Tramadol (Ultram)

ED / ICU / Transport

• Pain severe enough to require an opioid when alternatives are inadequate: adults only (FDA-labeled, IR tablets and oral solution). Use it when non-opioid options (acetaminophen, NSAIDs such as ketorolac) are not tolerated or not enough. For acute pain, use the lowest effective dose for the fewest days.
• Oral step-down or discharge analgesia: keep it to the lowest effective dose for the fewest days. Many acute pain conditions need no more than a few days of an opioid.
• Not preferred for acute musculoskeletal injury, low back pain or dental pain: the CDC 2022 guideline finds that non-opioids are at least as effective as opioids for these and other common acute pain conditions (sprains, strains, minor surgery, kidney stones, headache).
• Who may give it: an oral C-IV analgesic that an RN gives on prescriber order. It is not an EMS drug in the National EMS Scope of Practice Model. Continue a home dose in transport only on the sending order. Varies by state, agency and facility protocol.

Other Uses

• Severe, persistent pain needing extended opioid treatment (extended-release products): use it when alternatives, including immediate-release opioids, are inadequate. Not for acute or as-needed use (FDA-labeled).
• Acute pain, tramadol/acetaminophen combination: 5 days or less (FDA-labeled)

Adult doses are fixed. They don't scale with weight, so see the Adult Dosing table.

Available Forms

• Immediate-release (IR) tablets: 25, 50, 75 and 100 mg (strengths vary by manufacturer; 50 mg scored tablets are the most common).
• Oral solution: 5 mg/mL. A 50 mg dose is 10 mL.
• Extended-release (ER): capsules (ConZip) 100 mg, 200 mg and 300 mg; generic ER tablets are also marketed.
• Combination tablet: tramadol 37.5 mg with acetaminophen 325 mg.
• Route: every US product is oral. Injectable tramadol exists in some other countries, not in the US.

Adult Dosing

Pediatric Dosing

Weight-based alternatives: pediatric weight-based dosing.

Preparation & Administration

• Tablets: give with or without food.
• Oral solution: measure with a graduated oral syringe or cup in mL, never a household spoon; write and say every dose in mg and mL.
• ER capsules: swallow whole with liquid. Break, chew or dissolve one and the full dose releases at once, which can cause fatal overdose.
• Discharge: prescribe the smallest quantity needed, and discuss an opioid overdose reversal agent such as naloxone, especially with benzodiazepines or other sedatives, prior overdose or children at home. Hold off on driving or hazardous machinery until the patient knows how tramadol affects them.
• Stopping: after regular use, taper (for example no more than 10–25% of the daily dose every 2–4 weeks); never stop abruptly in a physically dependent patient.

Contraindications

• Children under 12 years, and post-tonsillectomy or adenoidectomy pain under 18 years
• Significant respiratory depression
• Acute or severe asthma in an unmonitored setting or without resuscitation equipment
• Known or suspected GI obstruction, including paralytic ileus
• Hypersensitivity to tramadol, any product component or opioids
• Monoamine oxidase inhibitor (MAOI) use now or within the last 14 days, including linezolid and IV methylene blue (see Interactions for unavoidable emergency methylene blue)

Precautions

• Seizure risk: epilepsy, head trauma, metabolic disorders, alcohol or drug withdrawal, CNS infection.
• Suicidal or addiction-prone patients: don't prescribe. Use caution with depression or heavy alcohol use.
• Chronic lung disease; older, cachectic or debilitated patients: apnea can happen at usual doses.
• Raised ICP, brain tumor or head injury: watch sedation and CO₂ retention closely. It may obscure the neuro exam. Avoid with impaired consciousness, coma or circulatory shock.
• Opioid-induced hyperalgesia/allodynia: pain that gets worse as the dose climbs, or pain from stimuli that shouldn't hurt, with no disease progression. Consider a lower dose or opioid rotation rather than escalation.
• Biliary tract disease or acute pancreatitis: it may cause sphincter of Oddi spasm and raise serum amylase. Monitor for worsening symptoms.
• Opioid-induced esophageal dysfunction: dysphagia, regurgitation or non-cardiac chest pain. These are more likely with higher doses or longer use. Adjust opioid therapy.
• CYP2D6 ultrarapid metabolizers; adolescents with hypoventilation risk factors: avoid.

