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For further information, see CMDT Part 38-56: Theophylline & Caffeine Overdose

Key Features

  • Methylxanthines including theophylline and caffeine are nonselective adenosine receptor antagonists

  • In overdose, toxicity results from the release of endogenous catecholamines with β1- and β2-adrenergic stimulation

  • Theophylline

    • May cause intoxication after an acute single overdose or

    • Intoxication may occur as a result of chronic accidental repeated overmedication or reduced elimination resulting from liver dysfunction or interacting drug (eg, cimetidine, erythromycin)

    • Usual serum half-life of theophylline is 4–6 h; this may increase to > 20 h after overdose

  • Caffeine in energy drinks or herbal or dietary supplement products can produce similar toxicity

Clinical Findings

  • Mild intoxication

    • Nausea

    • Vomiting

    • Tachycardia

    • Tremulousness

  • Severe intoxication (serum levels > 100 mg/L [555 mcmol/L])

    • Ventricular and supraventricular tachyarrhythmias

    • Hypotension

    • Seizures

  • Status epilepticus is common and often intractable to usual anticonvulsants

  • Symptoms may be delayed for hours after acute ingestion, especially if a sustained-release preparation was taken

  • Serious toxicity may develop at lower levels (40–60 mg/L [222–333 mcmol/L]) with chronic intoxication


  • Serum theophylline concentration

  • Hypokalemia, hyperglycemia, and metabolic acidosis are common after acute overdose


  • Activated charcoal

    • Give after acute ingestion

    • 60–100 g orally or via gastric tube, mixed in aqueous slurry

    • Do not use for comatose or convulsing patients unless it can be given by gastric tube and airway is protected by a cuffed endotracheal tube

    • Repeat doses may enhance gut decontamination and elimination by "gut dialysis"

  • Consider whole-bowel irrigation for large ingestions of sustained-release preparations

  • Indications for hemodialysis

    • Status epilepticus

    • Markedly elevated serum theophylline levels (eg, > 100 mg/L [555 mcmol/L] after acute overdose or possibly for levels > 60 mg/L [333 mcmol/L] with chronic intoxication)

  • Treatment of seizures

    • Lorazepam, 2–3 mg intravenously

    • Diazepam, 5–10 mg intravenously

    • Phenobarbital, 10–15 mg/kg intravenously

    • Phenytoin is not effective

  • Hypotension and tachycardia may respond to β-blocker therapy even in low doses

    • Esmolol, 25–50 mcg/kg/min by intravenous infusion

    • Propranolol, 0.5–1.0 mg intravenously

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