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  • CLASSES

    Antimalarials
    Other Antiinflammatory and Antirheumatic Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Oral disease-modifying antirheumatic drug (DMARD) with antimalarial properties
    Used for rheumatoid arthritis, systemic lupus erythematosus, and malaria
    Associated with ocular toxicity and cardiomyopathy

    COMMON BRAND NAMES

    Plaquenil, Quineprox

    HOW SUPPLIED

    Hydroxychloroquine/Hydroxychloroquine Sulfate/Plaquenil/Quineprox Oral Tab: 100mg, 200mg, 300mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of uncomplicated malaria due to susceptible strains of P. falciparum, P. knowlesi†, P. malariae, P. ovale, and P. vivax.
    Oral dosage
    Adults

    800 mg (620 mg base) PO, then 400 mg (310 mg base)/dose PO at 6, 24, and 48 hours after the initial dose for a total dose of 2,000 mg (1,550 mg base). For P. vivax or P. ovale, add primaquine phosphate or tafenoquine.

    Children and Adolescents weighing 23 kg or more

    13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after the initial dose for a total dose of 32.5 mg (25 mg base)/kg [Max: 2,000 mg (1,550 mg base)]. For P. vivax or P. ovale, add primaquine phosphate or tafenoquine (16 years and older).[41806]

    Infants† and Children† weighing less than 23 kg

    13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after the initial dose for a total dose of 32.5 mg (25 mg base)/kg [Max: 2,000 mg (1,550 mg base)]. For P. vivax or P. ovale, add primaquine phosphate.[41806]

    For malaria prophylaxis for travel to areas where chloroquine-resistance has not been reported.
    Oral dosage
    Adults

    400 mg (310 mg base)/dose PO once weekly, starting 1 to 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area.

    Children and Adolescents weighing 23 kg or more

    6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO once weekly, starting 1 to 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area.[41806]

    Infants† and Children† weighing less than 23 kg

    6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO once weekly, starting 1 to 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area. Guidelines suggest hydroxychloroquine as an alternative to chloroquine.

    For the treatment of rheumatoid arthritis.
    Oral dosage
    Adults

    400 to 600 mg (310 to 465 mg base) PO once daily or in 2 divided doses as monotherapy or part of combination therapy. After a clinical response is obtained, reduce dose to 200 mg (155 mg base) PO daily, 300 mg (232 mg base) PO daily, or 400 mg (310 mg base) PO daily given as a single dose or in 2 divided doses.[41806]

    For the treatment of systemic lupus erythematosus (SLE).
    Oral dosage
    Adults

    200 mg (155 mg base) PO daily, 300 mg (232 mg base) PO daily, or 400 mg (310 mg base) PO daily as a single dose or in 2 divided doses.

    Children† and Adolescents†

    4 to 6 mg (3.1 to 4.6 mg base)/kg/day PO.

    For the treatment of discoid lupus erythematosus.
    Oral dosage
    Adults

    200 mg (155 mg base) PO once daily or 400 mg (310 mg base) PO once daily or in 2 divided doses. May add quinacrine if a patient fails monotherapy.[62154] [65216]

    INVESTIGATIONAL USE: For the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection†, the virus that causes coronavirus disease 2019 (COVID-19)†.
    Oral dosage
    Adults weighing 50 kg or more

    Available data are limited and inconclusive. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of hydroxychloroquine for the treatment of COVID-19 patients.[65314] The FDA has revoked the Emergency Use Authorization (EUA) of hydroxychloroquine. Previously, the EUA suggested 800 mg (620 mg base) PO on day 1 then 400 mg (310 mg base) PO daily for 4 to 7 days.[65171] [65173] Other dosing regimens, alone and in combination, are being evaluated.

    Adolescents weighing 50 kg or more

    Available data are limited and inconclusive. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend against the use of hydroxychloroquine for the treatment of COVID-19 patients.[65314] The FDA has revoked the Emergency Use Authorization (EUA) of hydroxychloroquine. Previously, the EUA suggested 800 mg (620 mg base) PO on day 1 then 400 mg (310 mg base) PO daily for 4 to 7 days.[65171] [65173]

    For the treatment of lupus nephritis†.
    Oral dosage
    Adults

    200 to 400 mg/day (155 to 310 mg/day base) PO. Max: 5 mg/kg/day.

    For the suppression of polymorphous light eruption†.
    Oral dosage
    Adults

    200 to 400 mg (155 to 310 mg base) PO once daily or in 2 divided doses.

    For the treatment of refractory or severe cutaneous dermatomyositis†.
    Oral dosage
    Adults

    200 mg (155 mg base) PO once or twice daily or 400 mg (310 mg base) PO once daily.

