The older antihistamines caused this side effect in many patients

Antihistamine Risks

March/April 2013

By Mark D. Coggins, PharmD, CGP, FASCP
Aging Well
Vol. 6 No. 2 P. 6

Antihistamine medications block or reduce histamine-mediated effects at one of four identified histamine receptors (see Table 1 below). Currently the only FDA-approved histamine antagonist medications block the effects of histamine at H1 or H2 receptor sites.

The term “antihistamine” generally is used to describe those medications that antagonize histamine activity at H1 receptors. These include the first-generation H1 antagonists, or sedating antihistamines (eg, diphenhydramine, chlorpheniramine), and second-generation H1 receptor blockers, or nonsedating antihistamines (eg, loratadine, cetirizine).

Histamine Receptor Subtypes and Activity
Histamine Receptor Subtype Areas of High Histamine Receptor Concentration Histamine Receptor Mediation/Response
H1 Smooth muscle and endothelial cells Allergic responses
H2 Gastric parietal cells Stimulation of gastric acid
H3 Presynaptic receptors in central nervous system Release of neurotransmitters including histamine, acetylcholine, dopamine, norepinephrine, and others involved in cognition
H4 Hematopoietic cells such as eosinophils, mast cells, neutrophils, and dendritic cells Inflammatory responses

First-generation antihistamines are widely available without a prescription and commonly used to treat allergic symptoms, including rhinitis, conjunctivitis, pruritus, eczema, urticaria, and anaphylactic reactions. These sedating antihistamines often are used alone or in combination with other ingredients in cold and cough medications, and over-the-counter (OTC) sleep aid products.

Diphenhydramine (Benadryl) is the most common first-generation antihistamine found in OTC sleep aids, whether used alone or in combination with pain relievers, including acetaminophen (eg, Tylenol PM), ibuprofen (eg, Advil PM), and aspirin. Other sleep aids often contain the antihistamine doxylamine (eg, Unisom).

H2 blockers (eg, ranitidine, famotidine) commonly are used for the treatment of heartburn and gastroesophageal reflux disease. These medications decrease gastric acid secretion in the stomach by antagonizing the effects of histamine at H2 receptors found in gastrointestinal parietal cells.

Ongoing research efforts aim to develop potential agents to target the H3 and H4 receptor sites. H3 receptor antagonists could provide new treatment options for sleep disorders, weight loss, neuropathic pain, obesity, movement disorders, schizophrenia, attention deficit disorders, and Alzheimer’s dementia, while the development of antagonists for H4 receptors may lead to new treatment options for autoimmune inflammatory diseases.1,2

Antihistamine Risks and Anticholinergic Syndrome

The first H1 sedating antihistamines have been available for more than 60 years and were synthesized based on a chemical structure similar to that used to develop cholinergic muscarinic antagonists, tranquilizers, and antihypertensive agents. These antihistamines have low receptor specificity and interact with both peripheral and central histamine receptors and readily cross the blood-brain barrier. This leads to significant central nervous system side effects, including sedation, drowsiness, somnolence, fatigue, cognitive decline, psychomotor effects, and loss of coordination.

These antihistamines also are potent muscarinic receptor antagonists that can lead to serious anticholinergic side effects, such as sinus tachycardia, dry skin, dry mucous membranes, dilated pupils, constipation, ileus, urinary retention, and agitated delirium.3 The mnemonic “blind as a bat, dry as a bone, red as a beet, mad as a hatter, and hot as a hare” often is used to help describe and identify patients suffering from anticholinergic syndrome (see Table 2 below).

Anticholinergic Syndrome Mnemonic
Expression Anticholinergic Side Effects Described
“Blind as a bat”
“Dry as a bone”
“Red as a beet”
“Mad as a hatter”
“Hot as a hare”
Blurred vision, dilated pupils
Dry mouth and skin
Flushing
Confusion, delirium
Hyperthermia

Urinary retention and difficulty urinating can be particularly troublesome in male patients with enlarged prostates, and this retention can increase the risk of urinary tract infections, especially in women.4

The second-generation nonsedating antihistamines generally are considered as safer alternatives for use in older adults who require treatment for allergic rhinitis and other allergy symptoms. These antihistamines are more selective on peripheral H1 receptors and have a lower affinity for cholinergic and alpha-adrenergic receptor sites, which reduces the risk of anticholinergic and central nervous system side effects.

Considerations for Older Adults

Older adults are especially sensitive to the central nervous system- and anticholinergic-related side effects of sedating antihistamines because of decreased cholinergic neurons or receptors in the brain, reduced hepatic and renal function, and increased blood-brain permeability. These patients also often have coexisting conditions and often take multiple medications that increase the risk of drug-drug interactions and the potential for sedative adverse effects.

