This monograph discusses the assessment and management of less-sedating antihistamines. For management of sedating antihistamines, see Sedating Antihistamines.

Agents in this class include cetirizine, desloratadine, fexofenadine and loratadine. Loratadine and fexofenadine are available both in isolation as well as in co-formulation with pseudoephedrine.

Overdose of less-sedating antihistamines is usually benign, causing only minor sedation. Cardiac toxicity can occur in large ingestion but is rare.

Less-sedating antihistamines as a group block H1 peripheral receptors. In contrast to the traditional antihistamines, they have little anticholinergic or central effects in therapeutic doses.

The severe manifestations of non-sedating antihistamine poisoning are due to cardiac effects which are presumed to be due to blockade of potassium (hERG) channels.

Regardless of ingested dose, poisonings are normally benign.

Less-sedating antihistamines are generally well absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within 1 to 3 hours after oral administration.

These drugs are highly protein bound with a moderate to large volume of distribution. The volume of distribution is smaller than that of sedating antihistamines, as they do not penetrate the CNS well. Poor CNS penetration occurs secondary to lower lipophilicity and active efflux via P-glycoprotein.

Most less-sedating antihistamines undergo extensive hepatic metabolism, primarily via the cytochrome P450 system. Some agents, such as loratadine, require metabolism into their active form (desloratadine) whilst others are given in active for e.g. fexofenadine, cetirizine.

Elimination occurs via renal and/or biliary excretion, depending on the specific agent. Typical half-lives range from 8-24 hours.

In general ingestions of all agents in this group are benign lead to only mild sedation.

• CNS: sedation, anticholinergic toxicity (rare), seizures (rare).
• CVS: Tachycardia, postural hypotension, QT prolongation (rare).

Ingestion of these agents are generally benign and specific investigation are not normally required. Given the potential (very rare) for QT prolongation an ECG is a simple non-invasive investigation to undertake.

• ECG: looking for QT prolongation

Airway and breathing

Most ingestions will be asymptomatic or result in a short period of light sedation. The majority of cases can be managed well with supportive care alone.

In the rare cases of more significant sedation or seizures, with compromise to airway or breathing, intubate and ventilate.

Seizures are uncommon. They are generally self-terminating and short lived. Treat with benzodiazepines if recurrent or persistent.

Circulation

Hypotension can occur and is commonly related to alpha blockade induced vasodilation and responds to IV hydration.

If there is evidence QT-interval prolongation on ECG, then the patient should remain on continuous cardiac monitoring. Manage urgently according to advice on ECG in Toxicology

Most ingestions should be managed well with supportive care alone. However, if a patient presents within 2 hours following a large overdose, then consider offering single dose activated charcoal.

Give: 50g Activated Charcoal (Child: 1g/kg, max 50g) 

There is no role for enhanced elimination after ingestion of these agents.

There is no antidote for ingestion of less-sedating antihistamines.

Patients can be discharged at 6 hours post ingestion if they are asymptomatic with a normal ECG and have been able to pass urine.

Patients with signs of toxicity or abnormal ECG should be admitted until these signs have resolved and the patient has returned to their baseline status.

1. Poluzzi E, Raschi E, Godman B, Koci A, Moretti U, Kalaba M, et al. Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe. PLoS One 2015;10(3):e0119551. PDF