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Hydroxychloroquine: Drug information

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

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Plaquenil
Brand Names: Canada
  • APO-Hydroxyquine;
  • JAMP Hydroxychloroquine Sulf;
  • MINT-Hydroxychloroquine;
  • NRA-Hydroxychloroquine;
  • Plaquenil
Pharmacologic Category
  • Aminoquinoline (Antimalarial);
  • Antimalarial Agent;
  • Antirheumatic, Disease Modifying
Dosing: Adult

Dosage guidance:

Safety: To avoid retinopathy and permanent vision loss, do not exceed recommended maximum doses. Baseline and periodic screening for retinopathy is necessary for rheumatologic uses and in long-term therapy (eg, >1 to 5 years depending on patient risk factors) (Ref). To mitigate risk of cardiac arrhythmias, correct electrolyte imbalances prior to use.

Dosing: All doses below are expressed as hydroxychloroquine sulfate salt. Hydroxychloroquine sulfate salt 200 mg is equivalent to hydroxychloroquine base 155 mg. Variable daily dosing (eg, alternating or skipping doses on certain days each week) may be used to obtain the recommended dose for rheumatologic uses.

Clinical considerations: In addition to administering with food or milk, to improve tolerability of the common adverse effect of GI upset (nausea, vomiting, diarrhea), may also administer at bedtime; for sarcoidosis and rheumatologic conditions, may divide doses, or gradually escalate the dose upon initiation (Ref).

Dermatomyositis, cutaneous

Dermatomyositis, cutaneous (off-label use): Note: Used in combination with antipruritic medications, topical therapy, and nonpharmacologic measures (eg, photoprotection) (Ref).

Oral: 300 to 400 mg daily as a single daily dose or in 2 divided doses. Assess response after 3 months; may attempt to slowly taper after several months of satisfactory response (Ref). Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Lupus erythematosus

Lupus erythematosus:

Systemic lupus erythematosus: Note: In general, hydroxychloroquine (or chloroquine) is indicated for all patients with systemic disease; additional therapy is individualized according to predominant disease manifestations and activity (Ref).

Oral: 200 to 400 mg daily as a single daily dose or in 2 divided doses. Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Discoid lupus erythematosus and subacute cutaneous lupus erythematosus: For use if response to local therapy is inadequate or impractical due to widespread skin lesions (Ref):

Oral: 200 to 400 mg daily as a single daily dose or in 2 divided doses. Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Malaria

Malaria (alternative agent):

Prophylaxis: Note: Only for use in individuals traveling to malarious regions without chloroquine resistance (Ref).

Oral: 400 mg once weekly on the same day each week; begin 1 to 2 weeks before travel to malarious area; continue therapy while in malarious area and for 4 weeks after leaving the area (Ref).

Treatment, uncomplicated: Note: Only for treatment of nonsevere infections caused by chloroquine-sensitive malaria; for infection caused by Plasmodium vivax or Plasmodium ovale, give in combination with primaquine. Not recommended for treatment if chloroquine or hydroxychloroquine was given for chemoprophylaxis (Ref).

Oral: 800 mg once, followed by 400 mg at 6, 24, and 48 hours after initial dose (total dose: 2 g) (Ref).

Porphyria cutanea tarda

Porphyria cutanea tarda (off-label use): Oral: 100 mg twice weekly; continue until plasma or urine porphyrin levels are normal for at least several months (Ref).

Primary Sjögren disease

Primary Sjögren disease (off-label use): Note: For treatment of moderate to severe extraglandular manifestations (eg, arthralgias, myalgias, fatigue) or milder symptoms unresponsive to nonpharmacologic measures and nonsteroidal anti-inflammatory drugs (NSAIDs) (Ref); some experts also use in patients with major salivary enlargement resulting in cosmetic concerns or glandular pain (Ref).

Oral: Initial: 200 to 400 mg daily as a single daily dose or in 2 divided doses (Ref). Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Q fever

Q fever (Coxiella burnetii) (off-label use): Note: Given higher dose recommendations for Q fever, the CDC recommends routine therapeutic drug monitoring and ophthalmic exams for retinal toxicity (Ref).

Persistent localized infection (eg, endocarditis, osteoarticular infection, vascular infection) in nonpregnant patients: Oral: 200 mg 3 times daily in combination with doxycycline for ≥18 to 24 months, depending on site of infection and serologic response (Ref).

Prevention of persistent infection following acute Q fever: Note: Generally reserved for patients with valvulopathy/cardiomyopathy (Ref) or postpartum women with persistent serologic evidence of infection >12 months after delivery (Ref).

Oral: 200 mg 3 times daily in combination with doxycycline for 12 months (Ref).

Rheumatoid arthritis

Rheumatoid arthritis: Note: For use as monotherapy in disease-modifying antirheumatic drug (DMARD)–naive patients with low disease activity. May also be used as part of alternative combination therapy (with other nonbiologic DMARDs) in patients with moderate to severe disease whose treatment targets have not been met despite maximally tolerated methotrexate therapy (Ref).

Oral: 200 to 400 mg daily as a single daily dose or in 2 divided doses (Ref). Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Sarcoidosis

Sarcoidosis (off-label use):

Arthropathy: Note: As additional therapy for NSAID-resistant symptoms in patients with an inadequate response to glucocorticoids or who are unable to fully taper (Ref).

Oral: 200 to 400 mg daily as a single daily dose or in 2 divided doses. Therapy may be continued for ~1 year and then gradually tapered in patients who have responded and are stable on therapy (Ref). Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

Cutaneous disease, extensive: Oral: 200 to 400 mg daily as a single daily dose or in 2 divided doses for ≥3 months to evaluate for efficacy; if there is satisfactory improvement, may consider gradual tapering and discontinuation if response is maintained (Ref). Note: Due to the risk of retinal toxicity, most patients should not receive a daily dose >5 mg/kg/day using actual body weight or 400 mg, whichever is lower (Ref).

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

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Mild to severe impairment: There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage reduction may be needed with prolonged use (eg, systemic lupus erythematosus) (Ref); use with caution. With short-term use at recommended doses and durations (eg, malaria treatment), no dosage adjustment necessary (Ref).

Hemodialysis: Not dialyzable (Ref): There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage reduction may be needed with prolonged use (eg, systemic lupus erythematosus) (Ref); use with caution. With short-term use at recommended doses and durations (eg, malaria treatment), no dosage adjustment necessary (Ref).

Peritoneal dialysis: There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage reduction may be needed with prolonged use (eg, systemic lupus erythematosus) (Ref); use with caution. With short-term use at recommended doses and durations (eg, malaria treatment), no dosage adjustment necessary (Ref).

CRRT: Unlikely to be dialyzable (Ref): There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage reduction may be needed with prolonged use (eg, systemic lupus erythematosus) (Ref); use with caution. With short-term use at recommended doses and durations (eg, malaria treatment), no dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Hepatotoxicity associated with porphyria cutanea tarda (off-label use) during therapy: Interrupt treatment if ALT >3 times ULN and total bilirubin >2 times ULN.

Dosing: Obesity: Adult

Rheumatic diseases (eg, rheumatoid arthritis, lupus erythematosus, primary Sjögren disease [off-label use]): Available data do not specifically address dosing in obese patients; however, some experts recommend standard daily doses (non-weight-based) up to a maximum of 400 mg/day in patients weighing ≥80 kg (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

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

Dosage guidance:

Safety: To avoid retinopathy and permanent vision loss, do not exceed recommended maximum doses. Baseline and periodic screening for retinopathy is necessary for rheumatologic uses and in long-term therapy (eg, >1 to 5 years depending on patient risk factors) (Ref).

Dosing: All doses below expressed as hydroxychloroquine sulfate. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base.

Malaria

Malaria:

Chemoprophylaxis: Note: Only for use in individuals traveling to malarious regions without chloroquine resistance (Ref).

Infants, Children, and Adolescents: Oral: 6.5 mg/kg hydroxychloroquine sulfate once weekly on the same day each week; maximum dose: 400 mg/dose hydroxychloroquine sulfate; begin 1 to 2 weeks before travel to malarious area; continue while in malarious area and for 4 weeks after leaving the area (Ref).

Treatment, uncomplicated: Infants, Children, and Adolescents: Oral: Initial: 12.9 mg/kg/dose hydroxychloroquine sulfate (maximum initial dose: 800 mg/dose hydroxychloroquine sulfate); followed by 6.5 mg/kg hydroxychloroquine sulfate at 6, 24, and 48 hours after initial dose; maximum dose: 400 mg/dose hydroxychloroquine sulfate. For infection caused by Plasmodium vivax or Plasmodium ovale, use in combination with appropriate antirelapse treatment (ie, primaquine) (Ref).

Juvenile dermatomyositis, skin predominant

Juvenile dermatomyositis, skin predominant: Limited data available: Children and Adolescents: Oral: 5 mg/kg/day in 1 to 2 divided doses; maximum daily dose: 400 mg/day. Dosage range reported: 2 to 6 mg/kg/day (Ref); however, some experts recommend a maximum of 5 mg/kg/day to mitigate risk of retinal toxicity (Ref). Use in combination with nonpharmacologic measures (eg, photoprotection), topical therapies, and/or other systemic therapies (Ref).

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE): Limited data available: Children and Adolescents: 4 to 6.5 mg/kg/day in 1 to 2 divided doses; maximum daily dose: 400 mg/day (Ref); based upon data in adults, some experts recommend a maximum of 5 mg/kg/day to mitigate risk of retinal toxicity (Ref).

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

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Infants, Children, and Adolescents:

Note: Renal clearance accounts for 15% to 25% of total clearance (Ref).

Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Dosage adjustment may be considered with chronic use.

Hemodialysis: Not dialyzable (Ref): There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Dosage adjustment may be considered with chronic use.

Peritoneal dialysis: There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Dosage adjustment may be considered with chronic use.

Continuous renal replacement therapy (CRRT): Unlikely to be dialyzable based on wide volume of distribution and high lipophilicity (Ref): There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Dosage adjustment may be considered with chronic use.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Adverse Reactions (Significant): Considerations
Cardiomyopathy

A predominantly restrictive or diastolic cardiomyopathy presenting as heart failure has been reported following long-term use of antimalarials for rheumatic diseases (especially chloroquine but occasionally hydroxychloroquine); systolic impairment may also occur (Ref). Additionally, conduction abnormalities (eg, atrioventricular block, sick sinus syndrome, bundle branch block) and pulmonary hypertension have been reported (Ref). On imaging, myocardial hypertrophy is most common in patients who develop cardiomyopathy. Clinicians should note that some patients may not have any or very few clinical symptoms. Laboratory findings may include elevated creatine kinase, lactate dehydrogenase, and/or troponins (Ref). While some patients may experience improvement following discontinuation, others experience permanent damage that may result in the need for cardiac transplant or death (Ref).

