II. Indications
- Second-Line DMARD in Rheumatoid Arthritis
- Especially Antinuclear Antibody positive
- May be used in triple combination with Methotrexate and Sulfasalazine
- Indicated in moderate to severe disease refractory to single conventional synthetic DMARD
- Systemic Lupus Erythematosus
-
Malaria Prophylaxis and treatment
- Regions without Chloroquine resistance, non-severe infections
- Rheumatologic off-label uses
- Infectious off-label uses
- NOT indicated in COVID-19 outside of Clinical Trials
- Initial studies as of May 2020 suggest no benefit and adverse effect risk (including QTc Prolongation)
III. Contraindications
-
G6PD Deficiency
- Risk of Hemolytic Anemia
IV. Mechanism
- Antimalarial agent used in rheumatic disease
- Modified Chloroquine to reduce Retinopathy risk
- Blocks Sodium and Potassium channels
V. Dosing: Rheumatologic Disorders
- Varies significantly based on use
- Lower doses are used in infectious disease
- Dosing: Adults
- Initial: 400 to 600 mg (may consider starting at 200 mg) orally twice daily
- Maximum: 600 mg/day
- Expect symptom improvement by 2 to 4 months (discontinue if no effect by 6 months)
- Taper after 1-2 years when stable to 200 mg orally daily
VI. Dosing: Malaria
-
Malaria Prophylaxis
- Start 1-2 weeks before travel and continue for 4 weeks after leaving Malaria endemic region
- Adult: 400 mg salt (310 mg base) orally once weekly
- Child: 6.5 mg/kg salt (5 mg/kg base up to adult dose) orally once weekly
-
Malaria Treatment
- Adult: 800 mg salt (620 mg base) to start, then 400 mg salt (310 mg base) at 6, 24 and 48 hours after initial dose
- Child: 12.9 mg/kg salt (10 mg/kg base) to start, then 6.5 mg/kg salt (5 mg/kg mg base) at 6, 24 and 48 hours after initial dose
VII. Precautions
- One tablet may be lethal in children (lethal dose 30 mg/kg)
- Considered safe in pregnancy (all trimesters), despite initially labeled category D
VIII. Adverse Effects
- Eye-related Adverse Effects
- Epithelial Keratopathy and other Corneal disorders
- Retinopathy
- Uncommon to Rare (contrast with Chloroquine)
- Neurologic adverse effects
- Early toxicity (subsides within 2 weeks)
- Late toxicity requires medication discontinuation
- Tinnitus
- Decreased Hearing acuity
- Very rare toxicity
- Myopathy or muscular weakness
- Other adverse effects
- Confusion or Delirium
- Extrapyramidal Side Effects
- Hallucinations
- Seizures
- Gastrointestinal adverse effects
- Endocrine Adverse Effects
- Hematologic Adverse Effects
-
Electrolyte adverse effects
- Hypokalemia (in toxicity)
- Cardiovascular adverse effects
- Palpitations
- Hypotension (in toxicity)
- Premature Atrial Contractions
- Cardiomyopathy
- QRS Widening (in toxicity)
- QTc Prolongation (with risk of Ventricular Tachycardia or Drug-Induced Torsades de Pointes)
- Increased risk when combined with other agents causing QTc Prolongation (e.g. Azithromycin)
IX. Pharmacokinetics
- Onset: 2-4 hours after oral dose
- Half-Life: 20 to 40 days
- Lethal dose in young children as low as 750 mg
X. Efficacy: Rheumatoid Arthritis
- Response in 70-80% of cases
- Response occurs in 3-6 months
- Highest efficacy when used early in disease process
XI. Safety
- Considered safe in Lactation
- In pregnany, use if benefit outweighs risk
- Monitoring
- Routine Eye Exam every 6-12 months (including a baseline exam)
- Complete Blood Count (CBC) periodically
XII. Management: Hydroxychloroquine Overdose or Toxicity
- See ABC Management
- Activated Charcoal if <1 hour from ingestion and patient maintaining own airway
- Ventricular Arrhythmia
- Cardioversion
- Lidocaine
-
Wide QRS
- Bicarbonate (caution if Hypokalemia)
-
Hypokalemia
- Potassium Replacement (caution)
- Seizures
- Hypotension
- Other measures
- ECMO (refractory cardiovascular failure)
XIII. Resources
- Hydroxychloroquine Tablet (DailyMed)
XIV. References
- (2020) LexiComp, Hydroxychloroquine, accessed 5/6/2020
- Tomaszekski (2020) Crit Dec Emerg Med 14(4):32
- Matteson (2000) Mayo Clin Proc 75:669-74 [PubMed]
- Pincus (1999) Clin Rheumatol 17(6 Suppl 18):S2-S124 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
hydroxychloroquine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
HYDROXYCHLOROQUINE 100 MG TAB | Generic | $0.18 each |
HYDROXYCHLOROQUINE 200 MG TAB | Generic | $0.21 each |
Ontology: Hydroxychloroquine (C0020336)
Definition (NCI) | A 4-aminoquinoline with immunosuppressive, antiautophagy, and antimalarial activities. Although the precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines. As a lysosomotropic agent, hydroxychloroquine raises intralysosomal pH, impairing autophagic protein degradation; hydroxychloroquine-mediated accumulation of ineffective autophagosomes may result in cell death in tumor cells reliant on autophagy for survival. In addition, this agent is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum but not the gametocytes of P. falciparum. |
Definition (NCI_NCI-GLOSS) | A substance that decreases immune responses in the body. It is used to treat some autoimmune diseases, and is being studied as a treatment for graft-versus-host disease. Hydroxychloroquine belongs to the family of drugs called antiprotozoals. |
Definition (MSH) | A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) |
Definition (PDQ) | A 4-aminoquinoline with antimalarial and immunosuppressive properties. Although its precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines. This agent is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum but not the gametocytes of P. falciparum. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38571&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38571&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C557" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | D006886 |
SnomedCT | 373540008, 83490000 |
LNC | LP16163-5, MTHU016851 |
English | Hydroxychlorochin, Hydroxychloroquine, Oxychlorochin, Oxychloroquine, ethanol, 2-((4-((7-chloro-4-quinolinyl)amino)pentyl)ethylamino)-, Hydroxychloroquine [Chemical/Ingredient], HYDROXYCHLOROQUINE, hydroxychloroquine, Hydroxychloroquine (product), Hydroxychloroquine (substance), HCQ |
Swedish | Hydroxiklorokin |
Czech | hydroxychlorochin |
Finnish | Hydroksiklorokiini |
Russian | GIDROKSIKHLOROKHIN, OKSIKHLOROKHIN, PLAKVENIL, ГИДРОКСИХЛОРОХИН, ОКСИХЛОРОХИН, ПЛАКВЕНИЛ |
Polish | Hydroksychlorochina |
Japanese | オキシクロロキン, ヒドロキシクロロキン |
Spanish | hidroxicloroquina (producto), hidroxicloroquina (sustancia), hidroxicloroquina, Hidroxicloroquina, Oxicloroquina |
French | Hydroxychloroquine |
German | Hydroxychlorochin, Hydroxychloroquin, Oxychlorochin, Oxychloroquin |
Italian | Idrossiclorochina |
Portuguese | Hidroxicloroquina, Oxicloroquina |
Ontology: Plaquenil (C0699177)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | D006886 |
English | Plaquenil Sulfate, plaquenil sulfate, plaquenil, Plaquenil |