / Early / 10.0
    diarrhea / Early / 10.0
    nausea / Early / 10.0
    diaphoresis / Early / 10.0
    headache / Early / 10.0
    anorexia / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    tremor / Early / Incidence not known
    diplopia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    photosensitivity / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    fever / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    petechiae / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    weakness / Early / Incidence not known
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Major) When possible, avoid concurrent use of dolutegravir and quinine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Quinine is a mixed inducer/inhibitor of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Abiraterone: (Moderate) Use abiraterone, a strong CYP2C8 inhibitor, and quinine, a CYP2C8 substrate, together cautiously, as levels of quinine may be increased. Monitor closely for signs of quinine toxicity such as visual impairment, hypoglycemia, and cardiac arrhythmias. Additionally, quinine may inhibit drugs metabolized by CYP3A4, such as abiraterone, causing increased abiraterone levels.
    Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with quinine. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Acetaminophen; Dextromethorphan: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Acetaminophen; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including oxycodone.
    Acetaminophen; Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinine.
    Acetaminophen; Tramadol: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme including tramadol.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as quinine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or quinine.
    Albuterol: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Albuterol; Ipratropium: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Alfuzosin: (Major) Concurrent use of quinine and alfuzosin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Based on electrophysiology studies performed by the manufacturer, alfuzosin also has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. In addition, concentrations of alfuzosin may be increased with concomitant use of quinine. Alfuzosin is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Aliskiren; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Alosetron: (Moderate) Alosetron is metabolized by hepatic cytochrome P450 enzymes. Inhibitors of these enzymes, such as quinine, may decrease the clearance of alosetron and increase the systemic exposure of alosetron. Clinically, increased systemic exposure to alosetron may cause or worsen constipation, which might lead to serious adverse effects.
    Alvimopan: (Moderate) Alvimopan is a substrate of P-glycoprotein (P-gp). Although the concomitant use of mild to moderate inhibitors of P-gp did not influence the pharmacokinetics of alvimopan, the concomitant use of strong P-gp inhibitors, such as quinine has not been studied. Coadministration of quinine and alvimopan may result in elevated concentrations of alvimopan. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect of alvimopan.
    Amantadine: (Minor) Quinine appears to inhibit the renal tubular secretion of amantadine resulting in a slight increase in amantadine serum concentrations. The clinical significance of this drug interaction is unclear, however, patients, especially elderly patients, should be monitored for increased adverse reactions to amantadine if quinine is added.
    Ambenonium Chloride: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors such as ambenonium chloride, edrophonium, neostigmine, physostigmine, and pyridostigmine. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Amiodarone: (Major) Concurrent use of quinine and amiodarone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Amiodarone, a Class III antiarrhythmic agent, is also associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition, concentrations of both drugs may be increased during concomitant use. Amiodarone is a CYP3A4 substrate and P-glycoprotein (P-gp) inhibitor and quinine is a CYP3A4 inhibitor and P-gp substrate.
    Amitriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required. (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
    Amlodipine; Benazepril: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Telmisartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amoxapine: (Moderate) Concentrations of amoxapine may be increased with concomitant use of quinine. Amoxapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Amprenavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Antacids: (Major) Antacids may delay or decrease the absorption of quinine.
    Apomorphine: (Major) Concurrent use of quinine and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data indicate that QT prolongation is also possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended.
    Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of quinine with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased quinine or decreased aprepitant exposure may also occur. If coadministration cannot be avoided, use caution and monitor for quinine- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen, as well as a possible change in aprepitant efficacy. Quinine is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Additionally, quinine is a moderate CYP3A4 inducer in vitro and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for low-to-moderate inducers. Finally, quinine is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may additionally increase plasma concentrations of quinine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Arformoterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Aripiprazole: (Major) Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as quinine. Adult patients receiving Abilify Maintena with quinine for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP3A4 and CYP2D6 inhibitor. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions.
    Arsenic Trioxide: (Major) Concurrent use of quinine and arsenic trioxide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should also be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
    Artemether; Lumefantrine: (Major) Concurrent use of quinine and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if quinine must be used with or after artemether; lumefantrine treatment. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Administration of artemether; lumefantrine is also associated with prolongation of the QT interval. Further, concentrations of both drugs may be elevated with concomitant use. Artemether; lumefantrine is an inhibitor and quinine is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased quinine concentrations. Additionally, artemether; lumefantrine is a substrate and quinine is a substrate/inhibitor of the CYP3A4 isoenzyme; therefore, concomitant use may lead to increased concentrations.
    Asenapine: (Major) Concurrent use of quinine and asenapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Asenapine has also been associated with QT prolongation. In addition, concentrations of asenapine may be increased with concomitant use of quinine. Asenapine is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Aspirin, ASA; Oxycodone: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including oxycodone.
    Atazanavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Atazanavir; Cobicistat: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed. (Major) Coadministration of cobicistat with quinine is not recommended as there is a potential for elevated quinine concentrations and altered cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. The CYP3A4 isoenzyme is the major enzyme responsible for quinine metabolism. Quinine is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Also, quinine may induce or inhibit CYP3A4 and inhibit CYP2D6. Cobicistat is an inhibitor of CYP3A4, CYP2D6, and P-gp and is a substrate of CYP3A4.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and quinine are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as quinine may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
    Atorvastatin: (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
    Atorvastatin; Ezetimibe: (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
    Atracurium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Atropine; Edrophonium: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including quinine, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
    Axitinib: (Major) Avoid coadministration of axitinib with quinine if possible, due to the risk of decreased efficacy and increased adverse reactions related to axitinib. Axitinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Quinine is a moderate CYP3A4 inducer (in vitro) / inhibitor, as well as a CYP1A2 inducer and 2C19 inhibitor. Coadministration with a strong CYP3A4/5 inducer, rifampin, significantly decreased the plasma exposure of axitinib in healthy volunteers, while the strong CYP3A4/5 inhibitor, ketoconazole, significantly increased axitinib exposure. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors and avoidance with strong and moderate CYP3A4 inducers, but recommendations are not available for moderate or combination CYP3A4 inducer / inhibitors.
    Azithromycin: (Major) Concurrent use of quinine and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. There have also been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports. In addition, concentrations of quinine may be increased during concomitant use. Azithromycin is a P-glycoprotein (P-gp) inhibitor and quinine is a P-gp substrate.
    Barbiturates: (Major) Quinine may interfere with the hepatic metabolism of phenobarbital or other barbiturates, resulting in higher plasma concentrations of the barbiturate. One small study found the AUC and Cmax of phenobarbital increased by 81% and 53%, respectively, when administered concurrently with quinine. In addition, phenobarbital may induce the CYP3A4 metabolism of quinine, resulting in decreased quinine plasma concentrations. If these drugs must be administered together, frequent monitoring of the barbiturate concentrations is recommended.
    Bedaquiline: (Major) Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with bedaquiline include quinine. Quinine may also inhibit the CYP3A4 metabolism of bedaquiline, resulting in increased bedaquiline systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering quinine with boceprevir due to an increased potential for quinine-related adverse events. If quinine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinine and boceprevir. Quinine is a substrate, inducer, and inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of both medications may be altered.
    Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Quinine is a moderate inhibitor of both CYP3A4 and CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions.
    Brigatinib: (Moderate) Monitor for decreased efficacy of quinine if coadministration with brigatinib is necessary. Quinine is a CYP3A substrate and brigatinib induces CYP3A in vitro. Coadministration with a strong CYP3A4 inducer decreased the median AUC of quinine by 75% in patients with uncomplicated P. falciparum malaria (n = 29); the mean AUC and Cmax of quinine were decreased by 85% and 55% in healthy volunteers receiving a concomitant strong CYP3A4 inducer. Brigatinib may also decrease quinine exposure.
    Brimonidine; Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of quinine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may alter bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; quinine is both a moderate inhibitor and inducer of CYP3A4. The net effect on CYP3A4 substrates is unclear. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Budesonide; Formoterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4.
    Buprenorphine: (Major) Buprenorphine should be avoided in combination with quinine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and should be avoided in combination with other drugs that prolong the QT interval. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, the plasma concentrations of buprenorphine, a CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP3A4 inhibitor, further increasing the risk of toxicity. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with quinine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and should be avoided in combination with other drugs that prolong the QT interval. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, the plasma concentrations of buprenorphine, a CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP3A4 inhibitor, further increasing the risk of toxicity. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Cabozantinib: (Major) Avoid the concomitant use of quinine with cabozantinib due to the risk of increased quinine exposure and either increased or decreased cabozantinib exposure. Cabozantinib is primarily metabolized by CYP3A4, and is also a P-glycoprotein (P-gp) inhibitor. Quinine is a CYP3A4 inducer and inhibitor, as well as a P-gp substrate. Coadministration with a strong CYP3A4 inducer, rifampin (600 mg daily for 31 days), decreased cabozantinib (single dose) exposure by 77%. Coadministration with a strong CYP3A4 inhibitor, ketoconazole (400 mg daily for 27 days), increased cabozantinib (single dose) exposure by 38%. The clinical relevance of cabozantinib P-gp inhibition is unknown.
