Hydroxychloroquine

Generic Name

Hydroxychloroquine sulfate

Brand Names

Plaquenil

Hydroquin

Axemal

Quensyl

Dolquine

Formulations include film-coated oral tablets (most commonly 200 mg base equivalent to 155 mg base)

Drug Class

Aminoquinoline derivative

Antimalarial agent

Disease-modifying antirheumatic drug (DMARD)

Immunomodulator

Lysosomotropic agent

Mechanism of Action

Hydroxychloroquine exerts multiple pharmacodynamic actions depending on the disease context

In Malaria

Interferes with the lysosomal function of the Plasmodium parasite within red blood cells by accumulating in parasite food vacuoles

Inhibits polymerization of heme to hemozoin leading to toxic accumulation of free heme and parasite death

In Autoimmune Diseases

Accumulates in lysosomes and raises their pH, interfering with antigen presentation and TLR (Toll-like receptor) signaling

Suppresses proinflammatory cytokines such as TNF-α, IL-1, and IL-6

Inhibits autoantigen processing by dendritic cells

Reduces autoantibody production

Has photoprotective and antithrombotic properties

Indications

Approved and widely used for:

– Rheumatoid arthritis (RA)

– Systemic lupus erythematosus (SLE)

– Discoid lupus erythematosus

– Juvenile idiopathic arthritis

– Malaria prophylaxis and treatment (P. vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum)

Off-label uses:

– Sjögren's syndrome

– Dermatomyositis

– Porphyria cutanea tarda

– COVID-19 (off-label, investigational only, not recommended due to lack of efficacy and cardiac risks)

– Chronic Q fever endocarditis (with doxycycline)

– Antiphospholipid syndrome (as adjunct to reduce thrombotic risk)

Dosage and Administration

Rheumatoid Arthritis / Lupus

Initial: 400–600 mg daily (can be split into 2 doses)

Maintenance: 200–400 mg daily

Maximum dose should not exceed 5 mg/kg actual body weight per day (to reduce retinopathy risk)

Malaria Prophylaxis

Adults: 400 mg once weekly, starting 1–2 weeks before travel and continued for 4 weeks after return

Malaria Treatment

800 mg single dose, followed by 400 mg after 6–8 hours, then 400 mg daily for 2 more days (total dose: 2 g over 3 days)

Pediatric Dose

Dose based on body weight (5–6.5 mg/kg/day, not exceeding adult dose)

Used under specialist supervision

Administration Notes

Take with food or milk to reduce GI upset

Do not crush or chew the tablet

Regular ophthalmologic monitoring is required

Pharmacokinetics

Bioavailability: ~70%

Extensively distributed in tissues (skin, eyes, spleen, liver, kidney, lungs)

Highly protein bound

Half-life: ~40–50 days

Metabolized hepatically via CYP enzymes (CYP3A4, CYP2D6, CYP2C8)

Excreted renally (partially unchanged)

Contraindications

Hypersensitivity to hydroxychloroquine or 4-aminoquinoline compounds

Pre-existing retinopathy involving visual field changes

Children <6 years or those unable to swallow tablets (malaria-related)

Caution in patients with G6PD deficiency (risk of hemolysis)

Warnings and Precautions

Ophthalmologic Effects

Retinal toxicity and irreversible retinopathy possible with prolonged use

Risk factors: daily dose >5 mg/kg, duration >5 years, renal impairment, elderly, pre-existing retinal disease

Baseline and annual retinal exams recommended

Cardiac Effects

QT prolongation, torsades de pointes especially when used with other QT-prolonging drugs

Caution in patients with arrhythmias or structural heart disease

Can cause cardiomyopathy with chronic use

Neuropsychiatric Effects

Dizziness, seizures, hallucinations, agitation

Rare cases of psychosis and suicidal ideation

Myopathy and Neuropathy

Proximal muscle weakness and sensory neuropathy with prolonged use

Hypoglycemia

May enhance insulin and oral hypoglycemic effects

Monitor blood glucose levels in diabetics

Hematologic Effects

Rare: anemia, leukopenia, thrombocytopenia

Periodic CBC monitoring advised

Hepatic and Renal Impairment

Dose adjustment may be needed

Monitor liver enzymes and renal function periodically

Dermatologic

Photosensitivity, skin hyperpigmentation, pruritus, alopecia, exfoliative dermatitis

Gastrointestinal

Nausea, vomiting, diarrhea, abdominal cramps

Usually dose-dependent and mild

Adverse Effects

Very Common to Common

Gastrointestinal: nausea, vomiting, diarrhea

Skin: rash, pruritus, pigment changes

Eye: blurred vision, corneal deposits

CNS: headache, dizziness

Uncommon to Rare

Retinopathy

QT prolongation and arrhythmias

Cardiomyopathy

Neuropsychiatric symptoms (confusion, hallucinations, mood change)

Muscle weakness, peripheral neuropathy

Hematologic suppression

Hepatitis

Exfoliative skin reactions

Pregnancy and Lactation

Pregnancy Category

Safe for use in pregnancy for autoimmune diseases

No evidence of increased birth defects

Used throughout pregnancy in SLE to reduce flare risk

Lactation

Excreted in breast milk in small amounts

Considered compatible with breastfeeding by most rheumatology and obstetric societies

Drug Interactions

QT-Prolonging Agents

Additive QT prolongation with amiodarone, macrolides (e.g., azithromycin), fluoroquinolones, antipsychotics

Avoid combination or monitor ECG closely

CYP Inhibitors / Inducers

CYP3A4 inhibitors (e.g., ketoconazole) may increase levels

CYP inducers (e.g., rifampicin, phenytoin) may reduce effectiveness

Antidiabetic Agents

Potentiates hypoglycemic effect

Monitor blood glucose closely

Digoxin

May increase digoxin serum concentrations

Monitor digoxin levels

Methotrexate

Increased hepatotoxicity risk with concurrent use

Monitor liver function tests regularly

Antacids and Kaolin

May reduce hydroxychloroquine absorption

Separate administration by at least 4 hours

Monitoring Parameters

– Baseline and annual retinal exam (visual acuity, visual fields, OCT)

– CBC, LFTs, renal function every 3–6 months

– Blood glucose in diabetic patients

– ECG for patients with cardiac risk factors

– Muscle strength if symptoms develop

Counseling Points

Take with food or milk

Report visual disturbances immediately

Do not exceed prescribed dose

Avoid concurrent QT-prolonging drugs

Use sun protection due to photosensitivity risk

Inform physician before initiating other medications

Comparative Notes

Hydroxychloroquine vs Chloroquine

Hydroxychloroquine has a better safety profile

Less retinal toxicity and GI upset

More widely used in rheumatologic diseases

Hydroxychloroquine vs Methotrexate

Methotrexate more potent in RA, but hydroxychloroquine has fewer systemic toxicities

Often used in combination

Hydroxychloroquine vs Biologic DMARDs

Hydroxychloroquine is milder in effect

Used in early or mild disease or combined with other DMARDs before escalation to biologics

Legal and Regulatory Status

Prescription-only

Included in WHO Essential Medicines List

Tightly monitored for use in autoimmune diseases and malaria

Not approved or recommended for routine COVID-19 treatment due to safety concerns