ULTRAM ER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ULTRAM ER (ULTRAM ER).
Tramadol is a centrally acting synthetic opioid analgesic that binds to μ-opioid receptors and inhibits serotonin and norepinephrine reuptake.
| Metabolism | Metabolized primarily via CYP2D6 and CYP3A4; O-desmethyltramadol (M1) is the active metabolite formed by CYP2D6; tramadol and metabolites undergo further conjugation. |
| Excretion | Renal excretion of tramadol and its metabolites accounts for approximately 90% of total elimination. About 10% is excreted unchanged, 30% as O-desmethyltramadol (M1), and the remainder as other minor metabolites. Biliary/fecal excretion is minimal (<10%). |
| Half-life | The terminal elimination half-life of tramadol is approximately 6.3 hours (range 5-9 hours), while its active metabolite M1 has a half-life of about 7.4 hours. Clinically, this supports dosing every 24 hours for the extended-release formulation. |
| Protein binding | Approximately 20% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.6-3.0 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability of tramadol is approximately 75% after a single dose, increasing to 90-100% upon multiple dosing due to saturable first-pass metabolism. For ULTRAM ER, bioavailability is comparable to immediate-release formulations. |
| Onset of Action | For ULTRAM ER (oral extended-release), onset of analgesic action occurs within 1-2 hours after administration. |
| Duration of Action | Duration of analgesia is approximately 24 hours with ULTRAM ER, allowing once-daily dosing. Peak effects are sustained over the dosing interval. |
| Molecular Weight | 299.84 |
100 mg orally once daily initially, titrate up to 100 mg twice daily as needed; maximum 200 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-80 mL/min: no adjustment; GFR <30 mL/min: avoid or extend dosing interval to 12 hours; not recommended in GFR <15 mL/min. |
| Liver impairment | Child-Pugh Class A or B: use with caution, consider reducing total daily dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for use in pediatric patients <18 years due to risk of respiratory depression and lack of safety data. |
| Geriatric use | Start at lowest dose (100 mg once daily); titrate cautiously; monitor for CNS and respiratory depression; consider reduced clearance in elderly. |
| 1st trimester | Avoid use; associated with increased risk of congenital malformations when used in first trimester. |
| 2nd trimester | Use only if potential benefit justifies risk; may cause fetal respiratory depression and withdrawal if used near term. |
| 3rd trimester | Avoid prolonged use due to risk of neonatal opioid withdrawal syndrome and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for ULTRAM ER (ULTRAM ER).
| Placental transfer | Tramadol crosses the placenta; detectable in fetal plasma at concentrations similar to maternal plasma. Active metabolite (M1) also crosses. |
| Breastfeeding | Tramadol and its active metabolite (M1) are excreted into breast milk in small amounts. Low doses are likely compatible, but caution is advised due to potential infant sedation and withdrawal. Monitor infant for signs of opioid effects. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion in children can be fatal; neonatal opioid withdrawal syndrome; risk of medication errors with other tramadol products; interactions with CNS depressants; serotonin syndrome; contraindicated in patients with significant respiratory depression; contraindicated in patients with acute or severe bronchial asthma; contraindicated in patients with known or suspected gastrointestinal obstruction; contraindicated in patients with previous hypersensitivity to tramadol.
| Serious Effects |
Acute intoxication with alcohol, hypnotics, centrally-acting analgesics, opioids, or psychotropic drugsSevere respiratory depressionKnown hypersensitivity to tramadol or any excipientsUncontrolled seizures or epilepsyConcurrent use of MAOIs or within 14 days of discontinuation
| Precautions | Risk of respiratory depression; risk of serotonin syndrome with serotonergic drugs; risk of seizures especially in patients with epilepsy or risk factors; risk of adrenal insufficiency; risk of severe hypotension; risk of abuse and dependence; avoidance of abrupt discontinuation; use in renal or hepatic impairment; use in elderly; use in pregnancy and breastfeeding. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category C. First trimester: Limited data; avoid unless benefit outweighs risk due to potential neural tube defects. Second and third trimesters: Fetal dependence, neonatal withdrawal syndrome (seizures, irritability, respiratory depression) if used >7 days. Increased risk of preterm birth and low birth weight. |
| Fetal Monitoring | Monitor for maternal respiratory depression, sedation, constipation. Fetal: heart rate and growth if prolonged use. Neonatal: withdrawal symptoms (e.g., hypertonia, tremors) for at least 48 hours after delivery. |
| Fertility Effects | Tramadol may alter hormone levels (prolactin, LH) potentially reducing fertility. Human studies limited; advise prepregnancy counseling for chronic users. |
| Food/Dietary |
| Avoid alcohol. No specific food restrictions; however, taking with food may reduce nausea. Grapefruit juice may increase tramadol levels; consider limiting grapefruit intake. |
| Clinical Pearls | ULTRAM ER contains tramadol, an opioid agonist with SNRI properties. Do not crush or chew extended-release tablets; this can cause rapid release and fatal overdose. Use with caution in patients with seizure disorders or those taking SSRIs, SNRIs, MAOIs, or other drugs that lower seizure threshold. Avoid concurrent use with alcohol or CNS depressants. Monitor for serotonin syndrome when combined with serotonergic drugs. Do not discontinue abruptly after prolonged use; taper to avoid withdrawal symptoms. Not recommended for patients under 18. Crushing extended-release tablets is a safety hazard. |
| Patient Advice | Take ULTRAM ER exactly as prescribed, usually once daily. Swallow tablets whole; do not crush, chew, or break them. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) while taking this medication. · This medication has a risk of addiction, abuse, and misuse. Store securely and dispose of unused tablets properly. · Do not stop taking this medicine suddenly; withdrawal symptoms may occur. Follow your doctor's instructions for tapering. · Seek emergency medical help if you have trouble breathing, severe drowsiness, or slow heartbeat. · Inform your doctor if you have a history of seizures, head injury, or are taking antidepressants like MAOIs, SSRIs, or SNRIs. · ULTRAM ER may cause constipation, nausea, dizziness, or drowsiness. Increase fluid intake and fiber to prevent constipation. · Keep out of reach of children and pets. Accidental ingestion can be fatal. · Do not drive or operate heavy machinery until you know how ULTRAM ER affects you. |