Data from Other Trials One death occurred in a 54 year-old postmenopausal woman treated with 100 mg ADDYI taken at bedtime (ADDYI is not approved for the treatment of postmenopausal women with HSDD) [see Indications and Usage (1)]. This patient had a history of hypertension and hypercholesterolemia and baseline alcohol consumption of 1-3 drinks daily. She died of acute alcohol intoxication 14 days after starting ADDYI. Blood alcohol concentration on autopsy was 0.289 g/dL. The autopsy report also noted coronary artery disease. A relationship between this patient’s death and use of ADDYI is unknown [see Boxed Warning and Warnings and Precautions (5.1)]. Hypotension, Syncope, and CNS Depression in Studies of Healthy Subjects Hypotension, Syncope, and CNS Depression with Alcohol Alcohol and ADDYI Administration at the Same Time The first alcohol interaction study was conducted in 25 healthy subjects (23 men and 2 premenopausal women). The study excluded subjects who drank fewer than five alcoholic drinks per week and those with a history of orthostatic hypotension, or syncope. A single dose of 100 mg ADDYI was administered concurrently with 0.4 g/kg or 0.8 g/kg alcohol in the morning; alcohol was consumed over 10 minutes. Hypotension or syncope requiring therapeutic intervention (ammonia salts and/or placement in supine or Trendelenberg position) occurred in 4 (17%) of the 23 subjects co-administered 100 mg ADDYI and 0.4 g/kg alcohol (equivalent to two 12 ounce cans of beer containing 5% alcohol content, two 5 ounce glasses of wine containing 12% alcohol content, or two 1.5 ounce shots of 80-proof spirit in a 70 kg person). In these four subjects, all of whom were men, the magnitude of the systolic blood pressure reductions ranged from 28 to 54 mmHg and the magnitude of the diastolic blood pressure reductions ranged from 24 to 46 mmHg. In addition, 6 (25%) of the 24 subjects co-administered 100 mg ADDYI and 0.8 g/kg alcohol (equivalent to four 12 ounce cans of beer containing 5% alcohol content, four 5 ounce glasses of wine containing 12% alcohol content, or four 1.5 ounce shots of 80-proof spirit in a 70 kg person) experienced orthostatic hypotension when standing from a sitting position. The magnitude of the systolic blood pressure reduction in these 6 subjects ranged from 22 to 48 mmHg, and the diastolic blood pressure reductions ranged from 0 to 27 mmHg. One of these subjects required therapeutic intervention (ammonia salts and placement supine with the foot of the bed elevated). There were no events requiring therapeutic interventions when ADDYI or alcohol were administered alone. In this study, somnolence was reported in 67%, 74%, and 92% of subjects who received ADDYI alone, ADDYI in combination with 0.4 g/kg alcohol, and ADDYI in combination with 0.8 g/kg alcohol, respectively. [see Boxed Warning, Warnings and Precautions (5.1, 5.3and 5.4)]. In the second alcohol interaction study, 96 healthy premenopausal women received a single dose of 100 mg ADDYI concurrently with 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg alcohol (equivalent to one, two or three alcoholic drinks in a 70 kg person, respectively) in the morning. The study excluded subjects with a history of syncope, orthostatic hypotension, hypotensive events, and dizziness, and those with a resting systolic blood pressure less than 110 mmHg or diastolic blood pressure less than 60 mmHg. In this study, no subjects experienced syncope or hypotension requiring therapeutic intervention. However, subjects who were already hypotensive (blood pressure below 90/60 mmHg) or symptomatic (e.g., dizzy) while in the semi-recumbent position were not permitted to stand for orthostatic measurements, and those with blood pressures below 90/40 mmHg while in the semi-recumbent position had blood pressures repeated until it was deemed safe for them to change position. More subjects had missing or delayed orthostatic measurements (in general, due to hypotension or dizziness) when receiving ADDYI and alcohol, compared Reference ID: 4865026