Johns Hopkins ABX Guide
Hydroxychloroquine
INDICATIONS
FDA
- Indicated for the suppressive treatment and treatment of uncomplicated malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum
- NOTE: ineffective against chloroquine-resistant strains of P. falciparum, and do not use for complicated malaria, resistant infection, infections acquired where chloroquine resistance occurs, or malaria of unidentified species.
- Treatment of discoid and systemic lupus erythematosus, and rheumatoid arthritis
NON-FDA APPROVED USES
- Q fever (chronic, in combination with antibiotics)
- Whipple’s disease(in combination with antibiotics)
- Brucellosis (in combination with antibiotics, investigational)
FORMS
brand name | preparation | manufacturer | route | form | dosage | cost* |
Plaquenil; Sovuna | Hydroxychloroquine sulfate (HCQ) | Multiple manufacturers | PO | tablet | 100 mg | Generic: $0.17 |
PO | tablet | 200 mg | Generic: $0.30-$6.45 Brand (Plaquenil): $13.49 Brand (Sovuna): $16.13 | |||
PO | tablet | 300 mg | Generic: $0.51 Brand (Sovuna): $16.13 | |||
PO | tablet | 400 mg | Generic: $0.69 |
*Prices represent the cost per unit specified and are representative of "Average Wholesale Price" (AWP).
USUAL ADULT DOSING
200 mg of hydroxychloroquine sulfate = 155 mg base
- Malaria: treatment of chloroquine-susceptible infection.
- Treatment: 800 mg (620 mg base) at time 0, followed by 400 mg (310 mg base) at 6 h, 24 h and 48 h
- For P. vivax or P. ovale, anti-relapse therapy with primaquine or tafenoquine after quantitative G6PD testing.
- Do not use HCQ for severe malaria or malaria acquired where chloroquine resistance is expected.
- Uncomplicated P. falciparum only when infection was acquired in a chloroquine-sensitive area
- Current CDC specifically identifies Central America west of the Panama Canal, Haiti, and the Dominican Republic.
- P. vivax: HCQ is generally appropriate for chloroquine-sensitive P. vivax acquired outside Papua New Guinea or Indonesia; chloroquine resistance has been reported sporadically elsewhere.
- P. malariae or P. knowlesi should ideally be confirmed as monoinfection before using HCQ.
- P. knowlesi: hospitalization/close monitoring is advised because of potential rapid progression.
- Uncomplicated P. falciparum only when infection was acquired in a chloroquine-sensitive area
- Prophylaxis: 400 mg PO once weekly, beginning 1–2 weeks before travel, weekly during exposure, and for 4 weeks after leaving.
- Use only in areas with chloroquine-sensitive malaria.
- Treatment: 800 mg (620 mg base) at time 0, followed by 400 mg (310 mg base) at 6 h, 24 h and 48 h
- Persistent focalized Q fever (“chronic Q fever”), particularly endocarditis or vascular infection:
- Doxycycline: 100 mg PO q12h plus HCQ PO 200 mg q8h
- If clinical/serologic response is suboptimal, some experts monitor HCQ plasma concentrations (target 0.8–1.2 mg/L).
- Duration:
- Native-valve endocarditis: ≥18 months
- Prosthetic-valve endocarditis: ≥24 months.
- Vascular infection: generally ≥18 months
- Individualize according to clinical and serologic response.
- Doxycycline: 100 mg PO q12h plus HCQ PO 200 mg q8h
- Whipple’s disease:
- Doxycycline 100 mg PO q12h plus hydroxychloroquine 200 mg PO q12h for 12 months.
- This oral regimen was noninferior to ceftriaxone followed by TMP-SMX in a 2025 randomized trial.[2]
- Assess for CNS involvement; in the 2025 trial, patients with CSF PCR positivity received additional TMP-SMX until CSF clearance.
- This oral regimen was noninferior to ceftriaxone followed by TMP-SMX in a 2025 randomized trial.[2]
- Doxycycline 100 mg PO q12h plus hydroxychloroquine 200 mg PO q12h for 12 months.
- Brucellosis:
- HCQ has been studied as an adjunct to doxycycline plus streptomycin and may reduce treatment failure or relapse.
- Evidence remains limited and of very low certainty, and HCQ is not part of standard guideline-recommended therapy.
- HCQ has been studied as an adjunct to doxycycline plus streptomycin and may reduce treatment failure or relapse.
