Tramadol/APAP (Ultracet®)

  • Generic name: Tramadol hydrochloride 37.5 mg and Acetaminophen 325 mg
  • Brand names: Ultracet, Tramacet, ramse
  • Therapeutic class: Centrally-acting opioid/Non-narcotic analgesic combination

What is Tramadol/APAP used for?

  • Short-term (5 days or less) management of acute pain (e.g. muscle aches, back and neck pain, post-operative pain)
  • Chronic lower back pain 3
  • Tooth/dental pain 4
  • Migraine headaches 5
  • Fibromyalgia 6
  • Osteoarthritis pain 7

Strict Contraindications

Situations when and Tramadol 37.5 mg/APAP 325 mg combination tablets are absolutely inadvisable:

  • Allergy to tramadol, acetaminophen, opioids, or other components of the product.
  • Intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs.

Drug Interactions

  • Serotonergic drugs (SSRIs, MAOIs, triptans, linezolid, lithium, or St. John’s Wort): increased risk of serotonin syndrome and seizures when tramadol is used concomitantly with other drugs that affect the serotonergic neurotransmitter systems.
  • Carbamazepine: concomitant use is not recommended. Carbamazepine increases tramadol metabolism, leading to significantly reduced analgesic effect of tramadol and increased the risk of seizures.
  • Warfarin: possible alterations of warfarin effect, including elevation of prothrombin times.

Concurrent Use with Other Medications

Can you take Tramadol/APAP (Ultracet) and Ibuprofen (Motrin)?
There are no reported drug interactions2. Tramadol/APAP and ibuprofen can be taken together.

Acetaminophen-containing products: Due to the acetaminophen potential to cause hepatotoxicity (liver damage) at high doses, tramadol hydrochloride and acetaminophen tablets should not be used together with other acetaminophen-containing products2.
Do not to exceed the acetaminophen maximum total daily dose of 4 grams per day.


Usual dosage: The usual Tramadol/Acetaminophen 37.5-325 dosage for pain relief for adults and adolescents 16 years and older is 2 tablets every 4-6 hours as needed for up to 5 days.

Maximum dosage: 8 tablets per day. An overdose can be fatal.

Renal dosage adjustments: For patients with kidney function below normal (creatinine clearances less than 30 mL/min) the dosing interval should be increased not to exceed 2 tablets every 12 hours.
Maximum dose: 4 tablets per day.

How does Tramadol/APAP work?

Tramadol hydrochloride/Acetaminophen is a powerful pain medicine that combines 37.5 mg tramadol hydrochloride and 325 mg acetaminophen (paracetamol). The combination of two analgesics provides enhanced efficacy, faster onset of pain relief and longer duration of analgesia than either component alone. Tramadol APAP begins to work within 17 minutes and lasts for more than 5 hours1.

Tramadol is a unique non-scheduled opioid. Its analgesic action involves a complementary dual mechanism: mild µ-opioid receptor binding and inhibition of norepinephrine and serotonin reuptake.

Acetaminophen, also known as paracetamol, is sold over-the-counter under the brand Tylenol. It appears to work by increasing the pain threshold via inhibition of prostaglandin synthesis and indirect activation of cannabinoid CB(1) receptors.

The combination of analgesics with different mechanisms of action works by activating multiple pain-inhibitory pathways, and provides superior pain relief with no increase in adverse drug reactions.

The safety profile of this combination, especially the low incidence of tolerance, dependence, constipation and somnolence, makes it an attractive substitute for traditional opioid analgesics.

Further Reading


  • 1. Medve RA, Wang J, Karim R. Tramadol and acetaminophen for dental pain. Anesth Prog 2001;48: 79-81. PubMed
  • 2. Ultracet® (tramadol hydrochloride/acetaminophen) U.S. prescribing information. Janssen Pharmaceuticals PDF
  • 3. Ruoff GE, Rosenthal N, Jordan D, Karim R, Kamin M; Protocol CAPSS-112 Study Group. Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient study. Clin Ther. 2003 Apr;25(4):1123-41.
  • 4. Medve RA, Wang J, Karim R. Tramadol and acetaminophen tablets for dental pain. Anesth Prog. 2001 Summer;48(3):79-81.
  • 5. Silberstein SD, Freitag FG, Rozen TD, Kudrow DB, Hewitt DJ, Jordan DM, Fisher AC, Rosenthal NR; CAPSS-223 Investigators. Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial. Headache. 2005 Nov-Dec;45(10):1317-27.
  • 6. Bennett RM, Kamin M, Karim R, Rosenthal N. Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med. 2003 May;114(7):537-45.
  • 7. Silverfield JC, Kamin M, Wu SC, Rosenthal N; CAPSS-105 Study Group. Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Clin Ther. 2002 Feb;24(2):282-97.

Last updated: February, 2015

Good to know

Ultracet 37.5/325
  • Tramadol is not a scheduled substance in the Controlled Substances Act. However, in some states it is a schedule IV substance.
  • The combination of tramadol (a quasi-narcotic analgesic) with acetaminophen leverages the unique but complementary modes of action of each medicine to provide a better analgesia.