From the Guidelines
For patients with skeletal pain associated with multiple myeloma, a combination of zoledronic acid and extended-release oxycodone is the most effective approach, as it addresses both the underlying bone disease and provides direct pain relief. Zoledronic acid (4mg IV every 3-4 weeks) is recommended for bone disease in multiple myeloma as it reduces skeletal-related events and may provide some pain relief by stabilizing bone lesions and reducing bone resorption 1. However, it's not primarily a pain medication. Extended-release oxycodone is an effective opioid analgesic for managing moderate to severe pain, typically started at 10-15mg every 12 hours and titrated based on pain control.
The use of zoledronic acid has been shown to reduce mortality and improve progression-free survival (PFS) in patients with multiple myeloma, with a significant improvement in overall survival (OS) compared to clodronic acid 1. Additionally, a recent meta-analysis of 20 randomized controlled trials comparing bisphosphonates with either placebo or a different bisphosphonate as a comparator concluded that adding bisphosphonates to the treatment of MM reduces vertebral fractures and probably reduces pain 1.
Some key points to consider when using zoledronic acid and extended-release oxycodone include:
- Regular monitoring of renal function and dental exams to prevent osteonecrosis of the jaw (ONJ) 1
- Management of side effects such as constipation with oxycodone and renal monitoring with zoledronic acid
- Consideration of additional supportive measures like radiation therapy for localized bone pain
- Individualization of the treatment plan based on pain severity, renal function, and overall disease management strategy
It's also important to note that the NCCN Guidelines for MM recommend bisphosphonates (category 1) or denosumab for all patients receiving therapy for symptomatic MM regardless of documented bone disease, with denosumab preferred in patients with renal disease 1.
From the FDA Drug Label
Table 12: Overview of Efficacy Population for Phase III Studies ... Each study evaluated skeletal-related events (SREs), defined as any of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression. ... Table 13: Zoledronic Acid Injection Compared to Placebo in Patients with Bone Metastases from Prostate Cancer or Other Solid Tumors ... Table 14: Zoledronic Acid Injection Compared to Pamidronate in Patients with Multiple Myeloma or Bone Metastases from Breast Cancer
The best pain relief for skeletal pain and multiple myeloma is zoledronic acid.
- Zoledronic acid has been shown to reduce the risk of skeletal-related events (SREs) in patients with multiple myeloma and bone metastases from solid tumors.
- The recommended dose of zoledronic acid is 4 mg infused over no less than 15 minutes every 3 to 4 weeks.
- Extended release oxycodone is not mentioned in the provided drug labels as a treatment for skeletal pain and multiple myeloma. 2 2
From the Research
Comparison of Zoledronic Acid and Extended Release Oxycodone for Skeletal Pain and Multiple Myeloma
- Zoledronic acid has been shown to reduce skeletal-related events (SRE) in patients with multiple myeloma, with a low incidence of SRE and a 2-year incidence rate for osteonecrosis of jaw of 3.3% 3.
- The use of zoledronic acid in the management of bone disease in multiple myeloma has been demonstrated to have significant reductions in SRE compared with placebo or other agents, with acceptable tolerability 4.
- Zoledronic acid is considered the mainstay for the treatment of myeloma bone disease, and has been found to be superior to clodronate and pamidronate in terms of reduction of skeletal-related events and survival 5.
- Extended release oxycodone is not mentioned in the provided studies as a treatment for skeletal pain and multiple myeloma, therefore, it is not possible to compare its effectiveness with zoledronic acid based on the available evidence.
Efficacy and Safety of Zoledronic Acid
- Zoledronic acid has been shown to have a low SRE rate and can be safely administered for up to 4 years, with a mean SRE rate at year 2 of 0.01 per person-year 3.
- The recommended dose and schedule of zoledronic acid is 4 mg infused over 15 min every 3-4 weeks, with increased doses and shorter infusions not recommended due to potential renal toxicity 6.
- Zoledronic acid has been found to have antitumoural effects and a marginal survival benefit in multiple myeloma, although its role on survival remains unclear 4.
Treatment of Multiple Myeloma Bone Disease
- Bisphosphonates, including zoledronic acid, are the mainstay of myeloma bone disease treatment, with oral clodronate and intravenous pamidronate and zoledronic acid currently used drugs 7.
- Denosumab has comparable results with zoledronic acid on myeloma bone disease treatment, although its use has not been completely proven yet 7.
- Novel agents, such as proteasome inhibitors, are under investigation and have great potential to reduce the negative effects of myeloma cells on bone 7.