Short answer: Both are one tablet a day combining an estrogen with norethindrone acetate, for women with a uterus.12 Fyavolv uses ethinyl estradiol (2.5 or 5 mcg). Activella uses estradiol (1 mg or 0.5 mg). Both treat hot flashes and help prevent osteoporosis; only Activella is also approved for vaginal atrophy. Neither label compares them. Both carry a boxed warning.
| Fyavolv | Activella | |
|---|---|---|
| Strengths | Norethindrone acetate 0.5 mg/ethinyl estradiol 2.5 mcg, or 1 mg/5 mcg1 | Estradiol 1 mg/norethindrone acetate 0.5 mg, or 0.5 mg/0.1 mg2 |
| How taken | One tablet by mouth once daily1 | One tablet by mouth once daily2 |
| Approved for | Hot flashes; preventing postmenopausal osteoporosis1 | Hot flashes; vaginal atrophy (1 mg/0.5 mg); preventing postmenopausal osteoporosis2 |
| Breast pain | 9.0% and 7.8% vs 3.6% on placebo1 | 24% (12 months, 1 mg/0.5 mg); 21% vs 0% on placebo (3 months)2 |
| Endometrium | Hyperplasia 0 on either strength at 2 years; 2 on ethinyl estradiol 5 mcg alone1 | Hyperplasia 0.4% vs 14.6% on estradiol 1 mg alone at 12 months2 |
| Missed dose | No instruction in the label1 | No instruction in the label2 |
| Boxed warning | WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER1 | WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER2 |
The Fyavolv label's 2-year study compared norethindrone acetate and ethinyl estradiol with placebo and with ethinyl estradiol alone. At month 24, endometrial hyperplasia was 0 on both combination strengths, 1 on placebo and 2 on ethinyl estradiol 5 mcg alone. Spine bone density measured by QCT rose 3.1% on 1 mg/5 mcg and fell 6.3% on placebo.1
The Activella label's 12-month study compared 1 mg/0.5 mg with estradiol 1 mg alone: hyperplasia in 1 of 241 women (0.4%) vs 36 of 247 (14.6%).2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Fyavolv contains ethinyl estradiol, a different estrogen from the estradiol in Activella, at microgram doses. Its label pools controlled studies of norethindrone acetate and ethinyl estradiol. Both labels say to use the lowest effective dose for the shortest time, to consider non-estrogen medicines first when bone is the only goal, and to talk about the need for treatment every 3 to 6 months.12
Which, if either, fits is for your prescriber. More detail: Fyavolv side effects, Activella side effects, the Fyavolv and Activella dosing schedules, how to store Activella and Prempro vs Activella: how do the two combined HRT tablets differ?.