acetaminophen / oxycodone

What is in it

Each ingredient has its own full page with the FDA label, side-effect reports, recalls, evidence, and payments. Open them for the detail behind this grade.

Score breakdown (50/100)

Safety: 30

• Graded by its riskiest ingredient, oxycodone (30)
• Carries an FDA boxed warning, the strongest warning the FDA issues (-30)
• FDA issued 8 Drug Safety Communication(s) about this drug's class since 2010 (-8)
• 2,629 FDA reports naming it as the suspect drug per million Medicare fills, 0.9x the median drug on this site
• Subject to a REMS safety program: FDA requires special controls to use it (-10)
• Federally controlled substance: dependence and misuse risk (-10)
• Death appears in 2.6x the share of reports seen across all of FAERS (-12)

Evidence: 71

• Graded by its riskiest ingredient, oxycodone (71)
• 442 randomized trials and 35 systematic reviews/meta-analyses indexed in PubMed
• On the WHO Model List of Essential Medicines (shown for context; no score effect)
• 10 independent Cochrane review(s) exist
• Only 47% of completed registered trials posted results (-8)

Regulatory history: 70

• Graded by its riskiest ingredient, acetaminophen (70)
• Recalls since 2016: 3 Class I, 25 Class II, 0 Class III across 12 generic makers (-30)

Money & lawsuits: 15

• Graded by its riskiest ingredient, oxycodone (15)
• Maker paid $601 million in 2007 to settle federal allegations naming this drug (Off-label promotion) (-15)
• Pharma paid doctors $3,041,014 tied to this drug last year (-30)
• Named in 2 active federal multidistrict litigation(s) (-40)
• For the combination product itself:
• Pharma paid doctors $118,175 tied to this drug last year (-15)
• Named in 2 active federal multidistrict litigation(s) (-40)

Options: 90

• Graded by its riskiest ingredient, acetaminophen (90)
• Generic versions approved (12 applications)
• 1 same-class alternative(s) (-10)

FDA Drug Safety Communications naming this combination

• 07/2025 FDA is requiring opioid pain medicine manufacturers to update prescribing information regarding long-term use class-wide
• 04/2023 FDA updates prescribing information for all opioid pain medicines to provide additional guidance for safe use class-wide
• 06/2022 FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder class-wide
• 04/2019 FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering class-wide
• 01/2018 FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older class-wide
• 09/2017 FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks class-wide
• 08/2016 FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning class-wide
• 03/2016 FDA warns about several safety issues with opioid pain medicines; requires label changes class-wide

Money and lawsuits

In 2024, drug companies reported $118,175 in payments to US physicians and hospitals tied to this combination's brands across 5,749 transactions (Nalocet $111,032, Prolate $7,142).

Pending federal multidistrict litigation

• MDL 2804 National Prescription Opiate Litigation (OHN, actions pending)
• MDL 2996 McKinsey & Company, Inc., National Prescription Opiate Consultant Litigation (CAN, actions pending)

The ingredients' own payments and lawsuits are on their pages and already count toward this grade.

Who takes it and what it costs

Questions to ask your prescriber

1. This is a fixed combination of acetaminophen and oxycodone. Why both together, instead of only the one I need?
2. In 2013 the FDA issued a safety communication about this drug (FDA warns of rare but serious skin reactions with the pain reliever/fever reducer acetaminophen). Does that risk apply to me?
3. The most-reported problems in FDA's adverse event data are fatigue, nausea. How would we recognize and handle those?
4. Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?
5. Why this one over phenacetin? What would make you pick one of those instead?
6. This drug is in active federal litigation. What is the claim, and does it affect my risk?
7. What result are we expecting, by when, and what is the plan if it does not happen?
8. If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)
9. The maker paid $601 million in 2007 to settle federal allegations about how this drug was marketed. Is my use one of the uses that was promoted improperly?
10. This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?
11. This is a controlled substance. What is the plan for how long I take it and how I stop?
12. This drug has a REMS safety program. What monitoring does that require from us?
13. The most-reported problems in FDA's adverse event data are drug dependence, pain, overdose, emotional distress. How would we recognize and handle those?
14. Why this one over dihydrocodeine, hydromorphone, morphine? What would make you pick one of those instead?
15. The manufacturer pays physicians heavily to promote this drug. Have you received anything from them?