Some antihistamines cause drowsiness,which can be increased byalcohol. The detrimental effects of alcohol on driving skills areconsiderably increased by use of older more sedative antihistamines and appear to be minimal or absent with newernon-sedating antihistamines.
A double-blind study found that terfenadine 60 to 240mg alone did not affect psychomotor skills, nor did it affect adverse effects of alcohol (See reference number 1). Another study had similar findings (See reference number 2). However, a later study found that terfenadine 240mg slowed brake reaction times in laboratory when given either alone or with alcohol (See reference number 3). Acrivastine 4 and 8 mg,given with and without alcohol, was found in a study to behave like terfenadine (which interacts minimally or not at all) (See reference number 4). Other studies have shown that astemizole 10 to 30mg daily,(See reference number 5-7)desloratadine,(See reference number 8)ebastine 20 mg,(See reference number 9)fexofenadine 120 to 240 mg,(See reference number 10,11)levocabastine 2 nasal puffs of 0.5 mg/mL,(See reference number 12)loratadine 10 to 20 mg(See reference number 2,13) and mizolastine 10 mg(See reference number 14)do not interact with alcohol. Cetirizine 10mg did not appear to interact with alcohol in two studies(See reference number 14,15)but some slight additive effects were detected in other studies (See reference number 13,16). Similarly,a single oral dose of rupatadine 10 mg did not interact with alcohol, but a 20mg dose given with alcohol produced more cognitive and psycho-motor impairment than alcohol alone (See reference number 16).
The effects of alcohol (blood levels about 50 mg%) and antihistamines, alone or together, on performance of tests designed to assess mental and motor performance were examined in 16 subjects. Clemizole 40mg or tripelennamine 50mg alone did not significantly affect performance under stress of delayed auditory feedback, neither did they potentiate effect of alcohol (See reference number 17). Clemastine in 3mg doses had some additive detrimental effects with alcohol on co-ordination,whereas clemastine
1.5 mg and 1mg did not (See reference number 18,19). A study in 5 subjects showed that detrimental effects of 100 mL of whiskey on performance of driving tests on a racing car simulator (blood alcohol estimated as less than 80 mg% were not increased by cyclizine 50mg (See reference number 20). However 3 of subjects experienced drowsiness after cyclizine, and other studies have shown that cyclizine alone causes drowsiness in majority of subjects (See reference number 21). Significant impairment of psychomotor performance was seen in healthy subjects given chlorphenamine 12mg with alcohol 0.5 g/kg (See reference number 5). A further study similarly found significant impairment in driving skills when chlorphenamine was given with alcohol,see (c) below. In 13 healthy subjects alcohol
0.75 g/kg given with dexchlorpheniramine 4 mg/70 kg significantly impaired performance of a number of tests (standing steadiness, reaction time, manual dexterity, perception, etc.) (See reference number 22). A study in 17 subjects found that mebhydrolin 0.71 mg/kg enhanced alcohol-induced deficits in performance of a number of tests on perceptual, cognitive and motor functions (See reference number 23). No interaction was detected in one study of combined effects of pheniramine aminosalicylate 50mg or cyproheptadine hydrochloride 4mg and alcohol 0.95 mL/kg (See reference number 24). Triprolidine 10mg alone can significantly affect driving performance,(See reference number 2) and marked deterioration in driving skills has been demonstrated with 10 mL of Actifed Syrup (triprolidine with pseudoephedrine) alone and with a double whiskey (See reference number 25).
Diphenhydramine in doses of 25 or 50mg was shown to increase detrimental effects of alcohol on performance of choice reaction and coordination tests in subjects who had taken 0.5 g/kg of alcohol (See reference number 18). The interaction between diphenhydramine in doses of 50,75 or 100mg and alcohol in doses of 0.5 to 0.75 g/kg has been confirmed in other reports (See reference number 1,17,26-28). Emedastine in oral doses of 2 or 4mg twice daily was found to be sedating and impair driving ability in 19 healthy subjects. The addition of alcohol increased this impairment (See reference number 29). A marked interaction can also occur with hydroxyzine(See reference number 11,16) or promethazine (See reference number 30). A very marked deterioration in driving skills was clearly demonstrated in a test of car drivers given 20 mL of Beechams Night Nurse (promethazine with dextromethorphan),10 mL of Benylin (diphenhydramine with dextromethorphan), or 30 mL of Lemsip Night time flu medicine (chlorphenamine with dextromethorphan). Very poor scores were seen when they were also given a double Scotch whiskey about 1.5 hrs later (See reference number 25).
