What is the difference between tylenol 3 and hydrocodone

PHOENIX, Arizona — Hydrocodone/acetaminophen (Vicodin, AbbVie) was not superior to codeine/acetaminophen (Tylenol #3, McNeil) in acute pain relief reported by patients 24 hours after being discharged from the emergency department, according to a new study.

While Vicodin is the most popularly prescribed opioid in emergency departments, the drug and other hydrocodone combination formulations are under consideration by the US Food and Drug Administration (FDA) for rescheduling from a Schedule III drug to a more tightly regulated Schedule II drug. New York State has already made the change.

With Tylenol #3 representing a potentially ideal alternative, researchers sought to compare the 2 drugs — and found existing evidence was scant.

"The reason we conducted this study was because there was very little evidence supporting the superiority of Vicodin over Tylenol with codeine, despite its heavy preference in the emergency department setting," said lead author Andrew K. Chang, MD, MS, an associate professor of clinical emergency medicine at the Albert Einstein College of Medicine and attending physician at Montefiore Medical Center, Bronx, New York.

"There was no significant difference in side effects, [and] our results showed that Vicodin failed to provide superior pain relief compared to Tylenol with codeine."

The findings underscore that clinicians should consider prescribing Tylenol with codeine instead of Vicodin when discharging nonelderly patients with acute extremity pain from the emergency department, but Dr. Chang noted an important caveat: patients in groups known to not metabolize codeine normally.

"It's important to be aware that there are codeine hypermetabolizers — for example, up to 30% of African/Ethiopians, who rapidly metabolize codeine to morphine and hence can develop respiratory depression and even death," he cautioned. "At the same time there are some patients who cannot metabolize codeine at all, and hence receive no analgesic effect."

The study — which did not receive outside funding — was presented here at the American Academy of Pain Medicine (AAPM) 30th Annual Meeting.

Opiate-Naive Patients

For the double-blind study, Dr. Chang and his colleagues randomly assigned nonelderly, opiate-naive emergency department patients who had presented with acute traumatic extremity pain to a 3-day supply of hydrocodone/acetaminophen (5/500 mg; n = 88) or codeine/acetaminophen (30/300 mg; n = 93).

The researchers contacted the patients a median of 26 hours after discharge and asked for their 0 to 10 numeric rating scale pain scores just before and 2 hours following the most recent ingestion of the drug.

They found that the pain score before the most recent dose of pain medication was the same for both groups: 7.6. A high pain score was expected as that would prompt patients to take the prescribed pain medication. Patients reported the mean decrease in the pain scores 2 hours after pain medications to be 3.9 in the hydrocodone/acetaminophen group and 3.5 in the codeine/acetaminophen group, for a between-group difference of only 0.4.

"Both medications decreased pain scores by approximately 50%," the authors write. "However, hydrocodone/acetaminophen (Vicodin [5/500]) failed to provide clinically or statistically superior pain relief compared to codeine/acetaminophen (Tylenol#3 [30/300])."

Adverse events, mainly drowsiness, dizziness, and nausea, were not clinically or statistically different between the groups, the authors note.

The study also is being published in the March issue of Academic Emergency Medicine.

The authors noted that they found just 1 other trial, from the University of Pittsburgh, Pennsylvania, comparing the 2 drugs in an emergency setting. That study also showed no significant difference in the mean or median pain scores between 2 groups of patients taking either of the medications over 48 hours following ED discharge for acute musculoskeletal pain.

"It was surprising to find so few studies comparing hydrocodone/acetaminophen to codeine/acetaminophen for acute pain, including in the emergency department setting," Dr. Chang said.

"I think the reason for this is that in general, emergency physicians have the impression that Tylenol with codeine is a far inferior pain medication when compared to Vicodin."

"Impressions are not evidence-based, however, and our study questions that long-standing belief," he said.

Deep-Seated Perceptions

Andre P. Boezaart, MD, agrees that Vicodin's popularity over other alternatives is largely a matter of deep-seated physician perceptions.

"My personal opinion is that this is purely a marketing and cultural issue," said Dr. Boezaart, professor of anesthesiology and orthopedic surgery in the Division of Acute and Peri-operative Pain Medicine at the University of Florida College of Medicine in Gainesville.

"[Vicodin] is marketed in the US as a serious drug that one uses for serious pain. Common perceptions meanwhile suggest that Tylenol is a safe and mild drug given to children with fevers and colds and used for mild headaches, and is not a serious drug to use for real pain," he told Medscape Medical News.

Patients with acute pain who learn they are receiving Tylenol may have the impression that they are not being treated with a true pain medication, Dr. Boezaart said.

"We experience this every day when we prescribe the very effective [every 6 hours] scheduled [intravenous] Tylenol 1000 mg to patients with severe acute pain," he said. "Patients will be quick to tell you that their pain is real and will not respond to a mild drug like Tylenol."

For that reason, Dr. Boezaart suggested that the name "Tylenol" even be dropped from the formulation of codeine and acetaminophen and replaced with something else.

"The company manufacturing Tylenol #3 would do the population a great favor if they changed the name to something that does not contain the word 'Tylenol,' but something that suggested treatment for serious pain, and then actively market it for that purpose."

In the absence of a name change, studies such as Dr. Chang's can help establish the drug's efficacy in comparison with its more popular competitor, Dr. Boezaart said.

"This is certainly the first study that I am aware of that compares Vicodin (5/500 mg) with Tylenol (30/300 mg)," he said.

"Every instinct would dictate that the latter should be a safer choice, but only further studies like this one by Chang et al would clarify this claim."  

The study did not receive funding. Dr. Chang and Dr. Boezaart have disclosed no relevant financial relationships.

American Academy of Pain Medicine (AAPM) 30th Annual Meeting. Abstract 163. Presented March 8, 2014.

Acad Emerg Med. Published online March 13, 2014. Abstract

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