- Rheumatologic diseases: offered as examples of use in non-infectious diseases
- Lupus erythematosus: 200 once or twice daily to 400 mg once daily for several weeks to months, depending on patient response. Maintenance therapy is usually 200-400 mg daily to minimize toxicity.
- Rheumatoid arthritis: 400 to 600 mg daily
- Once a good response is obtained, reduce the dose to 200 to 400 mg daily.
ADULT RENAL DOSING
DOSING IN HEMODIALYSIS
Usual dose, unlikely to be dialyzable.
DOSING IN PERITONEAL DIALYSIS
Usual dose, unlikely to be dialyzable.
DOSING IN RENAL REPLACEMENT THERAPY
Usual dose, unlikely to be dialyzable.
Other Adult Renal Dosing Information
Usual dosing. The manufacturer recommends no renal adjustment; however, use caution in patients with renal impairment. Close monitoring for adverse events (e.g., retinal toxicity) with long-term use and high doses is recommended.
PEDIATRIC DOSING
USUAL PEDIATRIC DOSING
200 mg of hydroxychloroquine sulfate = 155 mg base; all doses below are expressed as hydroxychloroquine sulfate
- Malaria: see adult dosing for provisos.
- Treatment (Infants, children and adolescents): 12.9 mg/kg at time 0 (maximum initial dose = 800 mg), followed by 6.5 mg/kg at 6 h, 24 h, and 48 h after initial dose (maximum subsequent dose = 400 mg)
- Prophylaxis (infants, children and adolescents): 6.5 mg/kg weekly (maximum dose = 400 mg), start 1-2 weeks before exposure, weekly while in endemic region and continue for at least 4 weeks after leaving an endemic area.
- Juvenile rheumatoid arthritis (JRA) or systemic lupus erythematosus (SLE): 2 - 6 mg/kg/day divided into 1 - 2 doses (maximum 400 mg/day, some experts recommend a maximum of 5 mg/kg/day to mitigate risk of retinal toxicity).
PEDIATRIC RENAL DOSING
The manufacturer recommends no renal adjustment; however, use caution in patients with renal impairment. Close monitoring for adverse effects (ex., retinal toxicity) with long-term use and high doses is recommended.
OTHER PEDIATRIC INFORMATION
Administer with food or milk. Do not crush or divide film-coated tablets.
ADVERSE DRUG REACTIONS
GENERAL
- Warnings/Contraindications:
- Known hypersensitivity to 4-aminoquinolines.
- Long-term hydroxychloroquine use is a risk and requires monitoring in patients with preexisting retinopathy of the eye.
- Preexisting retinal/macular disease increases concern for retinal toxicity and may complicate screening.
- Use of hydroxychloroquine in patients with psoriasis may precipitate a severe attack of psoriasis.
COMMON
- Headache
- Gastrointestinal complaints (diarrhea, anorexia, nausea, abdominal cramps and, on rare occasions, vomiting)
- Blurring of vision due to a disturbance of accommodation; reversible and dose-dependent
- Skin rash, pruritus
OCCASIONAL
- Dizziness
- Abnormal liver function tests
- Sensory-motor disorders
- Nervousness
- Hydroxychloroquine can prolong the PR, QRS and QTc intervals, especially in patients with underlying risk factors or use in combination with other QT-prolonging drugs.
- In one systematic review of cardiac toxicity (n=127), conduction disorders were the most common.
- The median duration of treatment was 7 years (min 3 days –max of 35 years)[8].
RARE
- Cutaneous hypersensitivity reactions, ranging from maculopapular rash to severe cutaneous adverse reactions (SCARs), including AGEP, DRESS, SJS and TEN
- Cardiomyopathy have been rarely reported with high or prolonged doses of hydroxychloroquine
- Severe hypoglycemia
- Bone marrow suppression
- Fulminant hepatic failure
- Extrapyramidal reactions
- Suicidal behavior
- Retinal toxicity is generally dose-related and NOT reversible.
- Risk increases with daily doses > 5 mg/kg actual body weight, duration >5 years, renal impairment, concurrent tamoxifen, concurrent macular disease, and older age at HCQ initiation.[1]
- Recommends baseline OCT/FAF soon after therapy begins and annual screening while therapy continues, although screening can be deferred during the first 5 years in low-risk patients.