Mechanism: Time-related; exact mechanism is unknown. Hydroxychloroquine is hypothesized to bind to phospholipids within the myocyte, leading to accumulation in lysosomes and inhibiting lysosomal enzymes in several tissues, including peripheral nerve, cardiac, and skeletal muscle. The resulting intracellular degradation leads to accumulation of metabolic products (eg, phospholipids, glycogen) (Ref).

Onset: Delayed (Ref); patients may remain clinically asymptomatic for a long period of time with symptoms only appearing at a later stage and/or with high cumulative doses (eg, several years of therapy) (Ref). Some patients may experience improvement within 1 month to 1 year following discontinuation, others experience permanent damage that may result in the need for cardiac transplant or death (Ref).

Risk factors:

The following confers an increased risk (Ref):

• Longer duration of therapy

• Higher cumulative doses

• Older age

• Females

• Preexisting cardiac disease

• Kidney impairment

G6PD deficiency

Although the manufacturer's labeling recommends that hydroxychloroquine be used with caution in patients with glucose-6-phospate deficiency (G6PD) due to the potential for hemolysis (hemolytic anemia), there are limited data to support this risk. Many experts consider hydroxychloroquine, when given in usual therapeutic doses to WHO Class II and III G6PD deficient patients, to probably be safe (Ref). In a retrospective chart review, no incidence of hemolytic anemia was found among the 11 patients identified with G6PD deficiency receiving hydroxychloroquine therapy, despite >700 months of exposure (all patients were African-American and located in the US) (Ref). In addition, the ACR Rheumatology guidelines do not mention the need to evaluate G6PD levels prior to initiation of therapy (Ref).

Hypersensitivity reactions (delayed)

Cutaneous hypersensitivity reactions ranging from maculopapular rash to severe cutaneous adverse reactions (SCARs) may occur. Various delayed, nonlife-threatening reactions have been reported, including lichenoid, urticarial, and maculopapular eruptions (Ref). Reported SCARs include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS [also known as drug hypersensitivity syndrome]), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) (Ref). Hydroxychloroquine is also associated with phototoxic and photoallergic dermatitis (Ref).

Mechanism: Non-dose related; immunologic; delayed hypersensitivity reactions are mediated by T-cells or antibodies other than immunoglobulin E (IgE) (eg, IgG-mediated, such as some cytopenias) (Ref). SCARs are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).

Onset: Varied; most nonlife-threatening cutaneous reactions occurred 5 to 14 days after initiation of hydroxychloroquine (Ref). Onset of SCARs is generally days to weeks after administration of the causative drug (Ref) but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).

Risk factors:

• Prior hypersensitivity reaction to 4-aminioquinolines. Note: There is conflicting evidence regarding cross-reactivity between the 4-aminoquinolines (eg, chloroquine, hydroxychloroquine), although most reports suggest tolerance of chloroquine in patients with nonsevere cutaneous reactions to hydroxychloroquine (Ref).

• Patients with dermatomyositis, in particular those with anti-small ubiquitin-like modifier 1 activating enzyme (anti-SAE-1/2) autoantibodies (Ref).

Hypoglycemia

Severe hypoglycemia has rarely been reported in patients (both with and without diabetes) who were receiving hydroxychloroquine (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Chloroquine has been shown to reduce intracellular insulin degradation, increase intracellular insulin accumulation, slow receptor recycling, stimulate insulin-mediated glucose transport, and increase peripheral insulin sensitivity and secretion (Ref).

Onset: Unknown. In one case report, a patient was initiated on hydroxychloroquine and presented to the emergency department 2 months later with symptoms secondary to severe hypoglycemia (Ref).

Risk factors:

• Concomitant use of other medications known to lower blood glucose concentrations

Neuromuscular effects

Skeletal muscle myopathy or neuropathy leading to asthenia and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction have been reported (Ref). Symptoms ranged from painless proximal weakness in both upper and lower extremities to severe weakness requiring hospitalization and ventilatory support (Ref). Clinicians should note that patients with rheumatic disease may experience symptoms of their underlying disease that make diagnosis of myopathy difficult (Ref).

Mechanism: Time-related; exact mechanism is unknown. Hydroxychloroquine is hypothesized to bind to phospholipids within the myocyte, accumulating in lysosomes and inhibiting lysosomal enzymes in several tissues, including peripheral nerve, cardiac, and skeletal muscle. The resulting intracellular degradation leads to accumulation of metabolic products (eg, phospholipids, glycogen) (Ref). Muscle and nerve biopsies have been associated with curvilinear bodies and muscle fiber atrophy with vacuolar changes (Ref).

Onset: Delayed; varies from <1 year of therapy to >10 years (Ref). In addition, the response to discontinuation of hydroxychloroquine varies with some patients experiencing resolution of symptoms within weeks to months while others experience progression of symptoms (Ref).

Risk factors:

Risk factors are poorly defined but may include:

• White people (Ref)

• Kidney failure (Ref)

• Concomitant use of other myotoxic drugs, including corticosteroids (Ref)

Neuropsychiatric effects

Various neuropsychiatric effects have been reported with antimalarial agents, including hydroxychloroquine, in patients with and without a history of psychiatric disorders. Effects include agitation, anxiety, delusion, depression, hallucination, mania, paranoid ideation, psychosis, psychomotor agitation, sleep disorders (insomnia, night terrors, nightmares), suicidal ideation, and suicidal tendencies (Ref). One case report of neuropsychiatric effects following use of chloroquine demonstrated that effects may persist for several months (Ref).

Mechanism: Time-related; exact mechanism is not fully understood. Proposed hypotheses include a cholinergic imbalance related to the inhibition of the acetylcholinesterase, prostaglandin E antagonism, the accumulation of toxic metabolites in the lysosome, and the down-regulation of glycoprotein-P in the blood brain barrier (Ref).

Onset: Intermediate; typically occurs within the first month after initiation.

Risk factors:

• Family history of neuropsychiatric effects (Ref)

• Female patients (Ref)

• Concurrent medications known to increase hydroxychloroquine concentrations (Ref)

• Concurrent glucocorticoids (Ref)

• Concurrent alcohol (Ref)

• Low body weight (Ref)

QT prolongation

Long-term use or high doses of antimalarials (especially chloroquine but also hydroxychloroquine) have been associated with prolonged QT interval on ECG and subsequent ventricular arrhythmias (including torsades de pointes [TdP]), syncope, and sudden cardiac death (Ref).

Mechanism: Dose-related; exact mechanism is unknown. Hydroxychloroquine is hypothesized to abnormally affect ion currents (including hyperpolarization activated ion channels, delayed rectifier potassium currents, and L-type calcium ion currents). This may cause delayed depolarization and prolonged repolarization of cardiac myocytes, which can lead to QT interval prolongation (Ref).

Onset: Varied; effect is concentration-dependent; therefore, timing may be impacted by high doses or accumulation. In one study in healthy subjects administered chloroquine (100 mg base per day; n=3), QT prolongation was noted on day 3 of administration (Ref)

Risk factors:

In general, risk factors for drug-induced QT prolongation include:

• Females (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure) (Ref)

• Genetic defects of cardiac ion channels (Ref)

• Congenital long QT syndrome (Ref)

• Baseline QTc interval prolongation (eg, >450 msec) (Ref)

• Electrolyte disturbances (eg, hypokalemia or hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Coadministration of multiple medications that prolong the QT interval or drug interactions that increase serum concentration of QT-prolonging medications (Ref)

Retinal toxicity

Long-term use of hydroxychloroquine may result in retinopathy characterized by parafoveal retinal damage (Ref). The clinical picture is classically characterized as a bilateral “bull's-eye” maculopathy; visual acuity generally remains intact until more severe damage has been realized. As retinopathy progresses, the area of functional deficit may expand to the foveal center with decreased visual acuity, peripheral vision, and night vision; cystoid macular edema may also occur. Clinicians should note that some patients may not experience symptoms during the early stages of retinopathy and that retinopathy is irreversible (Ref).

Mechanism: Time-related; exact mechanism is not fully understood. A proposed mechanism is impaired lysosomal degradation of photoreceptor outer segments by the retinal pigment epithelium (Ref).

Onset: Delayed; most commonly occurring >5 years after initiation of therapy (Ref).

Risk factors:

• High daily doses relative to body weight (≥5 mg/kg actual body weight) and a duration of >5 years of use in the treatment of rheumatic diseases (Ref)

• Higher serum concentrations of hydroxychloroquine (Ref)

• Concurrent tamoxifen use (Ref)

• Kidney impairment (Ref)

• Lower body weight (Ref)

• Preexisting macular disease (Ref)

Adverse Reactions

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

1% to 10%: Ophthalmic: Retinopathy (4%; serum concentration dependent [Petri 2020b]; early changes reversible [may progress despite discontinuation if advanced])

<1%: Hematologic & oncologic: Hemolysis (rare; primarily a theoretical concern in patients with glucose-6-phosphate deficiency; data do not support withholding therapy in these patients [Luzzato 2016; Mohammad 2018])

Frequency not defined:

Cardiovascular: Sick sinus syndrome

Dermatologic: Exacerbation of psoriasis, exfoliative dermatitis, hair discoloration, pruritus, urticaria

Endocrine & metabolic: Weight loss

Gastrointestinal: Abdominal pain, anorexia

Hematologic & oncologic: Anemia, aplastic anemia, bone marrow depression, leukopenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests

Hypersensitivity: Angioedema

Nervous system: Ataxia, dizziness, emotional lability, fatigue, headache, irritability, nervousness, seizure, vertigo

Ophthalmic: Corneal changes (corneal edema, corneal opacity), nystagmus disorder, ophthalmic signs and symptoms (decreased dark adaptation)

Respiratory: Bronchospasm

Postmarketing:

