Another Look at First-Generation Antihistamines

The previous issue of this newsletter described how second- and third-generation antihistamines, including fexofenadine (ALLEGRA, CHILDREN’S ALLEGRA) and loratadine (ALAVERT, CLARITIN), can be useful for treating nasal allergy symptoms, including sneezing, itching, and runny or stuffy nose.[1]

First-generation or “sedating” antihistamines (see table) including diphenhydramine (BENADRYL, among other brands) and dimenhydrinate (DRAMAMINE, among other brands), carry a higher risk of sedating side effects than their second- and third-generation counterparts. While first-generation antihistamines are useful for treating motion sickness and certain other conditions, for nasal allergies and other uses the risks of these drugs outweigh their potential benefits.

It is especially important for patients to understand the risks and benefits before treating their symptoms with one of these widely used drugs.

First-Generation Antihistamines

* Some first-generation antihistamines also are available in injectable forms, which are not covered in this article.
** Available over the counter.
*** Do not use first-generation antihistamines to treat nasal allergy symptoms or colds.

Do not use for allergies

First-generation antihistamines have been commercially available in the U.S. since the 1940s, and one of these drugs, diphenhydramine, remains the most commonly used over-the-counter medication for nasal allergies.[2] Yet these common antihistamines have a host of potentially dangerous side effects.

Most notably, first-generation antihistamines are more easily able to cross from the bloodstream into the brain than newer antihistamines, leading to increased drowsiness and confusion.[3] Other side effects include dizziness, dry mouth, blurry vision and urinary retention.[4],[5]

There are now many second- and third-generation antihistamines available that also are effective in treating allergies but have fewer side effects.[6] These include the over-the-counter drugs fexofenadine and loratadine, as well as several prescription medications, such as cetirizine (ZYRTEC), desloratadine (CLARINEX) and levocetirizine (XYZAL).

For nasal allergy treatment, Public Citizen’s Health Research Group recommends that you avoid first-generation antihistamines and instead take a second- or third-generation antihistamine or another allergy treatment recommended on WorstPills.org.

Do not use for colds

Symptoms of the common cold are usually caused by a virus and tend to go away by themselves within a few days. Although diphenhydramine pills are sold over-the-counter to treat cold symptoms, diphenhydramine and several other first-generation antihistamines have never gone through Food and Drug Administration (FDA) approval and rigorous assessment for safety and effectiveness.[7] The FDA does not require rigorous testing or premarket approval for many over-the-counter products.

In fact, diphenhydramine and other first-generation antihistamines are only minimally effective for reducing cold symptoms.[8] (Second-generation antihistamines have no effectiveness.[9]) The average effectiveness of first-generation antihistamines is so small that it is hardly noticeable, and these drugs generally do not reduce the length of cold symptoms. Given the risk of side effects with these drugs, we recommend that you do not use antihistamines to treat cold symptoms.

Motion sickness

Motion sickness can cause nausea, vomiting, sweating, dizziness and other symptoms, often triggered when riding on a ship or in a car. Symptoms of motion sickness can be reduced or eliminated by repeated exposure to the same motion (habituation); taking deep, regular breaths; looking at a stable point, such as the horizon at sea; or lying down.[10]

A number of first-generation antihistamines, including dimenhydrinate and meclizine (ANTIVERT, among many brands), are legally sold in the U.S. for use in treating motion sickness (see table above). (Importantly, second- and third-generation antihistamines have not demonstrated effectiveness when tested for motion sickness.[11])

Another drug for motion sickness, scopolamine (TRANSDERM SCOP), is an FDA-approved prescription patch.[12] Scopolamine and first-generation antihistamines are similarly effective for motion sickness[13] and carry similar common side effects, including drowsiness, dizziness and blurred vision.[14],[15] First-generation antihistamines and scopolamine have anticholinergic effects, meaning that they can worsen certain conditions, including glaucoma and bladder problems.[16],[17]

Skin products

Diphenhydramine is sold over the counter in combination with zinc as a spray and cream for itch relief (BENADRYL EXTRA STRENGTH ITCH STOPPING, among other brands). Such skin products are generally safe when used according to the labeling.