Even when first-generation antihistamines are used at the lowest doses recommended by the manufacturer, they can cause serious central nervous system side effects, including dizziness, hypotension, and next-day sedation. These side effects can greatly increase the risk of falls and fall-related injury, with the impact of even one fall in an older adult potentially having tremendous negative consequences, including diminished quality of life and loss of independence.

An estimated 25% of patients over the age of 65 have some existing cognitive decline, which may not always be obvious or recognized by others.5 However, when given highly anticholinergic medications, these patients may present with symptoms resembling those of dementia, which may lead to an inappropriate diagnosis of clinical dementia.

In a meta-analysis of 27 studies conducted between 1966 and 2008, in 25 of the studies researchers confirmed a link between anticholinergic medication use and either delirium, cognitive impairment, or dementia.6 Other studies reviewing the effects of diphenhydramine and its use in OTC analgesic plus diphenhydramine products have shown they can significantly increase the risk of delirium.

Because delirium and hallucinations can result from the use of anticholinergics including sedating antihistamines, patients receiving these medications are at risk of being prescribed antipsychotic medications. Cognitive decline, falls, and behaviors such as hallucinations, delirium, and agitated aggressive behaviors may result in affected patients being hospitalized or admitted to long term care facilities.

Healthcare professionals working in long term care communities and skilled nursing facilities should work with families, prescribers, and other members of the healthcare team to discourage the use of first-generation antihistamines and other highly anticholinergic medications in older patients. In addition to causing significant patient harm, the use of anticholinergic medications in older nursing home patients negatively impacts Centers for Medicare & Medicaid Services quality measures, such as the use of high-risk antipsychotic medications, the percentage of patients with a decline in their ability to perform activities of daily living, the percentage of patients with falls and serious injury, and urinary tract infection rates.

Regardless of practice setting, healthcare professionals should take steps to increase the awareness of side effects associated with first-generation antihistamines. Educating older patients and their caregivers is especially important because of the widespread OTC availability of these antihistamines. Patients with Alzheimer’s disease are at particular risk as caregivers may purchase these medications without understanding the associated risk of exacerbating the disease.

Prescribers and nurses should discuss the potential risks of OTC medications during routine patients’ physician visits, and pharmacists should be proactive in seeking additional information from patients, including asking questions about OTC product use. It is also important to encourage patients to read product warnings and seek advice from healthcare providers before using OTC medications.

— Mark D. Coggins, PharmD, CGP, FASCP, is a director of pharmacy services for more than 300 skilled nursing centers operated by Golden Living and a director on the board of the American Society of Consultant Pharmacists. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

Anti-inflammatory properties

To date it has not been possible to establish whether the antiallergic/anti-inflammatory properties described in many experimental models do in fact exist, and, if so, what their true clinical significance is. These properties must be demonstrated in vivo, in humans, at therapeutic doses and under natural allergen exposure conditions.

For an H1 antihistamine to truly have antiallergic/anti-inflammatory properties it must manifest, in humans, superior efficacy to other therapies with the same properties (for example, corticosteroids). Since the greatest expression of allergic chronic inflammation is nasal obstruction, these anti-inflammatory properties must address this in a quantifiable manner. This must be demonstrated, in particular, in persistent AR, in which obstruction predominates over the other histamine-induced symptoms.

Potency, efficacy and effectiveness

The therapeutic index of an H1 antihistamine, defined as the risk-benefit relationship, is more important than its potency (determined in preclinical trials) or its efficacy (determined in clinical trials). In this sense, second-generation H1 antihistamines have more favorable therapeutic indices than the first generation ones, however none of them merit the designation “third-generation H1 antihistamine”. It is probable that a true third-generation H1 antihistamine will differ radically from existing compounds.

Absence of cardiotoxicity

Adverse cardiac effects, with risk of life (QT prolongation and torsades de pointes), were described with some second-generation H1 antihistamine (terfenadine and astemizole). These effects are the result of a direct block to a specific class of potassium channels which control the cardiac repolarization phase, and are not related to the blockade of the H1 receptor. Therefore, cardiotoxicity is not a class-specific effect.

Several different pharmacokinetic and pharmacodynamic properties may precipitate an episode of arrhythmia. Therefore, physicians using H1 antihistamines should be aware of these properties, in order to avoid exposing their patients to potentially dangerous effects.

Absence of cardiotoxic effects, a characteristic that is already present in certain second-generation H1 antihistamines, must be maintained in the development of new compounds. Preclinical and clinical trials investigating their potential to cause such effects should be performed before new molecules are released onto the market.

Drug interactions

The possibility of drug interactions should never be forgotten, primarily because H1 antihistamines are commonly employed for prolonged periods. Based on this, for an H1 antihistamine to be considered third-generation, it must not: a) affect the function of any of the cytochrome P 450 via enzymes; b) displace medications bonded to plasma proteins; or c) affect active transport mechanisms that are extremely important to the absorption and excretion of drugs.