Cardiovascular: Atrioventricular block (Bae 2012), bundle branch block (Costedoat-Chalumeau 2007), cardiomyopathy (AHA [Page 2016]; Fiehn 2020; Tönnesmann 2012; Tönnesmann 2013), heart failure (Figliozzi 2021), prolonged QT interval on ECG (Chatre 2018; Chen 2006; O’Laughlin 2016; Stas 2008), torsades de pointes (Chatre 2018; O’Laughlin 2016), ventricular arrhythmia (Chatre 2018; O’Laughlin 2016), ventricular tachycardia (Abdelmaseih 2020)

Dermatologic: Acute generalized exanthematous pustulosis (Charfi 2015; Soria 2015), alopecia (Sharma 2020), erythema multiforme (Abou Assalie 2017), erythroderma (Pai 2017), hyperpigmentation (Bahloul 2017; Sharma 2020), pustular psoriasis (Chen 2023), skin photosensitivity (Sharma 2020), skin rash (Borik 2019), Stevens-Johnson syndrome (Leckie 2002), toxic epidermal necrolysis (Lateef 2009; Soria 2015)

Endocrine & metabolic: Hypoglycemia (including severe hypoglycemia; Cansu 2008; FDA Safety Alert, April 1, 2020; Shojania 1999; Unübol 2011)

Gastrointestinal: Abdominal cramps (Abdelmaseih 2020), diarrhea (can be severe) (Abdelmaseih 2020), nausea (Abdelmaseih 2020), vomiting (Abdelmaseih 2020)

Genitourinary: Proteinuria

Hematologic & oncologic: Agranulocytosis (Andrès 2017), neutropenia (FDA Safety Alert, April 1, 2020), pancytopenia (FDA Safety Alert, April 1, 2020), thrombotic thrombocytopenic purpura (Arikan 2020)

Hepatic: Acute hepatic failure (Makin 1994)

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Soria 2015; Volpe 2008)

Nervous system: Agitation, anxiety, confusion (FDA Safety Alert, April 1, 2020), delirium (FDA Safety Alert, April 1, 2020), delusion, depression, extrapyramidal reaction (FDA Safety Alert, April 1, 2020), hallucination (Das 2014; FDA Safety Alert, April 1, 2020), mania, paranoid ideation, psychomotor agitation (FDA Safety Alert, April 1, 2020; Manzo 2017), psychosis (Das 2014), sleep disturbance (including insomnia, nightmares, night terrors), suicidal ideation (Mascolo 2018; Pinho de Oliveira Ribeiro 2013), suicidal tendencies (Mascolo 2018; Pinho de Oliveira Ribeiro 2013)

Neuromuscular & skeletal: Myopathy (including paralysis or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups; may be associated with mild sensory changes, loss of deep tendon reflexes, and abnormal nerve conduction; Casado 2006)

Ophthalmic: Blurred vision (Wang 2021), corneal deposits (Grierson 1997), decreased visual acuity (Eldeeb 2018), epithelial keratopathy (Dosso 2007), macular degeneration (Wang 2021), maculopathy (Warner 2001), photophobia (Grierson 1997), retinal pigment changes (Stelton 2013), scotoma (Eldeeb 2018, Stelton 2013), vision color changes (Stelton 2013), visual disturbance (Grierson 1997), visual field defect (Warner 2001)

Otic: Sensorineural hearing loss (Fernandes 2018), tinnitus (Fernandes 2018)

Renal: Kidney impairment (FDA Safety Alert, April 1, 2020)

Respiratory: Pulmonary hypertension (Bae 2012)

Contraindications

Known hypersensitivity to hydroxychloroquine, 4-aminoquinoline derivatives, or any component of the formulation.

Canadian labeling: Additional contraindications (not in the US labeling): Preexisting retinopathy; use in children <6 years or weighing <35 kg

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction may be needed.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition (Jallouli 2012; MGFA 2020).

• Porphyria: Avoid use in patients with porphyria unless benefits outweigh risks; may exacerbate or precipitate disease. Use in patients with porphyria cutanea tarda (off-label use) has resulted in hepatotoxicity and presented with marked elevations in transaminases within days to one month after initiation of treatment. In some patients, porphyria cutanea tarda was diagnosed after hepatotoxicity occurred when hydroxychloroquine was used for an approved indication.

• Psoriasis: Avoid use in patients with psoriasis unless benefits outweigh risks; may exacerbate or precipitate disease.

• Renal impairment: Use with caution in patients with renal impairment; dosage reduction may be needed.

Special populations:

• Glucose-6-phosphate dehydrogenase deficiency: Although the manufacturer's labeling recommends hydroxychloroquine be used with caution in patients with G6PD deficiency due to a potential for hemolytic anemia, there are limited data to support this risk. Many experts consider hydroxychloroquine, when given in usual therapeutic doses to the World Health Organization Class II and III G6PD deficient patients, to probably be safe (Cappellini 2008; Luzzatto 2016; Youngster 2010). In a retrospective chart review, no incidence of hemolytic anemia was found among the 11 patients identified with G6PD deficiency receiving hydroxychloroquine therapy, despite >700 months of exposure (all patients were African American and located in the United States) (Mohammad 2018). In addition, the American College of Rheumatology guidelines for the treatment of rheumatoid arthritis do not mention the need to evaluate G6PD levels prior to initiation of therapy (ACR [Fraenkel 2021]).

• Pediatric: Pediatric patients have an increased sensitivity to aminoquinolines.

Dosage Forms: US

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

Tablet, Oral, as sulfate:

Plaquenil: 200 mg [contains corn starch]

Generic: 100 mg, 200 mg, 300 mg, 400 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Hydroxychloroquine Sulfate Oral)

100 mg (per each): $2.24 - $2.69

200 mg (per each): $1.28 - $4.36

300 mg (per each): $6.72 - $8.06

400 mg (per each): $8.96 - $10.75

Tablets (Plaquenil Oral)

200 mg (per each): $0.18

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

Dosage Forms: Canada

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

Tablet, Oral, as sulfate:

Plaquenil: 200 mg

Generic: 200 mg

Administration: Adult

Oral: Administer with food or milk. Do not crush or divide film-coated tablets per the manufacturer; the tablets have a bitter taste (Ref). In patients unable to swallow tablets, it has been recommended that tablets may be crushed and mixed with a small amount of applesauce, chocolate syrup, or jelly (Ref), or an extemporaneous suspension may be compounded (See Extemporaneously Prepared).

Administration: Pediatric

Oral: Administer with food or milk. Do not crush or divide film-coated tablets per the manufacturer; the tablets have a bitter taste (Ref). In patients unable to swallow tablets, it has been recommended that tablets may be crushed and mixed with a small amount of applesauce, chocolate syrup, or jelly (Ref), or an extemporaneous suspension may be compounded (See Extemporaneous Preparations).

Use: Labeled Indications

Lupus erythematosus: Treatment of chronic discoid erythematosus and systemic lupus erythematosus in adults.

Malaria: Treatment of uncomplicated malaria caused by susceptible strains of Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium falciparum; prophylaxis of malaria in geographic areas where chloroquine resistance is not reported. Note: The CDC guidelines also recommend hydroxychloroquine for chloroquine-sensitive Plasmodium knowlesi malaria (CDC 2020).

Limitations of use: Hydroxychloroquine is not effective against chloroquine- or hydroxychloroquine-resistant malaria strains of Plasmodium species; not recommended for treatment of complicated malaria, malaria prophylaxis in regions with chloroquine resistance, or treatment when the Plasmodium species has not been identified; hydroxychloroquine alone does not prevent relapses of P. vivax and P. ovale infections because it is not effective against the hypnozoite liver stage forms of these parasites.

Rheumatoid arthritis: Treatment of acute and chronic rheumatoid arthritis in adults.

Use: Off-Label: Adult

Dermatomyositis, cutaneous disease; Porphyria cutanea tarda; Primary Sjögren disease (extraglandular manifestations); Q fever (Coxiella burnetii); Sarcoidosis, arthropathy; Sarcoidosis, cutaneous disease, extensive

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

Hydroxychloroquine may be confused with hydroCHLOROthiazide, hydrocortisone, hydroxyurea

Plaquenil may be confused with Platinol

Metabolism/Transport Effects

Substrate of CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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

Agalsidase Alfa: Hydroxychloroquine may diminish the therapeutic effect of Agalsidase Alfa. Risk C: Monitor therapy

Agalsidase Beta: Hydroxychloroquine may diminish the therapeutic effect of Agalsidase Beta. Risk C: Monitor therapy

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

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

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

Azithromycin (Systemic): May enhance the cardiotoxic effect of Hydroxychloroquine. Risk C: Monitor therapy

ChlorproMAZINE: Antimalarial Agents may increase the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Hydroxychloroquine. Risk X: Avoid combination

Ciprofloxacin (Systemic): Hydroxychloroquine may enhance the hyperglycemic effect of Ciprofloxacin (Systemic). Hydroxychloroquine may enhance the hypoglycemic effect of Ciprofloxacin (Systemic). Hydroxychloroquine may enhance the QTc-prolonging effect of Ciprofloxacin (Systemic). Risk C: Monitor therapy

Citalopram: May enhance the hypoglycemic effect of Hydroxychloroquine. Hydroxychloroquine may enhance the QTc-prolonging effect of Citalopram. Risk C: Monitor therapy

CycloSPORINE (Systemic): Hydroxychloroquine may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification

Digoxin: Hydroxychloroquine may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Escitalopram: May enhance the hypoglycemic effect of Hydroxychloroquine. Hydroxychloroquine may enhance the QTc-prolonging effect of Escitalopram. Risk C: Monitor therapy

Gemifloxacin: Hydroxychloroquine may enhance the hyperglycemic effect of Gemifloxacin. Hydroxychloroquine may enhance the hypoglycemic effect of Gemifloxacin. Hydroxychloroquine may enhance the QTc-prolonging effect of Gemifloxacin. Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

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

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

Levofloxacin-Containing Products (Systemic): Hydroxychloroquine may enhance the hyperglycemic effect of Levofloxacin-Containing Products (Systemic). Hydroxychloroquine may enhance the hypoglycemic effect of Levofloxacin-Containing Products (Systemic). Hydroxychloroquine may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Risk C: Monitor therapy

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

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

Mefloquine: Aminoquinolines (Antimalarial) may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial. Risk X: Avoid combination

Metoprolol: Hydroxychloroquine may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

