Indications
- Lupus erythematosus (FDA approaved for discoid lupus).
- Annular elastotic granuloma Lipodermatosclerosis.
- Antiphospholipid antibody syndrome.
- Atopic dermatitis.
- Morphea.
- Chronic granulomatous disease.
- Necrobiosis lipoidica.
- Dermatomyositis.
- Perniosis.
- Eosinophilic annular erythema.
- Polymorphous light eruption.
- Eosinophilic fasciitis.
- Porphyria cutanea tarda : hydroxychloroquine (100 mg three times weekly)
- Follicular mucinosis.
- Reticular erythematous mucinosis.
- Frontal fibrosing alopecia.
- Sarcoidosis.
- Granuloma annulare.
- Schnitzler syndrome.
- Kikuchi-Fujimoto disease.
- Scleromyxedema.
- Lichen planus.
- Systemic sclerosis.
- Lichen planopilaris.
- Urticaria.
- Lichen sclerosus.
- Cutaneous CD81 pleomorphic T-cell lymphoma.
- Urticarial vasculitis.
Dosage
- Daily doses should not exceed 5 mg/kg actual body weight or 400 mg daily to avoid the risk of retinopathy.
- After therpeutic response >> maintenance with hydroxychloroquine 100–200 mg daily.
- Hydroxychloroquine has a long half-life, alternate-day dosing can be used to optimise the average dose, for example alternating days of 400 and 200 mg.
Mechanism of action
- Photoprotective : perhaps through their effects on prostaglandin metabolism, inhibition of superoxide production, or their ability to bind to DNA.
- Immunomodulatory: hydroxychloroquine blocks Major Histocompatibility Complex class II-associated antigen presentation affecting the function of dendritic cells, monocytes, and macrophages.
- Immunosuppressive effects : Antimalarial compounds raise intracytoplasmic pH levels, stabilize the microsomal membrane and disrupt proper endosomal maturation, thus blocking Toll-like receptor interactions with ligands, including nucleic acids.
- Anti-inflammatory effects: stabilization of lysosomes within injured cells; inhibition of antigen presentation, cell-mediated immunity, and the synthesis of proinflammatory cytokines.
- Antimalarials have anticoagulant, lipid‐lowering and hypoglycaemic properties.
Baseline Monitoring
- Ocular
- Fundus examination, assessment of visual acuity and and visual feld testing.
- lab
- CBC (monthly for 3 months, then every 4–6 months).
- Liver and renal function tests.
- Hydroxychloroquine blood levels may be useful to predict response and identify patients who are noncompliant.
Follow Up Monitoring
- Ocular
- Annual ocular toxicity screening is recommended to begin only after 5 years of use unless patients are considered high-risk or develop ophthalmologic symptoms.
- For patients with major risk factors like high daily dose (>5mg/kg), kidney disease, or tamoxifen use, annual screening should begin sooner, after just 1 year of hydroxychloroquine treatment, and continue annually while on treatment.
- Discontinuing hydroxychloroquine treatment if bilateral field defects are confirmed.
- Lab
- CBC (monthly for 3 months, then every 4–6 months).
- Chemistry profile (after 1 month, after 3 months, and then every 4–6 months).
Side effects
- Ocular (reversible)
- Corneal deposition – halos, blurred vision, photophobia.
- Loss of accommodation.
- Premaculopathy – usually no visual change; typically retinal pigment deposition, paracentral and pericentral scotoma.
- Ocular– irreversible
- True retinopathy – ’bull’s eye’ pigment deposition, central scotoma, visual acuity changes.
- GIT: nausea, vomiting, and diarrhea.
- Metabolic: hypoglycemia
- SKIN : blue-gray hyperpigmentation, morbilliform and psoriasiform eruptions, acute generalized exanthematous pustulosis, erythroderma, toxic epidermal necrolysis, Sweet’s syndrome.
- Muscular : myopathy is rare and can affect skeletal and cardiac muscle.
- Blood: agranulocytosis, anemia, thrombocytopenia.
Contraindications
- Hypersensitivity to 4-aminoquinoline derivatives.
- Retinal or visual field changes due to 4-aminoquinoline compounds.
- Long-term therapy in children.
Interactions
- Drugs that reduce antimalarial serum levels due to decreased GI absorption.
- Antacids.
- Kaolin, magnesium trisalicylate.
- Drugs that increase antimalarial serum levels (and potential toxicity) due to decreased metabolism
- Cimetidine.
- Combination may increase risk of retinopathy
- Chloroquine and hydroxychloroquine .
- HCQ may increase serum levels (and potential toxicity) of these drugs
- Antiarrhythmic agents : Propafenone.
- Cardiac drugs : Digoxin.
- Ciclosporin and methotrexate.
- Others : Penicillamine; risk of severe hematologic or renal toxicity.
- Others
- Botulinum toxin; concomitant use may decrease botulinum toxin activity.
- It may reduce the effect of antiepileptics.
Pregnancy &Lactation
- Once clinically indicated : use it in pregnancy.
- Hydroxychloroquine is minimally excreted in human breast milk.
- According to the available evidence, hydroxychloroquine is compatible with breastfeeding.
Here is a rephrased version of the statement:
When hydroxychloroquine is prescribed at doses of 5 mg/kg of actual body weight per day or less, the risk of retinal toxicity remains below 2 percent even with treatment duration up to 10 years.
(Ref)
Precautions
- Discontinue in 6 months if improvement is inadequate.
- Use in patients with psoriasis may precipitate a severe attack of psoriasis; use with caution.
- The most critical risk factor for retinopathy is daily dose; those exceeding 5 mg per kg ABW daily had 10% retinopathy risk within 10 years and 40% risk after 20 years.
- Alternatively, those taking 4-5 mg/kg daily had 2% risk within 10 years and 20% risk after 20 years.
- Additional HCQ-induced retinopathy risk factors include renal disease, retinal disease, macular disease, and concurrent tamoxifen use.
- Risk is low during the first 5 years but increases sharply after 5-7 years.
- In individuals of Asian descent, retinal toxicity may first be noticed outside macula; it is recommended that visual field testing be performed in central 24 degrees instead of central 10 degrees.
- Postmarketing cases of life-threatening and fatal cardiomyopathy reported with use of hydroxychloroquine.
- No cardiotoxicity screening guidelines exist, but annual electrocardiograms have been suggested.
- Hydroxychloroquine should be discontinued if ocular toxicity is suspected and the patient should be closely observed given that retinal changes (and visual disturbances) may progress even after cessation of therapy.
- Use with caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Signs or symptoms of cardiac compromise have appeared during acute and chronic treatment; clinical monitoring for signs and symptoms of cardiomyopathy is advised, including use of appropriate diagnostic tools such as ECG to monitor patients for cardiomyopathy during therapy; if cardiotoxicity is suspected, prompt discontinuation may prevent life-threatening complications.
- Not for administration with other drugs that have potential to prolong QT interval.
- Suicidal behavior rarely reported.
- Use with caution in patients with kidney or liver dysfunction.
Drug Info
- Hydroxychloroquine does not work immediately and it may be 12 weeks or longer before any benefit is noted.
- It should be taken with or immediately after food.
- Because HCQ has a long elimination half-life, alternate-day dosing can be used to optimize daily dose.
- Smokers should be educated about benefits of cessation as Cigarette smoking has been associated with a poor response to hydroxychloroquine.
- Hemolysis with G6PD deficiency does not occur at recommended HCQ doses and routine G6PD-deficiency testing is not recommended.