    Children and Adolescents

    5 mg (3.875 mg base)/kg/dose (Max: 400 mg/dose or 310 mg base/dose) PO once daily.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    800 mg/dose (620 mg base/dose) PO for malaria up to a total of 2,000 mg (1,550 mg base) PO in 48 hours; 400 mg/week (310 mg base/week) PO for malaria prophylaxis; 600 mg/day (465 mg base/day) PO for rheumatoid arthritis; 400 mg/day (310 mg base/day) PO for systemic lupus erythematosus and chronic discoid lupus erythematosus

    Geriatric

    800 mg/dose (620 mg base/dose) PO for malaria up to a total of 2,000 mg (1,550 mg base) PO in 48 hours; 400 mg/week (310 mg base/week) PO for malaria prophylaxis; 600 mg/day (465 mg base/day) PO for rheumatoid arthritis; 400 mg/day (310 mg base/day) PO for systemic lupus erythematosus and chronic discoid lupus erythematosus

    Adolescents

    weighing 31 kg or more: 13 mg/kg/dose (10 mg base/kg/dose) [Max: 800 mg (620 mg base)] PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) [Max: 2,000 mg (1,550 mg base)] PO in 48 hours; 6.5 mg/kg/week (5 mg base/kg/week) [Max: 400 mg/week (310 mg base/week)] PO for malaria prophylaxis.
    weighing less than 31 kg: 13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

    Children

    weighing 31 kg or more: 13 mg/kg/dose (10 mg base/kg/dose) [Max: 800 mg (620 mg base)] PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) [Max: 2,000 mg (1,550 mg base)] PO in 48 hours; 6.5 mg/kg/week (5 mg base/kg/week) [Max: 400 mg/week (310 mg base/week)] PO for malaria prophylaxis.
    weighing less than 31 kg: 13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

    Infants

    13 mg/kg/dose (10 mg base/kg/dose) PO for malaria up to a total of 32.5 mg/kg (25 mg base/kg) PO in 48 hours has been used off-label; 6.5 mg/kg/week (5 mg base/kg/week) PO for malaria prophylaxis has been used off-label.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    A dosage reduction may be necessary in patients with hepatic disease or those taking concomitant medications known to affect the liver. However, no specific dosage adjustment guidelines are available for patients with hepatic impairment.

    Renal Impairment

    A dosage adjustment is not required in patients with renal impairment. However, a dosage reduction may be necessary in patients with renal disease or those taking concomitant medications known to affect the kidney. No specific dosage adjustment guidelines are available for patients with renal impairment.

    ADMINISTRATION

    Oral Administration

    Administer with food or milk to minimize gastric indigestion or irritation.

    Oral Solid Formulations

    200 mg tablets: The FDA-approved labeling states to not crush or divide the tablets. However, extemporaneously compounded solutions are prepared using crushed tablets after removal of the coating.[65138] [65145]
    300 mg tablets: Do not crush tablets; tablets may be divided into 2 equal halves along the scored line.

    Extemporaneous Compounding-Oral

    Extemporaneous 25 mg/mL oral suspension (using tablets)†
    NOTE: Extemporaneous compounding is not FDA-approved.
    Remove the coating of hydroxychloroquine tablets, if necessary, with a towel moistened with alcohol.
    Crush fifteen 200 mg hydroxychloroquine tablets into a fine powder in a mortar.
    Add approximately 15 mL of the vehicle (e.g., Oral Mix or Oral Mix SF) to the mortar and levigate to form a fine paste.
    Add the vehicle in geometric portions almost to volume and mix thoroughly after each addition.
    Transfer the contents of the mortar to a graduated cylinder.
    Rinse the mortar and pestle using a small amount of vehicle and transfer to the graduated cylinder.
    Add enough vehicle to bring the final volume to 120 mL and transfer to an amber bottle.
    Storage: The suspension is stable for 112 days under refrigeration (4 degrees C) or at room temperature (25 degrees C).[65138] [65145]

    STORAGE

    Generic:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Plaquenil:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Quineprox:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Apheresis, AV block, bradycardia, cardiac disease, cardiomyopathy, cardiotoxicity, celiac disease, females, fever, geriatric, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), ventricular arrhythmias

    Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with hydroxychloroquine. Signs and symptoms of cardiac compromise have occurred with acute and chronic hydroxychloroquine therapy. In multiple cases, endomyocardial biopsy revealed an association of cardiomyopathy with phospholipidosis in absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur in other organs. Consider chronic toxicity when conduction disorders (bundle-branch block, AV block) or biventricular hypertrophy are diagnosed. If cardiotoxicity is suspected or demonstrated by tissue biopsy, prompt discontinuation of hydroxychloroquine may prevent life-threatening cardiac complications.[41806] Hydroxychloroquine has a;sp caused fatal and life-threatening cases of ventricular arrhythmias. Hydroxychloroquine prolongs the QT interval; the magnitude of QT prolongation may increase with increasing drug concentrations. Avoid hydroxychloroquine in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, proarrhythmic conditions (e.g. bradycardia), AV block, cardiac disease, heart failure, stress-related cardiomyopathy, myocardial infarction, history of ventricular arrhythmias, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[41806] [28432] [28457] [56592] [65180] In patients taking hydroxychloroquine with another drug that also prolongs the QT interval (see Therapeutic Drug Monitoring for recommendations specific to azithromycin with hydroxychloroquine used together for COVID-19), obtain a pre-treatment QTc using a standard 12-lead ECG, telemetry, or mobile ECG device. Obtain baseline electrolytes, including calcium, magnesium, and potassium. Determine if the patient is currently on any QT-prolonging medications that can be discontinued. Document high-risk cardiovascular and comorbid conditions. If the baseline QTc is 500 msec or more and/or the patient has an inherent tendency to develop an exaggerated QTc response (i.e., change of 60 msec or more), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and proceed with close QTc surveillance. Obtain an initial on-therapy QTc approximately 2 to 4 hours after the first dose and then again at 48 and 96 hours after treatment initiation. If the baseline QTc is 460 to 499 msec (prepubertal), 470 to 499 msec (postpubertal males), or 480 to 499 msec (postpubertal females), correct contributing electrolyte abnormalities, review and discontinue other unnecessary QTc prolonging medications, and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation. If the baseline QTc is less than 460 msec (prepubertal), less than 470 msec (postpubertal males), or less than 480 msec (postpuberal females), correct electrolyte abnormalities and obtain an initial on-therapy QTc 48 and 96 hours after treatment initiation.