Hold / Reassess If

• Respiratory rate (RR) <10/min, hard to rouse or falling SpO₂ (per local sedation-scale protocol)
• Any seizure, or new clonus, hyperreflexia, tremor, agitation or fever (serotonin toxicity)
• New confusion: check glucose and sodium before the next dose
• Orthostatic hypotension or syncope
• CrCl falls below 30 mL/min: switch to every 12 hr (max 200 mg/day) and stop ER products

Common

• Dizziness or vertigo: 26% by day 7, 33% by day 90
• Nausea: 24% by day 7, 40% by day 90; vomiting: 9–17%
• Constipation: 24% by day 7, 46% by day 90
• Headache: 18–32%; somnolence: 16–25%
• CNS stimulation (nervousness, anxiety, agitation, tremor, euphoria, hallucinations): 7–14%
• Pruritus, sweating, dry mouth: 5–11%

Serious / Life-Threatening

Overdose & Toxicity Management

• Signs: somnolence to coma, respiratory depression, pinpoint pupils (mydriasis with hypoxia), flaccidity, cold clammy skin, bradycardia, hypotension, hypoglycemia, pulmonary edema, seizures and death. Delayed toxic leukoencephalopathy can show up hours to weeks after the patient seems to recover. Alcohol, benzodiazepines or other opioids push the risk of death higher.
• Immediate management: open and protect the airway and ventilate first; oxygen; vasopressors for shock; ACLS for arrest; check glucose; 12-lead ECG; call poison control (1-800-222-1222).
• Antidote: an opioid overdose reversal agent, naloxone (or nalmefene per its own label), for clinically significant respiratory or circulatory depression: adult naloxone 0.4–2 mg IV every 2–3 min, titrated to breathing (IM, subcut or intranasal if no IV); child: weight-based per the naloxone page. On regular or long-term opioids? Use smaller titrated increments. You want ventilation back without precipitated withdrawal. No response after 10 mg? Question the diagnosis. Naloxone reverses some effects, not all, and it may raise seizure risk. Never withhold ventilation or naloxone for apnea.
• Seizures: treat with a benzodiazepine (lorazepam or midazolam).
• Observation: naloxone wears off before tramadol does. Monitor until spontaneous breathing is reliably back, and longer after ER products. Treat any ingestion by a child as potentially fatal.
• Extracorporeal removal: not helpful. Hemodialysis removes less than 7% of a dose in 4 hr.

Clinically Significant Interactions

This drug is oral, and IV compatibility data don't apply to it. Never pair it with another tramadol-containing product.