    Calcium Carbonate: (Major) Antacids may delay or decrease the absorption of quinine.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Antacids may delay or decrease the absorption of quinine.
    Calcium Carbonate; Risedronate: (Major) Antacids may delay or decrease the absorption of quinine.
    Calcium; Vitamin D: (Major) Antacids may delay or decrease the absorption of quinine.
    Capecitabine: (Moderate) Use caution if coadministration of capecitabine with quinine is necessary, and monitor for an increase in quinine-related adverse reactions. CYP3A4 is the major enzyme responsible for quinine metabolism; other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%.
    Carbamazepine: (Major) One small study found the AUC and Cmax of carbamazepine increased by 104% and 56%, respectively, when administered concurrently with quinine. In addition, carbamazepine may induce the CYP3A4 metabolism of quinine, resulting in decreased quinine plasma concentrations. If these drugs must be administered together, frequent monitoring of carbamazepine concentrations is recommended.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Carbonic anhydrase inhibitors: (Moderate) Quinine and its metabolites are primarily excreted by the kidneys, and excretion is decreased when the urine is alkaline. Alkalinization of the urine by drugs such as acetazolamide and methazolamide can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Cardiac glycosides: (Major) Coadministration of digoxin and quinine increases the AUC of digoxin by 33%. Both digoxin and quinine are substrates for P-glycoprotein (P-gp). Measure serum digoxin concentrations before initiating quinine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Lower doses of quinine may have no effect on digitalis clearance.
    Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Quinine is a moderate inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
    Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, such as quinine, may inhibit the hepatic oxidative metabolism of carvedilol. The clinical significance of this pharmacokinetic interaction is unclear.
    Ceritinib: (Major) Avoid coadministration of ceritinib with quinine due to increased quinine exposure and the risk for QT prolongation. If coadministration cannot be avoided, periodically monitor electrolytes and ECGs; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Quinine is primarily metabolized by CYP3A4 and is also associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like quinine, would be expected to lead to an increase in cevimeline plasma concentrations.
    Chloroquine: (Major) Avoid concurrent use of quinine with other drugs that may cause QT prolongation and torsade de pointes (TdP), such as chloroquine. Quinine has been associated with QT prolongation and rare cases of TdP. Chloroquine is associated with an increased risk of QT prolongation and TdP; fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses.
    Chlorpheniramine; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Chlorpheniramine; Dextromethorphan: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpromazine: (Major) Concurrent use of quinine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Chlorpromazine has also been associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. In addition, concentrations of chlorpromazine may be increased with concomitant use of quinine. Chlorpromazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Cimetidine: (Minor) Cimetidine reduced the hepatic clearance of quinine and prolonged its half-life. Peak quinine serum concentrations were not affected. The clinical significance of this pharmacokinetic interaction is unclear.
    Ciprofloxacin: (Major) Concurrent use of quinine and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Rare cases of QT prolongation and TdP have also been reported with ciprofloxacin during post-marketing surveillance.
    Cisapride: (Severe) Concurrent use is contraindicated. Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Postmarketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, when known and potent inhibitors of CYP3A4 are coadministered with cisapride. Quinine has the potential to inhibit the metabolism of cisapride through CYP3A4. In addition, quinine has been associated with QT prolongation and rare cases of TdP.
    Cisatracurium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Citalopram: (Major) Concurrent use of quinine and citalopram should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Citalopram also causes dose-dependent QT interval prolongation. In addition, concentrations of citalopram may be increased with concomitant use of quinine. Citalopram is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Citric Acid; Potassium Citrate: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Clarithromycin: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Clindamycin: (Moderate) Concomitant use of clindamycin and quinine may alter clindamycin concentrations. Clindamycin is a CYP3A4 substrate; quinine is both a moderate inhibitor and inducer of CYP3A4. The net effect on CYP3A4 substrates is unclear. Caution and close monitoring for increased adverse reactions and/or loss of efficacy are advised if these drugs are used together.
    Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of quinine. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and quinine is an inhibitor of CYP2C19 in vitro. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
    Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1 and OCT2, and quinine, an inhibitor of OCT1 and OCT2, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 and OCT2 inhibitors.
    Clomipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Clopidogrel: (Major) Quinine may reduce the antiplatelet activity of clopidogrel by inhibiting clopidogrel's metabolism to its active metabolite. Use clopidogrel and quinine together with caution and monitor for reduced efficacy of clopidogrel. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps. The CYP3A4 isoenzyme is involved in one of the metabolic steps, and the CYP2C19 isoenzyme is involved in both steps. Quinine is an inhibitor of CYP3A4 and in vitro studies suggest it is an inhibitor of CYP2C19. Furthermore, at high concentrations in vitro, clopidogrel inhibits the activity of CYP2C9. Thus, clopidogrel could increase plasma concentrations of drugs metabolized by this isoenzyme, such as quinine. Although there are no in vivo data with which to predict the magnitude or clinical significance of this potential interaction, caution should be used when quinine is coadministered with clopidogrel.
    Clozapine: (Major) Both clozapine and quinine are associated with a possible risk for QT prolongation and torsade de pointes (TdP). Avoid concurrent use if possible. In addition, quinine is an inhibitor of CYP2D6 and CYP3A4, two of the isoenzymes responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP2D6 or CYP3A4 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer of clozapine, monitor for adverse reactions and consider reducing the clozapine dose during concomitant use of inhibitors of CYP2D6 or CYP3A4. If the inhibitor is discontinued, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Major) Coadministration of cobicistat with quinine is not recommended as there is a potential for elevated quinine concentrations and altered cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. The CYP3A4 isoenzyme is the major enzyme responsible for quinine metabolism. Quinine is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Also, quinine may induce or inhibit CYP3A4 and inhibit CYP2D6. Cobicistat is an inhibitor of CYP3A4, CYP2D6, and P-gp and is a substrate of CYP3A4.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of cobicistat with quinine is not recommended as there is a potential for elevated quinine concentrations and altered cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. The CYP3A4 isoenzyme is the major enzyme responsible for quinine metabolism. Quinine is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Also, quinine may induce or inhibit CYP3A4 and inhibit CYP2D6. Cobicistat is an inhibitor of CYP3A4, CYP2D6, and P-gp and is a substrate of CYP3A4. (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of cobicistat with quinine is not recommended as there is a potential for elevated quinine concentrations and altered cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. The CYP3A4 isoenzyme is the major enzyme responsible for quinine metabolism. Quinine is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Also, quinine may induce or inhibit CYP3A4 and inhibit CYP2D6. Cobicistat is an inhibitor of CYP3A4, CYP2D6, and P-gp and is a substrate of CYP3A4. (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with quinine due to altered cobimetinib exposure. Cobimetinib is a CYP3A substrate in vitro, and quinine is both a moderate inhibitor and a moderate in vitro inducer of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Additionally, based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer. Exposure to cobimetinib may be affected unpredictably if coadministered with quinine.
    Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Codeine; Guaifenesin: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Codeine; Phenylephrine; Promethazine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Codeine; Promethazine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Quinine inhibits CYP2D6 and may decrease the conversion of codeine to morphine; a corresponding decrease in analgesia is seen.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and quinine unless the use of both agents is imperative. Quinine can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like quinine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Conivaptan: (Major) Avoid coadministration of conivaptan, a CYP3A4/P-glycoprotein (P-gp) inhibitor and CYP3A4 substrate, and quinine, a CYP3A4/P-gp substrate and CYP3A4 inhibitor. Concurrent use may result in elevated concentrations of both drugs. According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as quinine, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with quinine. Treatment with quinine may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: (Major) Avoid concurrent use of crizotinib and quinine due to the risk of QT prolongation and torsade de pointes (TdP); increased exposure to crizotinib may also occur. If coadministration cannot be avoided, monitor ECGs and electrolytes. Crizotinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation. Quinine is a moderate CYP3A4 inhibitor that has also been associated with QT prolongation and rare cases of TdP.
    Cyclobenzaprine: (Major) Concurrent use of quinine and cyclobenzaprine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Cyclobenzaprine is also associated with a possible risk of QT prolongation and TdP, particularly in the event of acute overdose. In addition, concentrations of cyclobenzaprine may be increased with concomitant use of quinine. Cyclobenzaprine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Cyclosporine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP), and cyclosporine is a PGP substrate and inhibitor. Therefore, quinine concentrations could be increased with coadministration. Monitor patients for increased side effects of quinine if these drugs are given together.
    Dacarbazine, DTIC: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with quinine, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of quinine, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
    Dapagliflozin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
    Darunavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Darunavir; Cobicistat: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed. (Major) Coadministration of cobicistat with quinine is not recommended as there is a potential for elevated quinine concentrations and altered cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. The CYP3A4 isoenzyme is the major enzyme responsible for quinine metabolism. Quinine is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Also, quinine may induce or inhibit CYP3A4 and inhibit CYP2D6. Cobicistat is an inhibitor of CYP3A4, CYP2D6, and P-gp and is a substrate of CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate. (Major) Concurrent administration of quinine with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir is expected to result in elevated quinine plasma concentrations and altered concentrations of dasabuvir, paritaprevir, and ritonavir. Quinine's product labeling recommends avoiding concomitant use with ritonavir due to increased quinine concentrations and risk for toxicity. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life compared to when quinine was administered alone. The dosage of ritonavir in dasabuvir; ombitasvir; paritaprevir; ritonavir is lower than that studied; therefore, the degree of increase in quinine plasma concentrations with coadministration of these specific products in not known. Both ritonavir and quinine are substrates and inhibitors of the hepatic isoenzymes CYP3A4 and CYP2D. Paritaprevir and dasabuvir (minor) are also substrates of CYP3A4. Quinine is a P-glycoprotein (P-gp) substrate, and ritonavir and paritaprevir inhibit P-gp. Both ritonavir and quinine have been shown to prolong the QT interval in a concentration-dependent fashion. Caution and close monitoring are advised if these drugs are administered together.