Lack of CNS effects

Three factors establish the criteria for determining the nonsedative properties of an H1 antihistamine: a) incidence of subjective somnolence; b) the objective effect on cognitive and psychomotor functions; and c) quantification of H1 receptor occupation using positronic tomography. While the last two are particularly important, all three factors must be met to a minimum acceptable level before any new H1 antihistamine can be classed as a nonsedative drug.

Final comments

Although H1 antihistamines are useful for the treatment of allergic disorders, differences that are probably related to their pharmacokinetic, pharmacodynamic, antiallergic and anti-inflammatory properties mean that the many different compounds in existence are not equally effective for the control of symptoms of the skin, nose and lungs. Furthermore, not all patients respond in the same manner to all H1 antihistamines, and those who do not benefit from one compound may respond satisfactorily to another.

Their antiallergic and anti-inflammatory effects, together with the improved safety profile, make second-generation antihistamines important elements for continuous, long term regulation of both immediate and late phase allergic reactions. However, it would be premature to reclassify H1 antihistamines on the basis of available evidence, since the diverse facets of these medications have not yet been completely investigated and their relative contribution to the global efficacy of treatment for allergic disorders remains unknown.

Antihistamines act by biding with the H1 histamine receptors. Recent advances, after the gene that codes for the H1 receptor had been cloned, improved understanding of the interactions between the ligand and the receptor on the molecular level. There is evidence that H1 antihistamines may bind to the receptor in different ways in the third and fifth transmembrane domains, depending upon specific amino acid residues. Furthermore, differences in expression of the receptor or in the microenvironment around it may determine different signal paths to be activated after exposure to histamine. Evidence has been found that all the H1 antihistamines available act more like inverse agonists than like antagonists.6

Thus, with the cloning of the genes that code for the histamine H1 receptor, a new area has opened up in histamine research, increasing the chances that new H1 antihistamines will be developed with greater potency, safety and selectivity.

1. Simons FE. H1-Antihistamines: more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol. 2003;112:S42-52.

3. MacGlashan D Jr. Histamine: a mediator of inflammation. J Allergy Clin Immunol. 2003;112:S53-9.

4. Agrawal DK. Anti-inflammatory properties of desloratadine. Clin Exp Allergy. 2004;34:1342-8. Review.

5. Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108:S147-334.

8. Marshall GD Jr. Therapeutic options in allergic disease: antihistamines as systemic antiallergic agents. J Allergy Clin Immunol. 2000;106:S303-9.

9. Grant JA, Danielson L, Rihoux JP, DeVos C. A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects. Allergy. 1999;54:700-7.

10. Grant JA, Riethuisen JM, Moulaert B, DeVos C. A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects. Ann Allergy Asthma Immunol. 2002;88:190-7.

12. Ciprandi G, Ricca V, Tosca M, Landi M, Passalacqua G, Canonica GW. Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy. Allergy. 1999;54:358-65.

13. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC (Early Treatment of the Atopic Child). Pediatr Allergy Immunol. 1998;9:116-24.

14. Hindmarch I, Shamsi Z, Stanley N, Fairweather DB. A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function. Br J Clin Pharmacol. 1999;48:200-6.

16. Carmeliet E. Effects of cetirizine on the delayed K+ currents in cardiac cells: comparison with terfenadine. Br J Pharmacol. 1998;124: 663-8.

20. Tilement JP, Testa B, Bree F. Compared pharmacological characteristics in humans of racemic cetirizine and levocetirizine, two histamine H1 receptor antagonists. Biochem Pharmacol. 2003;66:1123-6.

22. Banfield C, Hunt T, Reyderman L, Statkevich P, Padhi D, Affrime M. Lack of clinically relevant interaction between desloratadine and erythromycin. Clin Pharmacokinet. 2002;41:29-35.

23. Banfield C, Herron J, Keung A, Padhi D, Affrime M. Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole. Clin Pharmacokinet. 2002;41:37-44.

24. Denham KJ, Boutsiouki P, Clough GF, Church MK. Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal, flare and itch in human skin. Inflamm Res. 2003;52:424-7.

25. Passalacqua G, Guerra L, Compalati E, Massacane P, Rogkakou A, Zanella C, et al. Comparison of the effects in the nose and skin of a single dose of desloratadine and levocetirizine over 24 hours. Int Arch Allergy Immunol. 2004;135:143-7.

26. Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal obstruction and modulates cytokine pattern in patients with seasonal allergic rhinitis: a pilot study. Clin Exp Allergy. 2004;34:958-64.

27. Deruaz C, Leimgruber A, Berney M, Pradervand E, Spertini F. Levocetirizine better protects than desloratadine in a nasal provocation with allergen. J Allergy Clin Immunol. 2004;113:669-76.

