From: H1 Antihistamines: Current Status and Future Directions
 | First Generation*,**,‡ | Second Generation**,‡ |
---|---|---|
CNS (mechanism: interference with neurotransmitter effect of histamine through H1 receptor) | After usual doses, may cause drowsiness, fatigue, somnolence, dizziness, impairment of cognitive function, memory, and psychomotor performance, headache, dystonia, dyskinesia, agitation, confusion, and hallucinations. | None with fexofenadine at doses up to 360 mg (off label); none with desloratadine 5 mg or loratadine 10 mg, although dose-related CNS effects may occur at higher doses; cetirizine doses 10 mg or higher may cause sedation in adults. |
 | May cause adverse CNS effects in newborns if taken by the mother immediately before parturition; may cause irritability, drowsiness, or respiratory depression in nursing infants | No CNS adverse effects reported in newborns or nursing infants |
Cardiac§ (mechanisms: multiple; antimuscarinic effects; α-adrenergic receptor blockade; blockade of cardiac ion currents [IKr and, less commonly, INa, Ito, IKi, and IKs]) | Dose-related sinus tachycardia; reflex tachycardia, prolonged atrial refractive period, and supraventricular arrhythmias; dose-related prolongation of the QTc interval and ventricular arrhythmias reported for cyproheptadine, diphenhydramine, doxepin, hydroxyzine, promethazine, and others | No major concerns in any country (such as the United States or Canada), in which regulatory approval was withdrawn for astemizole and terfenadine |
Other sites (mechanisms: blockade of muscarinic, α-adrenergic, and serotonin receptors) | After usual doses: may cause mydriasis (pupillary dilation), dry eyes, dry mouth, urinary retention and hesitancy, decreased gastrointestinal motility, constipation, memory deficits; peripheral vasodilation, postural hypotension, dizziness; appetite stimulation and weight gain (cyproheptadine, ketotifen); contraindicated in individuals with glaucoma or prostatic hypertrophy | None reported |
Toxicity after overdose (mechanisms: multiple) | CNS effects such as extreme drowsiness, lethargy, confusion, delirium, and coma in adults; paradoxical excitation, irritability, hyperactivity, insomnia, hallucinations, seizures, and respiratory depression/arrest in infants and young children; in both adults and children, CNS adverse effects predominate over cardiac adverse effects; death may occur within hours after ingestion of drug in untreated patients; rhabdomyolysis has also been reported | No serious toxicity or fatality reported |
Abuse of drugs (mechanisms: through H1 and other receptors in the CNS) | Euphoria, hallucinations and "getting high" reported for diphenhydramine, dimenhydrinate, and others | None reported |
Teratogenicity after use in pregnancy|| | FDA Category B (chlorpheniramine, diphenhydramine) or C (hydroxyzine, ketotifen) | FDA Category B (cetirizine, emedastine, levocetrizine, loratadine) or C (azelastine, epinastine, desloratadine, fexofenadine, olopatadine) |
Carcinogenicity/tumor promotion | None reported in humans | None documented in humans |