Tramadol ER

ULTRAM ER

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Pronunciation: TRA-ma-doel (UL-tram)

Tramadol ER ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Tramadol ER ballicule

Tramadol ER ULTRAM mascot mnemonic cartoon — Visual mnemonic: Tramadol ER mascot
**“Ultra-ram Trauma doll”**

What it isExtended-release mu-opioid agonist and serotonin-norepinephrine reuptake inhibitor (ULTRAM ER, 2005); around-the-clock chronic pain.

Why this oneOnce-daily delivery is unsuitable for as-needed pain or rapid titration; apparent half-life ~8 h (vs ~6 h IR).

What limits itCYP2D6 inhibition can blunt analgesia while seizures and serotonin toxicity remain. It retains full opioid dependence and respiratory risk.

Tramadol ER molecular structure (skeletal formula) — Molecular structure: Tramadol ER

FDA-approved for

chronic pain (around-the-clock) (2005)

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger4 / 4

Weight-gain liability0 / 4

Sedation liability2 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityRespiratory depression, dependence and overdose; risk rises sharply with sedatives or impaired clearance.

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Addiction/abuse/misuse; life-threatening respiratory depression (swallow whole); accidental ingestion; risks with benzodiazepines/CNS depressants; NOWS; Opioid REMS; ultra-rapid metabolism in children (contraindicated <12 y and <18 y post-tonsillectomy/adenoidectomy); CYP3A4/2D6 interactions

FDA dosing	Population	Start	Target	Max
Severe and persistent pain requiring an opioid, not adequately treated by alternatives (incl. IR opioids); not for PRN use	Adults	100 mg QD (tramadol IR: 24-hr IR dose rounded down to next lower 100 mg increment QD)	Titrate by 100 mg every 5 days to adequate analgesia	300 mg/day

Titration Increase by 100 mg every 5 days

Renal Severe (CLcr <30 mL/min): do not use (not studied; limited dose flexibility)

Hepatic Severe (Child-Pugh C): do not use (not studied; limited dose flexibility)

Some patients on tramadol IR may not be able to convert (limited dose flexibility); elderly: titrate slowly, extra caution >75 y

Instructions

Once daily at about the same time each day
Swallow whole with liquid; do not crush, chew, split, or dissolve
Take with or without food, but consistently
Do not use with other tramadol products
Do not abruptly discontinue — taper by ≤10% to 25% of total daily dose every 2 to 4 weeks
Discuss access to an opioid overdose reversal agent (e.g., naloxone, nalmefene)

Available strengths

ER tab 100, 200, 300 mg

Contraindications

Children younger than 12 years of age
Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy
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
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days

Cautions

Addiction, abuse, and misuse
Life-threatening respiratory depression
Risks with benzodiazepines/other CNS depressants
Neonatal opioid withdrawal syndrome
Opioid Analgesic REMS
Ultra-rapid metabolism / respiratory depression risk in children
CYP450 (3A4/2D6) interactions
Opioid-induced hyperalgesia and allodynia
Serotonin syndrome
Seizures
Suicide risk
Respiratory depression in chronic pulmonary disease, elderly, cachectic, debilitated
Adrenal insufficiency
Severe hypotension
Increased intracranial pressure, brain tumors, head injury, impaired consciousness
GI complications (sphincter of Oddi spasm)
Anaphylaxis and hypersensitivity
Withdrawal
Driving and operating machinery
Hyponatremia
Hypoglycemia

Adverse reactions

Dizziness
Nausea
Constipation
Headache
Somnolence
Flushing
Pruritus
Vomiting
Insomnia
Dry mouth

Pregnancy Prolonged use may cause NOWS; animal data suggest fetal risk; not recommended during or immediately before labor

Lactation Tramadol and M1 present in milk; breastfeeding not recommended (risk of infant sedation/respiratory depression)

Cost

Tramadol ER (ULTRAM ER)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	CostPlus
100 mg	ER tab	30 qd	$26.83	not offered
200 mg	ER tab	30 qd	$37.52	not offered
300 mg	ER tab	30 qd	$64.81	not offered

Other forms: Tramadol (ULTRAM)

Serotonin and MAOI

Provisional washout figures

SRI significance3 / 4

MAO-A inhibition0 / 4

Serotonin release0 / 4

Elevating mechanismSRI

Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition

Evidence confidenceHigh

InterpretationOpioid with clinically significant SRI activity; dangerous with meaningful MAO-A inhibition. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.