28. Lee DK, Gardiner M, Haggart K, Fujihara S, Lipworth BJ. Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis. Clin Exp Allergy. 2004;34:650-3.

29. Mullol J, Roca-Ferrer J, Alobid I, Pujols L, Valero A, Xaubet A, et al. Effect of desloratadine on epithelial cell granulocyte-macrophage colony-stimulating factor secretion and eosinophil survival. Clin Exp Allergy. 2006;36:52-8.

30. Cyr MM, Hayes LM, Crawford L, Baatjes AJ, Keith PK, Denburg JA. The effect of desloratadine on eosinophil/basophil progenitors and other inflammatory markers in seasonal allergic rhinitis: a placebo-controlled randomized study. Int Arch Allergy Immunol. 2005;138:209-16.

31. Meltzer EO, Jalowayski AA, Vogt K, Iezzoni D, Harris AG. Effect of desloratadine therapy on symptom scores and measures of nasal patency in seasonal allergic rhinitis: results of a single-center, placebo-controlled trial. Ann Allergy Asthma Immunol 2006;96:363-8.

32. Kim K, Sussman G, Hebert J, Lumry W, Lutsky B, Gates D. Desloratadine therapy for symptoms associated with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:460-5.

33. Nayak AS, Schenkel E. Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis. Allergy. 2001;56:1077-80.

34. Monroe E, Finn A, Patel P, Guerrero R, Ratner P, Bernstein D; Desloratadine Urticaria Study Group. Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2003;48:535-41.

35. Lachapelle JM, Decroix J, Henrijean A, Roquet-Gravy PP, De Swerdt A, Boonen H, et al. Desloratadine 5 mg once daily improves the quality of life of patients with chronic idiopathic urticaria. J Eur Acad Dermatol Venereol. 2006;20:288-92.

37. Howell G 3rd, West L, Jenkins C, Lineberry B, Yokum D, Rockhold R. In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine. BMC Pharmacol. 2005;18:5-13.

38. Nicholson AN, Handford AD, Turner C, Stone BM. Studies on performance and sleepiness with the H1-antihistamine, desloratadine. Aviat Space Environ Med. 2003;74:809-15.

39. Wilken JA, Kane RL, Ellis AK, Rafeiro E, Briscoe MP, Sullivan CL, et al. A comparison of the effect of diphenhydramine and desloratadine on vigilance and cognitive function during treatment of ragweed-induced allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91:375-85.

40. Russell T, Stoltz M, Weir S. Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers. Clin Pharmacol Ther. 1998;64:612-21.

41. Meeves SG, Appajosyula S. Efficacy and safety profile of fexofenadine HCl: a unique therapeutic option in H1-receptor antagonist treatment. J Allergy Clin Immunol. 2003;112:S69-77.

42. Boyle J, Ridout F, Meadows R, Johnsen S, Hindmarch I. Suppression of the histamine-induced wheal and flare response by fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily and placebo in healthy Japanese volunteers. Curr Med Res Opin. 2005;21:1495-503.

43. Asano K, Kanai KI, Suzaki H. Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitro. Clin Exp Allergy. 2004;34:1890-8.

44. Van Cauwenberge P, Juniper EF. Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis. Clin Exp Allergy. 2000;30:891-9.

45. Berger WE, Lumry WR, Meltzer EO, Pearlman DS. Efficacy of desloratadine, 5 mg, compared with fexofenadine, 180 mg, in patients with symptomatic seasonal allergic rhinitis. Allergy Asthma Proc. 2006;27:214-23.

46. Meltzer EO, Scheinmann P, Rosado Pinto JE, Bachert C, Hedlin G, Wahn U, et al. Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis—a pooled analysis of three studies. Pediatr Allergy Immunol. 2004;15:253-60.

47. Ngamphaiboon J, Direkwattanachai C, Visitsunthorn N, Vangveeravong M, Tiensuwan M. The efficacy and safety of 30 mg fexofenadine HCl bid in pediatric patients with allergic rhinitis. Asian Pac J Allergy Immunol. 2005;23:169-74.

48. Okubo K, Gotoh M, Shimada K, Ritsu M, Okuda M, Crawford B. Fexofenadine improves the quality of life and work productivity in Japanese patients with seasonal allergic rhinitis during the peak cedar pollinosis season. Int Arch Allergy Immunol. 2005;136:148-54.

49. Nelson HS, Reynolds R, Mason J. Fexofenadine HCl is safe and effective for treatment of chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2000;84:517-22.

52. Hindmarch I, Shamsi Z, Kimber S. An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers. Clin Exp Allergy. 2002;32:133-9.

53. Wu P, Mitchell S, Walsh GM. A new antihistamine levocetirizine inhibits eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions. Clin Exp Allergy. 2005;35:1073-9.

