title: Adverse reactions - Neonatal Intensive Care Drug Manual
text: Adverse reactions
  Administration-related reactions: Extravasation causes tissue inflammation and necrosis due to high pH and osmolality. Monitor IV insertion site. May cause bradycardia, arrhythmias, hypotension during infusion (more common if administration is too rapid). Pharmacological adverse reactions: Cardiac arrhythmias, hypotension, hyperglycaemia, constipation, interstitial nephritis, hepatitis, macrocytosis, megaloblastic anaemia (usually responds to folic acid supplementation) and blood dyscrasias. More likely with long-term use: Gingival hyperplasia, hirsutism, coarsening of facial features, folic acid deficiency, vitamin D deficiency, osteomalacia and hypothyroidism (only a few case reports in patients taking thyroxine, not in euthyroid patients). Rare but potentially fatal skin reaction: Phenytoin is associated with the anticonvulsant hypersensitivity syndrome a variant of Drug Reaction with Eosinophilia and Skin manifestations (DRESS). If DRESS is suspected, stop phenytoin immediately. Symptoms include: skin eruptions including Stevens Johnson syndrome or toxic epidermal necrolysis, eosinophilia, acute hepatotoxicity; fever; and abnormal lymph nodes; facial and/or tongue swelling; hives. There is marked cross-reactivity with other aromatic anti-epileptics.. The human leukocyte antigen (HLA) allele responsible for this reaction is almost exclusively expressed in patients of Asian ancestry including Chinese, Filipino, Malaysian, South Asian Indian, Korean, Japanese and Thai. Signs of phenytoin overdose: Nystagmus, cardiovascular collapse and/or CNS depression and dyskinesias. High serum concentrations are associated with seizures.
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