Do Antihistamines Relieve Drug-Induced Bone Pain?

Joanna M. Pangilinan, PharmD


January 14, 2008


Many patients receiving pegfilgrastim (Neulasta) for chemotherapy-induced neutropenia experience significant bone pain. Anecdotal reports suggest that nonsedating antihistamines offer relief. Is there a rationale for this?

Response From the Expert


Joanna M. Pangilinan, PharmD
Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan

The granulocyte colony-stimulating factor (G-CSF) medications filgrastim (Neupogen) and pegfilgrastim (Neulasta) are used to decrease infection risk associated with febrile neutropenia in patients receiving myelosuppressive chemotherapy.[1,2] However, bone pain is a common adverse effect of these drugs, occurring in 20% to 50% of patients; the incidence is similar for both filgrastim and pegfilgrastim.[3]

While G-CSF-associated bone pain is usually mild to moderate, severe pain may occur. Pain medications commonly prescribed for bone pain include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and narcotics.

The exact mechanisms of bone pain have yet to be elucidated, but possible causes include change in bone marrow pressure and inflammation.[4] Histamine has been suggested as a chemical mediator causing pain associated with bone marrow edema.[5] Although the role of G-CSF in histamine release is unclear, this concept could be the basis for anecdotal use of antihistamines to treat G-CSF-induced bone pain. Furthermore, second-generation antihistamines (eg, cetirizine and fexofenadine) may have anti-inflammatory properties.[6] This finding may also contribute to anecdotal use of antihistamines for G-CSF-associated bone pain.

To date, no known clinical trials have evaluated the use of antihistamines for treatment of G-CSF-associated bone pain; even published case reports suggesting the usefulness of antihistamines are sparse. Gudi and colleagues[7] described a case in which astemizole (since withdrawn from the US market) was given to relieve G-CSF-associated bone pain refractory to acetaminophen. In addition, Ogata and colleagues[8] described the use of hydroxyzine in 4 patients with G-CSF-associated bone pain refractory to NSAIDs. They found that hydroxyzine was not only effective but also prevented bone pain with the next cycle of G-CSF.

Despite the lack of evidence, some clinicians prescribe antihistamines for relief of G-CSF-associated bone pain when conventional methods of pain relief provide unsatisfactory results. Clinical trials are needed to determine the mechanism, safety, and efficacy of antihistamines in reducing bone pain caused by G-CSF before this practice can be recommended.


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