Diphenhydramine 25mg tablets
Available from a pharmacy with pharmacist advice
Antihistamines, hyposensitisation, and allergic emergencies
Safety information for pregnancy and breastfeeding
Pregnancy
Breastfeeding
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
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Official medicine documents
Safety monitoring data
Yellow Card reports
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Suspected adverse reactions reported for Diphenhydramine
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Interactive Drug Analysis Profiles for all medicines
Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Diphenhydramine
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EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
17 branded products available
Part of the Mandalyn brand family (generic: Diphenhydramine)
MHRA licensed products
View all licensed products for Diphenhydramine on the MHRA register
Histergan 25mg tablets
Lunox Sleep Aid 25mg tablets
Numark Night Time Sleep Aid 25mg tablets
Nytol 25mg tablets
Paxidorm 25mg tablets
Diphenhydramine 25mg tablets
Diphenhydramine 25mg tablets
Diphenhydramine 25mg tablets
Diphenhydramine 25mg tablets
This is the NHS Drug Tariff indicative price used for reimbursement purposes. It may not reflect the price paid by patients or pharmacies.
View full Drug TariffSource: NHS Drug Tariff via NHSBSA. Derived from dm+d VMPP (Virtual Medicinal Product Pack) pricing data. Contains public sector information licensed under the Open Government Licence v3.0.
WHO defined daily dose (DDD)
200 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Clinical guidelines and formulary information
British National Formulary
Diphenhydramine
Source: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(3)
Cough (acute): antimicrobial prescribing (NG120)
Omalizumab for previously treated chronic spontaneous urticaria (TA339)
Autoimmune haemolytic anaemia: rituximab (ESUOM39)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Pharmacy stock checkers
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Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
13 found
Half-life
2.4-9.3 hours
Mechanism
Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) recep…
Food interactions
2 warnings
Human targets
3 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
40%
[A644,…
Half-life
2.4-9.3 hours
Protein binding
78%
Volume of distribution
50 mg
Metabolism
Elimination
1%
[L5281,…
Clearance
50 mg
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Diphenhydramine is also used in combination with DB14132 as the anti-nausea drug DB00985 where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system [A1540].
Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid [A1539]. As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.
Additionally, when the use of oral diphenhydramine is impractical, there are also prescription-only formulations such as diphenhydramine injection products that are effective in adults and pediatric patients (other than premature infants and neonates) for:
i) the amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after acute allergic reaction symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated F3352;
ii) the active treatment of motion sickness F3352; and
iii) use in parkinsonism when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild cases of parkinsonism in other age groups, and in other cases of parkinsonism in combination with centrally acting anticholinergic agents F3352.
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 2301 interactions
[L5287]
Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse .
[L5287]
Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow F3394.
Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk F3394. This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant F3394.
Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults F3394.
Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects .
[L5287]
Avoid use in elderly patients with confusion .
[L5287]
The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) F3394.
After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease F3394. However, the mean plasma clearance and apparent volume of distribution were not significantly affected F3394.
LD50=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.
Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms [L5263, L5266, L5269, F3379, A174541]. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center [L5263, L5266, L5269, F3379, A174541].
Furthermore, H1 receptors are similar to muscarinic receptors [L5263, L5266, L5269, F3379, A174541]. Consequently, diphenhydramine also acts as an antimuscarinic [L5263, L5266, L5269, F3379, A174541]. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication [L5263, L5266, L5269, F3379, A174541].
Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties [L5263].
How the body processes this drug — absorption, distribution, metabolism, and elimination
[A644][L5287]
The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration .
[A644][L5287]
[L5287]
[A174577]
Additionally, the N,N-didesmethyl metabolite also undergoes some oxidation to generate the diphenylmethoxyacetic acid metabolite as well [F3394, L5287, A174577].
The remaining percentage of a dose of administered diphenhydramine is excreted unchanged [F3394, L5287, A174577]. The metabolites are further conjugated with glycine and glutamine and excreted in urine .
[L5287]
Moreover, studies have determined that a variety of cytochrome P450 isoenzymes are involved in the N-demethylation that characterizes the primary metabolic pathway of diphenhydramine, including CYP2D6, CYP1A2, CYP2C9, and CYP2C19 .
[A174574]
In particular, CYP2D6 demonstrates higher affinity catalysis with the diphenhydramine substrate than the other isoenzymes identified .
[A174574]
Consequently, inducers or inhibitors of these such CYP enzymes may potentially affect the serum concentration and incidence and/or severity of adverse effects associated with exposure to diphenhydramine .
[A174574]
[L5281][L5287]
Only about 1% of a single dose is excreted unchanged in urine .
[L5281][L5287]
The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites .
[L5281][L5287]
Proteins and enzymes this drug interacts with in the body
PMID:33828102 PMID:8280179
Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:9260930 PMID:9687576
Functions as a Na(+)-independent, bidirectional uniporter .
PMID:21128598 PMID:9687576
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient .
PMID:15212162 PMID:9260930 PMID:9687576
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow .
PMID:15783073
Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters .
PMID:16581093 PMID:17460754 PMID:9687576
Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system .
PMID:17460754
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) .
PMID:12089365 PMID:15212162 PMID:17072098 PMID:24961373 PMID:9260930
Mediates the uptake and efflux of quaternary ammonium compound choline .
PMID:9260930
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine .
PMID:12538837 PMID:21128598
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) .
PMID:12395288 PMID:16394027
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:10454528 PMID:10525100 PMID:10966938 PMID:17509700 PMID:20722056 PMID:33124720
Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium.
Relative uptake activity ratio of carnitine to TEA is 11.3 .
PMID:10454528 PMID:10525100 PMID:10966938
In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from B.subtilis which induces cytoprotective heat shock proteins contributing to intestinal homeostasis .
PMID:18005709
May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Involved compounds
ATC D04AA32
ATC R06AA02
ATC M01AE57
ATC D04AA33
ATC R06AA52
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Diphenhydramine
Additional database identifiers
Drugs Product Database (DPD)
182
Drugs Product Database (DPD)
1240
Drugs Product Database (DPD)
2429
ChemSpider
2989
BindingDB
50017674
PDB
2PM
Guide to Pharmacology
1224
ZINC
ZINC000000020244
HUGO Gene Nomenclature Committee (HGNC)
HGNC:5182
GenAtlas
HRH1
GeneCards
HRH1
GenBank Gene Database
Z34897
GenBank Protein Database
510296
Guide to Pharmacology
262
UniProt Accession
HRH1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1951
GenAtlas
CHRM2
GeneCards
CHRM2
GenBank Gene Database
M16404
GenBank Protein Database
177990
Guide to Pharmacology
14
UniProt Accession
ACM2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:5028
GenAtlas
HNMT
GeneCards
HNMT
GenBank Gene Database
D16224
UniProt Accession
HNMT_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9604
GenAtlas
PTGS1
GeneCards
PTGS1
GenBank Gene Database
M31822
GenBank Protein Database
387018
Guide to Pharmacology
1375
UniProt Accession
PGH1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10966
GeneCards
SLC22A2
GenBank Gene Database
X98333
GenBank Protein Database
2281942
Guide to Pharmacology
1020
UniProt Accession
S22A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10969
GenAtlas
SLC22A5
GeneCards
SLC22A5
GenBank Gene Database
AF057164
GenBank Protein Database
3273741
UniProt Accession
S22A5_HUMAN
International reference pricing
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
All patents expired, 3 expired
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
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