    Dasatinib: (Major) Concurrent use of quinine and dasatinib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. In vitro studies have shown that dasatinib also has the potential to prolong cardiac ventricular repolarization (prolong QT interval). In addition, concentrations of dasatinib may be increased with concomitant use of quinine. Dasatinib is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Daunorubicin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and its use with other drugs that may prolong the QT interval should be avoided. Acute cardiotoxicity can occur during administration of daunorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Deflazacort: (Major) Avoid concomitant use of deflazacort and quinine. Concurrent use may significantly alter concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy and/or increased risk of toxicity. Deflazacort is a CYP3A4 substrate; quinine is a mixed inducer/inhibitor of CYP3A. The net effect on CYP3A4 substrates is unknown. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
    Degarelix: (Major) Concurrent use of quinine and degarelix should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Degarelix may also cause QT prolongation.
    Desflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Desipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine with quinine. Clinically relevant QT prolongation may occur with deutetrabenazine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Guaifenesin: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Promethazine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Dextromethorphan; Quinidine: (Severe) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as quinidine. Coadministration may result in an elevated quinidine plasma concentration, causing an increased risk for adverse events, such as QT prolongation. Further, both quinine and quinidine are cinchona alkaloids; the possibility of cinchonism is increased if these drugs are administered concomitantly (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including dextromethorphan.
    Diltiazem: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and diltiazem is a PGP and CYP3A4 inhibitor. Therefore, quinine concentrations could be increased with coadministration. Monitor patients for increased side effects of quinine if these drugs are given together.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Disopyramide: (Major) Concurrent use of quinine and disopyramide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of disopyramide may be increased with concomitant use of quinine. Disopyramide is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Dofetilide: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use with other drugs that prolong the QT interval, such as quinine, is contraindicated.
    Dolasetron: (Major) Concurrent use of quinine and dolasetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Dolasetron has also been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. In addition, concentrations of dolasetron may be increased with concomitant use of quinine. Dolasetron is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Dolutegravir: (Major) When possible, avoid concurrent use of dolutegravir and quinine. Use of these drugs together may result in decreased dolutegravir plasma concentrations. Quinine is a mixed inducer/inhibitor of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quinine. In addition, concomitant use of quinine and donepezil may result in increased donepezil concentrations. Quinine is an inhibitor of CYP2D6 and CYP3A4, the two isoenzymes involved in the metabolism of donepezil.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quinine. In addition, concomitant use of quinine and donepezil may result in increased donepezil concentrations. Quinine is an inhibitor of CYP2D6 and CYP3A4, the two isoenzymes involved in the metabolism of donepezil. (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as quinine, could result in elevated serum concentrations of one or both drugs.
    Dorzolamide; Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
    Doxacurium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Doxepin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Doxorubicin: (Major) Avoid coadministration of quinine and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. Quinine is a CYP2D6 and CYP3A4 inhibitor, as well as a CYP3A4 inducer; doxorubicin is a major substrate of both CYP2D6 and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Quinine has a possible risk of causing QT prolongation and torsades de pointes (TdP) and this effect may be additive to other drugs that prolong the QT interval. Acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dronabinol, THC: (Moderate) Use caution if coadministration of dronabinol with quinine is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Quinine is a moderate inhibitor and inducer (in vitro) of CYP3A4. Concomitant use may result in altered plasma concentrations of dronabinol.
    Dronedarone: (Severe) Concomitant use of dronedarone with other drugs that prolong the QTc, such as quinine, may induce torsade de pointes (TdP) and is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Concurrent use of quinine and droperidol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Droperidol administration is also associated with an established risk for QT prolongation and TdP. In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. In addition, concentrations of droperidol may be increased with concomitant use of quinine. Droperidol is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of quinine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as quinine, should be avoided.
    Edrophonium: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Efavirenz: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP, such as efavirenz. In addition, concurrent use may alter the systemic concentration of efavirenz and decrease the concentration of quinine. Efavirenz is a CYP3A4 substrate and inducer, while quinine is a CYP3A4 substrate, inducer, and inhibitor.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP, such as efavirenz. In addition, concurrent use may alter the systemic concentration of efavirenz and decrease the concentration of quinine. Efavirenz is a CYP3A4 substrate and inducer, while quinine is a CYP3A4 substrate, inducer, and inhibitor.
    Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with quinine. Use of these drugs together may cause changes in the plasma concentrations of elbasvir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Quinine is an inhibitor and inducer of CYP3A; elbasvir is a substrate of CYP3A. (Major) If possible, avoid concurrent administration of grazoprevir with quinine. Use of these drugs together may cause changes in the plasma concentrations of grazoprevir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Quinine is an inhibitor and inducer of CYP3A; grazoprevir is a substrate of CYP3A. In addition, concentrations of quinine (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
    Eliglustat: (Severe) Coadministration of quinine and eliglustat is contraindicated. Quinine is a CYP2D6 and CYP3A4 inhibitor associated with QT prolongation and rare cases of torsade de points (TdP); its use should be avoided with other drugs that prolong the QT interval. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinine and eliglustat may result in additive effects on the QT interval and significantly increased plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
    Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as quinine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
    Elvitegravir: (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Encainide: (Major) Encainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering encainide with CYP2D6 inhibitors, such as quinine, since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
    Enflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Entecavir: (Major) Both entecavir and quinine are secreted by active tubular secretion. In theory, coadministration of entecavir with quinine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Epirubicin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and its use with other drugs that may prolong the QT interval should be avoided. Acute cardiotoxicity can occur during administration of epirubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: (Major) Eplerenone is metabolized by the CYP3A4 pathway. Quinine inhibits the hepatic CYP3A4 isoenzyme and therefore may increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. If these medications are given concurrently in post-myocardial infarction patients with heart failure, do not exceed an eplerenone dose of 25 mg PO once daily. If these medications are given concurrently, and eplerenone is used for hypertension, initiate eplerenone at 25 mg PO once daily. The dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response.
    Ergot alkaloids: (Major) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as quinine, may potentially increase the risk of ergot toxicity including vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects.
    Eribulin: (Major) Concurrent use of quinine and eribulin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Eribulin has also been associated with QT prolongation.
    Erlotinib: (Major) Avoid the coadministration of erlotinib with quinine due to an unpredictable effect on the efficacy and toxicity of erlotinib. Quinine is a CYP3A4 inhibitor and a CYP1A2 inducer; it also may induce CYP3A4 in vitro. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. In a single-dose pharmacokinetics trial in healthy volunteers, cigarette smoking (moderate CYP1A2 inducer) decreased the AUC of erlotinib by 64% (95% CI, 46% to 76%) in current smokers compared with former/never smokers. Steady-state trough concentrations of erlotinib were approximately 2-fold less in current smokers compared with former/never smokers in a separate study of patients with NSCLC. Coadministration of erlotinib with ketoconazole, a strong CYP3A4 inhibitor, increased the erlotinib AUC by 67%; coadministration with quinine may also increase erlotinib exposure.
    Erythromycin: (Major) Concurrent use of quinine with erythromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and erythromycin have been associated with prolongation of the QT interval. In addition, because both erythromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Erythromycin; Sulfisoxazole: (Major) Concurrent use of quinine with erythromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and erythromycin have been associated with prolongation of the QT interval. In addition, because both erythromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP2C19 and CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
    Ethinyl Estradiol; Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as quinine may increase the serum concentration of etonogestrel.
    Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as quinine may increase the serum concentration of etonogestrel.
    Etoposide, VP-16: (Major) Monitor for clinical efficacy of etoposide as well as an increased incidence of etoposide-related adverse effects if used concomitantly with quinine. Quinine is a CYP3A4 inducer and inhibitor; etoposide, VP-16 is a CYP3A4 and P-gp substrate. Coadministration may either increase or decrease etoposide concentrations.
    Etravirine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and etravirine is a PGP inhibitor and CYP3A4 inducer. Therefore, quinine concentrations could be altered with coadministration. Monitor patients for effectiveness and increased adverse effects of quinine if these drugs are given together.
    Ezetimibe; Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
    Ezogabine: (Major) Concurrent use of quinine and ezogabine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Ezogabine has also been associated with QT prolongation.
    Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as quinine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of quinine during coadministration with fenofibric acid.
