Drug reference

Tramadol

Opioid Analgesic · Analgesic

Also known as Tramadol hydrochloride, Ultram, Tramal, ConZip, Rybix ODT

START

Confirm moderate-severe pain; screen for seizure history, serotonergic medications, renal/hepatic impairment, substance abuse history. Start 25 mg PO daily; titrate every 3 days.

TYPICAL MAX

400 mg/day (IR); 300 mg/day (ER). Reduce to 200 mg/day if CrCl <30. Do NOT exceed 400 mg/day (seizure threshold lowered).

STOP IF

Seizures, signs of serotonin syndrome (agitation, hyperthermia, clonus, autonomic instability), respiratory depression, severe hypersensitivity, lack of efficacy after 4 weeks

WATCH

Pain scores, sedation level, bowel function (constipation), seizure threshold (especially with SSRIs/SNRIs), renal function, signs of dependence/abuse. CYP2D6 phenotype if available (Asian populations have high frequency of intermediate metabolizers).

CDSCO approvedSchedule HJan AushadhiATC N02AX02

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · 30-60 min (analgesic onset)
PEAK: 2h · 2 h (tramadol); 3 h (M1 metabolite)
t½: 6.5h · 6.3 h (tramadol); 7.4 h (M1)
DURATION: 6h · 4-6 h (IR); 24 h (ER)

EXCRETION

~30% renal unchanged; 60% renal as metabolites

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

FDA PLLR: Can cause fetal harm and neonatal opioid withdrawal syndrome if used during pregnancy. Use only if benefit clearly outweighs risk. Avoid near term (risk of respiratory depression in newborn). Not recommended for prolonged use during pregnancy.

FDA category + note

Top interactionssee all 12 →

PhenelzineContraindicatedDatabaseDDInter
SelegilineContraindicatedDatabaseDDInter
Mao InhibitorsContraindicatedDatabaseKimi deep-research + Cla
AlcoholSevereDatabase

Available in India

591 branded formulations and 744 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Tramadol is a centrally-acting synthetic opioid analgesic with a dual mechanism of action. The (+)-enantiomer and its O-desmethyl metabolite (M1) are mu-opioid receptor (MOR) agonists with approximately 6000-fold lower affinity than morphine. Additionally, (+)-tramadol inhibits serotonin (5-HT) reuptake and (-)-tramadol inhibits norepinephrine (NE) reuptake. These complementary monoaminergic and opioid pathways produce synergistic analgesia for moderate to moderately severe pain. The M1 metabolite is 200-300 times more potent at MOR than parent tramadol and has a longer half-life (7.4 hours vs 6.3 hours).

Indications

Moderate to moderately severe pain in adultsAcute pain (postoperative, trauma)Chronic pain (osteoarthritis, low back pain, neuropathic pain — off-label but widely used)Cancer pain (as step 2 on WHO analgesic ladder)Fibromyalgia (off-label)Premature ejaculation (off-label, topical or oral)Restless legs syndrome (off-label)

Dosing

Adult: Immediate-release (IR): 50-100 mg PO every 4-6 hours as needed (max 400 mg/day). Start 25 mg PO daily, titrate by 25 mg every 3 days to 25 mg QID, then increase by 50 mg every 3 days as tolerated. Extended-release (ER): 100 mg PO daily; titrate by 100 mg every 5 days (max 300 mg/day). Do NOT split/crush ER tablets.
Pediatric: Not recommended <12 years. 12-18 years: same as adult IR dosing; avoid in post-tonsillectomy/adenoidectomy. CYP2D6 ultra-rapid metabolizers: increased seizure/respiratory depression risk — avoid or use lowest effective dose.
Renal adjustment: CrCl <30: increase dosing interval to every 12 hours; max 200 mg/day (IR). ER: not recommended if CrCl <30. HD: give dose post-dialysis (7% removed).
Hepatic adjustment: Severe hepatic impairment (Child-Pugh C): not recommended. Mild-moderate: reduce dose by 50%; monitor for sedation and respiratory depression.
Geriatric: Start at lowest dose (25 mg/day); titrate slowly. Increased risk of respiratory depression, falls, cognitive impairment. Reduce max dose to 300 mg/day. Monitor renal function.
Max dose: 400 mg/day (IR); 300 mg/day (ER); 200 mg/day (CrCl <30)

Pharmacokinetics

Onset

Analgesic onset: 30-60 minutes (IR). Peak analgesia: 2-3 hours.

Peak effect

IR: peak plasma at 2 hours (tramadol), 3 hours (M1 metabolite). ER: peak at 12 hours (steady state).

Duration

IR: 4-6 hours. ER: 24 hours.

Half-life

Tramadol: 6.3 ± 1.4 hours. M1 metabolite: 7.4 ± 1.4 hours. Prolonged in renal/hepatic impairment and elderly.

Bioavailability

~75% (oral; due to first-pass metabolism). Food does not significantly affect absorption.

Protein binding

~20% (low; primarily to albumin).

Metabolism

Extensively hepatic via CYP2D6 (O-demethylation to active M1) and CYP3A4/CYP2B6 (N-demethylation to inactive M2). CYP2D6 polymorphism significantly affects efficacy: poor metabolizers (PM) have reduced analgesia; ultra-rapid metabolizers (UM) have increased M1 levels and toxicity risk.

Excretion

Renal: ~30% unchanged tramadol, ~60% metabolites (glucuronides and sulfates). Fecal: ~10%.

Contraindications

Hypersensitivity to tramadol or opioids
Children <12 years of age
Children <18 years post-tonsillectomy and/or adenoidectomy (risk of respiratory depression/death)
Children 12-18 years with risk factors for respiratory depression (obesity, OSA, severe lung disease)
Significant respiratory depression
Acute or severe bronchial asthma (in unmonitored settings or without resuscitative equipment)
Known or suspected gastrointestinal obstruction including paralytic ileus
Concurrent use of MAO inhibitors or within 14 days of MAOI discontinuation (serotonin syndrome risk)
Concurrent use of other serotonergic drugs (SSRIs, SNRIs, TCAs, triptans) — relative contraindication requiring caution

Side effects

Common

Nausea, vomiting, constipationDizziness, somnolence, headachePruritus, sweatingDry mouthFatigueDyspepsia

Serious

Respiratory depression (especially with CNS depressants, elderly, CYP2D6 ultra-rapid metabolizers)
Seizures (dose-dependent; risk increased at doses >400 mg/day, in epilepsy, head trauma, metabolic disorders, alcohol withdrawal, or with serotonergic drugs)
Serotonin syndrome (with SSRIs, SNRIs, MAOIs, triptans, linezolid — potentially fatal)
Opioid-induced hyperalgesia
Severe hypotension, syncope
Adrenal insufficiency
Androgen deficiency (long-term opioid use)
Neonatal opioid withdrawal syndrome (if used during pregnancy)
Anaphylaxis, angioedema
Suicidal ideation (rare)

Pregnancy & lactation

Pregnancy

Lactation

Excreted in breast milk (infant dose ~1-3% of maternal weight-adjusted dose). One reported infant death from tramadol exposure via breast milk (possible CYP2D6 ultra-rapid metabolizer mother or infant). Use with caution; monitor infant for excessive sedation, respiratory depression, poor feeding.