    Asian patients, ocular disease, ocular toxicity, visual disturbance

    Severe and irreversible retinal toxicity has been reported with the use of hydroxychloroquine and ocular toxicity is related to cumulative dosage and treatment duration. Risk factors for retinal damage include daily doses more than 6.5 mg/kg (5 mg/kg base) of actual body weight, durations of use greater than 5 years, renal dysfunction, use of concomitant drugs such as tamoxifen, and concurrent macular ocular disease. A baseline ocular exam should be performed within the first year of hydroxychloroquine treatment. This baseline exam should include best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT). Annual exams, which include BCVA, VF, and SD-OCT, are recommended for patients at higher risk of retinal damage. For patients without significant risk factors, annual ocular exams may be deferred until 5 years of treatment. In Asian patients, retinal toxicity may first be noticed outside the macula; therefore, visual field testing should be performed in the central 24 degrees instead of the central 10 degrees. Discontinue hydroxychloroquine if ocular toxicity is suspected and monitor the patient closely for retinal changes and visual disturbance which may progress even after discontinuation of therapy.

    Serious rash

    Hydroxychloroquine is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds. Serious adverse reactions have been reported with the use of hydroxychloroquine including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Advise patients to seek medical attention promptly if they experience signs and symptoms of serious rash or skin reactions such as blisters on the skin, eyes, lips or in the mouth, itching or burning, with or without fever. Discontinue hydroxychloroquine if these severe reactions occur.

    Porphyria, psoriasis

    Avoid hydroxychloroquine in patients with psoriasis or porphyria unless the benefit to the patients outweighs the possible risk. Hydroxychloroquine has been shown to precipitate severe flare-ups of psoriasis and exacerbate porphyria.

    Agranulocytosis, aplastic anemia, bone marrow suppression, G6PD deficiency, hemolytic anemia, leukopenia, thrombocytopenia

    Hydroxychloroquine may cause bone marrow suppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia. Monitor blood cell counts periodically in patients on prolonged therapy. If a treated patient develops myelosuppression that cannot be attributable to the disease, discontinue the drug. Administer hydroxychloroquine with caution in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) due to the risk of hemolysis. Monitor for hemolytic anemia, especially in patients taking other drugs associated with hemolysis.

    Myopathy, neurological disease, peripheral neuropathy

    Hydroxychloroquine should be used with caution in patients with neurological disease, peripheral neuropathy, or myopathy. Skeletal muscle myopathy or peripheral neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction have been reported. Muscle and nerve biopsies have shown associated phospholipidosis. Drug-induced phospholipidosis may occur in other organ systems. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with hydroxychloroquine. Advise patients to report any symptoms of muscle weakness. If muscle or nerve toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine therapy.

    Behavioral changes, depression

    Alert patients to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or mood or behavioral changes. The risk and benefit of continued treatment with hydroxychlorquine should be assessed for patients who develop these symptoms. Suicidal behavior has been reported in patients treated with hydroxychlorquine.

    Nephrotoxicity, renal disease, renal impairment

    A reduction in the dosage of hydroxychloroquine may be necessary in patients with renal disease. Renal impairment is a risk factor for retinal damage due to hydroxychloroquine, which is related to cumulative dosage and treatment duration. Hydroxychloroquine has been associated with nephrotoxicity. Cases of proteinuria with or without a moderate reduction in glomerular filtration rate have been reported with hydroxychloroquine therapy. Renal biopsy revealed phospholipidosis without immune deposits, inflammation, and/or increased cellularity. Phospholipidosis may be considered as a potential cause of renal injury in patients receiving hydroxychloroquine with underlying connective tissue disorders. Drug-induced phospholipidosis may occur in other organ systems. If renal toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine.

    Hepatic disease

    Hydroxychloroquine should be used with caution in patients with hepatic disease. A dose reduction may be necessary.

    Diabetes mellitus, hypoglycemia

    Use hydroxychloroquine with caution in patients with hypoglycemia or diabetes mellitus. Hydroxychloroquine can cause severe, life-threatening hypoglycemia in patients treated with or without antidiabetic medications. Warn patients about the risk of hypoglycemia and the associated clinical signs and symptoms. Monitor blood glucose and adjust treatment as necessary in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment.

    Pregnancy

    Prolonged clinical experience over decades of use and available data from published epidemiologic and clinical studies with hydroxychloroquine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine in utero. Available epidemiologic and clinical studies have methodological limitations including small sample size and study design. There are risks to the mother and fetus associated with untreated or increased maternal disease activity from malaria, rheumatoid arthritis, and systemic lupus erythematosus (SLE) during pregnancy that should be considered. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to hydroxychloroquine during pregnancy. Encourage patients to register by contacting 1-877-311-8972. Hydroxychloroquine is considered to be compatible for use during pregnancy in some anti-rheumatic guidelines, and may be continued in pregnancy for maintenance of remission or treatment of a disease flare. Hydroxychloroquine may also be appropriate for pregnancies complicated by lupus. Guidelines also recommend hydroxychloroquine as an alternative to chloroquine as a treatment option for acute malaria and for prophylaxis in pregnant women during all trimesters. Animal reproductive studies have not been conducted.

