Oral OTC Antihistamines

Oral antihistamines can be divided into 1st Generation (Benadryl/diphenhydramine, Unisom/Doxylamine) and 2nd/3rd generation (Claritin, Clarinex, Allegra, Zyrtec, Xyzal). There were other 2nd generation antihistamines in the past (Seldane, among others) that were pulled off the market because of cardiac and liver issues.

First-generation antihistamines cross the blood-brain barrier, allowing the medication to have a significantly more pronounced effect on the central nervous system, e.g., sedation. They are more powerful antihistamines but cause sleepiness/grogginess in most people (some seem less prone to this effect). It is why they are used as sleep aids (Benadryl/diphenhydramine in TylenolPM and ZzzQuil, Doxylamine in Unisom, for example).

They also can cause blurred near (accommodative) vision, dry mouth/nose, constipation, agitation or other mood changes, and, in much higher doses, cardiac arrhythmias (even coma). Doxylamine is a more potent antihistamine than diphenhydramine, but it is so sedating that very few people use it except to sleep. There are prescription and IV antihistamines (e.g., hydroxyzine) as well as multi-class drugs used for other purposes but with a pronounced antihistamine/anticholinergic effect (Antivert/Meclizine, which has both an anti-emetic and a weak vestibular suppressant effect).

Second- and third-generation antihistamines have significantly reduced blood-brain barrier penetration. They are commonly called “non-sedating,” though anyone can still be sedated by even the weakest of them. They are available in various strengths and formulations (pills, dissolving lozenges, liquid, child dose, etc.). In approximate order of strength from weakest to strongest: Claritin, Allegra, Clarinex, Zyrtec, Xyzal.

  • Claritin (loratidine) was the first 3rd gen antihistamine; it is effective for many people, but a substantial number find it ineffective. It can cause any of the same side effects as Benadryl but in much fewer people. As the weakest 3rd gen, it typically causes fewer side effects than the other 3rd generation medications.
  • Allegra (fexofenadine, a metabolite of Seldane) is a “middle of the road” 3rd generation antihistamine. It has a higher potency than Claritin while maintaining a low incidence of side effects.
    • Zyrtec (cetirizine) is one of the two most potent 3rd generation antihistamines. As such, there is a higher incidence of dry mouth and sedation (about 10%), although still much lower than that of Benadryl.
  • Clarinex (desloratadine) and Xyzal (levocetirizine) are somewhat special cases. Both are the active metabolite of their respective cousins (Claritin/Zyrtec). As such, they are more potent and dosed in half the strength (5mg vs. 10mg). They have increased potency compared to the precursor medication while, in many instances, reducing the side effect profile further.

All the above 3rd generation antihistamines are available in 12- or 24-hour formulations and can include long-acting pseudoephedrine (60 to 120mg), a nasal decongestant. Antihistamines alone are not very effective “pure” decongestants; they treat other allergy symptoms. “Boosting” the medication with the pseudophed, treats one of the most common complaints of allergy sufferers (nasal obstruction). Pseudophed is effective but can raise blood pressure and heart rate (and/or palpitations) and cause agitation or difficulty getting to sleep.

Sensitivity & Tolerance

The medication profiles above are accurate for most people; however, some respond ONLY to Claritin vs. Zyrtec, and plenty of “medication sensitive” people have side effects even from Claritin. Also, there is a phenomenon of “medication tolerance,” which appears to develop in some people on long-term antihistamine therapy; they may need to change doses or medications (e.g., switch from Claritin to Allegra) to maintain symptom control.

The Bottom Line

Antihistamines are generally regarded as “safe” to the extent that pregnant women can take them, if necessary (ALWAYS speak with your OB and follow their recommendations regarding medication taken during pregnancy), and children as young as 2 can take them in the appropriate dose.