Diphenhydramine Hydrochloride

Synonyms: Benzhydramine Hydrochloride; Difenhidramin Hidroklorür; Difenhidramin-hidroklorid; Difenhidramino hidrochloridas; Difenhydramiinihydrokloridi; Difenhydramin-hydrochlorid; Difenhydraminhydroklorid; Difenhydraminy chlorowodorek; Dimedrolum; Diphénhydramine, chlorhydrate de; Diphenhydramini hydrochloridum; Diphenhydraminium Chloride; Hidrocloruro de difenhidramina.
Cyrillic synonym: Дифенгидрамина Гидрохлорид.

💊 Chemical information

Chemical formula: C17H21NO,HCl = 291.8.
CAS — 147-24-0.
ATC — D04AA32; R06AA02.
ATC Vet — QD04AA32; QR06AA02.


In Chin., Eur., Jpn, and US. Jpn also includes Diphenhydramine Tannate.

Ph. Eur. 6.2

(Diphenhydramine Hydrochloride). A white or almost white, crystalline powder. Very soluble in water; freely soluble in alcohol. A 5% solution in water has a pH of 4.0 to 6.0. Protect from light.

USP 31

(Diphenhydramine Hydrochloride). A white, odourless, crystalline powder. It slowly darkens on exposure to light. Soluble 1 in 1 of water, 1 in 2 of alcohol and of chloroform, and 1 in 50 of acetone; very slightly soluble in ether and in benzene. Its solutions are neutral to litmus. Store in airtight containers. Protect from light.


Diphenhydramine hydrochloride has been reported to be incompatible with amphotericin B, cefmetazole sodium, cefalotin sodium, hydrocortisone sodium succinate, some soluble barbiturates, some contrast media, and solutions of alkalis or strong acids.

💊 Adverse Effects and Precautions


Reports of the abuse of diphenhydramine hydrochloride.
1. Anonymous. Is there any evidence that Benylin syrup is addictive? BMJ 1979; 1: 459
2. Smith SG, Davis WM. Nonmedical use of butorphanol and diphenhydramine. JAMA 1984; 252: 1010
3. Feldman MD, Behar M. A case of massive diphenhydramine abuse and withdrawal from use of the drug. JAMA 1986; 255: 3119–20
4. de Nesnera AP. Diphenhydramine dependence: a need for awareness. J Clin Psychiatry 1996; 57: 136–7
5. Dinndorf PA, et al. Risk of abuse of diphenhydramine in children and adolescents with chronic illnesses. J Pediatr 1998; 133: 293–5.

Extrapyramidal disorders.

Reports of dystonic extrapyramidal reactions to diphenhydramine.
1. Lavenstein BL, Cantor FK. Acute dystonia: an unusual reaction to diphenhydramine. JAMA 1976; 236: 291
2. Santora J, Rozek S. Diphenhydramine-induced dystonia. Clin Pharm 1989; 8: 471
3. Roila F, et al. Diphenhydramine and acute dystonia. Ann Intern Med 1989; 111: 92–3.


In an evaluation of 136 cases, one fatal, of intoxication with diphenhydramine, the plasma concentration was correlated with frequency or extent of symptoms.1 The most common symptom was impaired consciousness; psychosis, seizures, antimuscarinic symptoms such as mydriasis, tachycardia, and tachyarrhythmias, and respiratory failure were also observed. The positive association between dose and frequency and severity of symptoms was confirmed in a more recent study;2 it was also found that severe symptoms were more likely to occur when 1 g or more of diphenhydramine had been taken. There have been reports3,4 of rhabdomyolysis as an effect of oral diphenhydramine overdosage. The liberal application of a lotion containing diphenhydramine produced acute delirium with visual and auditory hallucinations in a 9-year-old boy5 and similar effects were seen in 3 children with varicella-zoster infection following the topical application of diphenhydramine (2 of these children also received oral diphenhydramine).6
1. Köppel C, Tenczer J. Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. Clin Toxicol 1987; 25: 53–70
2. Radovanovic D, et al. Dose-dependent toxicity of diphenhydramine overdose. Hum Exp Toxicol 2000; 19: 489–95
3. Hampel G, et al. Myoglobinuric renal failure due to drug-induced rhabdomyolysis. Hum Toxicol 1983; 2: 197–203
4. Haas CE, et al. Rhabdomyolysis and acute renal failure following an ethanol and diphenhydramine overdose. Ann Pharmacother 2003; 37: 538–42
5. Filloux F. Toxic encephalopathy caused by topically applied diphenhydramine. J Pediatr 1986; 108: 1018–20
6. Chan CYJ, Wallander KA. Diphenhydramine toxicity in three children with varicella-zoster infection. DICP Ann Pharmacother 1991; 25: 130–2.


