CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria

Table 1 H1 Antihistamines: pharmacokinetics and pharmacodynamics in healthy adults.

Orally administered H1-antihistamines	Time to maximum plasma concentration (h) after a single dose	Terminal elimination half-life (h)	Clinically relevant drug–drug interactions^a	Onset of action (h)^b	Duration of action (h)^b
First (old) generation
Chlorpheniramine^c	2.8 ± 0.8	27.9 ± 8.7	Possible	3	24
Diphenhydramine^c	1.7 ± 1.0	9.2 ± 2.5	Possible	2	12
Doxepin^c	2	13	Possible	NA	NA
Hydroxyzine^c	2.1 ± 0.4	20 ± 4.0	Possible	2	24
Second (new) generation
Bilastine	1.2	14.5	Unlikely	2	24
Cetrizine	1.0 ± 0.5	6.5–10	Unlikely	0.7	≥ 24
Desloratidine	1.0–3.0	27	Unlikely	2–2.6	≥ 24
Fexofenadine^a	1.0–3.0	11.0–15.0	Unlikely	1.0–3.0	24
Levocetirizine	0.8 ± 0.5	7 ± 1.5	Unlikely	0.7	> 24
Loratidine (metabolite: descarboethoxyloratidine)	1.2 ± 0.3 (1.5 ± 0.7)	7.8 ± 4.2 (24 ± 9.8)	Unlikely	2	24
Rupatadine	0.75–1.0	6 (4.3–14.3)	Unlikely	2	24

^aClinically relevant drug–drug interactions are unlikely with most of the 2nd generation H1-antihistamines. Clinically relevant drug-food interactions have been well studied for fexofenadine. Naringin, a flavonoid found in grapefruit juice, and hesperidin, a flavonoid in orange juice, reduce the oral bioavailability of fexofenadine through the inhibition of OATP 1A2. This interaction can be avoided by waiting for 4 h between juice ingestion and fexofenadine dosing
^bOnset/duration of action is based on wheal and flare studies
^cSix or seven decades ago, when many of the first-generation H₁-antihistamines were introduced, pharmacokinetic and pharmacodynamic studies were not required by regulatory agencies. They have subsequently been performed for some of these drugs; however, empiric dosage regimens persist. For example, the manufacturers’ recommended diphenhydramine dose for allergic rhinitis is 25 to 50 mg every 4 to 6 h, and the diphenhydramine dose for insomnia is 25 to 50 mg at bedtime. Despite the long terminal elimination half-life values identified for some of the medications (e.g., > 24 h for chlorpheniramine), based on tradition, extended release formulations remain in use

ISSN: 1710-1492