Hydroxychloroquine is an oral disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis and systemic lupus erythematosus. It also is used to prevent and treat malaria. Irreversible retinal damage has been observed with use, and cases of life-threatening and fatal cardiomyopathy, including ventricular arrhythmias and torsade de pointes, have been reported.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
-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).
Hydroxychloroquine can cause ocular toxicity including irreversible retinal damage related to cumulative dose and treatment duration. 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 are recommended for patients at higher risk of retinal damage. For patients without significant risk factors, annual 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 ocular disease (i.e., retinal changes) and visual disturbance which may progress even after discontinuation of therapy. Other ocular adverse events include retinopathy, retinal pigment changes (bull's eye appearance), visual field defects/visual impairment (paracentral scotomata), macular degeneration, decreased dark adaptation, corneal edema, and corneal opacification.
Serious skin reaction have been reported with the use of hydroxychloroquine and include Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), photosensitivity, and acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Patients should seek medical attention if they experience signs and symptoms of serious skin reactions, including blisters on the skin, eyes, lips, or inside the mouth; itching or burning; with or without fever. Other allergic or dermatologic reactions include Other allergic and dermatologic reactions have been reported with the use of hydroxychloroquine. These include alopecia, hair color changes (hair discoloration), rash, pruritus, photosensitivity, hyperpigmentation (skin discoloration), exfoliative dermatitis, erythema multiforme, urticaria, angioedema, and bronchospasm.
Hydroxychloroquine may precipitate a severe attack of psoriasis that may be associated with pyrexia and hyperleukocytosis. Monitor patients with known psoriasis for a flare-up of the psoriasis.
Skeletal muscle myopathy or peripheral neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes, and abnormal nerve conduction has been reported. Muscle and nerve biopsies have been associated with curvilinear bodies and muscle fiber atrophy with vacuolar changes. Muscle and nerve biopsies have showed 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. If muscle or nerve toxicity is suspected or demonstrated by tissue biopsy, discontinue hydroxychloroquine therapy.
Hematological adverse reactions of hydroxychloroquine include myelosuppression (bone marrow suppression), including anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia. Hemolysis/hemolytic anemia has been reported in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Monitor blood cell counts periodically if patients are given prolonged hydroxychloroquine therapy. If myelosuppression develops which is not attributable to the disease under treatment occurs, discontinue hydroxychloroquine.
Sensorineural hearing loss and tinnitus have been reported with hydroxychloroquine or other 4-aminoquinolines.
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 during acute and chronic treatment with the drug. Patients may present with ventricular hypertrophy, pulmonary hypertension, and conduction disorders including sick sinus syndrome. ECG findings include AV block or right or left bundle-branch block. In multiple cases, endomyocardial biopsy revealed an association of cardiomyopathy with phospholipidosis in absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur with other organs. Chronic toxicity should be considered when conduction disorders or biventricular hypertrophy are diagnosed. If cardiotoxicity is suspected or demonstrated by tissue biopsy, prompt discontinuation of hydroxychloroquine may prevent life-threatening cardiac complications. Additionally, hydroxychloroquine causes QT prolongation. The magnitude of QT prolongation may increase with increasing drug concentrations. Ventricular arrhythmias (i.e., ventricular fibrillation, ventricular tachycardia) and torsade de pointes have been reported in patients taking hydroxychloroquine. Monitor the ECG and cardiac function as indicated during hydroxychloroquine therapy. Cardiac disorders reported with the class of 4-aminoquinoline drugs postmarketing have included cardiomyopathy, heart failure, QT-interval prolongation, ventricular tachycardia, torsade de pointes, AV block, bundle-branch block, sick sinus syndrome, and pulmonary hypertension.
Adverse gastrointestinal (GI) effects reported with hydroxychloroquine or other 4-aminoquinolines include nausea, vomiting, abdominal pain, diarrhea, and anorexia. These effects are associated with oral administration and can be minimized by taking hydroxychloroquine with food. Abnormal liver function tests and fulminant hepatic failure have also been reported.
