Usage
Hydroxychloroquine is prescribed for the treatment and prevention of certain types of malaria, as well as autoimmune diseases such as rheumatoid arthritis, lupus erythematosus (both systemic and discoid), and juvenile idiopathic arthritis. It is also being investigated for use in other conditions.
It’s pharmacologically classified as an antimalarial and disease-modifying antirheumatic drug (DMARD).
Hydroxychloroquine’s mechanism of action is complex and not fully understood. In malaria, it interferes with the parasite’s ability to utilize heme, a compound toxic to the parasite. In autoimmune diseases, it appears to modulate the immune system by suppressing certain immune cell functions, including cytokine production and antigen presentation.
Alternate Names
The generic name is hydroxychloroquine. Brand names include Plaquenil, Quinoric, and others.
How It Works
Pharmacodynamics: Hydroxychloroquine exerts its antimalarial effect by interfering with the detoxification of heme into hemozoin within the malaria parasite’s food vacuole. The accumulation of heme disrupts parasite metabolism, leading to its death. In autoimmune conditions, hydroxychloroquine reduces the activity of immune cells involved in inflammation by impairing toll-like receptor signaling, antigen processing, and cytokine production.
Pharmacokinetics: Hydroxychloroquine is well-absorbed orally. It’s extensively distributed to tissues, with high concentrations found in the liver, lungs, kidneys, and eyes. The drug is metabolized in the liver and eliminated primarily in the urine, with a long half-life of 40-50 days.
Mode of Action: At the cellular level, hydroxychloroquine affects various processes within immune cells, including inhibiting antigen presentation by interfering with intracellular trafficking and decreasing T-cell activation. It may also stabilize lysosomal membranes and interfere with DNA and RNA synthesis.
Receptor Binding/Enzyme Inhibition: Hydroxychloroquine interacts with various cellular components. It inhibits toll-like receptor 7 and 9 activation, which play a role in innate immunity. It also appears to interact with tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) pathways, thus modulating inflammatory responses.
Elimination Pathways: Hydroxychloroquine is primarily excreted unchanged in the urine. Hepatic metabolism contributes to a lesser extent.
Dosage
Standard Dosage
Adults:
- Malaria Treatment: 800 mg (sulfate salt) initially, followed by 400 mg at 6, 24, and 48 hours. Some regimens use a single dose of 800 mg.
- Malaria Prevention: 400 mg weekly, starting two weeks before travel to a malarious area and continuing for four weeks after leaving.
- Rheumatoid Arthritis/Lupus: 400-600 mg daily initially, adjusted to a maintenance dose of 200-400 mg daily based on response. The maximum dose should not exceed 6.5 mg/kg/day based on ideal body weight.
Children:
- Malaria Treatment: 13 mg/kg (up to 800 mg) initially, followed by 6.5 mg/kg (up to 400 mg) at 6, 24, and 48 hours.
- Malaria Prevention: 6.5 mg/kg (up to 400 mg) weekly, as with adult prophylaxis.
- Juvenile Idiopathic Arthritis: Dosing should be individualized based on the child’s weight and condition, not exceeding 6.5 mg/kg/day of ideal body weight.
Special Cases:
- Elderly Patients: Use with caution and consider dose adjustments based on renal and hepatic function.
- Patients with Renal Impairment: Dose reduction may be required.
- Patients with Hepatic Dysfunction: Use with caution and consider dose reduction.
- Patients with Comorbid Conditions: Carefully evaluate coexisting conditions, especially cardiac disease, diabetes, and other autoimmune disorders.
Clinical Use Cases
Hydroxychloroquine’s use in intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is generally not indicated. It has not been established as a standard therapy in these settings.
Dosage Adjustments
Dosage adjustments are necessary based on individual patient factors, such as renal or hepatic impairment. Drug interactions and genetic polymorphisms affecting drug metabolism must also be considered. Therapeutic drug monitoring might be beneficial in some situations.
Side Effects
Common Side Effects:
Nausea, vomiting, abdominal discomfort, diarrhea, headache, dizziness, skin rash, itching, hair loss.
Rare but Serious Side Effects:
Retinopathy, cardiomyopathy, QT prolongation, torsade de pointes, hepatotoxicity, blood dyscrasias (e.g., agranulocytosis, aplastic anemia, thrombocytopenia), neuropsychiatric effects (e.g., mood changes, psychosis, suicidal thoughts).
Long-Term Effects:
Irreversible retinal damage is a significant concern with long-term hydroxychloroquine use. Regular eye examinations are essential for early detection.
Adverse Drug Reactions (ADR):
Cardiovascular events (QT prolongation, torsades de pointes), severe skin reactions, and blood disorders represent clinically significant ADRs requiring prompt intervention.
Contraindications
- Known hypersensitivity to 4-aminoquinoline compounds.
- Pre-existing maculopathy or retinal disease.
- Certain blood disorders (e.g., porphyria).
Drug Interactions
Hydroxychloroquine may interact with numerous drugs, including digoxin, insulin, antacids, tamoxifen, methotrexate, and certain antibiotics. It’s essential to review concomitant medications carefully and consider potential CYP450 enzyme interactions.
Pregnancy and Breastfeeding
Hydroxychloroquine is generally considered safe during pregnancy and breastfeeding. However, it’s crucial to weigh the benefits against potential risks, especially in the first trimester.
Drug Profile Summary
- Mechanism of Action: Antimalarial activity by heme accumulation within the parasite. Immunomodulatory effects in autoimmune conditions via various pathways.
- Side Effects: Nausea, vomiting, diarrhea, headache, skin rash, retinopathy (rare but serious).
- Contraindications: Hypersensitivity, maculopathy, porphyria.
- Drug Interactions: Digoxin, insulin, antacids, tamoxifen, methotrexate.
- Pregnancy & Breastfeeding: Generally considered safe.
- Dosage: Varies by indication and patient factors; see detailed dosage guidelines above.
- Monitoring Parameters: Ophthalmologic exams, complete blood count, liver and kidney function tests.
Popular Combinations
Hydroxychloroquine is often used in combination with other DMARDs in treating rheumatoid arthritis and lupus. Common combinations include methotrexate, sulfasalazine, and corticosteroids.
Precautions
- Baseline ophthalmologic assessment and periodic monitoring.
- Complete blood counts and liver/kidney function tests during treatment.
- Monitor for cardiac effects, particularly in patients at risk for arrhythmias.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydroxychloroquine?
A: Dosage depends on the indication and patient-specific factors. See detailed dosage section above.
Q2: What is the most serious side effect of long-term hydroxychloroquine use?
A: Irreversible retinopathy. Regular ophthalmological examinations are crucial.
Q3: Can hydroxychloroquine be used safely in pregnancy?
A: Generally considered safe, but benefits and risks should be carefully weighed.
Q4: What are the common gastrointestinal side effects?
A: Nausea, vomiting, diarrhea, and abdominal discomfort are common.
Q5: How should the dose be adjusted for patients with renal impairment?
A: Dose reduction might be necessary; consult renal function guidelines.
Q6: Does hydroxychloroquine interact with other medications?
A: Yes, significant interactions are possible. Review all concomitant medications and consult drug interaction resources.
Q7: What monitoring is required for patients on hydroxychloroquine?
A: Ophthalmologic evaluations, complete blood counts, liver and kidney function tests.
Q8: What is the mechanism of action of hydroxychloroquine in lupus?
A: It modulates the immune system by suppressing various immune cell functions, decreasing inflammation.
Q9: Is hydroxychloroquine effective against all types of malaria?
A: No, it’s primarily effective against chloroquine-sensitive malaria species. It’s not effective against gametocytes of P. falciparum.
