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# Drug Information Request: Tramadol
## Overview
Tramadol is a centrally acting synthetic opioid analgesic. It inhibits the reuptake of norepinephrine and serotonin, which contributes to its analgesic effect in addition to its weak affinity for the mu-opioid receptor.
## Primary Indications
* Management of moderate to moderately severe pain.
## Adult Dosing
* **Immediate-release (IR):** 50-100 mg every 4-6 hours as needed for pain. Maximum daily dose: 400 mg.
* **Extended-release (ER):** 100 mg once daily. May be increased by 100 mg every 3-5 days as needed, not to exceed 300 mg once daily. ER formulations are not intended for use as needed for pain.
## Pediatric Dosing
* **Children 1 to 15 years:** 1-2 mg/kg/dose every 4-6 hours as needed for pain. Maximum daily dose: 8 mg/kg/day or 400 mg/day, whichever is less. (Note: ER formulations are not approved for pediatric use).
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. For moderate hepatic impairment, consider reducing the dose by 50%.
* **Renal Impairment:** For moderate renal impairment (CrCl 30-60 mL/min), the dosing interval may be extended to every 8 hours. For severe renal impairment (CrCl <30 mL/min), avoid use.
## Contraindications
* Hypersensitivity to tramadol.
* Acute intoxication with alcohol, hypnotics, narcotics, psychotropic agents, or other centrally acting analgesics.
* Use within 14 days of monoamine oxidase inhibitor (MAOI) therapy.
* Patients who are CYP2D6 ultra-rapid metabolizers, particularly for extended-release formulations.
## Adverse Effects
* **Common:** Nausea, vomiting, constipation, dizziness, somnolence, headache, fatigue.
* **Serious:** Respiratory depression, seizures, serotonin syndrome, abuse/misuse/addiction, neonatal withdrawal syndrome, hypersensitivity reactions, suicidal behavior/ideation.
## Key Drug Interactions
* **CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine, quinidine):** Increased tramadol levels, increasing risk of toxicity.
* **CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin):** Increased tramadol levels, increasing risk of toxicity.
* **CNS Depressants (e.g., benzodiazepines, alcohol, opioids):** Additive CNS depression.
* **Serotonergic Agents (e.g., SSRIs, SNRIs, MAOIs, triptans):** Increased risk of serotonin syndrome.
* **Warfarin:** May increase INR.
## Monitoring
* Pain relief and effectiveness.
* Signs and symptoms of opioid withdrawal.
* Signs and symptoms of serotonin syndrome.
* Respiratory rate, sedation level.
* For patients on warfarin, monitor INR.
## Clinical Pearls
* Tramadol's dual mechanism of action may provide adequate pain relief for some patients when other opioids are insufficient or not tolerated.
* Risk of seizures is increased in patients with a history of seizure disorder, those taking medications that lower the seizure threshold, or at doses exceeding recommended maximums.
* Avoid use in patients with severe respiratory depression.
* Due to the risk of serotonin syndrome, use with extreme caution in patients taking other serotonergic medications.
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**Disclaimer:** This information is intended for healthcare professionals and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.
