Norco
Norco
Generic Name
Norco
Mechanism
- Oxycodone:
- Mu‑opioid receptor agonist → ↑cAMP inhibition via Gi protein → ↓neurotransmitter release (substance P, glutamate).
- Minor kappa and delta agonism contributes to analgesia and dysphoria.
- Acetaminophen:
- Inhibits COX‑1/COX‑2 in the CNS (especially COX‑3) → ↓ prostaglandin synthesis → ↓inflammatory pain signals.
- Synergistic effect: acetaminophen reduces required oxycodone dose, lowering abuse potential.
Pharmacokinetics
| Parameter | Oxycodone | Acetaminophen | Notes |
| Absorption | Oral T_max ≈ 1–1.5 h (bioavailability 30–60%) | T_max ≈ 0.5–1 h (high F) | Liquid vs tablet slightly faster. |
| Distribution | Volume 3–4 L/kg; lipophilic → CNS penetration | V_d ≈ 0.2–0.3 L/kg; distributes to all tissues | Oxycodone crosses BBB; acetaminophen is widespread. |
| Metabolism | Hepatic CYP2D6 (O-demethylation → oxymorphone) + CYP3A4 | Hepatic glucuronidation/sulfation (M1, M2) | Oxycodone susceptible to CYP2D6 polymorphisms. |
| Elimination | Half‑life 3–4 h (varies 2–7 h) | t½ ≈ 2–4 h | Renal excretion 70 % (metabolites) and 30 % biliary. |
| Drug Interactions | Strong inhibitors/inducers of CYP2D6/3A4 alter efficacy/toxicity | Antioxidants (vit C) ↓ acetaminophen toxicity | Avoid concomitant MAOIs + opioids. |
Indications
- Post‑operative pain of moderate to severe intensity.
- Acute traumatic injury requiring opioid analgesia.
- Cancer pain when acetaminophen tolerance safe.
- Emergency department short‑term management of breakthrough pain.
Contraindications
- Contraindicated:
- Severe respiratory depression or opioid dependence.
- Recent use of monoamine oxidase inhibitors (MAOI).
- Known allergy to oxycodone or acetaminophen.
- Warnings:
- Potential for hepatotoxicity with cumulative acetaminophen dosage > 4 g/day.
- Respiratory depression in opioid naïve or elderly patients.
- Risk of serotonin syndrome if combined with serotonergic agents.
- Overdose can cause CNS depression, respiratory arrest.
Dosing
- Adults (non‑opioid naïve): 5/500 mg (oxycodone/acetaminophen) PO q6‑8 h PRN.
- Maximum daily limit: 120 mg oxycodone ≈ 240 mg acetaminophen per day (≤ 4 g).
- Elderly / hepatic impairment: start 2.5/250 mg; titrate to effect.
- Children: not FDA‑approved; use with caution, weight‑based dosing (1–2 mg/kg oxycodone + 10–15 mg/kg acetaminophen).
Adverse Effects
- Common (≥ 10%):
- Somnolence, nausea, vomiting, constipation, dizziness.
- Dry mouth, dysphonia, mild pruritus.
- Serious (≤ 1%):
- Respiratory depression/central apnea.
- Hypotension (severe opioid effect).
- Severe hepatotoxicity (acute liver failure, especially > 4 g ac‑para).
- Allergic reactions (rash, Stevens–Johnson).
Monitoring
- Pain score (VAS/NRS) every 2–4 h initially.
- Respiratory rate and oxygen saturation ≥ 94 % in high‑risk patients.
- Liver function tests (AST, ALT, bilirubin) if daily acetaminophen > 2 g or prolonged use > 7 days.
- Renal function (CrCl) if chronic kidney disease.
- Urine dipstick for occult blood in case of GI bleeds.
Clinical Pearls
1. Use the lowest effective dose: The acetaminophen component halves the opioid requirement; start low, titrate.
2. Beware of “cold‑tolerance”: Elderly patients often fail to experience typical side‑effects; monitor respiration closely.
3. Cross‑talk with CYP polymorphisms: Poor metabolizers of CYP2D6 will have lower oxymorphone formation → milder effects.
4. Acetaminophen dosing ceiling: Even in non‑opioid users, cumulative daily dose must stay < 4 g to prevent hepatotoxicity.
5. Check for MAOI interaction: Patients on phenelzine or similar agents should avoid Norco; consider ibuprofen/acetaminophen alone.
6. Re‑dose schedule: 6–8 h intervals allow steady state; earlier dosing risks overdose; delayed dosing leads to breakthrough pain.
7. Patient education: Emphasize “do not crush or chew tablets to avoid excess acetaminophen” and the importance of reporting any breathing problems immediately.