54. Ciprandi G, Cirillo IG, Vizzaccaro A, Tosca MA. Levocetirizine improves nasal symptoms and airflow in patients with persistent allergic rhinitis: a pilot study. Allerg Immunol (Paris). 2005;37:25-9.

55. de Blic J, Wahn U, Billard E, Alt R, Pujazon MC. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol. 2005;16:267-75.

56. Potter PC; Paediatric Levocetirizine Study Group. Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial. Ann Allergy Asthma Immunol. 2005;95:175-80.

57. Patou J, De Smedt H, van Cauwenberge P, Bachert C. Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine. Clin Exp Allergy. 2006;36:972-81.

58. Kapp A, Pichler WJ. Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study. Int J Dermatol. 2006;45:469-74.

60. Karppinen A, Brummer-Korvenkontio H, Petman L, Kautiainen H, Herve JP, Reunala T. Levocetirizine for treatment of immediate and delayed mosquito bite reactions. Acta Derm Venereol. 2006;86:329-31.

61. Hindmarch I, Johnson S, Meadows R, Kirkpatrick T, Shamsi Z. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin. 2001;17:241-55.

62. Gandon JM, Allain H. Lack of effect of single and repeated doses of levocetirizine, a new antihistamine drug, on cognitive and psychomotor functions in healthy volunteers. Br J Clin Pharmacol. 2002;54:51-8.

63. Bachert C, Bousquet J, Canonica GW, Durham SR, Klimek L, Mullol J, et al. Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis. J Allergy Clin Immunol. 2004;114:838-44.

64. Izquierdo I, Merlos M, Garcia-Rafanell J. Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis. Drugs Today (Barc). 2003;39:451-68.

65. Barbanoj MJ, Garcia-Gea C, Morte A, Izquierdo I, Perez I, Jane F. Central and peripheral evaluation of rupatadine, a new antihistamine/platelet-activating factor antagonist, at different doses in healthy volunteers. Neuropsychobiology. 2004;50:311-21.

66. Queralt M, Brazis P, Merlos M, de Mora F, Puigdemont A. In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1. Inflamm Res. 2000;49:355-60.

68. Stuebner P, Horak F, Zieglmayer R, Arnaiz E, Leuratti C, Perez I, et al. Effects of rupatadine vs. placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber. Ann Allergy Asthma Immunol. 2006;96:37-44.

Correspondence:
Inês C. Camelo-Nunes
Av. Paes de Barros, 844/61
CEP 03114-000 – São Paulo, SP – Brazil
E-mail: [email protected]

The Food and Drug Administration (FDA) asked sleeping pill-makers in January to lower the dosage of their drugs, because medications like Ambien may leave some people feeling groggy in the morning, potentially leading to a traffic accident or other injuries.

Now, the FDA is reminding Americans that another common medication can lead to drowsiness behind the wheel: Allergy medicine.

With allergy season in full swing, the agency is saying people taking antihistamines should be especially cautious when getting behind the wheel.

“Any of these reactions can negatively interfere with driving or operating heavy machinery,” Dr. Jane File, a medical officer at the FDA’s Division of Nonprescription Regulation Development, said in the May 29 Consumer Update.

When your body comes in contact with something you’re allergic to — be it pollen, ragweed, molds, pet dander and dust mites, your body produces a chemical called histamines — according to WebMD. These chemicals cause the nose tissue to swell, which makes you stuffy. It can also lead to other symptoms including runny nose, watery eyes, redness and itching. Collectively, these seasonal allergies are referred to as hay fever.

Taking an antihistamine like diphenhydramine — sold as Benadryl — can reduce or block histamines, thereby stopping the symptoms. But, the FDA says some antihistamines can make you feel drowsy, unfocused and slow to react.

Filie added that you may experience slower reaction time, haziness, or mild confusion — even if you don’t feel drowsy after taking antihistamines.

Dr. Tamara Kuittinen, director of medical education and an emergency medicine physician at Lenox Hill Hospital in New York City, told CBSNews.com that some hospitals give their patients diphenhydramine if they’re having trouble sleeping, so the drowsiness effects are not benign.

She added that some people who take other popular allergy drugs like cetirizine (Zyrtec) and loratadine (Claritin) may also experience drowsiness.

Her advice? Read the label, know what you’re taking, and act accordingly.

“If you have to be awake or doing something that requires operating machinery, it’s better to take at nighttime,” she said.

Some allergy medicines may look similar, but contain different ingredients, so she reiterated the importance of knowing exactly what you’re taking.

“Really, checking the labels — I think it’s critical,” she said.

The FDA agrees. The agency says different antihistamines may be dosed differently, so if you run out of one that works for you and pick up a different kind at the store, you might not be getting a drug that works the same.

“If one specific antihistamine worked for you before, take note of the dosage and make sure you get the same medication the next time,” FDA pharmacist Ayana Rowley said in a statement.

