Hydroxychloroquine

Aka: Hydroxychloroquine, Plaquenil

1. Indications
   1. Early Rheumatoid Arthritis
      1. Especially Antinuclear Antibody positive
   2. Systemic Lupus Erythematosus
   3. Malaria Prophylaxis and treatment
      1. Regions without Chloroquine resistance, non-severe infections
   4. Rheumatologic off-label uses
      1. Dermatomyositis
      2. Sjogren Syndrome
      3. Sarcoidosis
   5. Infectious off-label uses
      1. Q Fever
   6. NOT indicated in COVID-19 outside of clinical trials
      1. Initial studies as of May 2020 suggest no benefit and adverse effect risk (including QTc Prolongation)
2. Mechanism
   1. Antimalarial agent used in rheumatic disease
   2. Modified Chloroquine to reduce Retinopathy risk
   3. Blocks Sodium and Potassium channels
3. Pharmacokinetics
   1. Onset: 2-4 hours after oral dose
   2. Elimination Half-Life: 12 hours
4. Efficacy: Rheumatoid Arthritis
   1. Response in 70-80% of cases
   2. Response occurs in 3-6 months
   3. Highest efficacy when used early in disease process
5. Dose: Rheumatologic Disorders
   1. Varies significantly based on use
      1. Lower doses are used in infectious disease
   2. Initial: 200 mg orally twice daily
   3. Taper after 1-2 years when stable: 200 mg PO qd
6. Dose: Malaria
   1. Malaria Prophylaxis
      1. Start 1-2 weeks before travel and continue for 4 weeks after leaving Malaria endemic region
      2. Adult: 400 mg salt (310 mg base) orally once weekly
      3. Child: 6.5 mg/kg salt (5 mg/kg base up to adult dose) orally once weekly
   2. Malaria Treatment
      1. 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
      2. 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
7. Precautions
   1. One tablet may be lethal in children (lethal dose 30 mg/kg)
   2. Considered safe in pregnancy (all trimesters), despite initially labeled category D
8. Adverse Effects
   1. Eye-related Adverse Effects
      1. Epithelial Keratopathy and other Corneal disorders
      2. Retinopathy
         1. Rare (contrast with Chloroquine)
   2. Neurologic adverse effects
      1. Early toxicity (subsides within 2 weeks)
         1. Irritability
         2. Insomnia
         3. Headache
      2. Late toxicity requires medication discontinuation
         1. Tinnitus
         2. Decreased Hearing acuity
      3. Very rare toxicity
         1. Myopathy or muscular weakness
      4. Other adverse effects
         1. Confusion or Delirium
         2. Extrapyramidal Side Effects
         3. Hallucinations
         4. Seizures
   3. Gastrointestinal adverse effects
      1. Increased stool frequency
      2. Diarrhea
      3. Bloating
      4. Nausea or Vomiting
   4. Endocrine Adverse Effects
      1. Hypoglycemia
   5. Hematologic Adverse Effects
      1. Neutropenia
      2. Pancytopenia
   6. Electrolyte adverse effects
      1. Hypokalemia (in toxicity)
   7. Cardiovascular adverse effects
      1. Palpitations
      2. Hypotension (in toxicity)
      3. Premature Atrial Contractions
      4. QRS Widening (in toxicity)
      5. QTc Prolongation (with risk of Ventricular Tachycardia or Drug-Induced Torsades de Pointes)
         1. Increased risk when combined with other agents causing QTc Prolongation (e.g. Azithromycin)
9. Monitoring
   1. Routine Eye Exam every 6-12 months
10. Management: Overdose or Toxicity
    1. See ABC Management
    2. Activated Charcoal if <1 hour from ingestion and patient maintaining own airway
    3. Ventricular Arrhythmia
       1. Cardioversion
       2. Lidocaine
    4. Wide QRS
       1. Bicarbonate (caution if Hypokalemia)
    5. Hypokalemia
       1. Potassium Replacement (caution)
    6. Seizures
       1. Benzodiazepines
    7. Hypotension
       1. Norepinephrine
    8. Other measures
       1. ECMO (refractory cardiovascular failure)
11. References
    1. (2020) LexiComp, Hydroxychloroquine, accessed 5/6/2020
    2. Tomaszekski (2020) Crit Dec Emerg Med 14(4):32
    3. Matteson (2000) Mayo Clin Proc 75:669-74 [PubMed]
    4. Pincus (1999) Clin Rheumatol 17(6 Suppl 18):S2-S124 [PubMed]