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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ULTRAM ER (ULTRAM ER).
| Breastfeeding | Ultram ER has an M/P ratio of 0.7-1.3. Small amounts excreted; can cause infant sedation and constipation. Use caution; monitor infant for drowsiness or feeding difficulties. |
| 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. |
■ 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 |
Hypersensitivity to tramadol or any formulation component; significant respiratory depression; acute or severe bronchial asthma in unmonitored settings; known or suspected gastrointestinal obstruction; concurrent use of MAOIs or within 14 days; use in children <12 years; use in children <18 years after tonsillectomy/adenoidectomy; use in patients with severe hepatic impairment.
| 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…
| 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. |