Also, mixing antihistamines with alcohol, sleeping pills or tranquilizers can lead to more drowsiness, and should be avoided, the FDA said. That information can be found on the Drug Facts label, Fille pointed out.

Lastly, if you’re having a bad allergy attack that still won’t go away with the antihistamine, fight the temptation to take more, said Rowley.

“If the correct dosage isn’t providing you the relief you expect, don’t simply keep taking more and more of that product,” she explained, “but instead, consult your health care professional”.

The FDA has more information on driving on medication.

Can Your Allergy Medicine Make Driving Dangerous?

As soon as allergy season hits, many people immediately reach for their allergy medication. Itchy eyes, sneezing, rashes – taking the right medication can quickly get rid of these irritating symptoms.

However, these same drugs, called antihistamines, can come with side effects that make driving more dangerous than you realize.

What Are Antihistamines?

In allergy sufferers, triggers such as pollen, dust mites, ragweed, and pet dander cause the body to produce chemicals called “histamines.” These histamines attach to the cells in your body and cause them to swell and leak fluid. This is what leads to classic allergy symptoms such as a runny nose, watery eyes, sneezing, congestion, etc.

Over-the-Counter Antihistamines

Antihistamines block the activity of histamines in your body. Over-the-counter antihistamines include:

  • Zyrtec (generic: Cetirizine)
  • Claritin (generic: Loratadine)
  • Alavert (generic: Loratadine)
  • Allegra (generic: Fexofenadine)

The medications above are called second-generation antihistamines. They are most commonly used for allergy symptoms only.

There are also first-generation antihistamines. This type is also used for allergies, but can also be used in over-the-counter cold medicines, to treat insomnia, and to treat motion sickness. These include:

  • Dimetapp Cold and Allergy Elixr (generic: Brompheniramine)
  • Chlor-Trimeton (generic: Chlorpheniramine)
  • Dramamine (generic: Dimenhydrinate)
  • Benadryl Allergy (generic: Diphenhydramine)
  • Nytol (generic: Diphenhydramine)
  • Sominex (generic: Diphenhydramine)
  • VicksNyQuil (generic: Doxylamine)
  • Alka-Seltzer Plus Night-Time Cold Medicine (generic: Doxylamine)

Prescription Antihistamines

There are also prescription-grade antihistamines. Some of these include:

Antihistamine Side Effects

The good news is that for many adults, antihistamines don’t have any noticeable side effects. However, side effects can be problematic for some people, especially older adults or those with health issues. This is particularly true of first-generation antihistamines, which can cause marked sleepiness. This drowsiness is significant – some hospitals actually use certain antihistamines to help patients sleep.

Furthermore, even if an antihistamine doesn’t make you drowsy, it can still lead to haziness, confusion, or slow reaction time.

All of this can add up to a dangerous situation if you get behind the wheel.

Drowsy driving is a real problem. According to the National Sleep Foundation, 60% of adult drivers have driven while drowsy in the past year. The National Highway Traffic Safety Administration estimates that every year, 100,000 police-reported car accidents are the result of driver drowsiness. This doesn’t take into consideration the accidents that aren’t reported to police.

Precautions You Should Take

The Food and Drug Administration has recommendations on precautions you should take when using antihistamines:

  • Be aware that different antihistamines can be dosed differently. You shouldn’t assume that if you switch from one allergy medication to another that the dosing will be the same.
  • Avoid drinking alcohol and taking sedatives or tranquilizers while using some antihistamines. They can increase drowsiness.
  • Keep in mind that some allergy medications take a longer time to work than others. You might feel the effects of some medications hours after you’ve taken them, and maybe even the next day.
  • Like with any medication, always read the drug’s label for warnings. Some medications may look similar but contain different ingredients.
  • If the correct dosage isn’t providing the relief you need, don’t increase the dosage amount. Talk to your healthcare provider about your options.
  • Finally, if you think that your medication may cause drowsiness, be safe and take it at bedtime.

Drowsy Driving Equals Dangerous Driving

Impaired driving doesn’t just refer to alcohol. Many medications – including some allergy medicines – can have side effects that make driving unsafe. If you, or someone you care about, was injured in an accident that involved any type of impaired driving, it only takes a few minutes to find out what your legal options are by filling out the form below.

Sources:
“Antihistamines: Understanding Your OTC Options.” FamilyDoctor.org. May 31, 2016.
“Stats About Drowsy Driving Prove Being Tired Behind the Wheel is More Serious Than You Think.” The Huffington Post. November 4, 2014.
“FDA: Allergy medications may make you too drowsy to drive.” CBSnews.com. June 2, 2013.

Can Allergy Meds Cause Mood Issues?

