Can bortezomib cause fasciculation?

Bortezomib and Fasciculation: A Neurological Side Effect

Yes, bortezomib can cause fasciculations as part of its neurological toxicity profile, particularly in the context of peripheral neuropathy which is one of its most common adverse effects.

Mechanism and Presentation of Bortezomib-Induced Neurological Effects

Bortezomib-induced peripheral neuropathy (BIPN) is primarily a sensory axonal polyneuropathy, but can also manifest with motor symptoms including fasciculations. The pathophysiology involves:

• Damage to dorsal root ganglia neurons 1
• Mitochondrial and endoplasmic reticulum damage in nerve cells 1
• Schwann cell and myelin pathological changes 1
• Axonal degeneration affecting both sensory and motor fibers 2

While primarily manifesting as sensory symptoms, motor involvement occurs in approximately 10% of patients, which can include:

• Fasciculations (muscle twitching)
• Distal weakness, particularly in lower limbs
• Reduced activity due to pain and stinging sensations 1

Risk Factors for Developing Neurological Complications

Several factors increase the risk of developing neurological complications with bortezomib:

• Pre-existing peripheral neuropathy 3
• Older age 4
• Diabetes or other comorbidities affecting peripheral nerves 1
• Higher cumulative dose of bortezomib 1
• Twice-weekly dosing schedule (versus weekly) 1
• Intravenous administration (versus subcutaneous) 5

Prevention and Management Strategies

To minimize the risk of neurological complications including fasciculations:

Dosing and Administration Modifications:

• Use subcutaneous administration rather than intravenous - reduces peripheral neuropathy risk (38% vs 53% for any grade) 5
• Consider weekly dosing instead of twice-weekly - significantly reduces grade 3-4 neuropathy (3-9% vs 12-18%) 1
• Start with lower doses in high-risk patients (0.7-1.0 mg/m²) and titrate up as tolerated 1

Monitoring and Early Intervention:

• Regular clinical evaluation for neurological symptoms
• Early detection of peripheral neuropathy is crucial
• Follow dose adjustment algorithms when neuropathy develops 1
• Consider treatment interruption for grade 2 neuropathy with pain or grade 3 neuropathy 1

Treatment of Established Neuropathy:

• Pregabalin (150-600 mg/day) for at least three months 1
• Gabapentin (300-2,400 mg/day) as an alternative 1
• Duloxetine (30-60 mg/day) as second-line therapy 1
• Tramadol for chronic pain management 1
• In severe cases, consider steroids or intravenous immunoglobulin 4

Clinical Pearls and Pitfalls

• Fasciculations may be an early sign of motor involvement and should prompt immediate evaluation
• Motor neuropathy from bortezomib can be severely debilitating and may not resolve despite discontinuation 4
• Prophylaxis against herpes zoster is strongly recommended for all patients on proteasome inhibitors 1
• Symptoms may continue to progress even after discontinuation before eventually improving
• Recovery from neurological symptoms can take several weeks to months 1
• Partial recovery is common, but complete resolution is not guaranteed 2

Bortezomib remains a cornerstone of multiple myeloma treatment despite these potential neurological complications. When neurological symptoms like fasciculations appear, prompt dose modification or discontinuation is essential to prevent permanent nerve damage while maintaining therapeutic efficacy.