• Pediatrics: Under 12, it is contraindicated, and so is pain relief after tonsillectomy or adenoidectomy under 18. At 12 to 18, avoid it with hypoventilation risk factors. Safety and effectiveness in children are not established. See the Pediatric Dosing block.
• Neonates: Exposure during labor can depress the newborn's breathing. Support ventilation first. An opioid reversal agent such as naloxone must be on hand for opioid-induced respiratory depression. Prolonged maternal use can cause neonatal opioid withdrawal syndrome (irritability, high-pitched cry, tremor, vomiting, poor weight gain). It can be life-threatening, and neonatal seizures have been reported. In a chronically exposed newborn, naloxone can trigger withdrawal, seizures included. Ventilate, and give it only on neonatology direction.
• Pregnancy: Human data are not enough to define a birth-defect or miscarriage risk. At maternally toxic doses, animal studies showed lower fetal weight and ossification, without malformations. Tramadol crosses the placenta (cord-to-maternal ratio 0.83). Not recommended during or just before labor, when other analgesic techniques fit better. In an emergency, don't hold back needed analgesia, but reach for titratable agents first.
• Lactation: Tramadol and M1 both pass into milk. Breastfeeding is not recommended during treatment, because infants of ultrarapid-metabolizer mothers can reach dangerous M1 levels. If an infant is exposed, watch for sedation and breathing problems.
• Older Adults: Over 75 years, the max is 300 mg/day, and titration should be slow. GI effects that stop treatment are more common. AGS Beers Criteria 2023 says use with caution. It may cause SIADH or hyponatremia, so monitor sodium. Avoid opioids with benzodiazepines or gabapentinoids. Avoid opioids with a history of falls or fractures, except for severe acute pain.
• Renal Impairment: At CrCl <30 mL/min, dose every 12 hr with a max of 200 mg/day, and do not use ER products (Beers: reduce the IR dose, avoid ER). Hemodialysis removes less than 7% of a dose. Give the regular dose on dialysis days. CRRT is not addressed in labeling.
• Hepatic Impairment: Plain IR tablets: in severe (advanced cirrhosis), use 50 mg every 12 hr, because half-lives climb to about 13 hr (tramadol) and 19 hr (M1). Mild to moderate has no labeled adjustment. Do not use ER products in Child-Pugh C. Tramadol/acetaminophen is not recommended in any hepatic impairment.
• Obesity / Dosing Weight: Adult doses stay fixed whatever the weight. Obesity and obstructive sleep apnea raise the risk of hypoventilation.
• CYP2D6 Phenotype: Ultrarapid metabolizers (about 1–10% of White, 3–4% of Black and 1–2% of East Asian people; over 10% in some groups) make toxic M1 levels. Avoid tramadol. Poor metabolizers (about 7%) get weak analgesia. CPIC also advises avoiding tramadol and choosing a non-codeine opioid if one is needed.
• Seizure Disorders, Depression: Seizure and suicide risk are higher here. Choose a non-opioid or a different analgesic.

Mechanism of Action

• Racemic tramadol: a weak μ-opioid agonist that also blocks norepinephrine and serotonin reuptake. That combination gives analgesia. The serotonergic action adds serotonin syndrome risk.
• CYP2D6 converts it to O-desmethyltramadol (M1). In animal models, M1 is up to 6 times more potent as an analgesic and 200 times more potent at μ-receptors.
• μ-receptor effects include brainstem respiratory depression, miosis, slowed GI motility and vasodilation (orthostatic hypotension, pruritus, sweating).
• In animal tests, naloxone only partly blocks tramadol analgesia.

Pharmacokinetics

• Half-life: tramadol 6.3 hr (about 7 hr with repeated dosing), M1 7.4 hr; about 11 hr with CrCl <30 mL/min. Steady state in 2 days (IR four times daily) or 4 days (ER).
• Metabolism: hepatic, by CYP2D6 (to active M1), CYP3A4, and glucuronide and sulfate conjugation.
• Active metabolite: M1 is the active metabolite. CYP2D6 poor metabolizers make about 40% less of it.
• Elimination: renal: about 30% unchanged and 60% as metabolites.
• Bioavailability / binding / Vd: oral bioavailability about 75%; about 20% protein-bound; Vd 2.6–2.9 L/kg.

Generic Name

Tramadol hydrochloride

Brand Names

Ultram (IR tablets) and Ultracet (with acetaminophen): original brands, now marketed mainly as generics; ConZip (ER capsules).

Pharmacologic Class

Opioid agonist with serotonin and norepinephrine reuptake inhibition

Therapeutic Class

Centrally acting analgesic

Controlled Substance

C-IV

ISMP High-Alert

Yes: ISMP high-alert medication (opioids, all routes of administration)

Look-Alike / Sound-Alike

traMADol / traZODone (FDA tall-man pair): confirm the indication before giving. Plain tramadol vs tramadol/acetaminophen tablets (duplicate tramadol and hidden acetaminophen); IR vs ER products: confirm the product name and strength