    Breast-feeding

    Data regarding the use of hydroxychloroquine during breast-feeding report that hydroxychloroquine is present in human milk at low levels. No adverse reactions have been reported in breastfed infants. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine through breastmilk. There is no information on the effect of hydroxychloroquine on milk production. Hydroxychloroquine is considered to be compatible for use during breast-feeding in some anti-rheumatic guidelines, and may be continued during lactation for maintenance of remission or treatment of a disease flare.  During lactation studies, breast milk concentrations ranged from 10.6 to 1,392 mcg/L  and breast-fed infants would likely receive 0.2 mg/kg or less of hydroxychloroquine. In infants monitored for up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision, or hearing. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the medication and any potential adverse effects on the breastfed child from hydroxychloroquine exposure or from the underlying maternal condition.

    ADVERSE REACTIONS

    Severe

    cardiomyopathy / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    suicidal ideation / Delayed / 0-1.0
    visual impairment / Early / Incidence not known
    corneal opacification / Delayed / Incidence not known
    retinopathy / Delayed / Incidence not known
    macular degeneration / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    porphyria / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    heart failure / Delayed / Incidence not known
    AV block / Early / Incidence not known
    cardiotoxicity / Delayed / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    nephrotoxicity / Delayed / Incidence not known

    Moderate

    corneal edema / Early / Incidence not known
    ocular toxicity / Delayed / Incidence not known
    scotomata / Delayed / Incidence not known
    psoriasis / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    hemolysis / Early / Incidence not known
    leukopenia / Delayed / Incidence not known
    bone marrow suppression / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    bundle-branch block / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    dyskinesia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    hypoglycemia / Early / Incidence not known
    proteinuria / Delayed / Incidence not known

