What is the cause of pain associated with hydroxyurea?

From the Guidelines

Hydroxyurea can cause pain, particularly due to its toxicity profile which includes bone marrow suppression, GI symptoms, and dermatologic reactions 1. This pain is often described as burning, tingling, or numbness, and can range from mild to severe. The specific cause of pain associated with hydroxyurea is not explicitly stated in the provided evidence, but it can be inferred that it is related to its hematologic and non-hematologic toxicities.

Possible Causes of Pain

• Bone marrow suppression: leading to anemia, neutropenia, or thrombocytopenia, which can cause pain due to decreased blood flow or increased risk of infection 1
• GI symptoms: such as stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation, which can cause abdominal pain or discomfort 1
• Dermatologic reactions: such as rash, ulceration, dermatomyositis-like skin changes, or alopecia, which can cause skin pain or discomfort 1 To manage this pain, it is recommended to stop or reduce the dose of hydroxyurea temporarily. Additionally, medications such as acetaminophen or ibuprofen may be used to alleviate the pain. In some cases, topical creams or ointments, such as urea or capsaicin, may also be applied to the affected areas to help reduce pain and discomfort. It is essential to consult a healthcare provider for proper evaluation and guidance on managing hydroxyurea-induced pain.

Key Points to Consider

• Dose adjustment: reducing the dose of hydroxyurea may help alleviate pain and other toxicities 1
• Monitoring: regular monitoring of blood counts, liver function, and kidney function is essential to detect potential toxicities early 1
• Alternative treatments: considering alternative treatments, such as other systemic agents or biologics, may be necessary if hydroxyurea-induced pain is severe or persistent 1

From the FDA Drug Label

Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have also been observed.

The cause of pain associated with hydroxyurea is mucocutaneous toxicity, which can manifest as soreness. Key points include:

• Soreness is a reported symptom
• Mucocutaneous toxicity is the underlying cause of soreness
• This occurs at dosages several times the therapeutic dose 2

From the Research

Causes of Pain Associated with Hydroxyurea

• Cutaneous side-effects, including xerosis, hyperpigmentation, skin atrophy, erythema, alopecia, skin tumours, and ulceration of the skin, particularly of the legs, have been reported in patients on long-term hydroxyurea therapy 3, 4
• Painful ulcers on the hands and heels have been observed in patients receiving hydroxyurea, which were resistant to therapy but healed after discontinuation of hydroxyurea therapy 3
• Hydroxyurea has been associated with hand-foot syndrome (HFS), a specific adverse effect of certain chemotherapy that may lead to dosage reduction or chemotherapy discontinuation in patients with cancer 5, 6
• Bone pain has been reported as a symptom in patients with mast cell activation syndrome (MCAS) treated with hydroxyurea, with significant reduction in bone pain observed in patients who continued therapy for ≥ 2 months 7

Mechanisms of Pain

• The exact mechanism of pain associated with hydroxyurea is not fully understood, but it is thought to be related to the drug's effects on DNA synthesis and cellular replication 4
• Hydroxyurea may cause damage to the skin and mucous membranes, leading to painful ulcers and other cutaneous side-effects 3, 4
• The drug's effects on mast cell activation and inflammation may also contribute to pain in patients with MCAS 7