1st Generation* Anticholinergic (non-selective)* Highly sedative

Less sedatingCetirizine*

Somnolence(%)Cetirizine 13.7Placebo 6.3

*Zyrtec Prescribing Information

Potentially sedative/ cardiotoxic ?LoratadinePotential blockage of K+ channels

2nd GenerationCetirizine, Loratadine,Fexofenadine

Non-sedatingLoratadine, Fexofenadine

Fexofenadine *Non- cardiotoxic *No anticholinergic side effects *Wide therapeutic index

Antihistamines

3rd Generation !!

Desloratadine* *Anticholinergic side effects

Levocetirizine* *Profile similar to cetirizine *Somnolence 4 times that of placebo

*Xyzal Prescribing Information*Ellis et al, AAAAI 2002

H1 Antihistamines: Generation ConceptH1 Antihistamines: Generation Concept

Antihistamines ComparogramAntihistamines Comparogram

Criteria Allegra Hydxyz Pmthz Ctzn Levo DCL

Genuinely non sedating (even at higher doses)

Yes No No No No No

Anti-cholinergic side effects No Yes Yes No No Reported+/-

Problems of drug interactions/ QTc prolongation

No Yes Yes No No Reported+/-

Dosage adjustment required (renal or hepatic impairment)

No Yes Yes Yes Yes Yes

Palatability esp. in children Very good OK OK OK OK OK

Loss of efficacy over time (Tachyphylaxis)

No Yes Yes No Data? No

Clinical data for usage across age groups

Yes No No Yes No Yes

Special label precaution for driving or operating heavy machinery

No Yes Yes Yes Yes Yes

Wide therapeutic index Yes No No No No No

Significantly improves QOL of the child

Yes No No Some data Some data Some data

Approved by US FDA Yes Yes Yes (Warning)

No/ Yes No/ Yes Yes

Available in how many countries > 125 > 100 > 100 >125 > 40 65

Drowsiness Drowsiness Anticholinergic effectAnticholinergic effect ImpairmentImpairment

DiphenhydramineDiphenhydramine ++++++ ++++++ ++++++

ChlorpheniramineChlorpheniramine ++++ ++++++ ++++

BrompheniramineBrompheniramine ++++ ++++++ ++++

ClemastineClemastine ++++++ ++++++ ++++++

LoratadineLoratadine 0,+(HD)0,+(HD) 00 0,+(HD)0,+(HD)

DesloratadineDesloratadine 0,+(HD)0,+(HD) +/-+/- 0,+(HD)0,+(HD)

CetrizineCetrizine +/-,+(HD)+/-,+(HD) 00 +/-,+(HD)+/-,+(HD)

FexofenadineFexofenadine 00 00 00

Shamsi Z, et al. Hum Psychopharmacol 2000; 15 (suppl 1): S3-S30

Welch MJ, et al. H1-Antihistamines in Allergic Disease, 2nd ed, 2002;337

HD = higher than recommended dose; +/- = exhibits effects

Antihistamines: Side effects & ImpairmentAntihistamines: Side effects & Impairment