When an interaction occurs it appears to be due to combined or additive central nervous depressant effects of both alcohol and antihistamine. The highly-sedating antihistamines are highly lipophilic and readily cross blood-brain barrier; consequently they have considerable sedative effects that may persist into next day. The sedating antihistamines do not cross blood-brain barrier so readily, and are therefore less sedating. Most of non-sedating antihistamines, such as fexofenadine, do not appear to cross blood-brain barrier (See reference number 11). The authors of one study found that sedating effects of cetirizine and emedastine were more marked in women than in men, and they noted that they had also previously seen this with acrivastine, clemastine and mizolastine (See reference number 29). The reason for this is not established although it has been suggested that a smaller volume of distribution in women may result in higher plasma antihistamine levels.
An adverse interaction between alcohol and highly-sedating antihistamines (see table 1 below,) is well established and clinically important. Marked drowsiness can occur with these antihistamines taken alone,which makes driving or handling other potentially dangerous machinery much more hazardous. This can be further worsened by alcohol. Patients should be strongly warned. Remember that some of these antihistamines are present in non-prescription products licensed as antiemetics and sedatives,and as components of cough, cold and influenza remedies
(e.g. some preparations of Benylin,Lemsip or Night Nurse). Emedastine may also cause marked sedation when used orally,but it is usually given as eye drops.
The situation with some of sedating antihistamines is less clear cut, and tests with some of them failed to detect an interaction with normal doses and moderate amounts of alcohol; however, it has been clearly seen with Actifed Syrup (containing triprolidine). It would therefore be prudent to issue some cautionary warning, particularly if patient is likely to drive.
The non-sedating antihistamines seem to cause little or no drowsiness in most patients and risks if taken alone or with alcohol appear to be minimal or absent. However, incidence of sedation varies with non-sedating antihistamine (e.g. sedation appears to be lower with fexofenadine and loratadine than with acrivastine or cetirizine)(See reference number 31) and with individual (e.g. women may be more affected than men) (See reference number 29). Therefore, patients should be advised to be alert to possibility of drowsiness if they have not taken drug before. Any drowsiness would be apparent after first few doses. The patient information leaflets for acrivastine and cetirizine suggest avoidance of alcohol or excessive amounts of alcohol,(See reference number 32-34)
The possible interactions of alcohol with other antihistamines not cited here do not seem to have been formally studied,but increased drowsiness and increased driving risks would be expected with any that cause some sedation. Patients should be warned about drinking alcohol when taking sedative antihistamines. The risks with antihistamines given as eye drops or nasal spray (e.g. azelastine,epinastine) are probably minimal, but this needs confirmation.
Moser L,Hüther KJ, Koch-Weser J, Lundt PV. Effects of terfenadine and diphenhydraminealone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings. Eur J Clin Pharmacol (1978) 14, 417–23.
O’Hanlon JF. Antihistamines and driving performance: The Netherlands. J Respir Dis (1988) (Suppl),S12–S17.
Bhatti JZ,Hindmarch I. The effects of terfenadine with and without alcohol on an aspect ofcar driving performance. Clin Exp Allergy (1989) 19, 609–11.
Cohen AF,Hamilton MJ, Peck AW. The effects of acrivastine (BW825C), diphenhydramineand terfenadine in combination with alcohol on human CNS performance. Eur J Clin Pharmacol (1987) 32, 279–88.
Hindmarch I,Bhatti JZ. Psychomotor effects of astemizole and chlorpheniramine, alone andin combination with alcohol. Int Clin Psychopharmacol (1987) 2, 117–19.
Bateman DN,Chapman PH, Rawlins MD. Lack of effect of astemizole on ethanol dynamicsor kinetics. Eur J Clin Pharmacol (1983) 25, 567–8.
Moser L,Plum H, Bückmann M. Interaktionen eines neuen Antihistaminikums mit Diazepamund Alkohol. Med Welt (1984) 35, 296–9.
Rikken G,Scharf M, Danzig M, Staudinger H. Desloratadine and alcohol coadministration:no increase in impairment of performance over that induced by alcohol alone. Poster at EAACI (European Academy of Allergy and Clinical Immunology) Conference, Lisbon, Portugal.2-4 July 2000.
Mattila MJ,Kuitunen T, Plétan Y. Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine ebastine with ethanol in healthy subjects. Eur J Clin Pharmacol (1992) 43, 179–84.
Vermeeren A,O’Hanlon JF. Fexofenadine’s effects, alone and with alcohol, on actual drivingand psychomotor performance. J Allergy Clin Immunol (1998) 101, 306–11.
Ridout F,Shamsi Z, Meadows R, Johnson S, Hindmarch I. A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180mg alone and with alcohol, with hydroxyzine hydrochloride 50mg as a positiveinternal control, on aspects of cognitive and psychomotor function related to driving a car.Clin Ther (2003) 25, 1518–38.
Nicholls A,Janssens M, James R. The effects of levocabastine and ethanol on psychomotorperformance in healthy volunteers. Allergy (1993) 48 (Suppl 16), 34.
Ramaekers JG,Uiterwijk MMC, O’Hanlon JF. Effects of loratadine and cetirizine on actualdriving and psychometric test performance, and EEG during driving. Eur J Clin Pharmacol (1992) 42, 363–9.
