Supplements and Diphenhydramine hydrochloride.
Diphenhydramine hydrochloride, sold under the brand names Histergan, Nytol Original, Nytol One-A-Night, Panadol Night, is an antihistamine.
Diphenhydramine hydrochloride is an antihistamine. The class divides into two generations. Older agents (chlorphenamine, promethazine, diphenhydramine) cross the blood brain barrier and cause sedation. Newer agents (cetirizine, loratadine, fexofenadine) mostly do not. UK community prescribing is mostly the newer agents for allergic rhinitis and urticaria. The supplement surface for them is small, because they have low CYP involvement and minimal additive sedation effect. The older agents stack with anything else sedating (alcohol, benzodiazepines, valerian, kava, magnesium glycinate at higher doses) and with anticholinergic supplements. The latter matters in older patients, given the cognitive decline signal in data on sustained anticholinergic burden. Fexofenadine specifically is a P-glycoprotein substrate and shows reduced absorption with fibre supplements at high intake, and with fruit juices. The BNF flag is real, but the clinical magnitude is small at standard doses.
Below are the 1 documented pair we have explicitly assessed against Diphenhydramine hydrochloride in the Distil database: 1 red. The pairs cluster around 1 mechanism: Additive serotonergic activity. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Last reviewed 13 September 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive serotonergic activity
Red Does 5-HTP interact with ?
5-HTP is turned into serotonin in the body, and diphenhydramine, the antihistamine in sleep aids such as Nytol Original and in some cough and cold medicines, also blocks the reuptake of serotonin, so taking the two together can cause serotonin syndrome (agitation, sweating, tremor, a racing heart, confusion). Do not take 5-HTP with diphenhydramine; if you already take both, tell your GP or pharmacist.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, and submit a missing item if you take something we have not catalogued.
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How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
Read the full methodologyA full supplement review, built around you, not a generic stack.
The free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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