Can morphine be administered with Benadryl (diphenhydramine) to alleviate itching in patients who experience pruritus from morphine?

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Last updated: June 17, 2025View editorial policy

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From the Guidelines

Yes, morphine can be administered with Benadryl (diphenhydramine) to alleviate itching in patients who experience pruritus from morphine. When considering the management of opioid-induced pruritus, it's crucial to assess for other causes of itching, such as the use of other medications 1. The use of antihistamines like diphenhydramine is a common approach for managing pruritus, with dosing typically ranging from 25-50 mg orally or intravenously every 4-6 hours as needed 1. However, it's essential to monitor for increased sedation when administering these medications together, as both morphine and diphenhydramine have sedative properties. Some key points to consider when using this combination include:

  • Monitoring for enhanced drowsiness, dizziness, and potential respiratory depression, particularly in elderly patients or those with respiratory conditions.
  • Recognizing that morphine-induced pruritus is not solely histamine-mediated, which may limit the effectiveness of diphenhydramine in some patients.
  • Considering alternative antipruritic options, such as other antihistamines like hydroxyzine, low-dose naloxone, or opioid rotation to a different opioid that may cause less itching, such as fentanyl or hydromorphone 1. Healthcare providers should adjust dosing based on individual patient response, age, and other medical conditions, prioritizing the management of morbidity, mortality, and quality of life.

From the Research

Morphine Administration with Benadryl for Itch Relief

  • Morphine can cause pruritus (itching) in some patients, and the use of Benadryl (diphenhydramine) to alleviate this symptom is a common practice 2, 3.
  • However, studies have shown that antihistamines like Benadryl may not be effective in relieving morphine-induced pruritus in all cases 2, 3.
  • In some cases, rotating to a different opioid, such as fentanyl or hydromorphone, may be more effective in alleviating pruritus 2, 3.
  • Other treatment options, such as ondansetron, have been shown to be effective in relieving pruritus in some patients 4.
  • Nalbuphine has also been found to be effective in treating opioid-induced pruritus, with greater efficacy compared to diphenhydramine and other pharmacologic agents 5.
  • Recent studies have shed light on the cellular basis of morphine-induced itch, suggesting that it is caused by disinhibition of spinal dynorphin neurons, rather than histamine release 6.
  • The use of antihistamines like Benadryl for morphine-induced itch is controversial, and alternative treatments like kappa-opioid receptor agonism may be more effective 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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