No dosage adjustment is needed for mild to moderate renal impairment or mild hepatic impairment, whereas appropriate dosage adjustment for end-stage kidney disease and severe hepatic impairment is unknown.Two 2020 meta-analyses reported that enzalutamide and apalutamide seemed to be more effective than darolutamide in improving metastasis-free survival (MFS), however 2021 matched adjusted indirect comparison showed no significant differences between drugs in terms of MFS. According to 2021 meta-analysis darolutamide was ranked first in terms of improving overall survival (OS). Also, darolutamide showed significantly lower rate of grade 3-5 adverse events (AE) compared to both enzalutamide and apalutamide. Available forms
Darolutamide is provided in the form of 300 mg oral film-coated tablets. Contraindications
Darolutamide has no contraindications in men. However, the medication may have teratogenic effects in male fetuses due to its antiandrogenic effects and hence should not be used by women who are pregnant. Side effects
The most common side effects of darolutamide in clinical trials (≥2% incidence) in castrated men included fatigue and asthenia (16% vs. 11% for placebo), pain in extremities (6% vs. 3% for placebo), and rash (3% vs. 1% for placebo). Darolutamide was also associated with higher incidences of ischemic heart disease (4.0% vs. 3.4% for placebo) and heart failure (2.1% vs. 0.9% for placebo). In terms of laboratory test abnormalities, darolutamide was associated with decreased neutrophil count (20% vs. 9% for placebo), increased aspartate aminotransferase (AST) (23% vs. 14% for placebo; Grade 3–4: 0.5% vs. 0.2% for placebo), and increased bilirubin (16% vs. 7% for placebo).
As a result, pressure rises in the atrium and is transmitted back to the pulmonary venous system, thereby increasing its hydrostatic pressure and promoting pulmonary edema. It may be misguided to classify the volume-overloaded heart as having diastolic dysfunction if it is behaving in a stiff and non-compliant manner. The term diastolic dysfunction should not be applied to the dilated heart. Dilated ("remodeled") hearts have increased volume relative to the amount of diastolic pressure, and therefore have increased (not decreased) distensibility. The term diastolic dysfunction is sometimes erroneously applied in this circumstance, when increased fluid volume retention causes the heart to be over-filled (High output cardiac failure).Although the term diastolic heart failure is often used when there are signs and symptoms of heart failure with normal left ventricular systolic function, this is not always appropriate. Diastolic function is determined by the relative end diastolic volume in relation to end diastolic pressure, and is therefore independent of left ventricular systolic function. A leftward shift of the end-diastolic pressure-volume relationship (i.e. decreased left ventricular distensibility) can occur both in those with normal and those with decreased left ventricular systolic function. Likewise, heart failure may occur in those with dilated left ventricular and normal systolic function. This is often seen in valvular heart disease and high-output heart failure.