- Risk increases with daily doses > 5 mg/kg actual body weight, duration >5 years, renal impairment, concurrent tamoxifen, concurrent macular disease, and older age at HCQ initiation.[1]
- Pigmentary changes in skin and mucous membranes, bleaching of hair, and alopecia
- Hemolytic anemia has been reported in G6PD deficiency; monitor for hemolysis.
- A small retrospective series found no HCQ-associated hemolysis among 11 G6PD-deficient patients, but numbers were insufficient to establish safety[9].
DRUG INTERACTIONS
Drug | Effect of Interaction | Recommendations/Comments |
Antacids | Antacids may reduce the absorption of hydroxychloroquine | Separate co-administration by 4-hour interval |
Antidiabetic drugs and insulin | Hydroxychloroquine may enhance the effects of a hypoglycemic treatment | Reduction in doses of antidiabetic agents may be needed |
Antiepileptic drugs | The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine | Monitor for seizures if coadministration can not be avoided |
Cimetidine | Cimetidine can inhibit the metabolism of chloroquine and increase serum concentrations, which would also be expected for hydroxychloroquine. | Avoid combination if possible or monitor for toxicity if the combination can not be avoided |
Cyclosporin | An increased plasma cyclosporine level was reported with co-administration with hydroxychloroquine | Monitor cyclosporine serum levels in patients receiving |
Digoxin | Hydroxychloroquine may increase digoxin serum levels | Monitor digoxin serum levels in patients receiving |
Co-administration of hydroxychloroquine with other antimalarials that are known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions | Avoid co-administration if possible or monitor for seizures if co-administration cannot be avoided | |
Chloroquine has been reported to reduce the bioavailability of praziquantel, which would also be expected for hydroxychloroquine | Avoid coadministration | |
Chloroquine can reduce antibody responses to intradermal pre-exposure rabies vaccination, and use the intramuscular route during concurrent chloroquine therapy. Unclear if the same would occur with hydroxychloroquine. | Use the IM route for rabies vaccination during chloroquine therapy; clinical significance with HCQ is uncertain. |
SPECTRUM
- Active against erythrocytic forms of chloroquine-susceptible P. falciparum, P. vivax, P. ovale, and P. malariae.
- HCQ may also be used for confirmed P. knowlesi monoinfection.
- In Q fever and Whipple disease, HCQ acts as an adjunct by raising the pH of acidic intracellular vacuoles, thereby enhancing antimicrobial activity against C. burnetii and T. whipplei.
RESISTANCE
HCQ has no activity against dormant hepatic hypnozoites of P. vivax or P. ovale; radical cure therefore requires primaquine or tafenoquine. Widespread chloroquine resistance among P. falciparum; high prevalence of chloroquine-resistant P. vivax in Papua New Guinea and Indonesia.
PHARMACOLOGY
MECHANISM
- Hydroxychloroquine belongs to the 4-aminoquinoline antimalarial class. Like chloroquine, it is a weak base and may act by concentrating the parasite’s acidic vesicles and inhibiting heme polymerization, although the exact mechanism against Plasmodium remains unknown.
- It accumulates in lymphocytes and macrophages, resulting in anti-inflammatory properties, which is the main reason for its use in rheumatoid arthritis and lupus erythematosus.
- HCQ has no clinical role in the treatment or prevention of COVID-19
PHARMACOKINETIC PARAMETERS
Absorption
HCQ is rapidly absorbed after oral administration; the mean fraction absorbed is ~74%, with peak concentrations at ~3–4 h.
Metabolism and Excretion
- Urine excretion of the unchanged drug was ~16-30% and did not correlate with creatinine clearance.
- Urine levels remained detectable after 3 months.
- Hydroxychloroquine is metabolized in the liver into 3 oxidative metabolites: bidesethyhydroxylchloroquine, desethylhydroxychloroquine, and desethylchloroquine.
Protein Binding
~50%
T1/2
Terminal half-life = 40-50 days
Distribution
Extensive tissue uptake and a large volume of distribution. The highest tissue distribution is in the choroid and ciliary body of the eye.
DOSING FOR DECREASED HEPATIC FUNCTION
- Use with caution in patients with hepatic impairment. The manufacturer recommends no dosing adjustment, but a reduction in dosage may be necessary
PREGNANCY RISK
- Available human data have not identified an increased risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes. HCQ crosses the placenta. HCQ may be used during pregnancy when indicated, including for chloroquine-sensitive malaria.