Other uses for first- generation antihistamines

Hydroxyzine (ATARAX, VISTARIL) and promethazine (PHENADOZ) are approved for a variety of uses, including several related to reducing the side effects of surgery and anesthesia.

The adverse effects of these drugs are stronger in elderly patients and may be magnified further by other depressants, including narcotic painkillers used in surgery. If offered these drugs before or after surgery, ask your doctor to start with a low dose and observe you carefully for side effects before increasing the dosage.

What You Can Do

First-generation antihistamines have usefulness limited to certain conditions — among them, treating motion sickness. For allergies and colds, the benefits of these drugs are outweighed by their risks, although these drugs have long been sold over the counter and are used widely for these conditions.

First-generation antihistamines should be avoided for these latter uses. A cold generally will get better within a few days and can best be treated safely and inexpensively with rest and plenty of fluids.

For more information on allergy treatments, see the April 2016 issue of Worst Pills, Best Pills News.[18]

References

[1] Treatment for nasal allergies: An updated review. Worst Pills, Best Pills News. April 2016. /newsletters/view/1027. Accessed April 11, 2016.

[2] Spangler DL, Brunton S. Efficacy and central nervous system impairment of newer-generation prescription antihistamines in seasonal allergic rhinitis. South Med J. 2006;99(6):593-599.

[3] Carson S, Lee N, Thakurta S. Drug Class Review: Newer Antihistamines: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; May 2010. Introduction. http://www.ncbi.nlm.nih.gov/books/NBK50554/. Accessed March 17, 2016.

[4] Collamati A, Martone AM, Poscia A, et al. Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence. Aging Clin Exp Res. 2016;28:25-35.

[5] De Sutter AIM, Saraswat A, van Driel ML. Antihistamines for the common cold. Cochrane Database of Systematic Reviews. 2015;(11). Art. No.: CD009345.

[6] Spangler DL, Brunton S. Efficacy and central nervous system impairment of newer-generation prescription antihistamines in seasonal allergic rhinitis. South Med J. 2006;99(6):593-599.

[7] Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antihisthmatic drug products for over-the-counter human use; final monograph for OTC antihistamine drug products. Federal Register. 1992;57(22):58356-58376. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm077724.pdf. Accessed March 21, 2016.

[8] De Sutter AIM, Saraswat A, van Driel ML. Antihistamines for the common cold. Cochrane Database of Systematic Reviews. 2015;(11). Art. No.: CD009345.

[9] Ibid.

[10] Golding JF, Gresty MA. Pathophysiology and treatment of motion sickness. Curr Opin Neurol. 2015;28:83-88.

[11] Cheung BS, Heskin R, Hofer KD. Failure of cetirizine and fexofenadine to prevent motion sickness. Ann Pharmacother. 2003;37(2):173-177.

[12] National Institutes of Health. DailyMed. Label: TRANSDERM SCOP- scopolamine patch, extended release. April 30, 2013. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e5dab9c-755b-460e-afe2-1ddfc4acfd96. Accessed February 12, 2016.

[13] Spinks A, Wasiak J. Scopolamine (hyoscine) for preventing and treating motion sickness. Cochrane Database of Systematic Reviews. 2011;(6). Art. No.: CD002851.

[14] National Institutes of Health. DailyMed. Label: TRANSDERM SCOP – scopolamine patch, extended release. April 30, 2013. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e5dab9c-755b-460e-afe2-1ddfc4acfd96. Accessed February 12, 2016.

[15] National Institutes of Health. DailyMed. Label: DIMENHYDRINATE – dimenhydrinate tablet. Updated November 17, 2011. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14ccdb11-5706-4007-aa27-a60ef3f09ce7. Accessed February 12, 2016.

[16] National Institutes of Health. DailyMed. Label: TRANSDERM SCOP – scopolamine patch, extended release. April 30, 2013. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e5dab9c-755b-460e-afe2-1ddfc4acfd96. Accessed February 12, 2016.

[17] National Institutes of Health. DailyMed. Label: DIMENHYDRINATE – dimenhydrinate tablet. Updated November 17, 2011. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14ccdb11-5706-4007-aa27-a60ef3f09ce7. Accessed February 12, 2016.

[18] Treatment for nasal allergies: An updated review. Worst Pills, Best Pills News. April 2016. /newsletters/view/1027. Accessed April 11, 2016.