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

Moxifloxacin (Systemic): Hydroxychloroquine may enhance the hyperglycemic effect of Moxifloxacin (Systemic). Hydroxychloroquine may enhance the hypoglycemic effect of Moxifloxacin (Systemic). Hydroxychloroquine may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk C: Monitor therapy

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

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

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

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

Rabies Vaccine: Aminoquinolines (Antimalarial) may diminish the therapeutic effect of Rabies Vaccine. Management: If coadministration is unavoidable during rabies post-exposure vaccination, give a 5th dose of the rabies vaccine. If coadministration is unavoidable during rabies pre-exposure vaccination, ensure antibody titers are greater than or equal to 0.5 IU/mL. Risk D: Consider therapy modification

Remdesivir: Hydroxychloroquine may diminish the therapeutic effect of Remdesivir. Risk X: Avoid combination

RifAMPin: May diminish the therapeutic effect of Hydroxychloroquine. Risk X: Avoid combination

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

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

Sparfloxacin: Hydroxychloroquine may enhance the hyperglycemic effect of Sparfloxacin. Hydroxychloroquine may enhance the hypoglycemic effect of Sparfloxacin. Hydroxychloroquine may enhance the QTc-prolonging effect of Sparfloxacin. Risk C: Monitor therapy

Tamoxifen: May enhance the adverse/toxic effect of Hydroxychloroquine. Specifically, concomitant use of tamoxifen and hydroxychloroquine may increase the risk of retinal toxicity. Risk C: Monitor therapy

Reproductive Considerations

Hydroxychloroquine is recommended for use in patients with rheumatic and musculoskeletal diseases who are planning to become pregnant. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).

Information related to paternal use of hydroxychloroquine is limited; however, available data have not shown hydroxychloroquine adversely impacts male fertility or increases the risk of adverse pregnancy outcomes when used prior to conception (Bermas 2019; Mouyis 2019). Hydroxychloroquine is recommended for use in patients with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

Pregnancy Considerations

Hydroxychloroquine can be detected in the cord blood at delivery in concentrations similar to those in the maternal serum (Costedoat-Chalumeau 2002).

Adverse perinatal outcomes have not been associated with daily maternal doses of hydroxychloroquine ≤400 mg (Bérard 2021; Birru Talabi 2020; Costedoat-Chalumeau 2003; Diav-Citrin 2013; Huybrechts 2020). Retinal toxicity is a known risk following long-term use or high doses of hydroxychloroquine. Although animal reproduction studies have shown accumulation of chloroquine in fetal ocular tissues, an association between hydroxychloroquine and fetal ocular toxicity has not been confirmed in available human studies (Gaffar 2019; Levy 2001; Motta 2005; Osadchy 2011).

Maternal lupus is associated with adverse maternal and fetal events. If pregnancy is detected during therapy, hydroxychloroquine should not be stopped; cessation of hydroxychloroquine could precipitate a flare in maternal disease. Continued treatment is needed to control maternal disease and decrease the risk of maternal thrombosis and congenital heart block (Baer 2011; Izmirly 2012; Levy 2001; Petri 2020a; Tunks 2013).

Available guidelines recommend treatment with hydroxychloroquine for systemic lupus erythematosus (SLE) during pregnancy. Hydroxychloroquine may be beneficial for some pregnant patients with antiphospholipid syndrome (ACR [Sammaritano 2020]; EULAR [Andreoli 2017]).

Malaria infection in pregnant patients may be more severe than in nonpregnant patients and has a high risk of maternal and perinatal morbidity and mortality. Therefore, pregnant patients and patients who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant patients should take precautions to avoid mosquito bites and use effective prophylactic medications. Hydroxychloroquine is recommended for the treatment of uncomplicated malaria during pregnancy in chloroquine-sensitive regions (refer to current guidelines) (CDC 2020).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of hydroxychloroquine may be altered during pregnancy; however, dosage adjustments are not needed (Balevic 2019b). In one study, hydroxychloroquine concentrations ≤100 ng/mL correlated with increased disease activity and adverse maternal/fetal outcomes in patients with SLE, but there was no association between disease activity, pregnancy outcomes, and hydroxychloroquine blood levels in pregnant patients under treatment for LN (Balevic 2019a). Due to tissue binding, if hydroxychloroquine is discontinued, it would take 6 to 8 weeks to be completely eliminated.

Data collection to monitor pregnancy and infant outcomes following exposure to hydroxychloroquine is ongoing. Patients exposed to hydroxychloroquine while pregnant are encouraged to enroll in the pregnancy registry (1-877-311-8972).

Breastfeeding Considerations

Hydroxychloroquine and the desethylchloroquine metabolite are present in breast milk (Cissoko 2010; Costedoat-Chalumeau 2002; Nation 1984; Ostensen 1985; Peng 2019).

Breast milk concentrations of hydroxychloroquine were evaluated in 33 women. All women were treated with hydroxychloroquine for at least 1 year for various connective tissue diseases and were 1 to 16 weeks' postpartum. Maternal doses ranged from 200 mg every other day to 200 mg twice daily. Sampling occurred over a 12-hour dosing period. The average relative infant dose (RID) of hydroxychloroquine was calculated by the authors of the study to be 1.9% to 3.2% of the weight-adjusted maternal dose. The highest RID (9.8%) was observed in one woman taking hydroxychloroquine 200 mg twice daily (Peng 2019).

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

Infants exposed to hydroxychloroquine via breast milk following chronic maternal administration, including one infant who was exposed for 30 months (Cimaz 2004), have been monitored for adverse effects; no negative impact on vision, growth, development, or otherwise has been noted (Cimaz 2004; Motta 2002; Motta 2005; Peng 2019; Tincani 2001).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Hydroxychloroquine is considered to be compatible for use in breastfeeding mothers with rheumatic and musculoskeletal diseases (ACR [Sammaritano 2020]). Clinicians should note that when hydroxychloroquine is administered to breastfeeding patients for malaria, insufficient amounts are transferred via breast milk to provide chemoprophylaxis to the infant (CDC Yellow Book 2020).

Monitoring Parameters

Note: Determinants for laboratory testing (ie, specific tests to monitor and frequency) should take into consideration patient's clinical status and duration of therapy (short-term versus long-term).

CBC (with differential), liver function, and renal function at baseline and periodically during therapy; blood glucose (if symptoms of hypoglycemia occur); muscle strength (especially proximal, as a symptom of neuromyopathy) during long-term therapy; in patients at elevated risk of QTc prolongation, monitor ECG and serum electrolytes at baseline and as clinically indicated and correct any electrolyte imbalances to mitigate the risk of developing torsades de pointes; certain findings may require not initiating or discontinuing therapy. Serum concentration monitoring is recommended in the treatment of Q fever (CDC [Anderson 2013]).

Ophthalmologic exam at baseline (fundus examination within the first year plus visual fields and spectral-domain optical coherence tomography if maculopathy is present) to screen for retinal toxicity, followed by annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]). If ocular toxicity is suspected, monitor closely (retinal changes and visual disturbances may progress after drug discontinuation). Additionally, the manufacturer recommends an ocular exam include best corrected distance visual acuity and an automated threshold visual field of the central 10 degrees (24 degrees in patients of Asian ancestry as retinal toxicity may appear outside of the macula). Consider annual exams (without deferring 5 years) in patients with significant risk factors (eg, renal disease).

Reference Range

Data suggest that individual blood concentrations do not correlate closely with dosage, weight, or clinical effectiveness. However, blood levels may be useful in patients with renal disease or as an aid in assessing compliance (Melles 2014). One study suggested a correlation of blood concentrations with ocular toxicity (ie, highest tertile of 1,177 to 3,503 ng/mL) and suggested dosage reduction in these patients (Petri 2020b); however, routine testing is not recommended by some experts (Wallace 2020). For the treatment of Q fever, a target range of 0.8 to 1.2 mg/L is recommended (CDC [Anderson 2013]; Petri 2020b).

Mechanism of Action

Antimalarial: Interferes with digestive vacuole function within sensitive malarial parasites by increasing the pH and interfering with lysosomal degradation of hemoglobin; inhibits locomotion of neutrophils and chemotaxis of eosinophils; impairs complement-dependent antigen-antibody reactions.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Rheumatic disease: May require several weeks to respond

Absorption: Incomplete and variable (~70% [range: 25 to 100%]) (Tett 1993)

Protein binding: ~40%, primarily albumin (Tett 1993)

Metabolism: Hepatic; metabolites include bidesethylchloroquine, desethylhydroxychloroquine, and desethylchloroquine (McChesney 1966)

Half-life elimination: ~40 days (Tett 1993)

Excretion: Urine (15% to 25% [Tett 1993]; as metabolites and unchanged drug [up to 60%, McChesney 1966]); may be enhanced by urinary acidification