BREASTFEEDING COMPATIBILITY
HCQ occurs in breast milk at low concentrations, and published experience has found no reported retinal, ototoxic, cardiac, growth, or developmental adverse effects in breastfed infants.
COMMENTS
- Hydroxychloroquine is a hydroxy-analog of chloroquine that is better tolerated.
- Initially developed for malaria treatment, it has been shown over the years also to have immunomodulatory properties and has been used to treat autoimmune diseases such as rheumatoid arthritis and lupus.
- Decades of use in chronic inflammatory conditions and malaria prophylaxis find the drug generally well tolerated when appropriately dosed and monitored.
- Cumulative retinal and cardiac toxicities are important with prolonged therapy.
- Retinopathy is one of the most serious adverse events associated with hydroxychloroquine, and it is typically irreversible [see ADR section].
- Cumulative retinal and cardiac toxicities are important with prolonged therapy.
Malaria: Globally, artemisinin-based combination therapies (ACTs) are preferred for most P. falciparum malaria.
- For chloroquine-susceptible non-falciparum malaria, WHO recommends either an ACT or chloroquine.
- HCQ is an alternative to chloroquine where appropriate.
- P. vivax/P. ovale additionally require anti-relapse therapy with an 8-aminoquinoline.
- Do not use HCQ for severe malaria.
References
- Marmor MF, Ahn SJ, Ehlers JP, et al. Special AAO Report: Recommendations on Screening for Hydroxychloroquine Retinopathy (2025 Revision). Ophthalmology. 2026;133(4):439-450. [PMID:41232611]
Comment: 2025 AAO revision: recommends HCQ ≤5 mg/kg/day based on actual body weight; renal disease, tamoxifen use, and older age at initiation increase risk. Baseline OCT/FAF is advised soon after starting therapy; annual OCT/FAF screening may be deferred during the first 5 years only in patients without significant risk factors.
OCT = optical coherence tomography — cross-sectional retinal imaging that can detect early structural damage, especially parafoveal or pericentral photoreceptor/RPE changes.
FAF = fundus autofluorescence — imaging of retinal pigment epithelium function that can show characteristic areas of abnormal autofluorescence from HCQ toxicity. - Moos V, Krüger J, Allers K, et al. Oral treatment of Whipple's disease with doxycycline and hydroxychloroquine versus intravenous therapy with ceftriaxone followed by oral trimethoprim-sulfamethoxazole in Germany: a phase 2/3, prospective, open-label, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2025;25(7):788-800. [PMID:39978372]
Comment: Phase 2/3 open-label randomized noninferiority trial of adults with classic Whipple disease. Oral doxycycline 100 mg BID + HCQ 200 mg BID for 12 months was noninferior to ceftriaxone for 14 days followed by TMP-SMX for 12 months; complete remission without recurrence occurred in 28/29 (97%) vs 25/31 (81%), with no relapses. CSF PCR-positive patients in the oral arm received additional TMP-SMX until clearance.
- Delahaye A, Eldin C, Bleibtreu A, et al. Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial. J Antimicrob Chemother. 2024;79(8):1725-1747. [PMID:38888195]
Comment: Comprehensive 2024 review of doxycycline-HCQ for persistent focalized Q fever. The regimen has the most clinical experience, but supporting evidence remains largely in vitro and observational, as no randomized clinical trials have shown superiority over alternative regimens.
- Silva SN, Cota G, Xavier DM, et al. Efficacy and safety of therapeutic strategies for human brucellosis: A systematic review and network meta-analysis. PLoS Negl Trop Dis. 2024;18(3):e0012010. [PMID:38466771]
Comment: Systematic review/network meta-analysis of 31 RCTs (4167 patients). Doxycycline-streptomycin-HCQ was associated with lower treatment failure than doxycycline-streptomycin (RR 0.08; 95% CI 0.01–0.76), but the certainty of evidence was very low. HCQ remains investigational if considered, rather than standard therapy.
- Daily JP, Minuti A, Khan N. Diagnosis, Treatment, and Prevention of Malaria in the US: A Review. JAMA. 2022;328(5):460-471. [PMID:35916842]
Comment: Clinical review of malaria diagnosis, treatment, and prevention, emphasizing species and geographic susceptibility, ACTs for falciparum malaria, IV artesunate for severe malaria, and the need for anti-relapse therapy for P. vivax/P. ovale.
