Fast Fact and Concept #51: Choosing an opioid combination product

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Title: Fast Fact and Concept #51: Choosing an opioid combination product

Author(s): Weissman, David E

There are over 50 different opioid combination products, available in a range of tablet strengths and liquids. Opioid combination products are typically used for moderate pain that is episodic (e.g. breakthrough pain) on a prn basis. These products contain either acetaminophen, aspirin or ibuprofen, with an opioid: codeine (e.g. Tylenol #2-4), hydrocodone (e.g. Lorcet, Lortab, Vicodin, Vicoprofen), oxycodone (e.g. Percocet, Percodan, Tylox, Roxicet) or propoxyphene (e.g. Darvocet, Wygesic). Other formulations also may contain caffeine and/or a barbiturate. This Fast Fact will review information for rationally choosing among the various products.

Intrinsic Analgesic Potency

Milligram for milligram, oxycodone and hydrocodone are the most potent opioids in this group; they are roughly equianalgesic to each other. Codeine is less potent and propoxyphene the least potent of the group; propoxyphene products are probably no more potent than aspirin or acetaminophen alone.


The dose limiting property of all the combination products is the aspirin, acetaminophen or ibuprofen, not the opioid (see below). Patients receiving any of the four opioids may experience classic opioid side effects: nausea, constipation, pruritus or sedation, along with the potential for tolerance and physical dependence with chronic use. Differences in side effect severity among the different opioids is largely idiosyncratic; there is anecdotal experience that codeine is the most, and hydrocodone the least, emetogenic among the four opioids. Propoxyphene's major metabolite is a CNS stimulant, increasing the likelihood of seizures in an overdose situation; it is also cardiotoxic, with lidocaine-like effects. Because of limited efficacy and increased toxicity, propoxyphene is not recommend, especially in the elderly.1


Generic products are readily available and typically much less expensive.

Range of available doses

Codeine products: 15-60 mg codeine/tablet
Oxycodone or hydrocodone: 2.5-10 mg oxycodone/tablet
Propoxyphene; 50-100 mg propoxyphene/tablet
Acetaminophen doses range from 325-750 mg/tablet

Recommendations for use

1. Propoxyphene should rarely, if ever, be prescribed; it should not be used in the elderly.
2. Prescribe generic products whenever possible.
3. Prescribe only one combination product at any given time; avoid writing orders that include multiple products; (e.g. "X" for mild pain, "Y" for moderate pain, etc). Rather, prescribe only one product, assess efficacy and toxicity, and modify accordingly.
4. Prescribe codeine, oxycodone and hydrocodone products at a q4h interval; not q 4-6 or q6h.2
5. Pay very close attention to the total daily dose of acetaminophen/aspirin/ibuprofen. Note: the dose of acetaminophen per tablet can range from 325--750 mg. Thus, with a recommended limit of < 4 gms per day, this equals 12 tablets @ 325 mg or 5 tablets @ 750 mg tablet. Patients with renal or liver dysfunction are at higher risk for adverse effects from the non-opioid.3


1. The Management of chronic pain in older persons. AGS panel on chronic pain in older persons JAGS 1998;46:635-651.
2. Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice Guideline No. 9. AHCPR Publication No. 94-0592. Rockville, MD. Agency for Health Care Policy and Research, U.S. Department of Health and Human Services, Public Health Service, 1994.
3. Principles of analgesic use in the treatment of acute pain and cancer pain. American Pain Society, 4th edition.1999.

Copyright and Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Fast Fact and Concept #50 Weissman DE. Choosing and opioid combination product. September, 2001. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Fast Facts and Concepts was originally developed as an end-of-life teaching tool by Eric Warm, MD, U. Cincinnati, Department of Medicine. See: Warm, E. Improving EOL care--internal medicine curriculum project. J Pall Med 1999; 2: 339-340.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 9/2001

Format: Handouts

Purpose: Instructional Aid, Self-Study Guide, Teaching

Training: Fellows, 1st/2nd Year Medical Students, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice
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ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Addiction, Chronic non-malignant pain, Controlled substance regulations, Pain, Pain assessment, Pain treatment

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