    Mild

    retinal pigment changes / Delayed / Incidence not known
    hair discoloration / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    photosensitivity / Delayed / Incidence not known
    rash / Early / Incidence not known
    skin discoloration / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    weakness / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    anorexia / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    emotional lability / Early / Incidence not known
    headache / Early / Incidence not known
    nightmares / Early / Incidence not known
    irritability / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    tremor / Early / Incidence not known
    dizziness / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    fatigue / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Acetazolamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as acetazolamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Acetohexamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Adagrasib: (Major) Concomitant use of adagrasib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Albiglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Alfuzosin: (Major) Concomitant use of hydroxychloroquine and alfuzosin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Alogliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Alpha-glucosidase Inhibitors: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Amiodarone: (Major) Concomitant use of hydroxychloroquine and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
    Amisulpride: (Major) Avoid coadministration of amisulpride and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Amisulpride causes dose- and concentration-dependent QT prolongation.
    Amobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as amobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of hydroxychloroquine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ampicillin: (Moderate) Administer oral ampicillin 2 hours before or 2 hours after hydroxychloroquine. Ampicillin bioavailability may be decreased with coadministration of hydroxychloroquine as a significant reduction in ampicillin bioavailability was observed with the structurally similar chloroquine in a study of healthy volunteers. The reduction of ampicillin bioavailability could be attributed to slower gastric emptying and enhancement of gut motility produced by chloroquine.
    Anagrelide: (Major) Avoid coadministration of anagrelide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects.
    Antacids: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Apomorphine: (Major) Avoid coadministration of apomorphine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Aripiprazole: (Major) Concomitant use of hydroxychloroquine and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Arsenic Trioxide: (Major) Avoid coadministration of arsenic trioxide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
    Artemether; Lumefantrine: (Major) Avoid coadministration of artemether; lumefantrine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval. (Major) Avoid coadministration of artemether; lumefantrine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval.
    Asenapine: (Major) Concomitant use of hydroxychloroquine and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Atomoxetine: (Major) Concomitant use of hydroxychloroquine and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Azithromycin: (Major) Concomitant use of hydroxychloroquine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bedaquiline: (Major) Avoid coadministration of bedaquline and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and bedaquiline prolong the QT interval. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 msec.
    Betrixaban: (Moderate) Use caution if hydroxychloroquine is coadministered with bextrixaban due to the potential for increased bextrixaban exposure which may increase the risk of bleeding. Bextrixaban is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Brivaracetam: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as brivaracetam. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Buprenorphine: (Major) Concomitant use of hydroxychloroquine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Buprenorphine; Naloxone: (Major) Concomitant use of hydroxychloroquine and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Cabotegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Calcium Carbonate: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium Carbonate; Risedronate: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium Carbonate; Simethicone: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Calcium; Vitamin D: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Carbamazepine: (Moderate) Monitor for a decrease in hydroxychloroquine and carbamazepine efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
    Ceritinib: (Major) Avoid coadministration of ceritinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Hydroxychloroquine also prolongs the QT interval.
    Chlorpromazine: (Major) Concomitant use of hydroxychloroquine and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Cimetidine: (Major) Avoid concomitant use of hydroxychloroquine and cimetidine as cimetidine may inhibit the metabolism of hydroxychloroquine, increasing its plasma concentration. This interaction has been observed on treatment with the structurally similar chloroquine and cannot be ruled out for hydroxychloroquine.
    Ciprofloxacin: (Major) Concomitant use of hydroxychloroquine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Cisapride: (Contraindicated) Avoid concomitant use of hydroxychloroquine and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Citalopram: (Major) Concomitant use of hydroxychloroquine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clarithromycin: (Major) Concomitant use of hydroxychloroquine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clobazam: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as clobazam. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Clofazimine: (Major) Concomitant use of clofazimine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clonazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant clonazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Clorazepate: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as clorazepate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Clozapine: (Major) Avoid coadministration of clozapine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Codeine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Crizotinib: (Major) Avoid coadministration of crizotinib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib can cause concentration-dependent QT prolongation. Hydroxychloroquine also prolongs the QT interval.
    Cyclosporine: (Major) Closely monitor serum cyclosporine concentrations and adjust the dose of cyclosporine as appropriate after starting or stopping hydroxychloroquine therapy. Increased serum concentrations of cyclosporine have been noted when coadministered with hydroxychloroquine. Monitor patients for cyclosporine-related adverse events such as nephrotoxicity or hepatic toxicity.
    Dabigatran: (Moderate) Use caution if hydroxychloroquine is coadministered with dabigatran due to the potential for increased dabigatran exposure which may increase the risk of bleeding. Dabigatran is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor.
    Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Dasatinib: (Major) Concomitant use of hydroxychloroquine and dasatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Degarelix: (Major) Concomitant use of hydroxychloroquine and degarelix increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Desflurane: (Major) Concomitant use of hydroxychloroquine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Diazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant diazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Digoxin: (Moderate) Monitor serum digoxin concentrations in patients receiving digoxin and hydroxychloroquine as coadministration may result in increased serum digoxin concentrations.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Disopyramide: (Major) Concomitant use of hydroxychloroquine and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dofetilide: (Major) Concomitant use of hydroxychloroquine and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dolasetron: (Major) Avoid coadministration of dolasetron and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Donepezil: (Major) Concomitant use of hydroxychloroquine and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Donepezil; Memantine: (Major) Concomitant use of hydroxychloroquine and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dronedarone: (Contraindicated) Avoid concomitant use of hydroxychloroquine and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Droperidol: (Major) Avoid coadministration of droperidol and hydroxychloroquine due to the risk of increased QT prolongation.If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Hydroxychloroquine prolongs the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP).
    Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Edoxaban: (Moderate) Use caution if hydroxychloroquine is coadministered with edoxaban due to the potential for increased edoxaban exposure which may increase the risk of bleeding. Edoxaban is a P-gp substrate; limited data suggests that hydroxychloroquine is a P-gp inhibitor.
    Efavirenz: (Major) Concomitant use of hydroxychloroquine and efavirenz increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of hydroxychloroquine and efavirenz increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of hydroxychloroquine and efavirenz increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Eliglustat: (Major) Avoid coadministration of eliglustat and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concomitant use of rilpivirine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of rilpivirine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Encorafenib: (Major) Concomitant use of hydroxychloroquine and encorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Entrectinib: (Major) Concomitant use of hydroxychloroquine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Eribulin: (Major) Concomitant use of hydroxychloroquine and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Erythromycin: (Major) Concomitant use of hydroxychloroquine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Escitalopram: (Major) Concomitant use of hydroxychloroquine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Eslicarbazepine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as eslicarbazepine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Ethosuximide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as ethosuximide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Ethotoin: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as ethotoin. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Felbamate: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as felbamate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Fingolimod: (Major) Avoid coadministration of fingolimod and hydroxychloroquine due to the risk of increased QT prolongation. If coadministration cannot be avoided, overnight monitoring with continuous ECG in a medical facility is advised after the first fingolimod dose for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). Also, avoid any non-essential QT prolonging drugs and correct electrolyte imbalances. Monitor ECG throughout therapy. Hydroxychloroquine prolongs the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. 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) Concomitant use of hydroxychloroquine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluconazole: (Major) Concomitant use of hydroxychloroquine and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluoxetine: (Major) Concomitant use of hydroxychloroquine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluphenazine: (Major) Concomitant use of hydroxychloroquine and fluphenazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluvoxamine: (Major) Concomitant use of hydroxychloroquine and fluvoxamine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Foscarnet: (Major) Concomitant use of hydroxychloroquine and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fosphenytoin: (Moderate) Monitor for a decrease in hydroxychloroquine and fosphenytoin efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer.