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Plaquenil;
  • (AR) Argentina: Axokine | Evoquin | Metirel | Narbon | Plaquenil;
  • (AU) Australia: Apo hydroxychloroquine | Apotex hydroxychloroquine | Hequinel | Hydroxychloroquine actavis | Hydroxychloroquine an | Hydroxychloroquine gh | Hydroxychloroquine rbx | Plaquenil | Terry white chemists hydroxychloroquine;
  • (BD) Bangladesh: Corofree | Kovicin | Quinivir | Reumaflex | Roxiquin;
  • (BE) Belgium: Plaquenil;
  • (BF) Burkina Faso: Immard;
  • (BG) Bulgaria: Morivid;
  • (BR) Brazil: Papilup | Plaquinol | Reuquinol | Sulfato de hidroxicloroquina;
  • (CH) Switzerland: Hydroxychloroquine Zentiva | Plaquenil;
  • (CL) Chile: Drolsan | Hidroxicloroquina | Ilinol | Parenquil | Plaquinol | Quinilen | Reumazine;
  • (CN) China: Fen le | Hydroxychloroquine | Plaquenil;
  • (CO) Colombia: Artroquin | Dimard | Dolquine | Hcqs | Hidroxicloroquina | Malarquin | Plaquinol;
  • (CZ) Czech Republic: Plaquenil;
  • (DE) Germany: Hydroxychloroquin aristo | Hydroxychloroquin axcount | Hydroxychloroquin heumann | Hydroxychloroquinsulfat Dr. Eberth | Plaquenil | Quensyl;
  • (DO) Dominican Republic: Corcirex | Hidroxicloroquina mamey | Plaquinol;
  • (EC) Ecuador: Concidor | Corcirex | Dimard | Etiquina | Hidroxicloroquina | Hidroxicloroquina bkf | Plaquinol;
  • (EE) Estonia: Hydroxychloroquine | Oxiklorin | Plaquenil;
  • (EG) Egypt: Futarhomal | Hydroquine | Plaquenil;
  • (ES) Spain: Dolquine | Duplaxil | Hidroxicloroquina aldo union | Hidroxicloroquina ratiopharm | Xanban;
  • (FI) Finland: Ercoquin | Oxiklorin;
  • (FR) France: Plaquenil;
  • (GB) United Kingdom: Hydroxychloroquine sulphate | Plaquenil | Quinoric;
  • (GR) Greece: Plaquenil | Plaquenil s;
  • (HK) Hong Kong: Apo hydroxyquine | Hcq | Plaquenil;
  • (HU) Hungary: Plaquenil;
  • (ID) Indonesia: Farneltik | Sanloquin;
  • (IE) Ireland: Plaquenil;
  • (IL) Israel: Plaquenil;
  • (IN) India: Axemal | Cartiquin | Coviq | Hcqs | Hetq | Hetquenil | Hiquine s | Hq fine | Hqtor | Hydire | Hydrocad | Hydroquin | Hydrowin | Imulast | Mcqs | Orthokind | Oxcq | Oxy q | Qdmrd | Ra quin | Rhq | Rutor | Vohq | Winflam | Zy q;
  • (IQ) Iraq: Plaquneer;
  • (IT) Italy: Idrossiclorochina Doc | Plaquenil;
  • (JO) Jordan: Advaquenil | Plaquenil;
  • (JP) Japan: Ercoquin | Plaquenil;
  • (KE) Kenya: Hcqs | Oxcq;
  • (KR) Korea, Republic of: Acyquin | Aruquin | Chloqueen | Duroc | Erquin | Folanil | Haloxin | Halrochrosin | Hydroquine | Hyrokin | Oxiklorin | Oxyquine | Rumaquine | Yuma;
  • (KW) Kuwait: Plaquenil;
  • (LB) Lebanon: Corvaquine | Dolquine | Plaquenil;
  • (LT) Lithuania: Plaquenil;
  • (LU) Luxembourg: Plaquenil;
  • (LV) Latvia: Plaquenil;
  • (MA) Morocco: Advaquenil;
  • (MX) Mexico: Himanix | Plaquenil;
  • (MY) Malaysia: Hcqs | Plaquenil | Uniquin;
  • (NL) Netherlands: Hydroxychloroquine | Hydroxychloroquinesulfaat focus | Plaquenil;
  • (NO) Norway: Ercoquin | Hydroxychloroquin | Plaquenil | Quinoric;
  • (NZ) New Zealand: Plaquenil;
  • (PE) Peru: Coronil | Droloquin | Hcqs | Hidroxicloroquina sulfato | Hidroxiplus | Plaquinol | Reumaquin;
  • (PH) Philippines: Hcqs | Plaquenil | Stalhyquin;
  • (PK) Pakistan: Alaska | Hcq | Hs 200 | Mcquine | Oxyclor | Plaquin h | Rheuquin | Roxyquin;
  • (PL) Poland: Duplaxil | Idrossiclorochina Doc | Plaquenil | Quensyl | Zy q;
  • (PR) Puerto Rico: Hydroxychloroquine | Plaquenil | Quineprox;
  • (PT) Portugal: Hidroxicloroquina | Plaquinol;
  • (PY) Paraguay: Hidroxicloroquina bioteng | Hidroxicloroquina dasanti | Hidroxicloroquina empa | Hidroxicloroquina heisecke | Hidroxicloroquina prosalud | Plaquinol | Supretic | Supretic forte;
  • (QA) Qatar: Advaquenil | Plaquenil;
  • (RU) Russian Federation: Hydroxychloroquine | Immard | Plaquenil;
  • (SA) Saudi Arabia: Apo hydroxychloroquine | Apo hydroxyquine | Arthosave | Plaquenil;
  • (SE) Sweden: Plaquenil;
  • (SG) Singapore: Haloxin | Plaquenil;
  • (SI) Slovenia: Hyplaxy | Quinoric;
  • (SK) Slovakia: Plaquenil;
  • (TH) Thailand: Hcqs | Hquine | Hydroquin | Plaquenil | Plaquenil sulfate | Quinnel | Zyquenil;
  • (TN) Tunisia: Plaquenil;
  • (TR) Turkey: Korokin | Plaquinol;
  • (TW) Taiwan: Be easy | Belian | Chloguin | Geniquin | Hydroquine | Lisen | Plaquenil | Plaquil;
  • (UA) Ukraine: Immard | Plaquenil | Xinoxis;
  • (UY) Uruguay: Evoquin | Hcqs | Metirel | Plaquinol;
  • (VE) Venezuela, Bolivarian Republic of: Plaquinol
  1. Abdel-Hamid H, Oddis CV, Lacomis D. Severe hydroxychloroquine myopathy. Muscle Nerve. 2008;38(3):1206‐1210. doi:10.1002/mus.21091 [PubMed 18720511]
  2. Abdelmaseih R, Abdelmasih R, Hasan M, Tadepalli S, Patel J. Serious adverse events associated with hydroxychloroquine amidst COVID-19 pandemic: case series and literature review. Cureus. 2020;12(6):e8415. doi:10.7759/cureus.8415 [PubMed 32626630]
  3. Abou Assalie N, Durcan R, Durcan L, Petri MA. Hydroxychloroquine-induced erythema multiforme. J Clin Rheumatol. 2017;23(2):127-128. doi:10.1097/RHU.0000000000000417 [PubMed 28099213]
  4. Agarwal V, Agrawal V, Aggarwal A, et al; Arthritis in Sarcoidosis Group (ASG). Arthritis in sarcoidosis: a multicentric study from India. Int J Rheum Dis. 2018;21(9):1728-1733. doi:10.1111/1756-185X.13349 [PubMed 30187668]
  5. Aggarwal R. Sarcoid arthropathy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 25, 2021.
  6. Anderson A, Bijlmer H, Fournier PE, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep. 2013;62(RR-03):1-30. [PubMed 23535757]
  7. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  8. Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76(3):476-485. doi:10.1136/annrheumdis-2016-209770 [PubMed 27457513]
  9. Ang GC, Werth VP. Combination antimalarials in the treatment of cutaneous dermatomyositis: a retrospective study. Arch Dermatol. 2005;141(7):855-859. doi: 10.1001/archderm.141.7.855 [PubMed 16027300]
  10. Arıkan F, Yıldız Y, Ercan T, et al. Hydroxychloroquine-associated thrombotic thrombocytopenic purpura. Turk J Haematol. 2020;37(4):302-304. doi:10.4274/tjh.galenos.2020.2020.0322 [PubMed 32702948]
  11. Avina-Zubieta JA, Johnson ES, Suarez-Almazor ME, Russell AS. Incidence of myopathy in patients treated with antimalarials. A report of three cases and a review of the literature. Br J Rheumatol. 1995;34(2):166‐170. doi:10.1093/rheumatology/34.2.166 [PubMed 7704464]
  12. Bae SM, Jung HO, Ihm SM, et al. Hydroxychloroquine-induced cardiomyopathy that presented as pulmonary hypertension: a newly noted complication. Cardiology. 2012;123(3):197-200. doi:10.1159/000343142 [PubMed 23154245]
  13. Baer AN, Vivino FB. Treatment of Sjögren's syndrome: Constitutional and non-sicca organ-based manifestations. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 15, 2019.
  14. Baer AN, Witter FR, Petri M. Lupus and Pregnancy. Obstet Gynecol Surv. 2011;66(10):639-653. [PubMed 22112525]
  15. Bahloul E, Jallouli M, Garbaa S, et al. Hydroxychloroquine-induced hyperpigmentation in systemic diseases: prevalence, clinical features and risk factors: a cross-sectional study of 41 cases. Lupus. 2017;26(12):1304‐1308. doi:10.1177/0961203317700486 [PubMed 28355984]
  16. Bailey K, McKee D, Wismer J, Shear N. Acute generalized exanthematous pustulosis induced by hydroxychloroquine: first case report in Canada and review of the literature. J Cutan Med Surg. 2013;17(6):414‐418. doi:10.2310/7750.2013.12105 [PubMed 24138979]
  17. Balevic SJ, Cohen-Wolkowiez M, Eudy AM, Green TP, Schanberg LE, Clowse MEB. Hydroxychloroquine levels throughout pregnancies complicated by rheumatic disease: implications for maternal and neonatal outcomes. J Rheumatol. 2019a;46(1):57-63. doi:10.3899/jrheum.180158 [PubMed 30275257]
  18. Balevic SJ, Green TP, Clowse MEB, Eudy AM, Schanberg LE, Cohen-Wolkowiez M. Pharmacokinetics of hydroxychloroquine in pregnancies with rheumatic diseases. Clin Pharmacokinet. 2019b;58(4):525-533. doi:10.1007/s40262-018-0712-z [PubMed 30255310]
  19. Barlow A, Landolf KM, Barlow B, et al. Review of emerging pharmacotherapy for the treatment of coronavirus disease 2019 [published online April 7, 2020]. Pharmacotherapy. doi:10.1002/phar.2398 [PubMed 32259313]
  20. Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J. 2021;58(6):2004079. doi:10.1183/13993003.04079-2020 [PubMed 34140301]
  21. Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973‐992. doi:10.1007/s40264-019-00825-2. [PubMed 31020549]
  22. Bérard A, Sheehy O, Zhao JP, Vinet E, Quach C, Bernatsky S. Chloroquine and hydroxychloroquine use during pregnancy and the risk of adverse pregnancy outcomes using real-world evidence. Front Pharmacol. 2021;12:722511. doi:10.3389/fphar.2021.722511 [PubMed 34408654]
  23. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) Recommendations For the Management of Adult and Paediatric Lupus Nephritis. Ann Rheum Dis. 2012;71(11):1771-1782. [PubMed 22851469]
  24. Birru Talabi M, Clowse MEB. Antirheumatic medications in pregnancy and breastfeeding. Curr Opin Rheumatol. 2020;32(3):238-246. doi:10.1097/BOR.0000000000000710 [PubMed 32205567]
  25. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183‐198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]
