Hydroxychloroquine sulfate

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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.


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