Tramadol

Tramadol Hydrochloride Extended-Release Capsules are indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Tramadol Hydrochloride Extended-Release Capsules are an opioid agonist indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids.

Tramadol Hydrochloride Extended-Release Capsules contain tramadol, an opioid agonist, and an inhibitor of reuptake of norepinephrine and serotonin. 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 of tramadol 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 6 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 opioid antagonist naloxone in several animal tests.

Tramadol Hydrochloride Extended-Release Capsules should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting 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 Extended-Release Capsules 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. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

Tramadol Hydrochloride Extended-Release Capsules are contraindicated for: All children younger than 12 years of age Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy Tramadol Hydrochloride Extended-Release Capsules is also contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment Known or suspected gastrointestinal obstruction, including paralytic ileus Hypersensitivity to tramadol (e.g., anaphylaxis) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days Children younger than 12 years of age.

Boxed warning: Tramadol Hydrochloride Extended-Release Capsules exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and reassess regularly for these behaviors and conditions. Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dosage increase. 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.

The following serious or otherwise important adverse reactions are described in greater detail, in other sections: Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Interactions with Benzodiazepines and Other CNS Depressants Neonatal Opioid Withdrawal Syndrome Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children Opioid-Induced Hyperalgesia and Allodynia Serotonin Syndrome Seizures Suicide Adrenal Insufficiency Severe Hypotension Gastrointestinal Adverse Reactions Hypersensitivity Reactions Withdrawal Most common adverse reactions (incidence ≥10% and twice placebo) are nausea, constipation, dry mouth, somnolence, dizziness, and vomiting.

Table 2 includes clinically significant drug interactions with Tramadol Hydrochloride Extended-Release Capsules. Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride Extended-Release Capsules Inhibitors of CYP2D6 Clinical Impact: The concomitant use of Tramadol Hydrochloride Extended-Release Capsules 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 Extended-Release Capsules is achieved. Since M1 is a more potent mu-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°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store Tramadol Hydrochloride Extended-Release Capsules securely and dispose of properly.