Acetaminophen and Tramadol

Tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use: Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including tramadol hydrochloride and acetaminophen tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Tramadol hydrochloride and acetaminophen tablets contain tramadol, an opioid agonist and inhibitor of norepinephrine and serotonin re-uptake, and acetaminophen. Although the mode of action of tramadol is not completely understood, the analgesic effect of tramadol is believed to be due to both binding to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity of tramadol is due to both low affinity binding of the parent compound and higher affinity binding of the O -demethylated metabolite M1 to µ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests.

Tramadol hydrochloride and acetaminophen tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of tramadol hydrochloride and acetaminophen tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.

Tramadol hydrochloride and acetaminophen tablets are contraindicated for: all children younger than 12 years of age post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Tramadol hydrochloride and acetaminophen tablets are also contraindicated in patients with: Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Patients with known or suspected gastrointestinal obstruction, including paralytic ileus. Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids.

Boxed warning (serious and life-threatening risks from use of tramadol hydrochloride and acetaminophen tablets): Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride and acetaminophen exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions. Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. Serotonin Syndrome: May be life-threatening.

The following serious adverse reactions are discussed, or described in greater detail, in other sections: Opioid-Induced Hyperalgesia and Allodynia Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Interactions with Benzodiazepines or Other CNS Depressants Neonatal Opioid Withdrawal Syndrome Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children Hepatotoxicity Serotonin Syndrome Seizures Suicide Adrenal Insufficiency Severe Hypotension Gastrointestinal Adverse Reactions Hypersensitivity Reactions Withdrawal The most common incidence of treatment-emergent adverse events (≥ 3%) in patients from clinical trials were constipation, diarrhea, nausea, somnolence, anorexia, dizziness, and sweating increased.

Table 2 includes clinically significant interactions with tramadol hydrochloride and acetaminophen. Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride and Acetaminophen Inhibitors of CYP2D6 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved. Since M1 is a more potent μ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol.

Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F). Store tramadol hydrochloride and acetaminophen tablets securely and dispose of properly.