Ultracet
Ultracet
Generic Name
Ultracet
Mechanism
- Tramadol
- Acts as a µ‑opioid receptor agonist (≈ 5–15 % of the potency of fentanyl).
- Inhibits reuptake of serotonin and norepinephrine, enhancing descending inhibitory pain pathways.
- Acetaminophen
- Likely modulates the endocannabinoid system and inhibits cyclo‑oxygenase‑2 (COX‑2) in the central nervous system, reducing prostaglandin‑mediated nociception.
- The combination yields additive analgesic effects with reduced opioid dose relative to tramadol alone, potentially decreasing opioid‑related adverse events.
---
Pharmacokinetics
| Parameter | Tramadol (200 mg) | Acetaminophen (30 mg) | |
| Absorption | Oral bioavailability ~ 70 %; peak plasma [Tmax] 1–2 h | Oral bioavailability ~ 88 %; Tmax 0.5–1 h | |
| Distribution | Volume of distribution ~ 5 L/kg; highly protein‑bound (~ 90 %) | Vd ~ 0.7 L/kg; protein binding ~ 20 % | |
| Metabolism | Hepatic CYP2D6 → O‑desmethyl‑tramadol (active metabolite); CYP3A4, CYP2B6 involved | N‑acetylation (AAC) and glucuronidation | |
| Excretion | Renal (≈ 12 % unchanged) and hepatic; half‑life 6–7 h (O‑desmethyl) | Renal; half‑life ~2 h |
*Key points*:
• Tramadol metabolism is polymorphic; poor CYP2D6 metabolizers may have reduced analgesia.
• Acetaminophen is safe at ≤ 4 g/day; above this threshold risks hepatotoxicity.
--
•
Indications
- Moderate to moderately‑severe acute pain
- Post‑surgical (e.g., orthopedic, dental)
- Post‑traumatic injuries
- Post‑procedural (e.g., colonoscopy)
- Preferred over tramadol alone when a lower opioid dose is desired or when adjunctive acetaminophen is indicated.
---
Contraindications
| Category | Details | |
| Contraindications |
• Known hypersensitivity to tramadol or acetaminophen. • Severe hepatic impairment (ALT/AST > 4× ULN). • Concurrent use of monoamine oxidase inhibitors (MAOIs) (within 14 days). • Seizure disorders (dose reduction < 6 hr interval). | |
| Warnings |
• Respiratory depression: risk increases with higher doses, elderly, or concurrent CNS depressants (benzodiazepines, alcohol). • Serotonin syndrome: combine with serotonergic agents (SSRIs, SNRIs, triptans). • Hepatotoxicity: cumulative acetaminophen exposure > 4 g/day. • Drug interactions: CYP2D6 inhibitors (e.g., fluoxetine) reduce tramadol efficacy; CYP2D6 inducers (e.g., carbamazepine) increase risk of toxicity. |
*Key note*: All clinicians should review the patient's medication list for serotonergic or CYP‑altering agents before prescribing.
--
•
Dosing
| Population | Dosage | Administration | Frequency | Notes |
| Adults (≥ 18 y) | 200 mg/30 mg or 400 mg/60 mg | Oral, tablets | Every 6–8 h as needed | Max daily 4 g acetaminophen. |
| Elderly (≥ 65 y) | 200 mg/30 mg | Oral | Every 8 h | Lower starting dose; titrate cautiously. |
| Renal/ hepatic impairment | Dose adjustment individual | Oral (avoid if severe hepatic disease) | As above | Monitor LFTs. |
| Pediatric (12–17 y) | Dose per weight (approx. 1 mg/kg tramadol + 15 mg/kg acetaminophen) | Oral | Every 6 h | Use weight‑based formulas; avoid > 4 g acetaminophen. |
• First dose: Give with food to reduce GI upset.
• Administration tips: Do not crush or chew tablets; they are coated to avoid acetaminophen irritation.
--
•
Adverse Effects
| Class | Common (≤ 10 %) | Serious (≤ 1 %) | |
| CNS | Nausea, dizziness, paresthesia, mild sedation | Respiratory depression, seizure (especially in CYP2D6 poor metabolizers), serotonin syndrome | |
| GI | Nausea, constipation, vomiting | Severe GI bleeding (rare) | |
| Hepatic | Mild transaminitis | Hepatotoxicity > 4 g acetaminophen, acute liver failure | |
| Cardiovascular | None significant | Rare QT prolongation with high doses |
*Takeaway*: Monitor for CNS signs of opioid overdose; advise patients to avoid alcohol.
--
•
Monitoring
- Baseline
- LFTs (ALT, AST, bilirubin) if hepatic disease.
- Renal function (CrCl) in CKD.
- Seizure history, serotonergic drug use.
- During therapy
- For > 7 days: repeat LFTs and urine drug screen if indicated.
- Monitor pain scores and respiratory rate (especially in the elderly).
- Watch for signs of serotonin syndrome (hyperreflexia, clonus).
---
Clinical Pearls
- Tailor the tramadol dose in poor CYP2D6 metabolizers; use pharmacogenetic testing if pain control is insufficient.
- Cap acetaminophen to 4 g/day; remind patients of other over‑the‑counter acetaminophen sources.
- Avoid Ultracet with MAOIs for at least 14 days or with SSRIs for patients prone to serotonin syndrome.
- For post‑operative pain in the elderly, start at 200 mg/30 mg and increase only if 4 h tolerability is clear.
- Alternate analgesic (e.g., NSAIDs) if susceptibility to opioid side effects is high; remember NSAIDs can increase renal risk.
- Patient education: Teach safe use, keep the medication in a child‑proof container, and report any dizziness or fall risk.
--
• References
1. FDA Prescribing Information – Ultracet.
2. Katzung & Trevor’s Pharmacology Examination & Board Review, 15th Edition.
3. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition.
4. UpToDate: “Tramadol and Acetaminophen Combination Therapies.”