Darolutamide and Lisinopril: Safety Profile
Yes, it is safe to combine darolutamide with lisinopril in patients with nonmetastatic castration-resistant prostate cancer and hypertension, though blood pressure monitoring is essential given darolutamide's association with increased hypertension risk.
Key Safety Considerations
Hypertension Risk with Darolutamide
Darolutamide is associated with increased hypertension rates compared to placebo. In the ARAMIS trial, hypertension occurred more frequently in the darolutamide group (13.7% vs 9.2% with placebo) 1.
A meta-analysis of novel hormonal agents (enzalutamide, apalutamide, and darolutamide) in nmCRPC demonstrated a significantly increased risk of grade 3-4 hypertension (RR = 1.53; 95% CI 1.19-1.97) when these agents were added to androgen deprivation therapy 2.
In the ARASENS trial evaluating darolutamide in metastatic hormone-sensitive prostate cancer, the frequency of grade 3 or 4 adverse events was similar between treatment arms (66.1% darolutamide vs 63.5% placebo), with hypertension being a known effect of androgen receptor pathway inhibitors 1, 3.
Favorable Aspects of This Combination
Darolutamide has a relatively favorable cardiovascular safety profile compared to other androgen receptor axis-targeted agents. The ARAMIS trial specifically noted that darolutamide was not associated with a higher incidence of hypertension than placebo in the primary analysis 4.
No specific drug-drug interactions are documented between darolutamide and ACE inhibitors like lisinopril in the available evidence.
Darolutamide appears to have a somewhat safer endocrine and metabolic profile compared to abiraterone (which causes mineralocorticoid excess and hypertension) and enzalutamide (which may induce or worsen hypertension) 5.
Clinical Management Algorithm
Before Initiating Darolutamide
- Ensure baseline blood pressure is controlled on current lisinopril regimen 1.
- Document baseline blood pressure readings and current antihypertensive medications.
During Darolutamide Treatment
- Monitor blood pressure closely, particularly during the first 3 months of therapy when hypertension risk may be highest 1.
- Check blood pressure at each clinic visit (recommended every 4-8 weeks initially).
- Be prepared to uptitrate lisinopril or add additional antihypertensive agents if blood pressure control deteriorates 1.
Blood Pressure Targets
- Target systolic blood pressure <130 mm Hg for patients with comorbidities, though lower targets may be beneficial in certain populations 1.
- More aggressive blood pressure control may be warranted given the dual cardiovascular risk from both cancer therapy and underlying hypertension.
Important Caveats
Cardiovascular risk assessment is essential before initiating darolutamide, as novel hormonal agents carry increased risk of cardiovascular events (RR = 1.71; 95% CI 1.29-2.27) 2.
The combination is not contraindicated, but requires vigilant monitoring rather than avoidance.
Real-world data on this specific combination remains limited, as most trial data compare novel hormonal agents to placebo rather than evaluating specific drug-drug interactions 2.
Patients should be counseled about the potential for worsening hypertension and the need for adherence to both cancer therapy and antihypertensive medications 1.