As a corollary, medication allergies are more common in people who have been exposed to a lot of medications, so your phobia may offer you some advantages. Always ask your doctor if an antibiotic or medication is really necessary. Many practitioners assume that patients want antibiotics and this influences their decision to prescribe them, when it may not be completely clear that one is needed. If you mention that you would rather avoid antibiotics when possible, you’ll probably find your doctor to be pleasantly surprised; he or she may suggest that you wait a week or so to see if the problem clears on its own. This advice applies best to colds, bronchitis, sinus infections, urinary tract infections, and minor skin infections. Although there are certain serious infections, most of which cause several days of high fever, for which treatment should not be delayed, and your doctor would inform you.

Q4. I have really bad hay fever in the spring and the fall, but I’m fine the rest of the year. How far in advance should I start taking my allergy medications?

You should start taking your medications at the same time the plants that trigger your allergies start to pollinate. The spring pollens are trees and grass. Trees start to pollinate at the beginning of March, and grass starts to pollinate at the beginning of May. For spring allergies, start medications in early March.

Fall pollens include ragweed and other weeds, which start to pollinate around the middle of August. So that’s when a fall allergic person should start treatment.

Learn more in the Everyday Health Allergy Center.

Allergies or ADHD? Hay Fever Can Look Like Behavior or Learning Issues

Constant sneezing, incessantly itchy eyes, and a runny nose can make people of all ages downright miserable during allergy season.

But while these symptoms generally aren’t considered a major health concern, they can make a big impact on a child’s ability to learn at school.

In fact, the symptoms of seasonal allergies can be confused with learning disabilities, or other conditions that can affect learning like attention deficit hyperactivity disorder (ADHD), said Dr. Maria Garcia-Lloret, a board-certified pediatric allergist at the UCLA Mattel Children’s Hospital.

“Adults can express their allergies more clearly, but allergies can leave kids in a fog. Children who are stuffed up can become unfocused and seen as inattentive in the classroom,” she said.

A child with untreated seasonal allergies may spend the entire lesson distracted by their discomfort, rather than learning — which can cause grades to drop and teachers to worry.

Furthermore, uncomfortable symptoms like congestion may lower the quality of kids’ sleep at night, making it even harder to focus at school, said Dr. Tania Elliott, a board-certified allergist and internist in New York.

“Kids spending all night stuffed up and mouth breathing will have their sleep pattern disrupted. They definitely won’t be as refreshed or attentive,” Elliott told Healthline.

How can you tell if it’s allergies or a learning disability?

Parents should consider when their child started struggling in school, how long it’s been going on, and whether they have traditional allergy symptoms.

“If the kid is thriving in every month except April and May, and all of a sudden you get calls that they’re not paying attention, it’s likely related to seasonal allergies,” said Elliott. “If you have a learning disability, you probably don’t have a chronic runny nose, for example.”

Allergies are the sixth-leading cause of chronic illness in the United States, according to the Centers for Disease Control and Prevention (CDC). They’re very common among both children and adults. In 2016, the CDC estimated that 5.5 million children had hay fever symptoms, while 7.6 million kids had respiratory allergies.

Garcia-Lloret estimates that about 20 to 30 percent of kids with allergies have trouble learning as a result of their symptoms.

“It might not be that they’re failing in school, but it affects their behavior. Teachers might say that the child is really fidgety,” Garcia-Lloret said. “Treating allergies can improve their concentration and ability to finish the work.”

How to stop allergy symptoms

If your child is having allergy symptoms, take them to their pediatrician or an allergist to figure out what’s to blame. Then, work with the doctor on a treatment plan.

“Many parents don’t want to give their kids medication, and I understand that. But if I find a connection between their lack of focus in school and their allergy symptoms, I ask them to go on an 8-week treatment plan,” said Garcia-Lloret.

Treatments for seasonal allergies traditionally include nasal steroid spray, an antihistamine, and allergy shots. Natural remedies — such as nasal saline sprays — can also help children find relief, said Elliott.

“Think about it: We wash our hands frequently, why shouldn’t we wash our nasal passages frequently? The nasal saline spray can wash the pollen out of your nasal passage, and kids can use it 5 to 10 times a day,” Elliott said.

Parents of children with moderate to severe symptoms should also take measures to reduce their exposure to seasonal allergens. Limit the time they spend outdoors when pollen counts are high, and have them wear removable clothes on their way to school.

“A light windbreaker, sunglasses, and a cap can help kids minimize the amount of pollen getting stuck on their clothes, eyes, and hair. Have them put those items in a closet as soon as they get to the classroom,” said Elliott.

Finally, see if the teacher will allow you to put an air filter in the classroom, she added. Minimizing triggers in class will keep kids with allergies more comfortable throughout the day.

Most people consider their seasonal allergies to be a short-term nuisance they deal with a couple of months out of the year. But when left untreated, their effects on everyday life can turn into long-term problems, including falling behind at school.

