Dosing and uses of Ultram, Ultram ER (tramadol)
Adult dosage forms and strengths
tablet: Schedule IV
- 50mg
suspension reconstituted
- 10 mg/mL
capsule, extended release: Schedule IV
- 100mg (ConZip, Ultram ER)
- 150mg (ConZip)
- 200mg (ConZip, Ultram ER)
- 300mg (ConZip, Ultram ER)
Moderate-to-Severe Pain
Immediate release
- Chronic: 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
- Acute: 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
Extended release
- 100 mg PO once daily initially; increased by 100 mg/day every 5 days; not to exceed 300 mg/day
- Conversion from immediate release to extended release: Round total daily dose down to nearest 100 mg
- Do not chew, crush, split, or dissolve
Dosing Considerations
Extended-release capsule/tablet must not be chewed, crushed, split, or dissolved
Also given in combination with acetaminophen
Dosing Modifications
Severe renal impairment (CrCl <30 mL/min): Immediate release, 50-100 mg PO q12hr; extended release not recommended
Severe hepatic impairment: Immediate release, 50 mg PO q12hr; extended release not recommended
HIV-Associated Neuropathy (Orphan)
Orphan indication sponsor
- TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212
Postherpetic Neuralgia (Orphan)
Orphan indication sponsor
- TheraQuest Biosciences, LLC, 146 Medinah Drive, Blue Bell, PA 19422-3212
Pediatric dosage forms and strengths
tablet: Schedule IV
- 50mg
suspension reconstituted
- 10 mg/mL
Moderate-to-Severe Pain
Immediate release
- <17 years: Safety and efficacy not established
- ≥17 years (acute): 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
- ≥17 years (chronic): 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days as separate doses up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
Extended release
- <18 years: Safety and efficacy not established
Geriatric dosage forms and strengths
>65 years: Initiate at lower end of dosing range; not to exceed 300 mg/day if >75 years
>75 years: Not to exceed 300 mg/day immediate release; use great caution with extended release
Ultram, Ultram ER (tramadol) adverse (side) effects
>10%
Constipation (24-46%)
Nausea (24-40%)
Dizziness (10-33%)
Vertigo (26-33%)
Headache (18-32%)
Somnolence (7-25%)
Vomiting (9-17%)
Agitation (7-14%)
Anxiety (7-14%)
Emotional lability (7-14%)
Euphoria (7-14%)
Hallucinations (7-14%)
Nervousness (7-14%)
Spasticity (7-14%)
Dyspepsia (5-13%)
Asthenia (6-12%)
Pruritus (8-11%)
1-10%
Diarrhea (5-10%)
Dry mouth (5-10%)
Sweating (6-9%)
Hypertonia (1-5%)
Malaise (1-5%)
Menopausal symptoms (1-5%)
Rash (1-5%)
Urinary frequency (1-5%)
Urinary retention (1-5%)
Vasodilation (1-5%)
Visual disturbance (1-5%)
<1%
Abnormal gait
Amnesia
Cognitive dysfunction
Depression
Difficulty in concentration
Dysphoria
Dysuria
Fatigue
Hallucinations
Menstrual disorder
Motor system weakness
Orthostatic hypotension
Paresthesia
Seizures
Suicidal tendencies
Syncope
Tachycardia
Tremor
Frequency not defined
Abnormal electrocardiogram (ECG)
Angioedema
Bronchospasm
Flushing
Hypertension
Hypotension
Myocardial ischemia
Palpitation
Urticaria
Withdrawal syndrome
Warnings
Contraindications
Hypersensitivity to tramadol or opioids
ER tablet formulation
- Acute intoxication with alcohol
- Concomitatn use with centrally acting analgesics, psychotropic drugs, opioids, hypnotics
- Severe renal or hepatic impairment
ER capsule formulation
- Severe/acute bronchial asthma, significant respiratory depression, hypercapnia
- Severe renal or hepatic impairment
Cautions
Renal impairment (reduce dose)
Anaphylactoid/fatal reactions including pruritus, hives, angioedema, epidermal necrolysis, and Stevens-Johnson syndrome reported with use; risk higher in patients with previous anaphylactoid reactions to opioids
Use caution when administering with other respiratory depressants and monoamine oxidase inhibitors (MAOIs); risk of respiratory depression or increased ICp
Increased risk of respiratory depression in patients with respiratory disorders including COPD, hypercapnia, cor pulmonale, or hypoxia
Seizure risk even at recommended dosage, epilepsy patients, or recognized risks (head trauma, metabolic disorders, alcohol and drug withdrawal, central nervous system [CNS] infections), concomitant administraiton with other opioids, SSRIs, tricyclic antidepressants, cyclobenzaprine, promethazine, neuroleptics, MAO inhibitors, or drugs that impair metabolism of tramadol (CYP2D6, 3A4)
Not recommended for obstetric preoperative medication or for postdelivery analgesia in nursing mothers
May impair ability to perform skilled or hazardous tasks
Serotonin syndrome (potentially life-threatening) may develop
Increased risk of serotonin syndrome if oadministered with serotonergic drugs (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], MAOIs, triptans) or drugs that may impair tramadol metabolism (CYP2D6 and CYP3A4 inhibitors) may increase risk for serotonin syndrome
May impair ability to diagnose or determine clinical course of patients with acute abdominal conditions
Use caution in patients with history of chemical dependency
Avoid use in patients who are suicidal; use caution in patients taking tranquilizers and/or antidepressants
Off-label use in children
- Severe respiratory depression reported with off-label use in children
- Tramadol undergoes extensive hepatic metabolism; it is metabolized by CYP2D6 to the active metabolite O-desmethyltramadol (M1), which has a 200-fold greater affinity for opioid receptors than does tramadol
- CYP2D6 poor metabolizers have shown a 20% increase in tramadol levels and a 40% decrease in O-desmethyltramadol (M1)
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug excreted at high concentration in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ultram, Ultram ER (tramadol)
Mechanism of action
Non-opioid-derived synthetic opioid; centrally acting analgesic, but may act at least partially by binding to opioid mu receptors, causing inhibition of ascending pain pathways
Absorption
Bioavailability: Immediate release, 75%; extended release, 85-90%
Onset: ~1 hr
Duration: 9 hr
Peak plasma time: Immediate release, 1.5 hr; extended release, 12 hr
Distribution
Protein bound: 20%
Vd: 2.5-3 L/kg
Metabolism
Metabolized in liver by CYP2D6 and CYP3A4 via N- and O-demethylation and glucuronidation/sulfation
Metabolites: M1 (O-desmethyltramadol; active); M1 metabolite has 200-fold greater affinity for opioid receptors than parent drug
In CYP2D6 poor metabolizers, tramadol levels may increase by 20% and M1 levels decrease by 40%
Elimination
Half-life: 6-8 hr
Excretion: Urine (90%)