    Fostemsavir: (Major) Avoid coadministration of hydroxychloroquine and fostemsavir due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gabapentin: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant gabapentin and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Gemifloxacin: (Major) Avoid coadministration of gemifloxacin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Gemifloxacin may 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 and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin.
    Gilteritinib: (Major) Concomitant use of hydroxychloroquine and gilteritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Glasdegib: (Major) Avoid coadministration of glasdegib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia.
    Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Glimepiride; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Goserelin: (Major) Concomitant use of hydroxychloroquine and goserelin acetate increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Granisetron: (Major) Concomitant use of hydroxychloroquine and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Halogenated Anesthetics: (Major) Concomitant use of hydroxychloroquine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Haloperidol: (Major) Avoid coadministration of haloperidol and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. QT prolongation and torsade de pointes (TdP) have 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.
    Histrelin: (Major) Concomitant use of hydroxychloroquine and histrelin acetate increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Hydroxyzine: (Major) Concomitant use of hydroxychloroquine and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ibutilide: (Major) Concomitant use of ibutilide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Iloperidone: (Major) Concomitant use of iloperidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Inotuzumab Ozogamicin: (Major) Concomitant use of inotuzumab and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Insulins: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Isoflurane: (Major) Concomitant use of hydroxychloroquine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Isoniazid, INH; Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Itraconazole: (Major) Concomitant use of itraconazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Dose reduce or interrupt ivosidenib therapy if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Hydroxychloroquine also prolongs the QT interval.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Lacosamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as lacosamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Lamotrigine: (Moderate) Monitor for seizures during concomitant use of hydroxychloroquine and lamotrigine. Hydroxychloroquine can lower the seizure threshold and the activity of antiepileptics may be impaired during concomitant use.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of hydroxychloroquine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like hydroxychloroquine, may interact with lanthanum carbonate. Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and lanthanum carbonate at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Lapatinib: (Major) Avoid coadministration of lapatinib and hydroxychloroquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
    Lefamulin: (Major) Avoid coadministration of lefamulin and hydroxychloroquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
    Lente Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Lenvatinib: (Major) Concomitant use of lenvatinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Leuprolide: (Major) Concomitant use of leuprolide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Leuprolide; Norethindrone: (Major) Concomitant use of leuprolide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Levetiracetam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant levetiracetam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Levofloxacin: (Major) Concomitant use of hydroxychloroquine and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Lithium: (Major) Concomitant use of hydroxychloroquine and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Lofexidine: (Major) Concomitant use of lofexidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Loperamide: (Major) Concomitant use of hydroxychloroquine and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Loperamide; Simethicone: (Major) Concomitant use of hydroxychloroquine and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lorazepam: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant lorazepam and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Macimorelin: (Major) Avoid coadministration of macimorelin and hydroxychloroquine due to an increased risk of QT prolongation and torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Hydroxychloroquine prolongs the QT interval.
    Maprotiline: (Major) Avoid coadministration of maprotiline and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Maprotiline has 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 torsade de pointes (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. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Major) Avoid coadministration of hydroxychloroquine with mefloquine due to an increased risk of QT prolongation and seizures. These drugs are both analogs of quinine. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Also, both drugs may lower the seizure threshold.
    Meglitinides: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Meperidine; Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Metformin; Repaglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Metformin; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Methadone: (Major) Avoid coadministration of methadone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). 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.
    Methotrexate: (Moderate) Monitor for increased methotrexate-related adverse reactions during concomitant hydroxychloroquine use. Concomitant use may increase the risk for methotrexate toxicity.
    Methsuximide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as methsuximide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Metronidazole: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midostaurin: (Major) Concomitant use of midostaurin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mifepristone: (Major) Concomitant use of hydroxychloroquine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Miglitol: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Mirtazapine: (Major) Concomitant use of hydroxychloroquine and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mobocertinib: (Major) Concomitant use of mobocertinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Concomitant use of hydroxychloroquine and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Nateglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Nilotinib: (Major) Concomitant use of nilotinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Octreotide: (Major) Concomitant use of octreotide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Octreotide has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and other conduction disturbances which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
    Ofloxacin: (Major) Concomitant use of hydroxychloroquine and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Olanzapine: (Major) Concomitant use of olanzapine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Olanzapine; Fluoxetine: (Major) Concomitant use of hydroxychloroquine and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of olanzapine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Olanzapine; Samidorphan: (Major) Concomitant use of olanzapine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Omeprazole; Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Ondansetron: (Major) Concomitant use of hydroxychloroquine and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
    Osilodrostat: (Major) Concomitant use of osilodrostat and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Osimertinib: (Major) Concomitant use of osimertinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Oxaliplatin: (Major) Concomitant use of oxaliplatin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ozanimod: (Major) Avoid coadministration of hydroxychloroquine and ozanimod due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
    Pacritinib: (Major) Concomitant use of pacritinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Concomitant use of paliperidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Panobinostat: (Major) Concomitant use of panobinostat and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pasireotide: (Major) Concomitant use of pasireotide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pazopanib: (Major) Concomitant use of pazopanib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
    Pentamidine: (Major) Concomitant use of pentamidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pentobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as pentobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Perampanel: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as perampanel. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Perphenazine: (Major) Concomitant use of perphenazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Perphenazine; Amitriptyline: (Major) Concomitant use of perphenazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Phenobarbital: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as phenobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Additionally, coadministration of phenobarbital may decrease exposure of hydroxychloroquine resulting in decreased efficacy.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as phenobarbital. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Additionally, coadministration of phenobarbital may decrease exposure of hydroxychloroquine resulting in decreased efficacy.