  26. Borik L, Petzelbauer P, Quint T, Wöhrl S, Kinaciyan T, Heil PM. Type IV allergy to antimalarials can mimic cutaneous manifestations of lupus erythematosus. J Eur Acad Dermatol Venereol. 2019;33(3):e94‐e96. doi:10.1111/jdv.15249 [PubMed 30223310]
  27. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94‐105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  28. Bustos MD, Gay F, Diquet B, Thomare P, Warot D. The pharmacokinetics and electrocardiographic effects of chloroquine in healthy subjects. Trop Med Parasitol. 1994;45(2):83‐86. [PubMed 7939166]
  29. Cansu DU, Korkmaz C. Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA. Rheumatology (Oxford). 2008;47(3):378-379. [PubMed 18222983]
  30. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371(9606):64-74. doi:10.1016/S0140-6736(08)60073-2 [PubMed 18177777]
  31. Caramaschi P, Barbazza R, Tinazzi I, Biasi D. Desensitization to hydroxychloroquine: 4 cases. J Rheumatol. 2011;38(10):2267. doi:10.3899/jrheum.110345 [PubMed 21965696]
  32. Carsons SE, Vivino FB, Parke A, et al. Treatment guidelines for rheumatologic manifestations of Sjögren's syndrome: use of biologic agents, management of fatigue, and inflammatory musculoskeletal pain. Arthritis Care Res (Hoboken). 2017;69(4):517-527. doi: 10.1002/acr.22968 [PubMed 27390247]
  33. Casado E, Gratacós J, Tolosa C, et al. Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients. Ann Rheum Dis. 2006;65(3):385‐390. doi:10.1136/ard.2004.023200 [PubMed 16096334]
  34. Centers for Disease Control and Prevention (CDC). CDC Yellow Book 2020: Health Information for International Travel. Oxford University Press; 2019.
  35. Centers for Disease Control and Prevention (CDC). Treatment of malaria: guidelines for clinicians (United States). https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html. Updated May 29, 2020. Accessed June 8, 2020.
  36. Charfi O, Kastalli S, Sahnoun R, Lakhoua G. Hydroxychloroquine-induced acute generalized exanthematous pustulosis with positive patch-testing. Indian J Pharmacol. 2015;47(6):693‐694. doi:10.4103/0253-7613.169589 [PubMed 26729969]
  37. Chatre C, Roubille F, Vernhet H, Jorgensen C, Pers YM. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018;41(10):919‐931. doi:10.1007/s40264-018-0689-4 [PubMed 29858838]
  38. Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila). 2006;44(2):173‐175. doi:10.1080/15563650500514558 [PubMed 16615675]
  39. Chen J, Falcone LM, Karunamurthy AD, Ho J, English JC 3rd. Hydroxychloroquine-induced repetitive atypical pustular drug eruptions in the same patient separated by 12 years. Clin Case Rep. 2023;11(7):e7677. Pdoi:10.1002/ccr3.7677 [PubMed 37484756]
  40. Chong WS, Tan HH, Tan SH. Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore. Clin Exp Dermatol. 2005;30(2):120-124. doi:10.1111/j.1365-2230.2005.01729.x [PubMed 15725234]
  41. Cimaz R, Brucato A, Meregalli E, Muscará M, Sergi P. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum. 2004;50(9):3056-3057; author reply 3057-3058. [PubMed 15457485]
  42. Cissoko HRJ, Zahr N, Darrouzain F, Jonville-Bera AP, Autret-Leca E. Breast milk concentrations of hydroxychloroquine. Fundam Clin Pharmacol. 2010;24(suppl 1):420. Abstract 420-106. doi.org/10.1111/j.1472-8206.2010.00819.x
  43. Clarke J. Initial management of discoid lupus erythematosus and subacute cutaneous lupus erythematosus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 5, 2020.
  44. Cosnes A, Amaudric F, Gherardi R, et al. Dermatomyositis without muscle weakness. Long-term follow-up of 12 patients without systemic corticosteroids. Arch Dermatol. 1995;131(12):1381-1385. doi: 10.1001/archderm.131.12.1381 [PubMed 7492125]
  45. Costedoat-Chalumeau N, Amoura Z, Aymard G, et al. Evidence of Transplacental Passage of Hydroxychloroquine in Humans. Arthritis Rheum. 2002;46(4):1123-1124. [PubMed 11953993]
  46. Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum. 2003;48(11):3207-3211. doi:10.1002/art.11304 [PubMed 14613284]
  47. Costedoat-Chalumeau N, Hulot JS, Amoura Z, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford). 2007;46(5):808-810. doi:10.1093/rheumatology/kel402 [PubMed 17202178]
  48. Costedoat-Chalumeau N, Isenberg D, Petri M. Letter in response to the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakis et al. Ann Rheum Dis. 2019;0:1.
  49. Das P, Rai A, Chopra A, Philbrick K. Psychosis likely induced by hydroxychloroquine in a patient with chronic Q fever: a case report and clinically relevant review of pharmacology. Psychosomatics. 2014;55(4):409‐413. doi:10.1016/j.psym.2013.06.017 [PubMed 24268495]
  50. Demarchi J, Papasidero S, Medina MA, et al. Primary Sjögren's syndrome: extraglandular manifestations and hydroxychloroquine therapy. Clin Rheumatol. 2017;36(11):2455-2460. doi:10.1007/s10067-017-3822-3 [PubMed 28913747]
  51. Diav-Citrin O, Blyakhman S, Shechtman S, Ornoy A. Pregnancy outcome following in utero exposure to hydroxychloroquine: a prospective comparative observational study. Reprod Toxicol. 2013;39:58-62. doi:10.1016/j.reprotox.2013.04.005 [PubMed 23602891]
  52. Dosso A, Rungger-Brändle E. In vivo confocal microscopy in hydroxychloroquine-induced keratopathy. Graefes Arch Clin Exp Ophthalmol. 2007; 245(2):318-320. [PubMed 16738856]
  53. Drugs for Parasitic Infections. Med Lett Drugs Ther. 1993;35(911):111-122. [PubMed 8246830]
  54. Duman H, Topal IO, Kocaturk E, Cure K, Mansuroglu I. Acute generalized exanthematous pustulosis induced by hydroxychloroquine: a case with atypical clinical presentation. An Bras Dermatol. 2017;92(3):404‐406. doi:10.1590/abd1806-4841.20175561 [PubMed 29186260]
  55. Eldeeb M, Chan EW, Omar A. Case report: hydroxychloroquine retinopathy. Optom Vis Sci. 2018;95(6):545-549. doi:10.1097/OPX.0000000000001226 [PubMed 29787487]
  56. Emery H. Clinical Aspects of Systemic Lupus Erythematosus in Childhood. Pediatr Clin North Am. 1986;33(5):1177-1190. [PubMed 3763254]
  57. Estes ML, Ewing-Wilson D, Chou SM, et al. Chloroquine neuromyotoxicity. Clinical and pathologic perspective. Am J Med. 1987;82(3):447‐455. doi:10.1016/0002-9343(87)90444-x [PubMed 3826099]
  58. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  59. Fanouriakis A, Bertsias G, Boumpas DT. Hydroxychloroquine dosing in systemic lupus erythematosus: response to 'Comment on the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus by Fanouriakis et al' by Costedoat-Chalumeau et al. Ann Rheum Dis. 2020;79(8):e91. [PubMed 31201171]
  60. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736-745. [PubMed 30926722]
  61. Fernandes MRN, Soares DBR, Thien CI, Carneiro S. Hydroxychloroquine ototoxicity in a patient with systemic lupus erythematosus. An Bras Dermatol. 2018;93(3):469-470. doi:10.1590/abd1806-4841.20187615 [PubMed 29924251]
  62. Fiehn C, Ness T, Weseloh C, et al. Safety management in treatment with antimalarials in rheumatology. Interdisciplinary recommendations on the basis of a systematic literature review. Z Rheumatol. Published online March 31, 2020. doi:10.1007/s00393-020-00785-4 [PubMed 32236844]
  63. Figliozzi S, Rizzo S, De Gaspari M, Tarantini G. End-stage heart failure secondary to low-dose hydroxychloroquine treatment. Eur Heart J. 2021;42(2):207. doi:10.1093/eurheartj/ehaa595 [PubMed 32725108]
  64. Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993;23(2)(suppl 1):S82-S91. [PubMed 8278823]
  65. Fox RI, Dixon R, Guarrasi V, Krubel S. Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus. 1996;5(suppl 1):S31-S36. [PubMed 8803908]
  66. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. doi:10.1002/acr.24596 [PubMed 34101387]
  67. Gaffar R, Pineau CA, Bernatsky S, Scott S, Vinet É. Risk of ocular anomalies in children exposed In utero to antimalarials: a systematic literature review. Arthritis Care Res (Hoboken). 2019;71(12):1606-1610. doi:10.1002/acr.23808 [PubMed 30418703]
  68. Giannini EH, Cawkwell GD. Drug Treatment in Children With Juvenile Rheumatoid Arthritis. Past, Present, and Future. Pediatr Clin North Am. 1995;42(5):1099-1125. [PubMed 7567188]
  69. Gonzalez CD, Hansen C, Clarke JT. Adverse cutaneous drug reactions with antimalarials in cutaneous lupus and dermatomyositis: A retrospective cohort study. J Am Acad Dermatol. 2019;81(3):859‐860. doi:10.1016/j.jaad.2019.04.068 [PubMed 31085265]
  70. Gottenberg JE, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA. 2014;312(3):249-258. doi:10.1001/jama.2014.7682 [PubMed 25027140]
  71. Gould FK, Denning DW, Elliott TS, et al. Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults: A Report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67(2):269-289. [PubMed 22086858]
  72. Grierson DJ. Hydroxychloroquine and visual screening in a rheumatology outpatient clinic. Ann Rheum Dis. 1997;56(3):188-190. doi:10.1136/ard.56.3.188 [PubMed 9135223]
  73. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology Guidelines For Screening, Treatment, and Management of Lupus Nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. [PubMed 22556106]
