<p>Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others <sup class="text-reference-group"><a class="reference-popover-link" data-content="Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Tablets Patient Information" href="#reference-L5266">10</a>,<a class="reference-popover-link" data-content="Electronic Medicines Compendium: Histergan (diphenhydramine hydrochloride) Cream Monograph" href="#reference-L5269">11</a>,<a class="reference-popover-link" data-content="Electronic Medicines Compendium: Boots Sleepeaze (diphenhydramine hydrochloride) 50mg Tablets Monograph" href="#reference-L5281">12</a>,<a class="reference-popover-link" data-content="Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph" href="#reference-L5287">13</a>,<a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>. Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes <sup class="text-reference-group"><a class="reference-popover-link" data-content="Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph" href="#reference-L5287">13</a></sup>. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse <sup class="text-reference-group"><a class="reference-popover-link" data-content="Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph" href="#reference-L5287">13</a></sup>. Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>.</p><p>Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>. This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>.</p><p>Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>. Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects <sup class="text-reference-group"><a class="reference-popover-link" data-content="Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph" href="#reference-L5287">13</a></sup>. Avoid use in elderly patients with confusion <sup class="text-reference-group"><a class="reference-popover-link" data-content="Electronic Medicines Compendium: Nytol One-A-Night (diphenhydramine hydrochloride) Monograph" href="#reference-L5287">13</a></sup>.</p><p>The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>.</p><p>After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>. However, the mean plasma clearance and apparent volume of distribution were not significantly affected <sup class="text-reference-group"><a class="reference-popover-link" data-content="Benylin Chesty Coughs UK MHRA Product Information" href="#reference-F3394">18</a></sup>.</p><p>LD<sub>50</sub>=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.</p>