National Stroke Foundation

Ultracet (acetaminophen and tramadol HCl)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved August 2001

Specific Treatments:

Acute pain

Therapeutic Areas

General Information

Ultracet has been approved by the FDA for the short-term (five days or less) management of acute pain. This medication is a centrally acting analgesic that controls pain through different mechanisms of action than non-steroidal anti-inflammatory drugs (NSAIDs), the most commonly used pain medications. As a result, Ultracet is not associated with the side effects that can result from NSAID use, such as gastrointestinal ulcers or bleeding.

Ultracet combines Ultram (tramadol HCl), a leading prescription pain reliever, with the common non-prescription pain treatment, acetaminophen. Clinical trials have shown that the combination is more effective than either drug alone, providing longer duration than acetaminophen and a faster onset of action than tramadol.

Clinical Results

Ultracet has been evaluated for efficacy and safety in pivotal single-dose trials in subjects with acute pain. In these trials, subjects with pain following oral surgical procedures who received two tablets of Ultracet experienced greater relief than placebo-treated subjects. Additionally, subjects treated with Ultracet experienced greater relief than subjects on either of the individual components given at the same dose. The onset of pain relief after Ultracet (occurring in less than one hour) was faster than with tramadol alone, whereas the duration of pain relief after Ultracet was longer than with acetaminophen alone. Analgesia was found to be generally comparable to ibuprofen.

Side Effects

Side effects reported with Ultracet include constipation, somnolence (sleepiness) and increased sweating.

Ultracet should not be used concomitantly with alcohol. Since tramadol can reinitiate physical dependence, Ultracet is not recommended for subjects disposed to drug or alcohol abuse.

Seizures have been reported in subjects receiving tramadol treatment. Data indicates that the risk of seizures is increased with doses of tramadol above the recommended range. Tramadol use has been shown to increase seizure risk in subjects taking the following medications:

  • Selective serotonin reuptake inhibitors
  • Tricyclic antidepressants
  • Opioids

Additionally, tramadol may enhance the risk of seizures in subjects taking the following:

  • MAO inhibitors
  • Neuroleptics
  • Other drugs that reduce the seizure threshold

As with any medication, please consult a physician to discuss possible adverse effects or contraindications.

Mechanism of Action

Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to mu-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.

Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu-opioid receptors. In animal models, M1 is up to six times more potent than tramadol in producing analgesia and 200 times more potent in mu-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound.

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol.

Acetaminophen is a non-opiate, non-salicylate analgesic. (from Ultracet Prescribing Information)

Additional Information

For additional information on Ultracet, please visit Ortho-McNeil Pharmaceutical.