  74. Huybrechts KF, Bateman BT, Zhu Y, et al. Hydroxychloroquine early in pregnancy and risk of birth defects. Am J Obstet Gynecol. Published online September 19, 2020. doi:10.1016/j.ajog.2020.09.007 [PubMed 32961123]
  75. Hydroxychloroquine tablet [prescribing information]. Durham, NC: Accord Healthcare Inc; September 2019.
  76. Hydroxychloroquine tablet [prescribing information]. Princeton, NJ: Dr. Reddy's Laboratories Inc; May 2018.
  77. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  78. Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal Use of Hydroxychloroquine Is Associated With a Reduced Risk of Recurrent Anti-SSA/Ro-Antibody-Associated Cardiac Manifestations of Neonatal Lupus. Circulation. 2012;126(1):76-82. [PubMed 22626746]
  79. Jallouli M, Galicier L, Zahr N, et al; Plaquenil Lupus Systemic Study Group. Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(8):2176-2184. doi:10.1002/art.39194 [PubMed 25989906]
  80. Jallouli M, Saadoun D, Eymard B, et al. The association of systemic lupus erythematosus and myasthenia gravis: a series of 17 cases, with a special focus on hydroxychloroquine use and a review of the literature. J Neurol. 2012;259(7):1290‐1297. doi:10.1007/s00415-011-6335-z [PubMed 22160434]
  81. James WD, Dawson N, Rodman OG. The treatment of dermatomyositis with hydroxychloroquine. J Rheumatol. 1985;12(6):1214-1216. [PubMed 4093940]
  82. Jones E, Callen JP. Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. J Am Acad Dermatol. 1990;23(3, pt 1):487-489. doi: 10.1016/0190-9622(90)70246-e [PubMed 2212149]
  83. Jones SK. Ocular Toxicity and Hydroxychloroquine: Guidelines for Screening. Br J Derm. 1999;140(1):3-7. [PubMed 10215761]
  84. Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018;14(12):693‐703. doi:10.1038/s41584-018-0111-8 [PubMed 30401979]
  85. Joyce E, Fabre A, Mahon N. Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review. Eur Heart J Acute Cardiovasc Care. 2013;2(1):77‐83. doi:10.1177/2048872612471215 [PubMed 24062937]
  86. Kim S, Kahn P, Robinson AB, et al. Childhood Arthritis and Rheumatology Research Alliance consensus clinical treatment plans for juvenile dermatomyositis with skin predominant disease. Pediatr Rheumatol Online J. 2017;15(1):1. [PubMed 28077146]
  87. Kliegman RM and St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Saunders Elsevier; 2020.
  88. Kruize AA, Hené RJ, Kallenberg CG, et al. Hydroxychloroquine treatment for primary Sjögren's syndrome: a two year double blind crossover trial. Ann Rheum Dis. 1993;52(5):360-364. doi:10.1136/ard.52.5.360 [PubMed 8323383]
  89. Kuhn A, Aberer E, Bata-Csörgő Z, et al. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2017;31(3):389-404. doi:10.1111/jdv.14053 [PubMed 27859683]
  90. Kumar P, Banik S. Pharmacotherapy options in rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:35-43. doi:10.4137/CMAMD.S5558 [PubMed 23997576]
  91. Lam NC, Ghetu MV, Bieniek ML. Systemic lupus erythematosus: primary care approach to diagnosis and management. Am Fam Physician. 2016;94(4):284-294. [PubMed 27548593]
  92. Lateef A, Tan KB, Lau TC. Acute generalized exanthematous pustulosis and toxic epidermal necrolysis induced by hydroxychloroquine. Clin Rheumatol. 2009;28(12):1449‐1452. doi:10.1007/s10067-009-1262-4 [PubMed 19727917]
  93. Leckie MJ, Rees RG. Stevens-Johnson syndrome in association with hydroxychloroquine treatment for rheumatoid arthritis. Rheumatology (Oxford). 2002;41(4):473‐474. doi:10.1093/rheumatology/41.4.473 [PubMed 11961185]
  94. Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in Lupus Pregnancy: Double-Blind and Placebo-Controlled Study. Lupus. 2001;10(6):401-404. [PubMed 11434574]
  95. Luzzatto L, Nannelli C, Notaro R. Glucose-6-phosphate dehydrogenase deficiency. Hematol Oncol Clin North Am. 2016;30(2):373-393. doi:10.1016/j.hoc.2015.11.006 [PubMed 27040960]
  96. Makin AJ, Wendon J, Fitt S, Portmann BC, Williams R. Fulminant hepatic failure secondary to hydroxychloroquine. Gut. 1994;35(4):569-570. doi:10.1136/gut.35.4.569 [PubMed 8175002]
  97. Manzo C, Gareri P, Castagna A. Psychomotor agitation following treatment with hydroxychloroquine. Drug Saf Case Rep. 2017;4(1):6. doi:10.1007/s40800-017-0048-x [PubMed 28258476]
  98. Marks SD, Tullus K. Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis. Acta Paediatr. 2010;99(7):967-974. [PubMed 20222881]
  99. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology (AAO). Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-1394. doi: 10.1016/j.ophtha.2016.01.058 [PubMed 26992838]
  100. Mascolo A, Berrino PM, Gareri P, et al. Neuropsychiatric clinical manifestations in elderly patients treated with hydroxychloroquine: a review article. Inflammopharmacology. 2018;26(5):1141‐1149. doi:10.1007/s10787-018-0498-5 [PubMed 29948492]
  101. Mates M, Zevin S, Breuer GS, Navon P, Nesher G. Desensitization to hydroxychloroquine--experience of 4 patients. J Rheumatol. 2006;33(4):814‐816. [PubMed 16463436]
  102. Mavragani CP, Moutsopoulos NM, Moutsopoulos HM. The management of Sjögren's syndrome. Nat Clin Pract Rheumatol. 2006;2(5):252-261. doi:10.1038/ncprheum0165 [PubMed 16932698]
  103. McChesney EW, Conway WD, Banks WF, et al. Studies of the metabolism of some compounds of the 4-amino-7-chloroquinolone series. J Pharmacol Exp Ther. 1966;151(3):482-493. [PubMed 4957157]
  104. McLaughlin GE. Coated plaquenil tablets: potential risk for children? JAMA. 1991;266(20):2832. [PubMed 1942444]
  105. Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy [published correction appears in JAMA Ophthalmol. 2014;132(12):1493]. JAMA Ophthalmol. 2014;132(12):1453-1460. [PubMed 25275721]
  106. Million M, Walter G, Thuny F, Habib G, Raoult D. Evolution from acute Q fever to endocarditis is associated with underlying valvulopathy and age and can be prevented by prolonged antibiotic treatment. Clin Infect Dis. 2013;57(6):836-844. doi:10.1093/cid/cit419 [PubMed 23794723]
  107. Modi S, Rosen T. Micropapular cutaneous sarcoidosis: case series successfully managed with hydroxychloroquine sulfate. Cutis. 2008;81(4):351-354. [PubMed 18491485]
  108. Mohammad S, Clowse MEB, Eudy AM, Criscione-Schreiber LG. Examination of hydroxychloroquine use and hemolytic anemia in G6PDH-deficient patients. Arthritis Care Res (Hoboken). 2018;70(3):481‐485. doi:10.1002/acr.23296 [PubMed 28556555]
  109. Motta M, Tincani A, Faden D, Zinzini E, Chirico G. Antimalarial agents in pregnancy. Lancet. 2002;359(9305):524-525. [PubMed 11853823]
  110. Motta M, Tincani A, Faden D, et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25(2):86-89. [PubMed 15496869]
  111. Muthukrishnan P, Roukoz H, Grafton G, Jessurun J, Colvin-Adams M. Hydroxychloroquine-induced cardiomyopathy: a case report. Circ Heart Fail. 2011;4(2):e7‐e8. doi:10.1161/CIRCHEARTFAILURE.110.959916 [PubMed 21406675]
  112. Myasthenia Gravis Foundation of America (MGFA). Drugs and MG: Cautionary Drugs. https://myasthenia.org/Portals/0/Cautionary_Drugs_2020_1.pdf. Accessed June 17, 2020
  113. Nation RL, Hackett LP, Dusci LJ, Ilett KF. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol. 1984;17(3):368-369.
  114. National Institute for Health and Care Excellence (NICE). Drug allergy: diagnosis and management. Clinical guideline [CG183]. September 3, 2014. https://www.nice.org.uk/guidance/cg183. Accessed May 26, 2020.
  115. O'Dell JR, Mikuls TR, Taylor TH, et al; CSP 551 RACAT Investigators. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307-318. doi:10.1056/NEJMoa1303006 [PubMed 23755969]
  116. O'Laughlin JP, Mehta PH, Wong BC. Life threatening severe QTc prolongation in patient with systemic lupus erythematosus due to hydroxychloroquine. Case Rep Cardiol. 2016;2016:4626279. doi:10.1155/2016/4626279 [PubMed 27478650]
  117. Olson NY, Lindsley CB. Adjunctive use of hydroxychloroquine in childhood dermatomyositis. J Rheumatol. 1989;16(12):1545-1547. [PubMed 2483176]
  118. Osadchy A, Ratnapalan T, Koren G. Ocular Toxicity in Children Exposed in utero to Antimalarial Drugs: Review of the Literature. J Rheumatol. 2011;38(12):2504-2508. [PubMed 22002012]
  119. Østensen M, Brown ND, Chiang PK, et al. Hydroxychloroquine in Human Breast Milk. Eur J Clin Pharmacol. 1985;28(3):357. [PubMed 4007043]
  120. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-e69. [PubMed 27400984]
  121. Pai SB, Sudershan B, Kuruvilla M, Kamath A, Suresh PK. Hydroxychloroquine-induced erythroderma. Indian J Pharmacol. 2017;49(1):132-134. doi:10.4103/0253-7613.201027 [PubMed 28458440]
  122. Pelle MT, Callen JP. Adverse cutaneous reactions to hydroxychloroquine are more common in patients with dermatomyositis than in patients with cutaneous lupus erythematosus. Arch Dermatol. 2002;138(9):1231‐1233. doi:10.1001/archderm.138.9.1231 [PubMed 12224986]
  123. Peng W, Liu R, Zhang L, Fu Q, Mei D, Du X. Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases. Eur J Clin Pharmacol. 2019;75(11):1547-1553. doi:10.1007/s00228-019-02723-z [PubMed 31375884]
  124. Pereira A, Cruz-Melguizo S, Adrien M, Fuentes L, Marin E, Perez-Medina T. Clinical course of coronavirus disease-2019 in pregnancy. Acta Obstet Gynecol Scand. Published online May 22, 2020. doi:10.1111/aogs.13921 [PubMed 32441332]
