Adverse Drug Reactions

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Plaquenil = Hydroxychloroquine

  • Indication: Malaria, Rheumatoid Arthritis, Systemic Lupus Erythematosus (SLE)
  • Side Effect: Chloroquine Maculopathy (advanced stage known as “Bull’s Eye Maculopathy”)
  • Differential Diagnoses
    • Age-Related Macular Degeneration (AMD)
    • Cone dystrophy
    • Stargardt disease
    • Albinism
  • Risk Factors
    • High dose and long duration of therapy
      • For Chloroquine (e.g., Chloroquine, Nivaquine): maintenance dose >3.5mg/kg/day (approximately 250mg)
      • For Hydroxychloroquine (Plaquenil): maintenance dose >5mg/kg/day
      • Therapy with Chloroquine/Hydroxychloroquine for over 5 years
    • Renal insufficiency
    • Pre-existing maculopathy
    • Concurrent use of Tamoxifen
  • Work-up
    • History taking: vision, scotomas, coloured halos, metamorphopsia, diplopia, etc.
    • Slit lamp examination: Cornea verticillata? Subcapsular lens opacities? (including dilated fundus examination) Peripheral pigment clumping?
    • Autofluorescence: RPE atrophy?
    • OCT
    • Visual field testing G2 (Asians) or M2 (Europeans) Octopus
    • (Farnsworth Colour Test)
    • In cases of suspected Chloroquine Maculopathy or with vision reduction/visual field defects, additional examinations like fluorescein angiography, photography, multifocal ERG, and consider therapy discontinuation
  • Follow-up
    • Initially within the first year of therapy to rule-out pre-existing maculopathy
    • thereafter, annually after 5 years from the start of therapy if no risk factors; earlier if risk factors are present

Ethambutol

  • Indication: Tuberculosis
  • Side Effect: Optic nerve damage
  • Risk Factors
    • Maintenance dose: Greater than 15mg/kg/day.
    • Renal insufficiency (Ethambutol dose not adjusted according to kidney function.
    • Diabetes mellitus
  • Work-up
    • History taking: vision, central clouding/blurry vision, colour vision
    • Farnsworth Colour Test
    • Ishihara
    • Dilated fundus examination
    • Consider visual field testing Octopus G2
    • Consider OCT of the macula and optic nerve
  • Follow-up
    • If the dose is <15mg/kg body weight per day: every 4 months
    • If the dose is >15mg/kg body weight per day: every 6 months

Lithium

  • Indication: Antidepressant, mood stabilizer
  • Side Effects
    • Pseudotumor Cerebri/Papilledema
    • Downbeat Nystagmus: Check in lateral/down gaze, as the nystagmus increases in down gaze (may only be visible there) and in lateral gaze, because it only beats downwards and not obliquely, unlike gaze-evoked nystagmus

 

Gilenya

  • Active Ingredient: Fingolimod, a selective immunosuppressant; modulator of the sphingosine-1-phosphate receptor
  • Indication: Multiple Sclerosis
  • Side Effect: Macular oedema
  • Work-up: OCT
  • Follow-up: Before starting and 3-4 months after beginning Gilenya therapy. Ophthalmic examination only if there is vision deterioration; annual checks may be recommended. (Vision tests every 6 months by the treating neurologist.)

Tysabri

  • Active Ingredient: Natalizumab, a selective immunosuppressant; anti-alpha-4-integrin antibody
  • Indication: Multiple Sclerosis
  • Side Effect: PML (Progressive Multifocal Leukoencephalopathy) involving the posterior visual pathway with homonymous or diffuse visual field defects (very rare!)
  • Work-up
    • PCR to rule out latent JC Virus infection before starting therapy
    • Goldman visual field testing if symptomatic
  • Follow-up: if symptomatic

Aminoglycosides (Gentamycin, Tobramycin, Amikacin)

Side Effects: Retinal toxicity after intravitreal injection of a toxic dose with white retinal areas (ischaemic), retinal haemorrhages, optic atrophy, pigment shifts

Thioridazin = Mellaril

  • Indication: Schizophrenia
  • Toxic Dose: typically 1200mg/day
  • Clinical Presentation:
    • Reduced vision
    • night blindness
    • +/-color vision impairment
  • Findings
    • Peripheral retinal pigmentary changes
    • Pigment deposits in the eyelids, cornea, and lens

Exjade = Deferasirox = Jadenu

  • Indication: Sickle Cell Anaemia
  • Side Effect: Cataract, maculopathy, optic neuropathy
  • Work-up:
    • Vision test
    • Visual field testing (Goldmann)
    • OCT and autofluorescence
    • Fundus examination in mydriasis
    • Fundus photography for documentation
  • Follow-up: Annually (every 12 months)

 

Orkambi

  • Active Ingredients: Lumacaftor und Ivacaftor
  • Indication: Cystic fibrosis
  • Side Effect: Cataract
  • Follow-up: Annually (every 12 months), especially in paediatric patients

Sources

  • EyeWiki
  • Compendium
  • Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision), Marmor, Michael F. et al. Ophthalmology, Volume 123, Issue 6, 1386 – 1394
  • The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease; Kalla Gervasio MD, Travis Peck MD et al; Lippincott Williams&Wilkins; 8th Edition (2021)
  • Kanski‚Äôs Clinical Ophthalmology: A Systematic Approach; John E Salmon MD; Elsevier; 9th Edition (2019)