Skip to main content

Diphenhydramine / pseudoephedrine Side Effects

Medically reviewed by Drugs.com. Last updated on Sep 23, 2023.

Applies to diphenhydramine / pseudoephedrine: oral liquid, oral tablet, oral tablet disintegrating.

Warning

Do not use diphenhydramine and pseudoephedrine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

Get emergency medical help if you have any of these signs of an allergic reaction while taking diphenhydramine / pseudoephedrine: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have:

Common side effects may include:

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to diphenhydramine / pseudoephedrine: oral liquid, oral tablet, oral tablet disintegrating.

Nervous system

Central nervous system (CNS) depression commonly occurs with diphenhydramine administration, resulting in drowsiness and sedation in nearly all patients treated. Motor skills may be impaired. Dystonic reactions have been reported after single doses of diphenhydramine.

Pseudoephedrine produces nervous system stimulation, resulting in tremor, anxiety, and nervousness. Insomnia is reported in up to 30% of pseudoephedrine-treated patients. Headache may also occur in patients receiving pseudoephedrine.[Ref]

The CNS depressant effect of diphenhydramine parallels its plasma concentrations. The plasma concentration threshold for sedation is 30 to 42 ng/mL, and to cause mental impairment is 58 to 74 ng/mL. Patients should be warned against driving while taking diphenhydramine, and should avoid concomitant ingestion of alcohol.

Dystonic reactions to diphenhydramine have been accompanied by dizziness, mental confusion, rigidity, lip and tongue protrusion, trismus, torticollis, and swallowing difficulties. These reactions generally resolve spontaneously. Toxic encephalopathy has been reported in a child with chicken pox treated generously with topical diphenhydramine.

Delirium has been reported in elderly patients with mild dementia following small oral doses of diphenhydramine.[Ref]

Cardiovascular

Pseudoephedrine causes vasoconstriction which generally does not produce hypertension, but may be problematic for patients with pre-existing hypertension. Arrhythmias may be produced in predisposed patients. Rarely, pseudoephedrine has been reported to cause coronary artery spasm and chest pain.[Ref]

Cardiovascular effects of diphenhydramine may include hypotension, tachycardia, and palpitations.

Cardiovascular adverse effects more commonly may be associated with pseudoephedrine. Pseudoephedrine generally causes a significant rise in heart rate. Hypertension and arrhythmias may be problematic in susceptible patients.[Ref]

Hypersensitivity

Hypersensitivity reactions may occur with diphenhydramine, generally resulting in rash, pruritus and eczema. Photosensitivity reactions have also been reported with diphenhydramine.

Hypersensitivity reactions to pseudoephedrine may also occur. Fixed drug eruptions secondary to pseudoephedrine have been reported.[Ref]

Most commonly, hypersensitivity to diphenhydramine manifests itself in patients receiving systemic drug after being sensitized to it by topical application. Sensitization with systemic administration has also been reported.[Ref]

Gastrointestinal

Gastrointestinal tract adverse effects of diphenhydramine are mild, and may include nausea, dry mouth, and constipation.

Gastrointestinal adverse effects of pseudoephedrine may include anorexia and gastric irritation in approximately 5% of patients. Dry mouth, nose, or throat may occur in up to 15% of patients.[Ref]

Ocular

Ocular affects of diphenhydramine may include blurred vision, diplopia, and dry eyes due to its anticholinergic effect.[Ref]

Genitourinary

The genitourinary tract may be adversely affected due to the anticholinergic effects of diphenhydramine, resulting in urinary retention and dysuria.[Ref]

Hematologic

Hematologic adverse effects such as hemolytic anemia, thrombocytopenia, and agranulocytosis may be rarely caused by antihistamines.[Ref]

References

1. Lavenstein BL, Cantor FK. Acute dystonia: an unusual reaction to diphenhydramine. JAMA. 1976;236:291.

2. Carruthers SG, Shoeman DW, Hignite CE, Azarnoff DL. Correlation between plasma diphenhydramine level and sedative and antihistamine effects. Clin Pharmacol Ther. 1978;23:375-82.

3. Gengo F, Gabos C, Miller JK. The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance. Clin Pharmacol Ther. 1989;45:15-21.