    Phentermine; Topiramate: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant topiramate and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Phenytoin: (Moderate) Monitor for a decrease in hydroxychloroquine and phenytoin efficacy if coadministration is necessary. Antiepileptic drug activity may be impaired if coadministered with hydroxychloroquine and concomitant use may decrease exposure of hydroxychloroquine. Hydroxychloroquine is a CYP3A substrate and phenytoin is a strong CYP3A inducer.
    Pimavanserin: (Major) Concomitant use of pimavanserin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pimozide: (Contraindicated) Avoid concomitant use of pimozide and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and hydroxychloroquine use; a metformin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Pitolisant: (Major) Concomitant use of pitolisant and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ponesimod: (Major) Avoid coadministration of hydroxychloroquine and ponesimod due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
    Posaconazole: (Major) Concomitant use of posaconazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pramlintide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including pramlintide, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Praziquantel: (Minor) Hydroxychloroquine may reduce praziquantel bioavailability and maximum serum concentrations as was observed with the structurally similar chloroquine. The mechanism of the interaction is not certain. Clinicians should be alert to the possibility of praziquantel failure if hydroxychloroquine is used.
    Pregabalin: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant pregabalin and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Primaquine: (Major) Concomitant use of primaquine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Primidone: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as primidone. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Procainamide: (Major) Concomitant use of procainamide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Prochlorperazine: (Major) Concomitant use of prochlorperazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Promethazine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Promethazine; Dextromethorphan: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Promethazine; Phenylephrine: (Major) Concomitant use of hydroxychloroquine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Propafenone: (Major) Concomitant use of hydroxychloroquine and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quetiapine: (Major) Concomitant use of hydroxychloroquine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quinidine: (Major) Concomitant use of quinidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quinine: (Major) Concomitant use of quinine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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) Concomitant use of ranolazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Relugolix: (Major) Concomitant use of relugolix and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of relugolix and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Remdesivir: (Major) Coadministration of remdesivir and hydroxychloroquine is not recommended. Based on data from cell culture experiments, the intracellular metabolic activation and antiviral activity of remdesivir may be antagonized by chloroquine phosphate in a dose-dependent manner.
    Repaglinide: (Moderate) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the meglitinides, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Ribociclib: (Major) Concomitant use of ribociclib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Rifampin: (Major) Avoid concomitant use of hydroxychloroquine and rifampin as lack of efficacy of hydroxychloroquine was reported when administered together. Coadministration may decrease the exposure of hydroxychloroquine. Hydroxychloroquine may be a CYP3A4 substrate in vitro, and rifampin is a strong CYP3A4 inducer.
    Rilpivirine: (Major) Concomitant use of rilpivirine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Risperidone: (Major) Concomitant use of risperidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Rituximab: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine, may result in an increased risk of infection. Hydroxychloroquine itself does not increase immunosuppression or infection risk, but, is often used in DMARD regimens where infection risk is increased. Monitor patients closely for signs or symptoms of infection.
    Rituximab; Hyaluronidase: (Moderate) The concomitant use of rituximab with other disease modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine, may result in an increased risk of infection. Hydroxychloroquine itself does not increase immunosuppression or infection risk, but, is often used in DMARD regimens where infection risk is increased. Monitor patients closely for signs or symptoms of infection.
    Romidepsin: (Major) Concomitant use of romidepsin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Rufinamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as rufinamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Saquinavir: (Major) Avoid coadministration of saquinavir and hydroxychloroquine due to an increased risk of QT prolongation. If no acceptable alternative therapy is available, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Hydroxychloroquine prolongs the QT interval.
    Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Selpercatinib: (Major) Concomitant use of selpercatinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Sertraline: (Major) Concomitant use of hydroxychloroquine and sertraline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
    Sevoflurane: (Major) Concomitant use of hydroxychloroquine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and hydroxychloroquine use; a SGLT2 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Simvastatin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Siponimod: (Major) Concomitant use of siponimod and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Sodium Bicarbonate: (Major) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
    Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Solifenacin: (Major) Concomitant use of solifenacin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sorafenib: (Major) Concomitant use of sorafenib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sotalol: (Major) Concomitant use of hydroxychloroquine and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Sunitinib: (Major) Concomitant use of sunitinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Tacrolimus: (Major) Concomitant use of tacrolimus and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Tamoxifen: (Major) Concomitant use of tamoxifen and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the risk of retinal toxicity. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Telavancin: (Major) Concomitant use of telavancin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Telbivudine: (Minor) Monitor patients for signs or symptoms of unexplained muscle pain, tenderness, or weakness during concomitant treatment with hydroxychloroquine and telbivudine. Interrupt telbivudine therapy if myopathy is suspected and discontinue telbivudine if myopathy is confirmed. It is unknown if the risk of myopathy during treatment with telbivudine is increased with coadministration of other drugs associated with myopathy, like hydroxychloroquine.
    Telithromycin: (Major) Concomitant use of telithromycin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Tetrabenazine: (Major) Concomitant use of tetrabenazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and hydroxychloroquine use; a thiazolidinedione dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Tiagabine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as tiagabine. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Tolazamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Tolbutamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and hydroxychloroquine use; a sulfonylurea dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Tolterodine: (Major) Concomitant use of tolterodine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The risk for tolterodine-associated QT/QTc prolongation may be increased in poor CYP2D6 metabolizers.
    Topiramate: (Moderate) Monitor persons with epilepsy for seizure activity during concomitant topiramate and hydroxychloroquine use. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Toremifene: (Major) Concomitant use of toremifene and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Trazodone: (Major) Concomitant use of hydroxychloroquine and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Triclabendazole: (Major) Concomitant use of triclabendazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Trifluoperazine: (Major) Concomitant use of trifluoperazine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Triptorelin: (Major) Concomitant use of triptorelin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ultralente Insulin: (Moderate) Monitor blood glucose during concomitant insulin and hydroxychloroquine use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
    Valproic Acid, Divalproex Sodium: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as valproic acid. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Vandetanib: (Major) Concomitant use of vandetanib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Vardenafil: (Major) Concomitant use of hydroxychloroquine and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Vemurafenib: (Major) Concomitant use of vemurafenib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Venlafaxine: (Major) Concomitant use of hydroxychloroquine and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Vigabatrin: (Major) Vigabatrin should not be used with hydroxychloroquine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. Additionally, hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Voclosporin: (Major) Concomitant use of voclosporin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of hydroxychloroquine and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Voriconazole: (Major) Avoid coadministration of voriconazole and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
    Vorinostat: (Major) Concomitant use of vorinostat and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ziprasidone: (Major) Concomitant use of ziprasidone and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Zonisamide: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as zonisamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.

