"There is absolutely no indication that this is anything but an accident," chief coroner investigator Craig Harvey said.
Penn, 40, the younger brother of Sean Penn, was found dead in his Santa Monica condominium on Jan. 24, but the results of his autopsy and toxicology tests were not released until Monday.
The primary cause of death was "nonspecific cardiomyopathy," an oversized heart, with the "effects of multiple medication intake," according to a statement issued by the coroner's office.
"We know he had several prescriptions, including promethazine with codeine, which featured predominantly in his death," Harvey said.
Promethazine with codeine is known as a highly addictive prescription medication. Promethazine is an antihistamine that prevents vomiting, while codeine suppresses coughing and relieves pain, Harvey said.
"We don't know how much he ingested or when," Harvey said. "There are a lot of 'what ifs' to be factored in."
A full coroner's report with further details will be available in a few weeks, Harvey said.
Penn's heart weighed 700 grams, a few hundred grams more than an average heart. Harvey said Penn was not taking heart medication at the time of his death.
Penn appeared in such films as "Reservoir Dogs," "Rush Hour," "Starsky amp; Hutch" and "Corky Romano."