    Fesoterodine: (Moderate) Fesoterodine is rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4. In theory, the CYP3A4 inhibitory effects of quinine may result in an increase in plasma concentrations of 5-hydroxymethyltolterodine. The need for fesoterodine doses greater than 4 mg/day should be carefully evaluated prior to increasing the dose during concurrent use of mild to moderate 3A4 inhibitors.
    Fingolimod: (Major) Concurrent use of quinine and fingolimod should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP, such as quinine. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Flecainide clearance can be modestly inhibited by quinine, increasing flecainide serum concentrations. Quinine is a CYP2D6 inhibitor, and flecainide is a CYP2D6 substrate. Additionally, both drugs are associated with prolongation of the QT internal. Until more data are available, concomitant use of these two drugs should be avoided whenever possible.
    Flibanserin: (Severe) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as quinine, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
    Fluconazole: (Severe) Concurrent use of fluconazole and quinine is contraindicated due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP). Both fluconazole and quinine have been associated with QT prolongation and rare cases of TdP. In addition, fluconazole is an inhibitor of CYP3A4 and quinine is a CYP3A4 substrate. Coadministration may result in an elevated quinine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates, such as fluoxetine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Fluoxetine; Olanzapine: (Major) Concurrent use of quinine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of olanzapine may be increased with concomitant use of quinine. Olanzapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor. (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates, such as fluoxetine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Fluphenazine: (Major) Concurrent use of quinine and fluphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Fluphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
    Fluticasone; Salmeterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Fluvoxamine: (Major) It is recommended to avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP. Quinine has been associated with QT prolongation and rare cases of torsade de pointes. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Food: (Major) Clinicians should be aware that some food and beverage products contain quinine. Tonic water commonly contains quinine and may have additive effects when taken with quinine medications. One study reported that the concentrations of quinine in tonic water are not significant enough to result in drug interactions with CYP2D6 substrates. (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with quinine. Quinine is an inhibitor and an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with quinine, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be altered. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Formoterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Formoterol; Mometasone: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Fosamprenavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as quinine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Quinine has also been associated with QT prolongation and rare cases of TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, leading to reduced efficacy of the concomitant medication. Medications that may be affected include quinine. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy.
    Gefitinib: (Major) Monitor for clinical response of gefitinib and an increased incidence of gefitinib-related adverse effects if gefitinib and quinine are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and to a lesser extent, by CYP2D6; quinine is a moderate inhibitor of both CYP3A4 and CYP2D6, as well as a moderate CYP3A4 inducer in vitro. Coadministration may alter gefitinib serum concentrations. While the manufacturer has provided no guidance regarding the use of gefitinib with mild or moderate CYP3A4 inhibitors or inducers, administration of a single 250 mg gefitinib dose with a strong CYP3A4 inhibitor (itraconazole) increased the mean AUC of gefitinib by 80%; administration of a single dose of gefitinib with a strong CYP3A4 inducer (rifampin) decreased mean AUC by 83%.
    Gemfibrozil: (Moderate) Coadministration may result in a significant increase in quinine exposure. A dose reduction of quinine may be required if used concomitantly with gemfibrozil. Use quinine and gemfibrozil together with caution. Quinine is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor.
    Gemifloxacin: (Major) Concurrent use of quinine and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with quinine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Quinine has been associated with QT prolongation and rare cases of TdP.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Glycopyrrolate; Formoterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Goserelin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including goserelin. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Major) Concurrent use of quinine and granisetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Granisetron has also been associated with QT prolongation. In addition, concentrations of granisetron may be increased with concomitant use of quinine. Granisetron is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Grapefruit juice: (Moderate) Quinine pharmacokinetics were not affected by grapefruit juice in a study of 10 healthy volunteers who were administered 5 days of grapefruit juice prior to receiving a single 600 mg quinine dose. However, there is a case report in which a 19 year old patient with known asymptomatic long QT syndrome developed torsade de pointes (TdP) after ingesting excessive amounts of grapefruit juice and quinine-containing tonic water. The TdP stopped 48 hours after discontinuing these drinks. Use of quinine and grapefruit juice should be done with caution, especially with large or multiple doses of quinine or if co-administered in patients with potential cardiac abnormalities.
    Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Guanfacine: (Major) Quinine may significantly alter guanfacine plasma concentrations. Guanfacine is primarily metabolized by CYP3A4. Quinine is a moderate inhibitor of CYP3A4; in vitro data suggests it may also moderately induce CYP3A4. The net effect of this potential interaction is unclear, but guanfacine dosage adjustments, most likely a dose decrease, may be required. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if used with a moderate to strong CYP3A4 inhibitor, the guanfacine dosage should be decreased to half of the recommended dose and the patient should be closely monitored for alpha-adrenergic effects (e.g., hypotension, drowsiness, bradycardia). However, if used with a moderate to strong CYP3A4 inducer, labeling recommends to consider doubling the recommended dose of guanfacine ER; if the inducer is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If the inducer or inhibitor is discontinued, guanfacine ER should return to its recommended dose (with downward titration occurring over 1 to 2 weeks). Specific recommendations for immediate-release (IR) guanfacine are not available.
    Halofantrine: (Major) Concurrent use of quinine may increase the risk of halofantrine cardiotoxicity via inhibition of halofantrine metabolism. Halofantrine is considered to have a well-established risk for QT prolongation and torsade de pointes (TdP). Although not available in the United States, halofantrine is widely available overseas, and US health care providers might choose to caution patients before travel to avoid the use of halofantrine if possible if a patient is already taking quinine. If co-use is medically necessary, ECG monitoring may be helpful.
    Halogenated Anesthetics: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Haloperidol: (Major) Concurrent use of quinine and haloperidol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Further, quinine is a substrate of CYP3A4 and an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
    Halothane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Homatropine; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) Metoprolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair metoprolol metabolism; the clinical significance of such interactions is unknown. Clinicians should be alert to exaggerated beta-blocker effects if metoprolol is given with quinine.
    Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
    Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and quinine are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Quinine is both an inhibitor and an inducer of CYP3A4. Coadministration may cause an increase or decrease in hydrocodone plasma concentrations, which could increase or prolong adverse effects or decrease analgesic effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as quinine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and quinine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Quinine has also been associated with QT prolongation and rare cases of TdP.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include quinine.
    Ibritumomab Tiuxetan: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Ibrutinib: (Major) If coadministered with quinine, initiate ibrutinib therapy at a reduced dose of 140 mg/day PO for the treatment of B-cell malignancy or 420 mg/day PO for the treatment of chronic graft-versus-host disease; monitor patients more frequently for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the Cmax and AUC values of ibrutinib were increased by 3.4-fold and 3-fold, respectively.
    Ibuprofen; Oxycodone: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including oxycodone.
    Ibutilide: (Major) Concurrent use of quinine and ibutilide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
    Idarubicin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and its use with other drugs that may prolong the QT interval should be avoided. Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinine, a CYP3A substrate, as quinine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Major) Concurrent use of quinine and iloperidone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Iloperidone has also been associated with QT prolongation; however, TdP has not been reported. In addition, concentrations of iloperidone may be increased with concomitant use of quinine. Iloperidone is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Imipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Indacaterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Indinavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quinine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinine has been associated with QT prolongation and rare cases of TdP.
    Irinotecan Liposomal: (Moderate) Use caution if irinotecan liposomal is coadministered with quinine, a CYP3A4 inhibitor, due to increased risk of irinotecan-related toxicity. The metabolism of liposomal irinotecan has not been evaluated; however, coadministration of ketoconazole, a strong CYP3A4 and UGT1A1 inhibitor, with non-liposomal irinotecan HCl resulted in increased exposure to both irinotecan and its active metabolite, SN-38. Quinine is also a substrate and moderate inducer of CYP3A4 in vitro; however, coadministration with dexamethasone, a moderate CYP3A4 inducer, did not alter the pharmacokinetics of irinotecan HCl.
    Irinotecan: (Moderate) Quinine is a moderate inhibitor and inducer of CYP3A4; irinotecan is a CYP3A4 substrate. Coadministration may affect irinotecan exposure. Use caution if concomitant use is necessary and monitor for efficacy as well as increased irinotecan side effects, including diarrhea, nausea, vomiting, and myelosuppression.
    Isavuconazonium: (Major) Concomitant use of isavuconazonium with quinine may result in increased serum concentrations of quinine and altered concentrations of isavuconazonium. Quinine is a substrate/inhibitor/inducer of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
    Isoniazid, INH; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
    Itraconazole: (Moderate) Monitor patients for increased quinine-related adverse effects if coadministration of itraconazole is necessary. Quinine is a substrate of P-glycoprotein (P-gp) and CYP3A4, and itraconazole is a P-gp and CYP3A4 inhibitor. Therefore, quinine concentrations could be increased with coadministration.
