- Patient has significant impairment of liver or renal function (alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) 2.5 times the upper limit of normal; creatinine clearance <30mL/minute (min), estimated using serum creatinine with the formula [(140 - age in years) × weight in kg]/[(72 × serum creatinine in mg/dl) × 0.85 for female patients].