4. Burns M, Moskowitz H. Effects of diphenhydramine and alcohol on skills performance. Eur J Clin Pharmacol. 1980;17:259-66.

5. Roila F, Donati D, Basurto C, Del Favero A. Diphenhydramine and acute dystonia . Ann Intern Med. 1989;111:92-3.

6. Davenport PM, Wilhelm RE. An unusual vasculitis due to diphenhydramine. Cutaneous and central nervous system involvement. Arch Dermatol. 1965;92:577-80.

7. Filloux F. Toxic encephalopathy caused by topically applied diphenhydramine. J Pediatr. 1986;108:1018-20.

8. Brait KA, Zagerman AJ. Dyskinesias after antihistamine use . N Engl J Med. 1977;296:111.

9. Jones B, Lal S. Tardive dyskinesia uncovered after ingestion of Sominex, an over-the- counter drug. Can J Psychiatry. 1985;30:370-1.

10. Santora J, Rozek S, Samie MR. Diphenhydramine-induced dystonia . Clin Pharm. 1989;8:471.

11. Borbely AA, Youmbi-Balderer G. Effect of diphenhydramine on subjective sleep parameters and on motor activity during bedtime. Int J Clin Pharmacol Ther Toxicol. 1988;26:392-6.

12. Stroh JE, Jr Ayars GH, Bernstein IL, Kemp JP, Podleski WK, Prenner BM, Schoenwetter WF, Salzmann JK. A comparative tolerance study of terfenadine-pseudoephedrine combination tablets and pseudoephedrine tablets in patients with allergic or vasomotor rhinitis. J Int Med Res. 1988;16:420-7.

13. Loizou LA, Hamilton JG, Tsementzis SA. Intracranial haemorrhage in association with pseudoephedrine overdose. J Neurol Neurosurg Psychiatry. 1982;45:471-2.

14. Dickerson J, Perrier D, Mayersohn M, Bressler R. Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man. Eur J Clin Pharmacol. 1978;14:253-9.

15. Covington TR, eds., Lawson LC, Young LL. Handbook of Nonprescription Drugs. Washington, DC: American Pharmaceutical Association. 1993.

16. Tejera CA, Saravay SM, Goldman E, Gluck L. Diphenhydramine-induced delirium in elderly hospitalized patients with mild dementia. Psychosomatics. 1994;35:399-402.

17. Mariani PJ. Pseudoephedrine-induced hypertensive emergency: treatment with labetalol. Am J Emerg Med. 1986;4:141-2.

18. Rosen RA. Angina associated with pseudoephedrine . Ann Emerg Med. 1981;10:230-1.

19. Wiener I, Tilkian AG, Palazzolo M. Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudoephedrine ingestion. Cathet Cardiovasc Diagn. 1990;20:51-3.

20. Gordon RD, Ballantine DM, Bachmann AW. Effects of repeated doses of pseudoephedrine on blood pressure and plasma catecholamines in normal subjects and in patients with phaeochromocytoma. Clin Exp Pharmacol Physiol. 1992;19:287-90.

21. Horio T. Allergic and photoallergic dermatitis from diphenhydramine. Arch Dermatol. 1976;112:1124-6.

22. Emmett EA. Diphenhydramine photoallergy. Arch Dermatol. 1974;110:249-52.

23. Coskey RJ. Contact dermatitis caused by diphenhydramine hydrochloride. J Am Acad Dermatol. 1983;8:204-6.

24. Lawrence CM, Byrne JP. Eczematous eruption from oral diphenhydramine. Contact Dermatitis. 1981;7:276-7.

25. Shelley WB, Shelley ED. Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline. J Am Acad Dermatol. 1987;17:403-7.

26. Tomb RR, Lepoittevin JP, Espinassouze F, Heid E, Foussereau J. Systemic contact dermatitis from pseudoephedrine. Contact Dermatitis. 1991;24:86-8.

27. Camisa C. Fixed drug eruption due to pseudoephedrine. Cutis. 1988;41:339-40.

28. Schuller DE, Turkewitz D. Adverse effects of antihistamines. Postgrad Med. 1986;79:75-86.

29. Seedor JA, Lamberts D, Bergmann RB, Perry HD. Filamentary keratitis associated with diphenhydramine hydrochloride (Benadryl). Am J Ophthalmol. 1986;101:376-7.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.