Patat A,Stubbs D, Dunmore C, Ulliac N, Sexton B, Zieleniuk I, Irving A, Jones W. Lack ofinteraction between two antihistamines, mizolastine and cetirizine, and ethanol in psychomotor and driving performance in healthy subjects. Eur J Clin Pharmacol (1995) 48, 143–50.
Doms M,Vanhulle G, Baelde Y, Coulie P, Dupont P, Rihoux J-P. Lack of potentiation bycetirizine of alcohol-induced psychomotor disturbances. Eur J Clin Pharmacol (1988) 34, 619–23.
Barbanoj MJ,García-Gea C, Antonijoan R, Izquierdo I, Donado E, Pérez I, Solans A, Jané F.Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers. Hum Psychopharmacol (2006) 21, 13–26.
Hughes FW,Forney RB. Comparative effect of three antihistaminics and ethanol on mentaland motor performance. Clin Pharmacol Ther (1964) 5, 414–21.
Linnoila M. Effects of antihistamines,chlormezanone and alcohol on psychomotor skills related to driving. Eur J Clin Pharmacol (1973) 5, 247–54.
Franks HM,Hensley VR, Hensley WJ, Starmer GA, Teo RKC. The interaction between ethanol and antihistamines. 2. Clemastine. Med J Aust (1979) 1, 185–6.
Hughes DTD,Cramer F, Knight GJ. Use of a racing car simulator for medical research. Theeffects of marzine and alcohol on driving performance. Med Sci Law (1967) 7, 200–4.
Brand JJ,Colquhoun WP, Gould AH, Perry WLM. (–)-Hyoscine and cyclizine as motionsickness remedies. Br J Pharmacol Chemother (1967) 30, 463–9.
Franks HM,Hensley VR, Hensley WJ, Starmer GA, Teo RKC. The interaction between ethanol and antihistamines. 1: Dexchlorpheniramine. Med J Aust (1978) 1, 449–52.
Franks HM,Lawrie M, Schabinsky VV, Starmer GA, Teo RKC. Interaction between ethanoland antihistamines. 3. mebhydrolin. Med J Aust (1981) 2, 477–9.
Landauer AA,Milner G. Antihistamines, alone and together with alcohol, in relation to driving safety. J Forensic Med (1971) 18, 127–39.
Carter N. Cold cures drug alert. Auto Express (1992) November Issue 218,15–16.
Baugh R,Calvert RT. The effect of diphenhydramine alone and in combination with ethanolon histamine skin response and mental performance. Eur J Clin Pharmacol (1977) 12, 201–4.
Burns M,Moskowitz H. Effects of diphenhydramine and alcohol on skills performance. Eur J Clin Pharmacol (1980) 17, 259–66.
Burns M. Alcohol and antihistamine in combination: effects on performance. Alcohol Clin Exp Res (1989) 13,341.
Vermeeren A,Ramaekers JG, O’Hanlon JF. Effects of emedastine and cetirizine, alone and with alcohol, on actual driving of males and females. J Psychopharmacol (2002) 16, 57–64.
Hedges A,Hills M, Maclay WP, Newman-Taylor AJ, Turner P. Some central and peripheraleffects of meclastine, a new antihistaminic drug, in man. J Clin Pharmacol (1971) 11, 112–
19.
Mann RD,Pearce GL, Dunn N, Shakir S. Sedation with “non-sedating” antihistamines: fourprescription-event monitoring studies in general practice. BMJ (2000) 320, 1184–6.
Semprex (Acrivastine). Glaxo Wellcome. UK Patient information leaflet,February 2002.
Cetirizine. Actavis UK Ltd. UK Patient information leaflet,January 2004.
Zirtek Allergy (Cetirizine). UCB Pharma Ltd. UK Patient information leaflet,December2005.
Xyzal (Levocetirizine). UCB Pharma Ltd. Patient information leaflet,February 2006.
| Table 1 Systemic antihistamines (classified by sedative potential) and topical antihistamines | |
|---|---|
| Sedative potential | Antihistamine |
| Non-sedative | Acrivastine, Astemizole,* Cetirizine, Desloratadine, Ebastine,* Fexofenadine, Levocetirizine, Loratadine, Mizolastine,* Rupatadine, Terfenadine* |
| Sedating | Azatadine, Brompheniramine, Buclizine, Chlorphenamine, Cinnarizine, Clemastine, Cyclizine, Cyproheptadine, Dexchlorpheniramine, Flunarizine, Meclozine, Mepyramine, Mequitazine, Pheniramine, Tripelennamine, Triprolidine |
| Significantly sedating | Alimemazine, Bromazine, Carbinoxamine, Dimenhydrinate, Diphenhydramine, Doxylamine, Hydroxyzine, Promethazine, Trimeprazine |
| Topical use (mainly) | Antazoline, Azelastine, Emedastine, Epinastine, Levocabastine, Olopatadine |