- Desmarais J, Rosenbaum JT, Costenbader KH, et al. American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity. Arthritis Rheumatol. 2021;73(12):2151-2160. [PMID:34697918]
Comment: The American College of Rheumatology publication addressing hydroxychloroquine cardiac toxicity, noting hydroxychloroquine and chloroquine are both associated with QT prolongation by directly affecting cardiac repolarization and long-term use may lead to cardiomyopathy with arrhythmias and heart failure. Prescribing clinicians should be cognizant of this effect, especially with concomitant QTc-prolonging medications.
- Majzoobi MM, Hashemi SH, Mamani M, et al. Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind, randomized clinical trial. Int J Antimicrob Agents. 2018;51(3):365-369. [PMID:28826825]
Comment: Single-blind RCT (n=177) comparing doxycycline-streptomycin with or without HCQ; adjunctive HCQ was associated with higher clinical response and lower relapse, but the finding remains insufficient to establish HCQ as standard brucellosis therapy.
- Chatre C, Roubille F, Vernhet H, et al. Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature. Drug Saf. 2018;41(10):919-931. [PMID:29858838]
Comment: A systematic review of reported CQ/HCQ cardiotoxicity found conduction disorders to be the most common, typically after prolonged exposure. Evidence derives largely from case reports/series and is subject to reporting bias.
- Mohammad S, Clowse MEB, Eudy AM, et al. Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients. Arthritis Care Res (Hoboken). 2018;70(3):481-485. [PMID:28556555]
Comment: In a retrospective review of 275 patients who had G6PD levels measured and were on hydroxychloroquine, only 11 patients (4%) were G6PD deficient (all African American). Two patients developed hemolysis while they were not taking hydroxychloroquine. No hemolysis was reported in more than 700 months of hydroxychloroquine exposure among the 11 G6PD-deficient patients. Such small numbers should not imply a lack of a safety signal.
- Million M, Thuny F, Richet H, et al. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis. 2010;10(8):527-35. [PMID:20637694]
Comment: Long-term observational cohort of 104 patients with Q-fever endocarditis. Findings support doxycycline-HCQ for 18 months for native-valve and 24 months for prosthetic-valve infection, with longer therapy guided by serologic response.
- Raoult D, Houpikian P, Tissot Dupont H, et al. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999;159(2):167-73. [PMID:9927100]
Comment: Comparative observational study (35 patients) in which doxycycline-HCQ was associated with fewer relapses and shorter treatment duration than doxycycline-ofloxacin; foundational but nonrandomized evidence supporting the regimen.
- CDC Yellow Book™: Health Information for International Travel. 2026
Comment: Current travel-medicine guidance for HCQ chemoprophylaxis and drug-vaccine interactions. HCQ is an alternative to chloroquine only in chloroquine-sensitive areas; concomitant chloroquine can reduce responses to intradermal rabies vaccine, so IM vaccination is recommended.
- Label: HYDROXYCHLOROQUINE SULFATE tablet, film coated. [revised 12/2025; accessed 9/10/26].
Comment:
Current U.S. prescribing information covering malaria indications/dosing, retinal and cardiac toxicity, drug interactions, pregnancy/lactation, and product-specific pediatric administration limitations. - WHO Guidelines for Malaria, August 2025
Comment:
Current WHO global malaria guideline. ACTs are preferred for falciparum malaria; in areas with chloroquine-susceptible non-falciparum malaria, either ACTs or chloroquine may be used, with anti-relapse therapy required for P. vivax/P. ovale. - CDC. Clinical Guidance for Q fever. [revised 3/5/2025, accessed 9/10/2026].
Comment:
Current CDC clinical guidance for acute and chronic Q fever. For endocarditis or vascular infection, it recommends doxycycline 100 mg q12h plus HCQ 200 mg q8h for at least 18 months, with duration guided by clinical and serologic response. - CDC Guidelines for the treatment of malaria: [https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html] (accessed 8/28/2026).
Comment: Current CDC malaria treatment tables. HCQ is an option for chloroquine-sensitive uncomplicated malaria. P. vivax/P. ovale additionally require anti-relapse therapy with primaquine or tafenoquine after quantitative G6PD testing. HCQ should not be used for severe malaria.
Rating: Important
