[1][3] Serious side effects include addiction, decreased rate of breathing, low blood pressure, severe allergic reactions, and liver failure.

In-drug evidence was submitted to U.S. federal state and local forensic laboratories as reported by the Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information from Drug Evidence (STRIDE).

Most of the cases of liver injury are associated with the use of paracetamol at doses that exceed 4000 milligrams per day, and often involve more than one paracetamol-containing product.

[2][1] Hydrocodone: Respiratory depression, extreme somnolence progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur.

[14] Concurrent use of paracetamol with alcohol products may increase the risk of acute liver failure.

[2] In June 2009, a US Food and Drug Administration (FDA) advisory panel voted by a narrow margin to advise the FDA to remove Vicodin and another opioid, Percocet, from the market because of "a high likelihood of overdose from prescription narcotics and acetaminophen products".

[21] The panel also cited concerns of liver damage from their paracetamol component, which is also the main ingredient in commonly used nonprescription drugs such as Tylenol.

[11] Even though there are legitimate medical uses for hydrocodone combination products, data suggest that a significant number of individuals misuse them.

[11] Actor Matthew Perry struggled with his addiction to Vicodin for many years after a jet ski accident in 1997.