In short
Diphenhydramine DI(acefyllinate) is a first-generation antihistamine used mainly for allergy symptoms and, in clinical research, as a supportive medicine to prevent infusion reactions. The EU Clinical Trials Information System lists eight authorised trials in which diphenhydramine appears, including a Phase 3 study in IgA nephropathy with 660 participants and a Phase 3 study in B-cell lymphoma with 556 participants.
Key points
- Diphenhydramine is a sedating antihistamine that blocks histamine H1 receptors.
- It is used in eight authorised clinical trials as a supportive medicine, not as the main study drug.
- The largest trial is a Phase 3 study in IgA nephropathy with 660 participants.
- Another Phase 3 study in B-cell lymphoma enrols 556 participants.
- Diphenhydramine is given orally or intravenously in these trials.
- Common side effects include drowsiness and dry mouth.
What is diphenhydramine DI(acefyllinate)?
Diphenhydramine DI(acefyllinate) is a salt form of diphenhydramine, a first-generation sedating antihistamine. The substance is classified as a histamine H1 receptor antagonist, meaning it blocks the action of histamine in the body. In the EU Clinical Trials Information System, the therapeutic area for the records containing this substance is diseases of the neoplasms category, because diphenhydramine appears as a supportive medicine in cancer trials. Diphenhydramine is also known by trade names such as Benadryl and Nytol, and by chemical names including benzhydramine and probedryl. It is an authorised over-the-counter medicine for allergy relief in the United States.
How does diphenhydramine work?
Diphenhydramine works by blocking histamine H1 receptors in the body. Histamine is a substance released during allergic reactions that causes symptoms such as runny nose, sneezing, itchy and watery eyes, and itching of the nose or throat. By blocking the H1 receptor, diphenhydramine temporarily relieves these symptoms. Because it is a first-generation antihistamine, it can cross into the brain and cause drowsiness, which is why it is described as sedating. In clinical trials, diphenhydramine is typically used to prevent infusion-related reactions when other medicines are given intravenously.
Which conditions is it used or studied for?
- Hay fever and upper respiratory allergies — diphenhydramine temporarily relieves runny nose, sneezing, itchy and watery eyes, and itching of the nose or throat.
- Common cold — it temporarily relieves runny nose and sneezing due to the common cold.
- Conventional chondrosarcoma — diphenhydramine is used as a supportive medicine in a Phase 2 trial of INBRX-109 in this bone and joint cancer.
- Hereditary spastic paraplegia type 50 (SPG50) — diphenhydramine appears in a Phase 3 trial of MELPIDA for this rare inherited condition.
- B-cell lymphoma — diphenhydramine is used in Phase 3 trials of epcoritamab for relapsed or refractory diffuse large B-cell lymphoma.
- IgA nephropathy — diphenhydramine is used in a Phase 3 trial of felzartamab for this kidney disease.
- Presymptomatic type 1 diabetes (stage 1) — diphenhydramine is used in a Phase 2 trial of regulatory T cells and rituximab in children.
- Multiple myeloma — diphenhydramine is used in Phase 2 trials of isatuximab for relapsed or refractory multiple myeloma.
How is diphenhydramine given?
Diphenhydramine is available as an oral tablet for over-the-counter use, with a strength of 25 mg per tablet. The oral tablets are taken every 4 to 6 hours, with adults and children 12 years and over taking 1 to 2 tablets per dose. In the clinical trials listed in the EU Clinical Trials Information System, diphenhydramine is given by oral use or intravenous use, depending on the trial. For example, in the Phase 2 chondrosarcoma trial, diphenhydramine is given intravenously at a dose of 50 mg. In the Phase 3 B-cell lymphoma trial, diphenhydramine is given orally at a dose of 50 mg. In the Phase 3 IgA nephropathy trial, diphenhydramine is given intravenously at a dose of 50 mg. In some trials, the dose is reported as 0 mg or 0 DF dosage form, which means the dose was not reported in the register.
What do the clinical trials show?
Eight authorised trials in the EU Clinical Trials Information System list diphenhydramine as an intervention. In all of these trials, diphenhydramine is a supportive medicine, not the main study drug. The trials cover a range of conditions, including conventional chondrosarcoma, hereditary spastic paraplegia type 50, B-cell lymphoma, IgA nephropathy, presymptomatic type 1 diabetes, and multiple myeloma.–[8]
What phases and status do the trials have?
The trials are in Phase 1/2, Phase 2, or Phase 3. All eight trials have the status "Authorised", meaning they have been approved to proceed.–[8]The largest trial is a Phase 3 study in IgA nephropathy with 660 participants, and the smallest is a Phase 3 study in hereditary spastic paraplegia type 50 with 24 participants.
What do the trials measure?
Because diphenhydramine is a supportive medicine in these trials, the primary outcomes measure the effects of the main study drugs. For example, the Phase 2 chondrosarcoma trial measures progression-free survival (PFS), which is the time a person lives without the cancer getting worse. The Phase 3 IgA nephropathy trial measures the percent change in proteinuria, which is the amount of protein in the urine, as measured by the urine protein-to-creatinine ratio (UPCR). The Phase 3 B-cell lymphoma trial measures overall survival and progression-free survival determined by Lugano criteria. The Phase 2 multiple myeloma trial measures the overall response rate (ORR), which is the proportion of participants whose cancer shrinks or disappears.
Who can take part in these trials?
The trials enrol adults or children depending on the condition. The Phase 2 chondrosarcoma trial enrols adults with unresectable or metastatic conventional chondrosarcoma. The Phase 2 trial in presymptomatic type 1 diabetes enrols paediatric participants with stage 1 type 1 diabetes. The Phase 3 trial in hereditary spastic paraplegia type 50 enrols participants with SPG50. The Phase 3 trials in B-cell lymphoma and IgA nephropathy enrol adults with those conditions.
What side effects are known?
According to the product information, drowsiness may occur when using diphenhydramine. Alcohol, sedatives, and tranquilizers may increase drowsiness. Excitability may occur, especially in children. The product information advises being careful when driving a motor vehicle or operating machinery because of the risk of drowsiness. Diphenhydramine is classified as a sedating antihistamine in the NHS formulary.