Suicidal behavior, suicidal ideation, and other neuropsychiatric adverse events have been reported in patients treated with hydroxychlorquine. Neuropsychiatric adverse events typically occur within the first month after starting hydroxychloroquine and have been reported in patients with and without prior history of psychiatric disorders. Psychiatric and CNS adverse events reported with hydroxychloroquine or other 4-aminoquinolines include headache, dizziness, affect/emotional lability, irritability, psychosis, nervousness, depression, hallucinations, anxiety, agitation, confusion, delusions, paranoia, mania, sleep disorders (insomnia, night terrors, nightmares), vertigo, nystagmus, ataxia, seizures, and extrapyramidal disorders such as dystonic reaction, dyskinesia, and tremor. Assess the risk and benefit of continued treatment in patients who develop neuropsychiatric reactions, including new or worsening depression, suicidal thoughts or behavior, or mood changes. Given the long half-life of the drug, it may take several weeks for the symptoms to partially or fully abate after stopping hydroxychlorquine.
Weight loss and fatigue have been reported with the use of hydroxychloroquine or other 4-aminoquinolines.
Hydroxychloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with or without antidiabetic medications. Monitor blood glucose and adjust treatment as necessary in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment.
Hydroxychloroquine may cause 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.
Use of hydroxychloroquine in patients with porphyria has been shown to exacerbate porphyria. Additionally, in patients with porphyria cutanea tarda (PCT), cases of hepatotoxicity have developed following administration of hydroxychloroquine at doses ranging from 200 mg twice weekly to 400 mg daily. For most PCT-related cases, patients presented with markedly elevated hepatic enzymes (greater than 20-times upper limit of normal) within days to months of starting hydroxychloroquine. If a patient is found to have an abnormal liver function test (e.g., ALT greater than 3-times ULN, total bilirubin greater than 2-times ULN), interrupt treatment with hydroxychloroquine and investigate for the probable cause.
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. Hydroxychloroquine has 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.
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, duration 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.
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.
Avoid use of hydroxychloroquine in patients with psoriasis unless the benefit to the patients outweighs the possible risk. Hydroxychloroquine has been shown to precipitate severe flare-ups of psoriasis.
Avoid use of hydroxychloroquine in patients with porphyria, as treatment has been shown to exacerbate porphyria. Additionally, the safe and effective use of hydroxychloroquine for the treatment of porphyria cutanea tarda (PCT) has not been established; the drug is not approved for this indication. In patients with PCT, cases of hepatotoxicity have developed following administration of hydroxychloroquine at doses ranging from 200 mg twice weekly to 400 mg daily. For most PCT-related cases, patients presented with marked elevations in transaminases (greater than 20-times upper limit of normal) within days to months of starting hydroxychloroquine. In some cases, the diagnosis of PCT was not made until after hydroxychloroquine-induced liver injury occurred. Some cases were associated with other risk factors for hepatic injury (e.g., alcohol use, concomitant hepatotoxic medications). Promptly measure liver function tests in patients who report symptoms that may indicate hepatic injury (e.g., fatigue, rash, nausea, dark urine, jaundice). If a patient is found to have an abnormal liver function test (e.g., ALT greater than 3-times ULN, total bilirubin greater than 2-times ULN), interrupt treatment with hydroxychloroquine and investigate for the probable cause.
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.
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.
Suicidal behavior, suicidal ideation, and other neuropsychiatric events have been reported in patients treated with hydroxychlorquine. A neuro-psychiatric event will typically occur within the first month after starting hydroxychloroquine and these events have been reported in patients with and without prior history of psychiatric disorders. Alert patients to contact their healthcare provider if they experience new or worsening depression, suicidal ideation or thoughts, or mood or behavioral changes. Asses the risk and benefit of continued treatment with hydroxychlorquine for patients who develop these symptoms. Given the long half-life of the drug, it may take several weeks for the symptoms to partially or fully abate.
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.
A reduction in the dosage of hydroxychloroquine may be necessary in patients with renal disease, including renal impairment or renal failure. Additionally, renal impairment is a risk factor for retinal damage due to hydroxychloroquine, which is related to cumulative dosage and treatment duration. Hydroxychloroquine has also 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.
Hydroxychloroquine should be used with caution in patients with hepatic disease. A dose reduction may be necessary.
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.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
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).
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.
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 200mg/day (155 mg base/day), 300 mg/day (232 mg base/day), or 400 mg/day (310 mg base/day) in 1 or 2 divided doses.