    PREGNANCY AND LACTATION

    Pregnancy

    Prolonged clinical experience over decades of use and available data from published epidemiologic and clinical studies with hydroxychloroquine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Hydroxychloroquine readily crosses the placenta with cord blood levels corresponding to maternal plasma levels. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine in utero. Available epidemiologic and clinical studies have methodological limitations including small sample size and study design. There are risks to the mother and fetus associated with untreated or increased maternal disease activity from malaria, rheumatoid arthritis, and systemic lupus erythematosus (SLE) during pregnancy that should be considered. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to hydroxychloroquine during pregnancy. Encourage patients to register by contacting 1-877-311-8972. Hydroxychloroquine is considered to be compatible for use during pregnancy in some anti-rheumatic guidelines, and may be continued in pregnancy for maintenance of remission or treatment of a disease flare. Hydroxychloroquine may also be appropriate for pregnancies complicated by lupus. Guidelines also recommend hydroxychloroquine as an alternative to chloroquine as a treatment option for acute malaria and for prophylaxis in pregnant women during all trimesters. Animal reproductive studies have not been conducted.

    Data regarding the use of hydroxychloroquine during breast-feeding report that hydroxychloroquine is present in human milk at low levels. No adverse reactions have been reported in breastfed infants. No retinal toxicity, ototoxicity, cardiotoxicity, or growth and developmental abnormalities have been observed in children who were exposed to hydroxychloroquine through breastmilk. There is no information on the effect of hydroxychloroquine on milk production. Hydroxychloroquine is considered to be compatible for use during breast-feeding in some anti-rheumatic guidelines, and may be continued during lactation for maintenance of remission or treatment of a disease flare.  During lactation studies, breast milk concentrations ranged from 10.6 to 1,392 mcg/L  and breast-fed infants would likely receive 0.2 mg/kg or less of hydroxychloroquine. In infants monitored for up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision, or hearing. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the medication and any potential adverse effects on the breastfed child from hydroxychloroquine exposure or from the underlying maternal condition.

    MECHANISM OF ACTION

    Hydroxychloroquine, a 4-aminoquinolone antimalarial, is a weak base and may exert its antimalarial effect by concentrating in the acid vesicles of the plasmodia and by inhibiting the polymerization of heme. It can also inhibit certain enzymes by its interaction with DNA. Organisms with reduced susceptibilities to chloroquine also show reduced susceptibilities to hydroxychloroquine.[41806]
     
    Although the mechanisms underlying the antiinflammatory and immunomodulatory effects of hydroxychloroquine in the treatment of rheumatoid arthritis, chronic discoid lupus erythematous, and systemic lupus erythematosus are not fully known, several possible mechanisms of action have been proposed. It is unclear if these mechanisms work similarly for rheumatic and autoimmune diseases. Potential mechanisms include reduced cytokine production, inhibition of immune effector cells, inhibition of platelet function, protection of the cell surface from external disturbances, competitive binding to nucleic acid ligands or toll-like receptors (TLRs), interference with lysosomal function, reduction of leakage of lysosomal enzymes, and interference with endosomal NADPH oxidase (NOX).[41806] [61727] [61728] [61729]
     
    There are several potential mechanisms by which hydroxychloroquine may be active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These include inhibition of viral enzymes or processes such as viral DNA and RNA polymerase, viral protein glycosylation, virus assembly, new virus particle transport, and virus release. Other mechanisms may also involve ACE2 cellular receptor inhibition, acidification at the surface of the cell membrane inhibiting fusion of the virus, and immunomodulation of cytokine release.[61729] [61732] [65120] [65121] [65139] [65140] [65141] [65142] [65143]

    PHARMACOKINETICS

    Hydroxychloroquine is administered orally. It is widely distributed into body tissues, with high concentrations in the bone marrow, liver, kidneys, lungs, adrenal gland, and pituitary gland. Hydroxychloroquine has a high affinity for melanin and thus is concentrated in the choroid and ciliary body of the eye, which may account for the retinal toxicity. Cellular concentrations have been shown to be higher in mononuclear cells than in polymorphonuclear leukocytes.[41806] [61731] [61732]
     
    Hydroxychloroquine is partially metabolized in the liver to 3 metabolites. These include the major metabolite, desethylhydroxychloroquine (DHCQ), as well as desethylchloroquine (DCQ) and bidesethylhydroxychloroquine (BDCQ). Renal clearance of unchanged drug ranges from 16% to 30% and does not change with chronic dosing. A half-life of 123.5 days in plasma were observed after a single 200 mg dose in healthy male volunteers. Urine hydroxychloroquine levels were still detectable after 3 months with approximately 10% of the dose excreted as parent drug. Results after a single 200 mg oral dose versus a single 155 mg IV dose demonstrated a half-life of about 40 days and large volume of distribution. After chronic oral administration, the absorption half-life was approximately 3 to 4 hours and th terminal half-life ranged form 40 to 50 days.[41806]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP2D6, CYP3A4, P-gp
    In vitro data suggest that hydroxychloroquine is metabolized primarily by CYP2C8 and CYP3A4, and to a much lesser extent, by CYP2D6.[65236] [65239] It has also been shown to be an inhibitor of the drug transporter P-glycoprotein (P-gp).[65237]

    Oral Route

    Bioavailability is approximately 74%. Hydroxychloroquine displays linear kinetics. Tmax was 3.3 to 3.7 hours. Peak blood concentrations of metabolites were observed at the same time as peak hydroxychloroquine levels. In rheumatoid arthritis patients, there is a large variability in absorption (30% to 100%) with mean concentrations significantly higher in patients with less disease activity.