From the Guidelines
It is not recommended to give intramuscular (IM) diphenhydramine (DPH) with IM chlorpheniramine if the last dose of Benadryl (diphenhydramine) 25mg was at 5pm. These medications are both antihistamines that work through similar mechanisms, and administering them together increases the risk of additive side effects such as excessive sedation, confusion, urinary retention, dry mouth, and blurred vision. The typical duration of action for diphenhydramine is 4-6 hours, so if the last dose was at 5pm, the medication may still be active in the system 1. Some key points to consider when administering antihistamines include:
- First-generation antihistamines, such as diphenhydramine, have significant potential to cause sedation, performance impairment, and anticholinergic effects 1
- The use of first-generation antihistamines should be approached with caution, especially in older adults, due to increased sensitivity to psychomotor impairment and adverse anticholinergic effects 1
- Antihistamines are often used as adjunctive therapy for cutaneous signs and symptoms associated with anaphylaxis, but should not be administered before, or in place of, epinephrine 1 If additional antihistamine therapy is needed, it would be safer to either wait until the diphenhydramine has cleared (approximately 6 hours after the last dose) before administering chlorpheniramine, or continue with diphenhydramine alone at appropriate intervals. If the allergic reaction is severe or not responding adequately to the initial treatment, seeking immediate medical attention would be more appropriate than combining antihistamines. Key considerations for treatment of anaphylaxis include:
- Epinephrine is the first-line treatment of anaphylaxis due to its faster onset of action and more appropriate pharmacologic action compared with antihistamines 1
- Glucocorticoids have a limited role in the acute management of anaphylaxis due to their slow onset of action and inability to reverse acute symptoms 1
From the FDA Drug Label
DOSAGE AND ADMINISTRATION THIS PRODUCT IS FOR INTRAVENOUS OR INTRAMUSCULAR ADMINISTRATION ONLY. DOSAGE SHOULD BE INDIVIDUALIZED ACCORDING TO THE NEEDS AND THE RESPONSE OF THE PATIENT. Maximum daily dosage is 300 mg for Pediatric Patients and 400 mg for Adults.
The FDA drug label does not answer the question.
From the Research
Administration of IM Diphenhydramine with IM Chlorpheniramine
- The administration of Intramuscular (IM) Diphenhydramine (DPH) with IM Chlorpheniramine is a consideration that requires careful evaluation of potential interactions and the timing of previous doses of similar medications, such as Benadryl (Diphenhydramine) 2, 3, 4, 5.
- Given that the last dose of Benadryl (Diphenhydramine) 25mg was at 5pm, it is essential to consider the pharmacokinetics and pharmacodynamics of Diphenhydramine and Chlorpheniramine to assess the safety of co-administration.
Pharmacological Considerations
- Diphenhydramine and Chlorpheniramine are both antihistamines that can cause sedation and impairment, especially at or above recommended doses 2.
- The combination of these medications could potentially increase the risk of adverse effects such as sedation, dry mouth, and urinary retention.
- There is evidence that Diphenhydramine and Chlorpheniramine can inhibit the cytochrome P450 2D6 enzyme, which may lead to interactions with other medications that are metabolized by this enzyme 4.
Clinical Applications and Safety
- Chlorpheniramine has been used for various clinical applications, including the treatment of allergic conditions, asthma, and depression, with a relatively safe profile when used appropriately 5.
- However, the safety of co-administering IM Diphenhydramine with IM Chlorpheniramine, especially in relation to the timing of the last dose of Benadryl, needs to be carefully evaluated to minimize potential risks.