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.
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 systemic lupus erythematosus (SLE):
Oral dosage:
Adults: 200 to 400 mg (155 to 310 mg base) PO once daily or in 2 divided doses. Usual dose: 300 to 400 mg/day (232 to 310 mg base/day). Max: 5 mg/kg/day. Consider tapering dose to 200 mg/day (155 mg base/day) in persons in remission.
Children* and Adolescents*: 4 to 5 mg (3.1 to 3.8 mg base)/kg/day PO. Max: 400 mg/day (310 mg base/day).
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.
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.
For the treatment of sarcoidosis*:
Oral dosage:
Adults: 200 to 400 mg (155 to 310 mg base) PO once daily.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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.
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.
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.
Aluminum 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).
Aluminum Hydroxide; Magnesium 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).
Aluminum Hydroxide; 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).
Aluminum Hydroxide; 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).
Aluminum Hydroxide; Magnesium Trisilicate: (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).
Amiodarone: (Major) Concomitant use of amiodarone 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. 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.
Bexagliflozin: (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.
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; 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.
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.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine 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.
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.
Etrasimod: (Major) Concomitant use of etrasimod 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. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
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.
Fexinidazole: (Major) Concomitant use of fexinidazole 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.
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.
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.
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.
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).
Magnesium Salts: (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).
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.
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; 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) Concomitant use of methadone 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.
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.
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) Monitor for altered clinical response to praziquantel if concomitant use with hydroxychloroquine is necessary. Concomitant use of praziquantel with chloroquine has been observed to reduce praziquantel exposure which may reduce its efficacy. A similar interaction may occur with hydroxychloroquine.
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.
Quizartinib: (Major) Concomitant use of quizartinib 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.
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.
Sotagliflozin: (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.
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.
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.
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.
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.
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.
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).
Hydroxychloroquine is administered orally. It is approximately 50% bound to plasma proteins and 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. Hydroxychloroquine is primarily metabolized by CYP2C8, CYP3A4, and CYP2D6 as well as by flavin-containing monooxygenase 1 (FMO-1) and monoamine oxidase A (MAO-A). Three metabolites have been identified, including 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. The half-life of a single 200 mg oral dose is approximately 40 days. Following chronic administration, the absorption half-life is approximately 3 to 4 hours and the terminal half-life in whole blood ranges from 40 to 50 days. In rheumatoid arthritis (RA) patients, the effective half-life is likely to be shorter.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP2D6, CYP3A4, P-gp, MATE1, MATE2-K
In vitro data suggest that hydroxychloroquine is metabolized primarily by CYP2C8 and CYP3A4, and to a much lesser extent, by CYP2D6. It has also been shown to be an inhibitor of the drug transporter P-glycoprotein (P-gp). An in vitro study suggests that hydroxychloroquine also has the potential to inhibit CYP2D6, CYP3A4, and multidrug and toxin extrusion transporters MATE1 and MATE2-K.
-Route-Specific Pharmacokinetics
Oral Route
The mean absolute oral bioavailability of hydroxychloroquine is 79% under fasting conditions. In rheumatoid arthritis (RA) patients, there is a large variability in absorption (30% to 100%) with mean concentrations significantly higher in patients with less disease activity. Following a singe 200 mg dose to healthy volunteers, the peak whole blood concentration (Cmax) was 129.6 ng/mL (plasma Cmax was 50.3 ng/mL) and the time to reach peak blood concentration (Tmax) was 3.3 hours (plasma Tmax was 3.7 hours). Peak blood concentrations of the metabolites were observed at the same time as peak hydroxychloroquine levels. Steady state concentrations are achieved by 6 weeks after oral administration of 400 mg daily in RA patients. At steady state, the whole blood concentration of hydroxychloroquine is dose proportional over a range of 200 to 400 mg daily in patients with RA and lupus.
Intravenous Route
Following a single 155 mg intravenous infusion of hydroxychloroquine in healthy volunteers, peak blood concentrations (Cmax) ranged from 1,161 ng/mL to 2,436 ng/mL (mean 1,918 ng/mL). The Cmax range after a single 310 mg infusion was 2,290 ng/mL and 4,211 ng/mL; thus, indicating linear pharmacokinetics.