Dosing and uses of Ultracet (tramadol/acetaminophen)
Adult dosage forms and strengths
tramadol/acetaminophen
tablet: Schedule IV
- 37.5mg/325mg
Acute, Short-Term Pain
2 tablets PO q4-6hr PRN; not to exceed 8 tablets/day
Treatment duration: 5 days or less
Dosage modifications
Renal impairment: If CrCl <30 mL/min, 2 tablets PO q12hr; treatment duration should not exceed 5 days
Hepatic impairment: Do not administer
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times daily (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4000 mg/day)
Pediatric dosage forms and strengths
tramadol/acetaminophen
tablet: Schedule IV
- 37.5mg/325mg
Acute, Short-Term Pain
<16 years: Safety and efficacy not established
≥16 years: 2 tabs PO q4-6hr PRN; not to exceed 8 tablets/day
Treatment duration: ≤5 days
Ultracet (tramadol/acetaminophen) adverse (side) effects
1-10%
Abdominal pain
Anxiety
Anorexia
Asthenia
Confusion
Constipation
Diarrhea
Dizziness
Dry mouth
Dyspepsia
Euphoria
Fatigue
Flatulence
Headache
Hot flushes
Insomnia
Nausea
Nervousness
Pruritus
Rash
Somnolence
Sweating
Tremor
Vomiting
<1%
Abnormal hepatic function
Abnormal thinking
Abnormal vision
Aggravated hypertension
Aggravated migraine
Albuminuria
Amnesia
Anemia
Arrhythmia
Ataxia
Chest pain
Convulsions
Depersonalization
Depression
Drug abuse
Dysphagia
Dyspnea
Emotional lability
Hallucination
Hypertension
Hypertonia
Hypotension
Impotence
Involuntary muscle contractions
Melena
Micturition disorder
Migraine
Oliguria
Palpitation
Paresthesias
Paroniria
Rigors
Stupor
Syncope
Tachycardia
Tinnitus
Tongue edema
Urinary retention
Vertigo
Weight decrease
Withdrawal syndrome
Frequency not defined
Allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson Syndrome/TENS)
Cognitive dysfunction
Depression
Difficulty concentrating
Gastrointestinal bleeding
Warnings
Black box warnings
Contains acetaminophen
Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products the patient is taking, including PRN doses and OTC products
Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplant and death
New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times daily (12 dosage units) and still not exceed the maximum daily dose of acetaminophen (ie, 4000 mg/day)
Contraindications
Hypersensitivity
Obstetric postoperative or post-delivery analgesia
Acute intoxication with alcohol, narcotics, hypnotics, opioids, centrally-acting analgesics, or other psychotropic drugs
Cautions
Hepatitis liver failure
Myocardial ischemia
Orthostatic hypotension
Pulmonary edema
Suicidal tendency
Vasodilation
Risk of seizures
As of January 2011, the FDA has mandated a dosage limit for all prescription medications that contain acetaminophen, allowing no more than 325 mg/dosage unit
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black box warnings)
Acetaminophen may cause rare serious skin reactions (eg, acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome, toxic epidermal necrolysis), which can be fatal; discontinued at the first appearance of skin rash
Serotonin syndrome (potentially life-threatening) may develop
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: Use caution
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 Ultracet (tramadol/acetaminophen)
Mechanism of action
Tramadol: Nonopioid-derived synthetic opioid, centrally acting analgesic, but may act at least partially by binding to opioid mu receptors
Acetaminophen: Acts on the hypothalamus to produce antipyresis and analgesia
Absorption
Bioavailability: 75%
Peak plasma time: 2-3 hr
Distribution
VD: 2.6-2.9 L/kg
Protein bound: 20%
Metabolism
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)
Acetaminophen
- Undergoes glucuronide and sulfate conjugation
Elimination
Half-life
- Tramadol: 5-7 hr
- Acetaminophen: 2-4 hr
Excretion
- Tramadol: Primarily renal excretion
- Acetaminophen: Less than 9% excreted unchanged in urine
Pharmacogenomics
Genetic testing laboratories
- The Roche Cytochrome AmpliChip P450 2D6/2C19 Genotyping and Phenotyping Assay can be used to identify 26 different alleles of CYP2D6
- The following companies offer testing for CYP2D6 variants
- DxS (https://www.dxsdiagnostics.com/)
- Genelex (https://www.genelex.com)
- LabCorp (https://www.labcorp.com/)
- Luminex (https://www.luminexcorp.com)
