The Nashville and Heroes star, 36, was found unresponsive in a flat in the city of Greenville in South Carolina last month.
Ruling that her death was an accident, Greenville County Coroner Mike Ellis said an autopsy found no signs of trauma that would have contributed to her death.
Her cause of death was ruled as “the toxic effects of fentanyl, 4-ANPP (fentanyl’s chemical byproduct), Alprazolam, Methocarbamol and Quetiapine,” Sky’s US partner NBC said.
Alprazolam is an anti-anxiety medicine, Methocarbamol is a muscle relaxer, while Quetiapine is used to treat major depression and other serious mental health disorders.
Panettiere’s on-and-off boyfriend Brian Hickerson and his brother Zach Hickerson were also in the apartment at the time.
Asked for her reaction to the report, Kasey Kitchen, a publicist for her family, said “the investigation is still ongoing and the case is complex”.
Greenville Police said they are still investigating Panettiere’s death.
Paramedics performed CPR on her for 40 minutes, as well as trying other advanced resuscitation efforts, before declaring her dead.
The police report released after her death mentioned a list of medications Panettiere was taking, but the names of the drugs were redacted.
Panettiere, who also appeared in the Scream horror movie franchise, released her memoirs earlier this year, opening up about her experiences with postpartum depression, addiction, and recovery.
Read more on Sky News:
Morgan to sue Spencer – latest
Four die in house fire
Sheeran ‘sorry’ over Palestine row
This led to her decision to give custody of her only child, Kaya, in 2018, to her former partner, Ukrainian professional boxer Wladimir Klitschko, Kaya’s father.
Panettiere first appeared in adverts when she was just 11 months old – and went on to become a child actor with roles in soap operas including One Life To Live and Guiding Light.
Her first major feature-film role came when she was nine years old, as the voice of Princess Dot in A Bug’s Life.