    Ivabradine: (Major) Avoid coadministration of ivabradine and quinine as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; quinine is an inhibitor of CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and quinine concurrently; the clinical effect of this interaction is unknown. Ivacaftor is a CYP3A substrate, and quinine is a CYP3A inhibitor and can also act as an inducer. Co-administration may lead to altered ivacaftor exposure. Ivacaftor is also an inhibitor of CYP3A , CYP2C9, and P-glycoprotein (Pgp); quinine is partially metabolized by CYP3A, CYP2C9 and is a substrate of Pgp. Co-administration may increase quinine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ketoconazole: (Major) Ketoconazole, a potent CYP3A4 inhibitor, may inhibit the metabolism of quinine, a CYP3A4 substrate. Co-administration with ketoconazole decreases the oral clearance of quinine by 31 percent and reduces the AUC of 3-hydroxyquinine.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like quinine sulfate, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Lapatinib: (Major) Concurrent use of quinine and lapatinib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, both drugs are substrates and inhibitors of CYP3A4; coadministration may increase concentrations of both drugs.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of quinine-associated adverse reactions is advised with concomitant administration of ledipasvir. Quinine is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase quinine plasma concentrations.
    Lenvatinib: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that prolong the QT, including lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Levalbuterol: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Levobupivacaine: (Minor) Quinine may inhibit the metabolism of levobupivacaine. Concurrent administration of quinine and levobupivacaine may result in increased systemic levels of levobupivacaine resulting in toxicity.
    Levofloxacin: (Major) Concurrent use of quinine and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Levofloxacin has also been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin.
    Lidocaine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4.
    Lithium: (Major) Lithium should be avoided in combination with quinine. Lithium has been associated with QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP.
    Long-acting beta-agonists: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Loperamide: (Major) Loperamide should be avoided in combination with quinine. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP. In addition, the plasma concentrations of loperamide, a CYP3A4 and CYP2D6 substrate, may be increased when administered concurrently with quinine, a CYP3A4 and CYP2D6 inhibitor, further increasing the risk of toxicity. If coadministration cannot be avoided, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Major) Loperamide should be avoided in combination with quinine. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP. In addition, the plasma concentrations of loperamide, a CYP3A4 and CYP2D6 substrate, may be increased when administered concurrently with quinine, a CYP3A4 and CYP2D6 inhibitor, further increasing the risk of toxicity. If coadministration cannot be avoided, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate. (Major) Concurrent use of quinine and lopinavir; ritonavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Lopinavir; ritonavir is also associated with QT prolongation. In addition, concomitant use of quinine (a CYP3A4 substrate/inhibitor) and lopinavir; ritonavir (a CYP3A4 substrate/inhibitor) may increase the serum concentrations of both quinine and lopinavir.
    Lovastatin: (Moderate) Lovastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of lovastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant lovastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of lovastatin should be considered while patients are receiving quinine.
    Lovastatin; Niacin: (Moderate) Lovastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of lovastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant lovastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of lovastatin should be considered while patients are receiving quinine.
    Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of quinine, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of quinine, such as QT prolongation and cinchonism. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of quinine by decreasing its systemic exposure. If used together, monitor patients closely for loss of quinine efficacy. Quinine is primarily metabolized by CYP3A4 and is also a substrate of CYP2C8, CYP2C9, CYP2C19, and the drug transporter P-glycoprotein (P-gp). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8, CYP2C9, and P-gp. (Moderate) Use caution when administering ivacaftor and quinine concurrently; the clinical effect of this interaction is unknown. Ivacaftor is a CYP3A substrate, and quinine is a CYP3A inhibitor and can also act as an inducer. Co-administration may lead to altered ivacaftor exposure. Ivacaftor is also an inhibitor of CYP3A , CYP2C9, and P-glycoprotein (Pgp); quinine is partially metabolized by CYP3A, CYP2C9 and is a substrate of Pgp. Co-administration may increase quinine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of quinine by decreasing its systemic exposure. If used together, monitor patients closely for loss of quinine efficacy. Quinine is primarily metabolized by CYP3A4 and is also a substrate of CYP2C8, CYP2C9, CYP2C19, and the drug transporter P-glycoprotein (P-gp). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8, CYP2C9, and P-gp.
    Lurasidone: (Major) Results of in vivo and in vitro drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4. Because lurasidone is primarily metabolized by CYP3A4, concurrent use of quinine can theoretically lead to an increased risk of lurasidone-related adverse reactions.
    Maprotiline: (Major) Concurrent use of quinine and maprotiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, concentrations of maprotiline may be increased with concomitant use of quinine. Maprotiline is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Maraviroc: (Moderate) Use caution if coadministration of maraviroc with quinine is necessary as altered maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A; quinine is an inhibitor and inducer of CYP3A4. Monitor for decreased efficacy and/or an increase in adverse effects with concomitant use.
    Mefloquine: (Severe) Due to the risk for QT prolongation and seizures, do not administer mefloquine until at least 12 hours after quinine discontinuation have passed. Both drugs have been associated with QT prolongation. In addition, quinine is an inhibitor of CYP3A4, and mefloquine is a CYP3A4 substrate. Coadministration has resulted in a 22% increase in mefloquine systemic exposure, causing an increased risk for adverse events, such as QT prolongation and seizures.
    Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as quinine, could result in elevated serum concentrations of one or both drugs.
    Meperidine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of drugs metabolized by this enzyme, such as meperidine. Because large increases in serum concentrations of meperidine may be associated with severe adverse reactions, caution is recommended during coadministration with quinine.
    Meperidine; Promethazine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of drugs metabolized by this enzyme, such as meperidine. Because large increases in serum concentrations of meperidine may be associated with severe adverse reactions, caution is recommended during coadministration with quinine.
    Metaproterenol: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Metformin; Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Quinine has been shown to be an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
    Metformin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
    Methadone: (Major) Concurrent use of quinine and methadone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, concentrations of methadone may be increased with concomitant use of quinine. Methadone is a CYP3A4 and CYP2D6 substrate and quinine is a CYP3A4/CYP2D6 inhibitor.
    Methamphetamine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates, such as methamphetamine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
    Metoprolol: (Minor) Metoprolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair metoprolol metabolism; the clinical significance of such interactions is unknown. Clinicians should be alert to exaggerated beta-blocker effects if metoprolol is given with quinine.
    Mexiletine: (Moderate) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair mexiletine metabolism; the clinical significance of such interactions is unknown.
    Midazolam: (Minor) Quinine does not induce the metabolism of midazolam. In a study of 23 subjects receiving multiple doses of quinine for 7 days and a single dose of midazolam, the mean AUC and Cmax of midazolam and 1-hydroxymidazolam were not significantly affected.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and quinine; both drugs have been reported to increase the QT interval. If coadministration cannot be avoided, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation has been reported with quinine therapy; rarely, potentially fatal cardiac arrhythmias (e.g., torsades de pointes and ventricular fibrillation) have occurred.
    Mifepristone, RU-486: (Major) Concurrent use of quinine and mifepristone (RU-486) should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. In addition, both drugs are inhibitors and substrates of CYP3A4; coadministration may result in increased concentration of both drugs.
    Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as quinine may be increased when co-administered with mirabegron. Quinine has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and quinine. Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP. Quinine has been associated with QT prolongation and rare cases of torsade de pointes. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mitotane: (Major) Use caution if mitotane and quinine are used concomitantly, and monitor for decreased efficacy of quinine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and quinine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quinine. Another strong CYP3A inducer, rifampin, has been shown to significantly decreases the AUC (75% to 85%) and Cmax (55%) of quinine, resulting in treatment failures; concomitant use should be avoided.
    Mivacurium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Moxifloxacin: (Major) Concurrent use of quinine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Prolongation of the QT interval has also been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with quinine. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with quinine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as quinine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with quinine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as quinine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nelfinavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Neostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Neratinib: (Major) Avoid concomitant use of quinine with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
    Neuromuscular blockers: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Niacin; Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
    Nicardipine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and nicardipine is a PGP inhibitor; therefore, quinine concentrations could be increased with coadministration. Monitor patients for increased adverse effects of quinine if these drugs are given together.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval such as quinine. Nilotinib is an inhibitor of CYP3A4 and CYP2D6 and an inhibitor and inducer of CYP2C9. Quinine is a substrate, inhibitor, and inducer of CYP3A4, a CYP2D6 substrate and inhibitor, and a CYP2C9 substrate. Administering these drugs together may result in altered levels of either drug. If the use of quinine is required, hold nilotinib therapy. Monitor patients closely for toxicity (e.g., QT interval prolongation) and efficacy if these drugs are used together.
    Nintedanib: (Major) Quinine is a moderate inhibitor of CYP3A4 and, in vitro, is also a CYP3A4 inducer. Nintedanib is a minor CYP3A4 substrate. Coadministration of nintedanib with a CYP3A4 inhibitor could increase the concentration and clinical effect of nintedanib, while concomitant use of a CYP3A4 inducer could decrease exposure to nintedanib. Avoid coadministration of nintedanib with CYP3A4 inducers such as quinine as these drugs may compromise nintedanib efficacy.
    Norfloxacin: (Major) Concurrent use of quinine and norfloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Quinolones have also been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during post-marketing surveillance of norfloxacin.
    Nortriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Octreotide: (Major) Concurrent use of quinine and octreotide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Arrhythmias, sinus bradycardia, and conduction disturbances have also occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Concurrent use of quinine and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Some quinolones, including ofloxacin, have also been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Concurrent use of quinine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of olanzapine may be increased with concomitant use of quinine. Olanzapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Olaparib: (Major) Avoid coadministration of olaparib with quinine and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure. If concomitant use is unavoidable, reduce the dose of olaparib tablets to 150 mg twice daily; reduce the dose of olaparib capsules to 200 mg twice daily. Olaparib is a CYP3A4/5 substrate and quinine is a moderate CYP3A4 inhibitor.
    Olodaterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate. (Major) Concurrent administration of quinine with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir is expected to result in elevated quinine plasma concentrations and altered concentrations of dasabuvir, paritaprevir, and ritonavir. Quinine's product labeling recommends avoiding concomitant use with ritonavir due to increased quinine concentrations and risk for toxicity. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life compared to when quinine was administered alone. The dosage of ritonavir in dasabuvir; ombitasvir; paritaprevir; ritonavir is lower than that studied; therefore, the degree of increase in quinine plasma concentrations with coadministration of these specific products in not known. Both ritonavir and quinine are substrates and inhibitors of the hepatic isoenzymes CYP3A4 and CYP2D. Paritaprevir and dasabuvir (minor) are also substrates of CYP3A4. Quinine is a P-glycoprotein (P-gp) substrate, and ritonavir and paritaprevir inhibit P-gp. Both ritonavir and quinine have been shown to prolong the QT interval in a concentration-dependent fashion. Caution and close monitoring are advised if these drugs are administered together.
    Omeprazole; Sodium Bicarbonate: (Major) Antacids may delay or decrease the absorption of quinine.
    Ondansetron: (Major) Concurrent use of quinine and ondansetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of ondansetron may be increased with concomitant use of quinine. Ondansetron is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Oritavancin: (Moderate) Coadministration of oritavancin and quinine may result in increases or decreases in quinine exposure and may increase side effects or decrease efficacy of quinine. Quinine is primarily metabolized by CYP3A4, but is also metabolized by CYP2D6, CYP2C9, and CYP2C19. Oritavancin weakly induces CYP3A4 and CYP2D6, while weakly inhibiting CYP2C9 and CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
    Osimertinib: (Major) Avoid coadministration of quinine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinine has also been associated with QT prolongation and rare cases of TdP.
    Oxaliplatin: (Major) Avoid coadministration of quinine with oxaliplatin due to the risk of additive QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Oxycodone: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions including oxycodone.
    Paliperidone: (Major) Concurrent use of quinine and paliperidone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Paliperidone has also been associated with QT prolongation. In addition, concentrations of paliperidone may be increased with concomitant use of quinine. Paliperidone is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
    Pancuronium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Panobinostat: (Major) The co-administration of panobinostat with quinine is not recommended; QT prolongation has been reported with both agents. Quinine is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of quinine and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
    Paroxetine: (Major) Both paroxetine and quinine are substrates of CYP2D6. In addition, quinine is a moderate inhibitor of CYP2D and paroxetine is a potent inhibitor of CYP2D6. One or both medications may inhibit the metabolism of the other. Patients should be monitored for an increase in adverse effects of paroxetine (e.g., serotonin syndrome, anticholinergic effects) or quinine (e.g., QT prolongation) during concurrent therapy. In addition, because quinine is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events.
    Pasireotide: (Major) Concurrent use of quinine and pasireotide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pasireotide may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Concurrent use of quinine and pazopanib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pazopanib has also been reported to prolong the QT interval. In addition, both drugs are CYP3A4 inhibitors and substrates; coadministration may increase serum concentrations of both drugs. Dose adjustment of pazopanib may be necessary when coadministration of pazopanib and quinine is required.
    Peginterferon Alfa-2b: (Major) Monitor for adverse effects associated with increased exposure to quinine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while quinine is a substrate of both these enzymes.
    Penicillamine: (Severe) Antimalarials have adverse reactions similar to those of penicillamine. Concomitant use is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
    Pentamidine: (Major) Concurrent use of quinine and pentamidine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pentamidine has also been associated with QT prolongation. In addition, concentrations of pentamidine may be increased with concomitant use of quinine. Pentamidine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Perindopril; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Perphenazine: (Major) Concurrent use of quinine and perphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP. In addition, concentrations of perphenazine may be increased with concomitant use of quinine. Perphenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Perphenazine; Amitriptyline: (Major) Concurrent use of quinine and perphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP. In addition, concentrations of perphenazine may be increased with concomitant use of quinine. Perphenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor. (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Phenytoin: (Moderate) Hydantoin anticonvulsants such as phenytoin induce CYP3A4 hepatic enzymes. Concomitant administration of hydantoins with quinine may increase the metabolism of quinine, leading to decreased quinine plasma concentrations.
    Physostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Pimavanserin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as pimavanserin. Co-administration may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pimozide with other QT prolonging drugs, such as quinine, is contraindicated. In addition, pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Quinine is an inhibitor of CYP3A4 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
    Pirbuterol: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Pomalidomide: (Moderate) Use pomalidomide and quinine together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and quinine is a CYP1A2 inducer.
    Posaconazole: (Severe) Concurrent use of posaconazole and quinine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinine. Further, quinine is an inhibitor of the drug efflux protein, P-glycoprotein (P-gp), for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinine.
    Potassium Citrate: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Potassium Salts: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
    Pramipexole: (Moderate) Population pharmacokinetics suggest that coadministration of drugs secreted by the cationic transport system, such as quinine, decreases the clearance of pramipexole by about 20 percent. An increase in pramipexole levels secondary to the use of quinine, may result in an increased risk of somnolence, postural hypotension, or other clinically significant events.
    Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with quinine, a CYP3A4 inducer and inhibitor, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include quinine.
    Procainamide: (Major) Concurrent use of quinine and procainamide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
    Prochlorperazine: (Major) Concurrent use of quinine and prochlorperazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Phenothiazines, such as prochlorperazine, have also been reported to prolong the QT interval.
    Propafenone: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of both CYP3A4 and CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4/CYP2D6 substrates. such as propafenone, which also may prolong the QT interval. Coadministration may result in an elevated plasma concentrations, as quinine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme, such as propafenone. Also, quinine is a substrate of P-glycoprotein (P-gp) and propafenone is a P-gp inhibitor; therefore, quinine concentrations could be increased with coadministration. Caution is recommended. Monitor patients for increased side effects, such as fast, irregular heartbeat, if these drugs must be used together. Consider alternative therapy to quinine if possible.
    Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like quinine.
    Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
    Protriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Pyridostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
    Quetiapine: (Major) Concurrent use of quinine and quetiapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of quetiapine may be increased with concomitant use of quinine. Quetiapine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Quinidine: (Severe) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as quinidine. Coadministration may result in an elevated quinidine plasma concentration, causing an increased risk for adverse events, such as QT prolongation. Further, both quinine and quinidine are cinchona alkaloids; the possibility of cinchonism is increased if these drugs are administered concomitantly
    Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Ranolazine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that prolong the QT, such as ranolazine. In addition, quinine is an inhibitor of both CYP3A4 and CYP2D6. Ranolazine is primarily metabolized by CYP3A. According to the manufacturer, the ranolazine dosage should be limited to 500 mg PO twice daily for patients receiving drugs known to be moderate CYP3A inhibitors. Conversely, ranolazine is a P-glycoprotein (P-gp) and CYP3A inhibitor, and quinine is a substrate for P-gp and CYP3A. Ranolazine may theoretically increase plasma concentrations of quinine and increase the risk for adverse effects, such as QT prolongation.
    Rapacuronium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Regadenoson: (Major) Concurrent use of quinine and regadenoson should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Regadenoson has also been associated with QT prolongation.
    Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Quinine has been shown to be an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
    Ribociclib: (Major) Avoid coadministration of ribociclib with quinine due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of both drugs may be affected resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation) or altered efficacy of ribociclib. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Quinine has been associated with QT prolongation and rare cases of TdP. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; quinine is a moderate CYP3A4 inhibitor and inducer as well as a CYP3A4 substrate.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quinine due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of both drugs may be affected resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation) or altered efficacy of ribociclib. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Quinine has been associated with QT prolongation and rare cases of TdP. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; quinine is a moderate CYP3A4 inhibitor and inducer as well as a CYP3A4 substrate.
    Rifabutin: (Major) Rifabutin is an inducer of hepatic metabolism and may significantly accelerate quinine clearance and reduce its half-life. Higher doses of quinine may be required in patients receiving rifabutin.
    Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
    Rifapentine: (Major) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Drugs metabolized by CYP3A4 and CYP2C8/9, such as quinine, may require dosage adjustments when administered concurrently with rifapentine.
    Rilpivirine: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Risperidone: (Major) Concurrent use of quinine and risperidone should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
    Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and quinine may result in increases or decreases in rivaroxaban exposure and may increase bleeding risk or decrease efficacy of rivaroxaban. Quinine is an inhibitor and inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding and lack of efficacy.
    Rocuronium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Romidepsin: (Major) Concurrent use of quinine and romidepsin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Romidepsin has also been reported to prolong the QT interval. In addition, concentrations of romidepsin may be increased with concomitant use of quinine. Romidepsin is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Rufinamide: (Minor) The potential interaction between quinine and rufinamide is unpredictable. CYP isozymes 3A4 and, to a lesser extent, 2E1 are involved in quinine metabolism. In theory, plasma concentrations of CYP2E1 substrates may be increased due to the weak 2E1 inhibitory effects of rufinamide. Conversely, the weak CYP3A4 inducer effects of rufinamide may result in decreased exposure of drugs that are metabolized by this isozyme.
    Salmeterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Sapropterin: (Moderate) Caution is advised with the concomitant use of sapropterin and quinine as coadministration may result in increased systemic exposure of quinine. Quinine is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of quinine.
    Saquinavir: (Severe) Concurrent use of saquinavir boosted with ritonavir and quinine is contraindicated due to the potential for life threatening arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is an inhibitor of CYP3A4 and of the drug efflux protein, P-glycoprotein (P-gp). Quinine is a substrate for P-gp, as well as a substrate and inhibitor of CYP3A4. These drugs used together may result in altered serum concentrations of both saquinavir and quinine, which could cause drug related adverse events. In addition, saquinavir boosted with ritonavir causes dose-depnedent QT prolongation; avoid use in combination with other drugs that may prolong the QT interval such as quinine.
    Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
    Sevoflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
    Short-acting beta-agonists: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Simeprevir: (Major) Interactions between simeprevir and quinine are complicated and coadministration should be avoided. Simeprevir concentrations may be altered as it is a substrate of CYP3A4, while quinine is an inhibitor and an inducer of CYP3A4. Additionally, quinine concentrations may be increased due to inhibition of CYP1A2 and P-glycoprotein (P-gp) as well as mild intestinal CYP3A4 inhibition by simeprevir.
    Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
    Simvastatin; Sitagliptin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
    Sodium Bicarbonate: (Major) Antacids may delay or decrease the absorption of quinine.
    Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with quinine. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a CYP3A4 substrate, while quinine is a mixed inducer/inhibitor or CYP3A4. Additionally, velpatasvir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Coadministration with substrates of this transporter, such as quinine, may increase their exposure.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with quinine. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a CYP3A4 substrate, while quinine is a mixed inducer/inhibitor or CYP3A4. Additionally, velpatasvir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Coadministration with substrates of this transporter, such as quinine, may increase their exposure. (Moderate) Plasma concentrations of quinine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    Solifenacin: (Major) Concurrent use of quinine and solifenacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Solifenacin has also been associated with dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined. Solifenacin is significantly metabolized via the CYP3A4 pathway. Patients receiving CYP3A4 inhibitors, such as quinine, should not receive solifenacin doses greater than 5 mg per day.
    Sorafenib: (Major) Concurrent use of quinine and sorafenib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Sorafenib has also been associated with QT prolongation.
    Sotalol: (Major) Concurrent use of quinine and sotalol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol therapy and after each upward dosage adjustment.
    St. John's Wort, Hypericum perforatum: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and St. John's Wort, Hypericum perforatum is an inducer of PGP and CYP3A4. Monitor patients for decreased efficacy of quinine if these drugs are given together.
    Succinylcholine: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Sunitinib: (Major) Concurrent use of quinine and sunitinib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Sunitinib can also prolong the QT interval. In addition, concentrations of sunitinib may be increased with concomitant use of quinine. Sunitinib is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Tacrolimus: (Major) Concurrent use of quinine and tacrolimus should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tacrolimus also causes QT prolongation. In addition, concentrations of tacrolimus may be increased with concomitant use of quinine. Tacrolimus is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor. Reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended when coadministrating tacrolimus with inhibitors of CYP3A4 that also have the potential to prolong the QT interval.
    Tamoxifen: (Major) Avoid coadministration of tamoxifen with quinine due to an increased risk of QT prolongation and torsade de pointes (TdP); increased quinine exposure and reduced tamoxifen efficacy and/or increased tamoxifen toxicity are also possible. If coadministration is unavoidable, monitor for QT prolongation and other quinine-related adverse effects as well as changes in therapeutic efficacy/toxicity of tamoxifen. Quinine has been associated with QT prolongation and rare cases of TdP. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Quinine may reduce the conversion of tamoxifen to other potent active metabolites via inhibition of CYP2D6. In a clinical trial, there was a significantly higher rate of breast cancer recurrence in patients who had received a CYP2D6 inhibitor with tamoxifen. In another observational study, no clinically significant differences were observed with the addition of a CYP2D6 inhibitor to tamoxifen therapy; however, only 215 patients of 1,990 were administered a CYP2D6 inhibitor. Tamoxifen may also increase exposure to quinine via inhibition of CYP3A4 and P-glycoprotein (P-gp).
    Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of quinine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as quinine, should be avoided.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering quinine with telaprevir due to an increased potential for quinine-related adverse events. If quinine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of quinine and telaprevir. Quinine is a substrate, inducer, and inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is a substrate and an inhibitor of this isoenzyme. When used in combination, the plasma concentrations of both medications may be altered.
    Telavancin: (Major) Concurrent use of quinine and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Telavancin has also been associated with QT prolongation.
    Telithromycin: (Major) Concurrent use of quinine with telithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and telithromycin have been associated with prolongation of the QT interval. In addition, because both telithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and quinine is necessary, as the systemic exposure of quinine may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of quinine; consider increasing the dose of quinine if necessary. Quinine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temsirolimus: (Major) Avoid the concomitant use of quinine with temsirolimus if possible, due to the risk of either an increase in temsirolimus adverse reactions or a decrease in temsirolimus efficacy as well as an increase in exposure to quinine. Temsirolimus is a CYP3A4 substrate and an in vitro inhibitor of P-glycoprotein (P-gp). Quinine is a moderate inhibitor/inducer (in vitro) of CYP3A4 and a P-gp substrate. The manufacturer of temsirolimus recommends a dose increase if coadministered with a strong CYP3A4 inducer or inhibitor, but recommendations are not available for concomitant use of moderate or combination CYP3A4 inhibitors or inducers. Coadministration of temsirolimus with rifampin, a strong CYP3A4/5 inducer, had no significant effect on the AUC or Cmax of temsirolimus, but decreased the sirolimus AUC and Cmax by 56% and 65%, respectively. Coadministration of temsirolimus with ketoconazole, a strong CYP3A4 inhibitor, had no significant effect on the AUC or Cmax of temsirolimus, but increased the sirolimus AUC and Cmax by 3.1-fold and 2.2-fold, respectively. Pharmacokinetic data are not available regarding the magnitude of effect of P-gp induction on temsirolimus exposure.
    Terbinafine: (Moderate) Caution is advised when administering terbinafine with quinine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C19, and CYP3A4; quinine is a substrate of CYP2D6, an inhibitor of CYP2C19, an inducer of CYP1A2, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Terbutaline: (Minor) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Terfenadine: (Severe) Use together is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Terfenadine has a well-established risk for QT prolongation and torsade de pointes (TdP). Other drugs that have also been independently associated with QT prolongation, such as quinine, should not be used concomitantly with terfenadine. Quinine also has the potential to inhibit the metabolism of terfenadine through CYP3A4.
    Teriflunomide: (Moderate) Use caution when administering teriflunomide and quinine concurrently. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2 and an inhibitor of CYP2C8. Coadministration of teriflunomide with CYP1A2 and CYP2C8 substrates, such as quinine, may lead to increases in adverse effects or possible efficacy reduction.
    Tetrabenazine: (Major) Concurrent use of quinine and tetrabenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc). In addition, concentrations of tetrabenazine may be increased with concomitant use of quinine. Tetrabenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Tetracycline: (Moderate) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
    Theophylline, Aminophylline: (Major) The coadministration of theophylline, aminophylline with quinine may increase the Cmax and AUC of quinine and decrease the AUC of theophylline, aminophylline. This interaction may be due to the potential induction of the CYP1A2 isoenzyme by quinine as the CYP1A2 isoenzyme is the primary route of metabolism for theophylline, aminophylline. Coadministration does not require any dosage changes; however, side effects of quinine should be monitored and plasma concentrations of theophylline should be frequently monitored to ensure therapeutic concentrations.
    Thioridazine: (Severe) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use with quinine, which when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
    Tiotropium; Olodaterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Tipranavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
    Tizanidine: (Major) Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including tizanidine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration increases the risk for QT prolongation and torsade de pointes.
    Tobacco: (Minor) Tobacco used in cigarette smoking induces the CYP1A2 isoenzyme and thereby my decrease quinine concentrations. In healthy male smokers, the single dose AUC of quinine was reduced 44% and the Cmax was 18% lower than in non-smokers. However, in malaria patients receiving a 7 day course of quinine, the AUC was only reduced by 25% and the Cmax decreased 16.5% in smokers. Acute malaria may already reduce quinine concentrations. Additive reduction of quinine concentrations by cigarette smoking may be diminished in these patients. Additionally, cigarette smoking did not appear to influence therapeutic outcomes; therefore, increasing the dose of quinine in smokers is not recommended.
    Tolterodine: (Major) Concurrent use of quinine and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In a small portion of patients who poorly metabolize tolterodine via CYP2D6, the CYP3A4 pathway becomes important in tolterodine elimination. Quinine is an inhibitor of both CYP2D6 and CYP3A4; coadministation may result in increased tolterodine concentrations.
    Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Quinine is a moderate inhibitor and inducer of CYP3A4. Coadministration may cause a marked increase or decrease in tolvaptan concentrations and should be avoided. If coadministration is unavoidable, a change in the dose of tolvaptan may be necessary and patients should be monitored closely for side effects and changes in efficacy.
    Toremifene: (Major) Concurrent use of quinine and toremifene should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Trabectedin: (Moderate) Use caution if coadministration of trabectedin and quinine is necessary, due to the risk of altered trabectedin exposure. Trabectedin is a CYP3A substrate and quinine is a moderate CYP3A inhibitor and, in vitro, a CYP3A inducer. There are no specific recommendations for concomitant use of moderate CYP3A inhibitors or inducers with trabectedin. If concomitant use is necessary, monitor the patient closely for chemotherapeutic efficacy and adverse effects.
    Tramadol: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme including tramadol.
    Trandolapril; Verapamil: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4 and verapamil is a PGP and CYP3A4 inhibitor; therefore, quinine concentrations could be increased with coadministration. Additionally, verapamil is a CYP3A4 substrate and quinine can inhibit CYP3A4; therefore, verapamil concentrations could also be increased with coadministration. Monitor patients for increased side effects of quinine and verapamil if these drugs are given together.
    Tricyclic antidepressants: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Trifluoperazine: (Major) Concurrent use of quinine and trifluoperazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
    Trimipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
    Trospium: (Moderate) Both trospium and quinine are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or quinine due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or quinine is recommended.
    Tubocurarine: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Ulipristal: (Moderate) Ulipristal is a substrate of CYP3A4 and quinine is a CYP3A4 inhibitor and inducer. Concomitant use may increase or decrease the plasma concentration of ulipristal resulting in an increased risk for adverse events or decrease in efficacy. In addition, in vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as quinine may increase the concentration of the P-gp substrates; use caution. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Umeclidinium; Vilanterol: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists.
    Vandetanib: (Major) Avoid coadministration of vandetanib and quinine if possible due to an increased risk of QT prolongation and torsade de pointes (TdP); additionally, an increase in quinine-related adverse reactions and a decrease in exposure of vandetanib are possible if these drugs are coadministered. Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; quinine also has a possible risk for QT prolongation and TdP. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then vandetanib may be resumed at a reduced dose. Additionally, quinine is a P-glycoprotein (P-gp) substrate. Coadministration with vandetanib increased the Cmax and AUC of another P-gp substrate by 29% and 23%, respectively. Quinine is an inducer of CYP3A4; coadministration of vandetanib with rifampin, a CYP3A4 inducer, decreased the mean AUC of vandetanib by 40% (90% CI, 56% to 63%); the AUC and Cmax of active metabolite, N-desmethyl-vandetanib, increased by 266% and 414%, respectively.
    Vardenafil: (Major) Concurrent use of quinine and vardenafil should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil also produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). In addition, concentrations of vardenafil may be increased with concomitant use of quinine. Vardenafil is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Vecuronium: (Moderate) Quinine can potentiate the pharmacologic effects of neuromuscular blockers.
    Vemurafenib: (Major) Concurrent use of quinine and vemurafenib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both drugs have been associated with prolongation of the QT interval. In addition, both drugs are substrates of CYP3A4, quinine is a CYP3A4 inhibitor, and vemurafenib is a CYP3A4 inducer; coadministration may increase concentrations of vemurafenib and reduce concentrations of quinine.
    Venlafaxine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions, such as venlafaxine.
    Verapamil: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4 and verapamil is a PGP and CYP3A4 inhibitor; therefore, quinine concentrations could be increased with coadministration. Additionally, verapamil is a CYP3A4 substrate and quinine can inhibit CYP3A4; therefore, verapamil concentrations could also be increased with coadministration. Monitor patients for increased side effects of quinine and verapamil if these drugs are given together.
    Vincristine Liposomal: (Moderate) Quinine inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Moderate) Quinine inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vinorelbine: (Moderate) Monitor patients for an changes in the severity of adverse effects and efficacy if vinorelbine is used concomitantly with quinine, as the metabolism of vinorelbine may be affected. Quinine is a CYP3A4 inhibitor and inducer, and vinorelbine is a CYP3A4 substrate.
    Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and quinine. Quinine inhibits CYP3A and induced CYP3A4 in an in vitro study. Increased or decreased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with quinine. Increased exposure to vorapaxar may increase the risk of bleeding complications while decreased exposure to vorapaxar may reduce efficacy.
    Voriconazole: (Major) Concurrent use of quinine and voriconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of voriconazole may be increased with concomitant use of quinine. Voriconazole is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Vorinostat: (Major) Concurrent use of quinine and vorinostat should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Vorinostat therapy is also associated with a risk of QT prolongation.
    Warfarin: (Moderate) Quinine may potentiate the anticoagulation effects of warfarin; bleeding has been reported. This interaction is probably due to additive hypoprothrombinemia associated with concomitant administration of warfarin and quinine. Close monitoring of the INR is required when quinine is added to warfarin therapy.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including quinine.
    Zolpidem: (Moderate) It is advisable to closely monitor zolpidem tolerability and safety during concurrent use of quinine, a moderate CYP3A4 inhibitor, since CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism. There is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and quinine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Quinine is classified as pregnancy category C by the manufacturer. Adequate and well-controlled studies of quinine during pregnancy are not available. Quinine crosses the placenta and results in measurable fetal blood concentrations; however, fetal blood concentrations may not be therapeutic. Rare and isolated case reports have included deafness and optic nerve hypoplasia in children exposed in utero to maternal ingestion of high doses of quinine. Based on clinical data and epidemiological surveys, quinine does not cause congenital malformation and is not associated with an increased risk of stillbirth. Quinine does not cause uterine contractions at recommended therapeutic doses, however, large doses may be oxytocic. Historically, quinine has been used as an abortifacient. Apart from effects on the fetus, quinine is also more likely to induce low blood sugars in pregnant women. Other less toxic drugs are available to treat malaria during pregnancy and should be considered. If quinine is used during pregnancy, or if the patient becomes pregnant while taking quinine, the patient should be apprised of the potential hazards to the fetus.

    Quinine is excreted into breast milk. However, the manufacturer and the American Academy of Pediatrics (AAP) consider quinine to be compatible with breast-feeding. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1—10 days) was administered to 25 lactating women. In one study, quinine concentrations in placental cord blood and breast milk were approximately 32% and 31%, respectively, of concentrations in maternal plasma. It is estimated from this study that the breast-fed infant would receive less than 2—3 mg per day of quinine base (< 0.4% of the maternal dose) via breast milk. Both the mother and the infant should be ruled out for Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, an infant who requires chemoprophylaxis must receive the recommended dosages of antimalarial drugs. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: The drug's exact mechanism of antiprotozoal action in the treatment of malaria is not fully understood, but quinine concentrates in the parasitized erythrocytes and has a schizontocidal action. Quinine elevates the pH of parasitic acid vesicles and may upset molecular transport and phospholipase activity. It is active against the asexual erythrocytic forms of Plasmodium falciparum, P. malariae, P ovale, or P. vivax. Quinine does not provide a cure for malaria because it is not effective against exoerythrocytic forms of the parasite.Antimyotonic activity occurs through direct action on the muscle fiber, increasing the refractory period. It also decreases the excitability of the motor end-plate, reducing response to repeated nerve stimulation. Quinine also affects calcium distribution within the muscle fiber. Quinine has a curare-like action and counteracts the effects of neostigmine and physostigmine.Quinine produces cardiovascular effects similar to those of quinidine, but normal oral dosage levels have little effect in patients without cardiac dysfunction. Intravenous dosage, no longer used in the U.S., can produce severe hypotension. Quinine has been shown to prolong the Q-T interval.

    PHARMACOKINETICS

    Quinine is administered orally. Plasma levels are higher in patients with malaria because malaria can cause a decrease in hepatic function, with a consequent reduction in clearance. It distributes widely into liver, lungs, kidneys, and spleen, but the volume of distribution is lower in patients with malaria. There is some distribution into CSF, and the drug crosses the placenta and is excreted into breast milk. In healthy adults, about 70% is bound to plasma protein; binding is greater in patients with malaria. Plasma half-life is between 8—21 hours, and is lower in children and higher in patients with malaria. Acid urine increases the rate of excretion, which is largely of metabolites, with only a small amount as unchanged drug. Small amounts may be excreted in the feces.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, P-gp
    Quinine is extensively metabolized in the liver, mainly to hydroxy-metabolites. In vitro studies have shown the CYP3A4 isoenzyme is the major enzyme responsible for metabolism, and it is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism; however, the extent of involvement of each of these differs depending on methodology used in the in vitro studies. In vivo drug interactions have been observed with drugs that induce or inhibit the CYP3A4 isoenzyme. Similarly, other in vivo drug interactions have been reported with drugs that inhibit or induce CYP isoenzymes that may contribute to the metabolism of quinine such as CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. In vivo and in vitro drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4 and CYP2D6, as well as inhibit the biliary excretion of some drugs. An in vitro study showed quinine increased the metabolic activities of CYP1A2 and CYP3A4.

    Oral Route

    Quinine is almost completely absorbed from the GI tract, and peak serum levels are achieved in about 1—3 hours.