Often, medications taken to treat a variety of ailments — from depression to diabetes to seizures — come with an unwelcome side effect: weight gain. And that’s something doctors often fail to warn their patients about.

But at a time when 40 percent of adults and almost 20 percent of children and adolescents in the U.S. are obese, it’s important to be aware that a medicine that is improving your health in one way may be hurting it in another. Excess weight increases risk of heart disease and other illnesses.

The good news is alternative drugs often are just as effective without causing weight gain. As with most things medical, treating an illness is often a matter of balancing the good with the bad. So, as a rule of thumb, talk to your doctor about treatment options if, after starting a new drug, you find yourself gaining 8 to 10 percent of your initial body weight.

And don’t stop taking a prescription drug on your own, which can have dangerous consequences. It can, for example, make depression worse and more difficult to treat, or cause rebound seizures in those with that condition.

Here’s a look at some commonly used categories of drugs that can lead to weight gain, and some possible alternatives to discuss with your doctor.

Antidepressants

Worldwide, depression is the No. 1 cause of ill health and disability, according to the World Economic Forum. And the Centers for Disease Control and Prevention estimates that 1 in 10 people older than 12 take medication for the condition.

One common symptom of depression is loss of appetite. So when patients start taking antidepressants, including selective serotonin reuptake inhibitors such as paroxetine (Paxil) and fluvoxamine (Luvox), their appetite often comes roaring back. And with it, the pounds.

“In this case, the weight gain is good news because it means the drug is working,” said Lucy Wilkening, an assistant professor at the Feik School of Pharmacy at the University of the Incarnate Word. “Patients are feeling better and want to eat again.”

Wilkening said that patients who are concerned should ask their doctor about alternatives medicines not associated with weight gain, including fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft) and bupropion (Wellbutrin).

Antihistamines

Taken occasionally for allergies, antihistamines shouldn’t cause weight problems, but many people are so fearful of the symptoms, they use them year-round, according to Christina Guerra Long, assistant professor of pharmacy practice at the Feik School.

A 2010 study in the journal Obesity found those who took antihistamines daily had larger waistlines and higher insulin levels, a sign of obesity.

Older antihistamines such as diphenhydramine (Benadryl) trigger weight gain by boosting appetite and making users drowsy so they aren’t as physically active and burn fewer calories. Newer drugs, including cetirizine (Zyrtec), fexofenadine (Allegra) and loratadine (Claritin), are less likely to cause weight gain, according to Long.

Still, there’s an easy way to avoid the problem.

“You need to be smart about these drugs and use them only when you really need them, which is during allergy season,” Long said.

Anti-seizure drug

The mechanism by which the anti-seizure medicine divalproex (Depakote) causes weight gain is not well understood, although it may be because the drug, which is also prescribed to treat frequent migraine headaches and bipolar disorder, increases cravings for carbohydrates. In a 2007 study in the journal Seizure, for example, a quarter of men and almost half of women who took the drug for a year or more gained an average of 14 pounds.

But that may not be reason enough for most patients to stop taking it.

“Seizures are a serious medical condition, and divalproex is an effective drug,” Wilkening said. “Doctors may be hesitant to take patients off it if it’s working.”

There is another anti-seizure drug, lamotrigine (Lamictal), that is less likely to lead to weight gain, but Wilkening said patients’ best bet may be to adjust their diet and exercise regimen to help keep weight under control.

Corticosteroids

This is a class of steroid hormones prescribed for a variety of chronic conditions, including asthma, rheumatoid arthritis and lupus, as well as to those who’ve received an organ transplant. Not only do they increase appetite, these drugs also redistribute body fat to the abdominal area, so any weight gain is more noticeable.

For patients with the medical need for these drugs, the best way to minimize weight gain is through diet and exercise.

Diabetes drugs

This increasingly common disease occurs when muscle and brain cells become resistant to insulin, the hormone that signals body cells to absorb glucose (sugar) to use for energy.

Some popular oral diabetes meds in the sulfonylurea class, including chlorpropamide (Diabinese) and glyburide (Mocronase), work by stimulating the pancreas to release more insulin.

“That causes insulin to store excess glucose as fat, so you gain weight,” said Oralia Bazaldua, a pharmacist and professor of family and community medicine at UT Health San Antonio. “And some people also tend to eat more for fear of hypoglycemia, or low blood sugar.”

Another class of drugs, called thiazolidines, include pioglitazone (Actos) and rosiglitazone (Avandia) that help insulin work better, so less sugar is lost in the urine. This can lead to weight gain and fluid retention.

One popular alternative to these drugs, according to Bazaldua, is metformin (Glucophage), which makes cells more sensitive to insulin. This allows the liver to produce less sugar, reducing risk of weight gain. Newer, self-injectable drugs like once-a-day liraglutide (Victoza) and once-a-week dulaglutide (Trulicity) work similarly.

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *