Hydroxychloroquine (HCQ) : Therapeutic uses, Clinical uses, Indications, Dosage, Side Effects, Warnings, Interactions, Precautions, Contraindications & Brand names
Hydroxychloroquine sulfate (HCQ) is a quinoline drug, useful in treating malaria, certain autoimmune diseases like rheumatoid arthritis, lupus erythematosus.
Dose : 200-800 mg [200 mg salt = 155 mg HCQ base]
Route : Oral
Onset of action : ?
Plasma half-life : 30-60 days (~40 days)
Duration of action : N/A
Bioavailability : Incomplete & variable (~70%)
Plasma protein binding : 40%
Metabolism : Hepatic (Metabolites include bidesethylchloroquine, desethylHCQ, desethylchloroquine)
Pregnancy risk category : NA
Chemical formula : C18H26ClN3O
IUPAC name : (RS)-2-[{4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino]ethanol
Trade name : Plaquenil, Quineprox, Hydroquin, Axemal, Dolquine, Quensyl, Quinoric, Zhquine, ZyQ
Therapeutic uses : Hydroxychloroquine sulfate has following usage :
- Used to prevent & treat the uncomplicated malaria due to susceptible strains.
- Used to treat certain auto-immune diseases (lupus, rheumatoid arthritis).
- Off Label Uses: Coronavirus Disease 2019 (COVID-19), Dermatomyositis, Photosensitivity diseases – porphyria cutanea tarda & severe polymorphous light eruption, Primary Sjögren syndrome, Q fever, Sarcoidosis.
Is hydroxychloroquine effective for COVID-19?
Few studies find hydroxychloroquine is not effective for COVID-19 and few studies find it is. Hence, more trials are needed before we will know for sure if hydroxychloroquine is effective for COVID-19.
Mechanism of action
Malaria
- Hydroxychloroquine interfere with heme detoxification.
Hydroxychloroquine, a weak base, concentrates in the highly acidic digestive vacuoles of susceptible Plasmodium, where it binds to heme and disrupts its sequestration.
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Inhibiting polymerization of heme
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Failure to inactivate heme or even enhanced toxicity of drug-heme complexes is thought to kill the parasites via oxidative damage to membranes, digestive proteases, or other critical biomolecules.
Autoimmune diseases
- Exact mechanism unknown but may include inhibition of phospholipase A2 and platelet aggregation, membrane stabilization, effects on the immune system, and antioxidant activity.
Coronavirus Disease 2019 (COVID-19)
- Hampers low PH dependant steps of viral replication.
Side effects : Hydroxychloroquine is safe when taken in proper doses and for recommended total durations. Commonly observed side effects are as following:
Common
- GI upset such as nausea, vomiting, loss of appetite, diarrhea,
- Dizziness, or headache,
- Urticaria, Pruritus.
Uncommon
- Blurring of vision, diplopia,
- Confusion, convulsions,
- Lichenoid skin eruptions, bleaching of hair,
- Widening of the QRS interval (QTc prolongation), T-wave abnormalities,
- Hemolysis and blood dyscrasias particularly in G6PD,
- Discoloration of nail beds & mucous membranes,
- Retinopathy (dose-dependent),
- Ototoxicity.
Acute toxicity: HCQ acute toxicity is encountered most frequently when therapeutic or high doses are administered too rapidly because its safety margin is narrow.
- Toxic manifestations: Cardiovascular effects (include hypotension, vasodilation, suppressed myocardial function, cardiac arrhythmias, and eventual cardiac arrest), CNS effects (include confusion, convulsions, & coma).
- Treament: Prompt treatment with mechanical ventilation, epinephrine, and diazepam.
Patients receiving long-term, high-dose therapy should undergo ophthalmological and neurological evaluations every 3-6 months.
Drug Interactions : Hydroxychloroquine may interact with following drugs :
- Mefloquine × HCQ : Increased risk for QTc-prolongation & seizures, lack of added benefit.
- QT-prolonging Agents × HCQ : Enhancing the QTc-prolonging effect of QT-prolonging Agents (Highest Risk).
- Digoxin × HCQ : Increases the serum concentration of digoxin.
- Cyclosporine × HCQ : Increases the serum concentration of digoxin.
- Antidiabetic Agents × HCQ : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
- Yellow fever vaccine × HCQ: Attenuates the efficacy of vaccine when administered at the same time.
- Antiepileptics × HCQ : Activity of antiepileptic drugs might be impaired.
- Penicillamine × HCQ
Precautions
Before using this medication, tell your doctor or pharmacist
- If you are allergic to it; or if you have any other allergies.
- Your medical history, especially of G6PD deficiency, eye problems, ear problems, kidney disease, liver disease, regular alcohol use/abuse, skin problems such as psoriasis, blood disorders such as porphyria, seizures, myasthenia gravis.
Cautions
- HCQ should be used cautiously if at all in the presence of advanced liver disease or severe GI, neurological, or blood disorders.
- In individuals with decreased renal function, dosage should be adjusted to avoid elevated plasma concentrations.
- HCQ is not recommended for treating individuals who have epilepsy or myasthenia gravis.
- Concomitant use of gold or phenylbutazone with HCQ, in the treatment of rheumatoid arthritis, should be avoided because of the tendency of all three agents to produce dermatitis.
- HCQ should not be prescribed for patients with psoriasis or other exfoliative skin conditions because it can cause severe reactions.
- Because of the danger of cutaneous reactions, it should also not be used to treat malaria in patients with porphyria cutanea tarda; however it can be used in lower doses for treatment of manifestations of this form of porphyria.
Contraindications
- Known hypersensitivity to hydroxychloroquine, 4-aminoquinoline derivatives, or any component of the formulation.
- Preexisting retinopathy.
- Children <6 years or weighing <35 kg.
For detailed query or in case of uncertainty, Always consult your doctor or pharmacist.
