Is alectinib (generic name) renal toxic, causing impaired renal function?

Alectinib and Renal Toxicity

Summary of Evidence

Yes, alectinib can cause renal toxicity and impaired renal function. Multiple case reports document severe acute kidney injury associated with alectinib use, including cases requiring dialysis.

Mechanism and Incidence

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor used in the treatment of ALK-positive non-small cell lung cancer (NSCLC). While the FDA label 1 does not specifically highlight renal toxicity as a major concern, several case reports document significant nephrotoxicity:

• Cases of acute tubular necrosis requiring emergency dialysis have been reported 2
• Progressive glomerulonephritis developing after alectinib initiation 3
• Anuric acute kidney injury in patients on alectinib therapy 4

Risk Factors

Patients with the following characteristics appear to be at higher risk for alectinib-induced nephrotoxicity:

• Pre-existing renal impairment
• Advanced age
• Diabetes
• Concomitant use of other nephrotoxic medications
• Volume depletion

Monitoring Recommendations

Based on the evidence of potential nephrotoxicity:

• Baseline renal function should be assessed before starting alectinib
• Regular monitoring of serum creatinine is essential during treatment
• More frequent monitoring may be needed in patients with pre-existing renal disease
• Particular vigilance is required during the first few months of therapy, as several cases developed nephrotoxicity within 6 weeks to 1 year of starting treatment

Management of Renal Toxicity

If renal toxicity develops:

1. Consider temporary discontinuation of alectinib
2. Assess for other causes of renal dysfunction
3. Provide supportive care, including hydration
4. In severe cases, dialysis may be required
5. Consider dose reduction upon rechallenge (if clinically appropriate)
6. Consider alternative ALK inhibitors if nephrotoxicity recurs

Pharmacokinetics and Renal Impairment

According to the FDA label 1:

• Alectinib is primarily metabolized by CYP3A4 with minimal renal excretion (less than 0.5% excreted unchanged in urine)
• Mild to moderate renal impairment (creatinine clearance 30-89 mL/min) does not significantly affect alectinib exposure
• The pharmacokinetics in severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease have not been studied

Case Management Examples

One documented approach for patients who develop renal toxicity but require continued ALK inhibition includes:

• Dose reduction (e.g., to 140 mg twice daily instead of standard 600 mg twice daily)
• Implementing treatment breaks (e.g., 2 weeks on, 2 weeks off) 5
• Switching to an alternative ALK inhibitor (e.g., brigatinib) 4

Conclusion

While alectinib's FDA label does not prominently feature renal toxicity warnings, multiple case reports document severe nephrotoxicity, including acute tubular necrosis and progressive glomerulonephritis. Clinicians should monitor renal function regularly in patients receiving alectinib, especially those with pre-existing risk factors for kidney injury.