  125. Petri M, Elkhalifa M, Li J, Magder LS, Goldman DW. Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy. Arthritis Rheumatol. 2020b;72(3):448-453. doi:10.1002/art.41121 [PubMed 31532077]
  126. Petri M. Pregnancy and systemic lupus erythematosus. Best Pract Res Clin Obstet Gynaecol. 2020a;64:24-30. doi:10.1016/j.bpobgyn.2019.09.002 [PubMed 31677989]
  127. Pinho de Oliveira Ribeiro N, Rafael de Mello Schier A, Ornelas AC, Pinho de Oliveira CM, Nardi AE, Silva AC. Anxiety, depression and suicidal ideation in patients with rheumatoid arthritis in use of methotrexate, hydroxychloroquine, leflunomide and biological drugs. Compr Psychiatry. 2013;54(8):1185‐1189. doi:10.1016/j.comppsych.2013.05.010 [PubMed 23829886]
  128. Plaquenil (hydroxychloroquine) [prescribing information]. Dublin, Ireland: Concordia Pharmaceuticals Inc; July 2023.
  129. Plaquenil (hydroxychloroquine) tablets, USP [product monograph]. Laval, Quebec, Canada: Sanofi-aventis Canada Inc; January 2023.
  130. Prystowsky S, Sanchez M. Cutaneous sarcoidosis: Management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2021.
  131. Rath T, Rubbert A. Drug combinations with methotrexate to treat rheumatoid arthritis. Clin Exp Rheumatol. 2010;28(5)(suppl 61):S52-S57. [PubMed 21044434]
  132. Refer to manufacturer's labeling.
  133. Riley K, Schwager Z, Stern M, Vleugels RA, Femia A. Assessment of antimalarial therapy in patients who are hypersensitive to hydroxychloroquine. JAMA Dermatol. 2019;155(4):491‐493. doi:10.1001/jamadermatol.2018.5212 [PubMed 30758479]
  134. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013‐1022. doi:10.1056/NEJMra032426 [PubMed 14999113]
  135. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529-556. doi:10.1002/art.41191 [PubMed 32090480]
  136. Sharma AN, Mesinkovska NA, Paravar T. Characterizing the adverse dermatologic effects of hydroxychloroquine: a systematic review. J Am Acad Dermatol. 2020;83(2):563-578. doi:10.1016/j.jaad.2020.04.024 [PubMed 32289395]
  137. Shojania K, Koehler BE, Elliott T. Hypoglycemia induced by hydroxychloroquine in a type II diabetic treated for polyarthritis. J Rheumatol. 1999;26(1):195‐196. [PubMed 9918262]
  138. Singal AK, Kormos-Hallberg C, Lee C, et al. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2012;10(12):1402-1409. doi:10.1016/j.cgh.2012.08.038 [PubMed 22985607]
  139. Singal AK, Anderson KE. Porphyria cutanea tarda and hepatoerythropoietic porphyria: Management and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 19, 2023.
  140. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1-26. doi:10.1002/art.39480 [PubMed 26545940]
  141. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis [published correction appears in Lancet. 2016;388(10055):1984]. Lancet. 2016;388(10055):2023-2038. doi:10.1016/S0140-6736(16)30173-8 [PubMed 27156434]
  142. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655 [PubMed 31969328]
  143. Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509. doi:10.1136/annrheumdis-2013-204573 [PubMed 24161836]
  144. Soria A, Barbaud A, Assier H, et al. Cutaneous adverse drug reactions with antimalarials and allergological skin tests. Dermatology. 2015;231(4):353‐359. doi:10.1159/000438787 [PubMed 26457932]
  145. Stas P, Faes D, Noyens P. Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. Int J Cardiol. 2008;127(2):e80‐e82. doi:10.1016/j.ijcard.2007.04.055 [PubMed 17590456]
  146. Stelton CR, Connors DB, Walia SS, Walia HS. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clin Rheumatol. 2013;32(6):895-898. doi:10.1007/s10067-013-2226-2 [PubMed 23515601]
  147. Takamasu E, Yokogawa N, Shimada K, Sugii S. Simple dose-escalation regimen for hydroxychloroquine-induced hypersensitivity reaction in patients with systemic lupus erythematosus enabled treatment resumption. Lupus. 2019;28(12):1473‐1476. doi:10.1177/0961203319879987 [PubMed 31575325]
  148. Tal Y, Maoz Segal R, Langevitz P, Kivity S, Darnizki Z, Agmon-Levin N. Hydroxychloroquine desensitization, an effective method to overcome hypersensitivity-a multicenter experience. Lupus. 2018;27(5):703‐707. doi:10.1177/0961203317735185 [PubMed 28992797]
  149. Targoff IN. Initial treatment of dermatomyositis and polymyositis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 24, 2022.
  150. Telgt DS, van der Ven AJ, Schimmer B, Droogleever-Fortuyn HA, Sauerwein RW. Serious psychiatric symptoms after chloroquine treatment following experimental malaria infection. Ann Pharmacother. 2005;39(3):551‐554. doi:10.1345/aph.1E409 [PubMed 15728331]
  151. Tett SE. Clinical pharmacokinetics of slow-acting antirheumatic drugs. Clin Pharmacokinet. 1993;25(5):392-407. doi:10.2165/00003088-199325050-00005 [PubMed 7904547]
  152. Thorbinson C, Oni L, Smith E, Midgley A, Beresford MW. Pharmacological management of childhood-onset systemic lupus erythematosus. Paediatr Drugs. 2016;18(3):181-195. [PubMed 26971103]
  153. Tincani A, Faden D, Lojacono A, et al. Hydroxychloroquine in pregnant patients with rheumatic disease. Arthritis Rheum. 2001;44 (Suppl 9):S397.
  154. Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2013;6(4):479‐487. doi:10.1161/CIRCOUTCOMES.113.000152 [PubMed 23716032]
  155. Tisdale JE, Jaynes HA, Kingery JR, et al. Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2014;7(3):381‐390. doi:10.1161/CIRCOUTCOMES.113.000651 [PubMed 24803473]
  156. Tönnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy - a review of the literature. Immunopharmacol Immunotoxicol. 2013;35(3):434‐442. doi:10.3109/08923973.2013.780078 [PubMed 23635029]
  157. Tönnesmann E, Stroehmann I, Kandolf R, et al. Cardiomyopathy caused by longterm treatment with chloroquine: a rare disease, or a rare diagnosis? J Rheumatol. 2012;39(5):1099‐1103. doi:10.3899/jrheum.110959 [PubMed 22550010]
  158. Travassos M, Laufer MK. Antimalarial drugs: An overview. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 15, 2019.
  159. Tsang-A-Sjoe MW, Bultink IE. Systemic lupus erythematosus: review of synthetic drugs. Expert Opin Pharmacother. 2015;16(18):2793-2806. doi:10.1517/14656566.2015.1101448 [PubMed 26479437]
  160. Tunks RD, Clowse ME, Miller SG, Brancazio LR, Barker PC. Maternal autoantibody levels in congenital heart block and potential prophylaxis with antiinflammatory agents. Am J Obstet Gynecol. 2013;208(1):64.e1-64.e647. doi:10.1016/j.ajog.2012.09.020 [PubMed 23063019]
  161. Unübol M, Ayhan M, Guney E. Hypoglycemia induced by hydroxychloroquine in a patient treated for rheumatoid arthritis. J Clin Rheumatol. 2011; 17(1):46-47. [PubMed 21169846 ]
  162. Vleugels RA. Cutaneous dermatomyositis in adults: Overview and initial management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 21, 2020.
  163. Volpe A, Marchetta A, Caramaschi P, Biasi D, Bambara LM, Arcaro G. Hydroxychloroquine-induced DRESS syndrome. Clin Rheumatol. 2008;27(4):537‐539. doi:10.1007/s10067-007-0772-1 [PubMed 17952481]
  164. Wallace DJ. Antimalarial drugs in the treatment of rheumatic disease. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 25, 2022.
  165. Wang C, Fortin PR, Li Y, Panaritis T, Gans M, Esdaile JM. Discontinuation of antimalarial drugs in systemic lupus erythematosus. J Rheumatol. 1999;26(4):808‐815. [PubMed 10229401]
  166. Wang G, Zhuo N, Liao Z, et al. Retinal toxicity caused by hydroxychloroquine in patients with systemic lupus erythematosus: a case report. Medicine (Baltimore). 2021;100(22):e25688. doi:10.1097/MD.0000000000025688 [PubMed 34087822]
  167. Warner AE. Early hydroxychloroquine macular toxicity. Arthritis Rheum. 2001;44(8):1959-1961. doi:10.1002/1529-0131(200108)44:8<1959::AID-ART334>3.0.CO;2-A [PubMed 11508449]
  168. Wolstencroft PW, Casciola-Rosen L, Fiorentino DF. Association between autoantibody phenotype and cutaneous adverse reactions to hydroxychloroquine in dermatomyositis. JAMA Dermatol. 2018;154(10):1199‐1203. doi:10.1001/jamadermatol.2018.2549 [PubMed 30140893]
  169. World Health Organization (WHO). Guidelines for the Treatment of Malaria. 3rd ed. Geneva, Switzerland: World Health Organization; April 2015. https://apps.who.int/iris/bitstream/handle/10665/162441/9789241549127_eng.pdf;jsessionid=5E6B69DD1F9A124C2DFEA30D5F8D6E8E?sequence=1. Accessed August 15, 2019.
  170. World Health Organization (WHO). International travel and health. World Health Organization; 2012. Available at https://www.who.int/publications/i/item/9789241580472
  171. World Health Organization (WHO). The cardiotoxicity of antimalarials. Geneva, Switzerland: World Health Organization; March 2017. https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxicity-report-session2.pdf. Accessed May 26, 2020.
  172. Woo TY, Callen JP, Voorhees JJ, Bickers DR, Hanno R, Hawkins C. Cutaneous lesions of dermatomyositis are improved by hydroxychloroquine. J Am Acad Dermatol. 1984;10(4):592-600. doi: 10.1016/s0190-9622(84)80263-7 [PubMed 6715608]
  173. Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Saf. 2010;33(9):713-726. doi:10.2165/11536520-000000000-00000 [PubMed 20701405]
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