Diphenhydramine has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.


A pregnant woman who was receiving diphenhydramine hydrochloride 150 mg daily for a pruritic rash gave birth to an infant who developed diarrhoea and generalised tremulousness 5 days later.1 The delay in appearance of withdrawal symptoms was considered to be due to reduced activity of glucuronyl conjugating enzymes in the first few days of life. For discussion of the use of antihistamines in pregnancy, including a suggestion of a relationship between inguinal hernia or genito-urinary malformations and diphenhydramine exposure. See also under Interactions, below, for a report of perinatal death possibly associated with temazepam and diphenhydramine.
1. Parkin DE. Probable Benadryl withdrawal manifestations in a new-born infant. J Pediatr 1974; 85: 580.

💊 Interactions

Diphenhydramine inhibits the cytochrome P450 isoenzyme CYP2D6 that is partly responsible for the metabolism of some beta blockers including metoprolol and the antidepressant venlafaxine.


There has been a report1 suggesting that a reduction in temazepam metabolism caused by diphenhydramine may have contributed to perinatal death after ingestion of these drugs by the mother.
1. Kargas GA, et al. Perinatal mortality due to interaction of diphenhydramine and temazepam. N Engl J Med 1985; 313: 1417–18.

💊 Pharmacokinetics

Diphenhydramine hydrochloride is well absorbed from the gastrointestinal tract, although high first-pass metabolism appears to affect systemic availability. Peak plasma concentrations are achieved about 1 to 4 hours after oral doses. Diphenhydramine is widely distributed throughout the body including the CNS. It crosses the placenta and has been detected in breast milk. Diphenhydramine is highly bound to plasma proteins. Metabolism is extensive. Diphenhydramine is excreted mainly in the urine as metabolites; little is excreted as unchanged drug. The elimination half-life has been reported to range from 2.4 to 9.3 hours.
1. Glazko AJ, et al. Metabolic disposition of diphenhydramine. Clin Pharmacol Ther 1974; 16: 1066–76
2. Paton DM, Webster DR. Clinical pharmacokinetics of H -receptor antagonists (the antihistamines). Clin Pharmacokinet 1985; 10: 477–97. (includes studies indicating a correlation between plasma concentrations and both antihistaminic and sedative effects)
3. Simons KJ, et al. Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children. J Clin Pharmacol 1990; 30: 665–71
4. Scavone JM, et al. Pharmacokinetics and pharmacodynamics of diphenhydramine 25 mg in young and elderly volunteers. J Clin Pharmacol 1998; 38: 603–9.

💊 Uses and Administration

Diphenhydramine, a monoethanolamine derivative, is a sedating antihistamine with antimuscarinic and pronounced sedative properties. It is used for the symptomatic relief of allergic conditions including urticaria and angioedema, rhinitis and conjunctivitis, and in pruritic skin disorders. It is also used for its antiemetic properties in the treatment of nausea and vomiting, particularly in the prevention and treatment of motion sickness (when it should be given at least 30 minutes before travelling), and in the treatment of vertigo of various causes. Diphenhydramine is used for its antimuscarinic properties in the control of parkinsonism and drug-induced extrapyramidal disorders (although the possibility that diphenhydramine itself may cause extrapyramidal symptoms should be remembered). Diphenhydramine has pronounced central sedative properties and may be used as a hypnotic in the short-term management of insomnia. It is a common ingredient of compound preparations for symptomatic treatment of coughs and the common cold. However, such preparations should be used with caution in children, and generally avoided in those under 2 years of age. It may also be given in combination preparations containing analgesics, particularly paracetamol. Diphenhydramine may be used parenterally as an adjunct in the emergency treatment of anaphylactic shock or when oral therapy is not feasible. For most indications, diphenhydramine hydrochloride is given in usual oral doses of 25 to 50 mg three or four times daily. The dose for children is 6.25 to 25 mg three or four times daily, or a total daily dose of 5 mg/kg may be given in divided doses. The maximum dose in adults and children is about 300 mg daily. A dose of 20 to 50 mg may be used as a hypnotic in adults and children over 12 years old. When oral therapy is not feasible, diphenhydramine hydrochloride may be given by deep intramuscular injection or by intravenous injection using concentrations of 1% or 5%. Usual doses are 10 to 50 mg, although doses of 100 mg have been given. No more than 400 mg should be given in 24 hours. Children may be given 5 mg/kg daily in divided doses to a maximum of 300 mg in 24 hours. Diphenhydramine hydrochloride is applied topically, usually in preparations containing 1 to 2% although, as with other antihistamines, there is a risk of sensitisation. Diphenhydramine citrate is given orally in a dose of 76 mg at night in combination preparations for its hypnotic action. Diphenhydramine di(acefyllinate) is given as an antiemetic for the prevention and treatment of motion sickness. The usual oral dose is 90 to 135 mg, which may be repeated if necessary at intervals of at least 6 hours, to a maximum of 540 mg daily. Other diphenhydramine salts that have been used include the polistirex, the salicylate, and the tannate by mouth, the methylbromide rectally, and the metilsulfate applied topically. Dimenhydrinate is diphenhydramine teoclate and mefenidramium metilsulfate is diphenhydramine methylsulfomethylate.

💊 Preparations

BP 2008: Diphenhydramine Oral Solution; USP 31: Acetaminophen and Diphenhydramine Citrate Tablets; Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Tablets; Diphenhydramine and Pseudoephedrine Capsules; Diphenhydramine Hydrochloride Capsules; Diphenhydramine Hydrochloride Elixir; Diphenhydramine Hydrochloride Injection.

Proprietary Preparations

Arg.: Alermina; Amodormin; Benadryl; Benadryl Antialergico†; Caladryl D; Drepatil†; Fabolergic; Histaler; Klonadryl; Mudantos H†; Austral.: Snuzaid; Unisom; Austria: Calmaben; Dermodrin; Dibondrin; Histaxin; Noctor; Sleepia†; Belg.: Azaron; Benylin; Diphamine; Nuicalm†; Nustasium; R Calm; Braz.: Difenidrin; Canad.: Aller-Aide; Allerdryl; Allergy Caplets; Allergy Elixir; Allergy Formula; Allernix; Benadryl; Calmex; Children’s Allergy Formula; Dormex; Dormiphen; Insomnal; Jack & Jill Bedtime; Jack & Jill Thin Strips Cough & Cold; Neo Citran Nighttime Cough; Nytol; Simply Sleep; Sleep Aid; Sleep-Eze D; Sominex; Triaminic Thin Strips Nighttime Cough & Runny Nose; Unisom; Chile: Jaquedryl; Pasifen†; Somol; Cz.: Benadryl N†; Psilo-Balsam; Fr.: Butix; Nautamine; Ger.: Benadryl N†; Betadorm D; Dolestan; Dormutil N†; Emesan; Halbmond†; Hevert-Dorm; Moradorm; nervo OPT N; ratioAllerg†; S.8; Sedativum-Hevert; Sediat; Sedopretten; Sleepia†; Vivinox Sleep; Gr.: Benadryl; Hong Kong: Benadryl†; Calox†; Hydramine Cream†; Unisom; Hung.: Psilo-Balsam; India: Benadryl; Cofryl; Dimiril†; Indon.: Arcodryl; Benadryl; Otede; Paradryl; Recodryl; Sidiadryl; Israel: Nytol; Ital.: Aliserin; Allergan; Nytol†; Mex.: Benadryl; Bionaryl; Bonanoti; Drafen; Glicodril; Histadryl; Indumir; Lurispan; Nytol; Tzoali†; Ulcoid; Unisom†; NZ: Unisom; Philipp.: Allerin AH; Benadryl Antihistamine; Benaxil; Dramelin; Port.: Benaderma; Benergina; Codilergi; Nytol†; Rus.: Psilo-Balsam (Псило-Бальзам); S.Afr.: Betasleep; Sleepeze-PM; Singapore: Benocten; Paxidorm; Spain: Benadryl; Neosayomol; Nytol; Sonodor; Swed.: Desentol; Switz.: Bedorma; Benocten; Comprimes somniferes "S"; Dobacen†; Sleepia†; Thai.: Benadryl; Turk.: Allenik; Allerjin; Benison; Fenotral; UAE: Amydramine II; UK: Adult Chesty Cough; Child Chesty Cough; Dreemon; Histergan; Mandalyn Paediatric; Nightcalm; Nytol; Paxidorm; Sleep Aid; Sleepeaze; USA: 40 Winks; Aler-Dryl; AllerMax; Altaryl Childrens Allergy; Banophen Allergy; Ben-Tann; Benadryl; Benadryl Allergy; Benadryl Childrens Allergy; Benadryl Itch; Childrens PediaCare Nighttime Cough; Compoz Night-time Sleep Aid; Dermamycin; Diphen AF; Diphenhist; Dormin; Dytan; Dytuss; Genahist; Maximum Strength Sleepinal; Maximum Strength Unisom SleepGels; Miles Nervine; MouthKote P/R†; Nytol; Scot-Tussin Allergy; Siladryl; Silphen; Simply Sleep; Sleep-Ettes D; Sleepwell 2-nite; Snooze Fast; Sominex; Triaminic Cough & Runny Nose; Tusstat; Twilite; Venez.: Benadryl; Di-Fedril†; Ystal†.
Published December 07, 2018.