Hydrocodone/Acetaminophen (Norco) | Medication Reference

Bedside Snapshot

Core Use: Moderate to moderately severe pain; step-down oral analgesic for post-acute pain management
Onset/Duration: Onset 30-60 minutes; peak 1-2 hours; duration 4-6 hours
Key Danger: Respiratory depression, hepatotoxicity from acetaminophen, opioid use disorder
Critical Ceiling: Total daily acetaminophen from ALL sources must not exceed 4 g/day (many institutions target ≤3 g/day to prevent hepatic injury)
Special Considerations: Schedule II controlled substance; short-course use only; always track total APAP intake

Brand & Generic Names

Generic Name: Hydrocodone bitartrate and acetaminophen
Brand Names: Norco, Vicodin, Lortab, Lorcet, various generics
Regulatory Status: Schedule II controlled substance (DEA)

Medication Class

Combination opioid analgesic containing hydrocodone (semi-synthetic opioid, μ-opioid receptor agonist) and acetaminophen (non-opioid analgesic with COX inhibition and central pain modulation)

Pharmacology

Mechanism of Action:

Hydrocodone: Semi-synthetic opioid that acts as a μ-opioid receptor agonist in the CNS and periphery
Metabolized by CYP3A4 and CYP2D6 enzymes to active metabolites including hydromorphone
Provides analgesia, euphoria, sedation, and respiratory depression in dose-dependent manner
Acetaminophen: Central non-opioid analgesic with weak COX inhibition and modulation of serotonergic pathways
Synergistic effect: combination provides multimodal analgesia superior to either agent alone

Pharmacokinetics:

Onset: 30-60 minutes orally
Peak Effect: 1-2 hours
Duration: 4-6 hours
Hydrocodone Half-Life: 3-4 hours
Acetaminophen Half-Life: 2-3 hours
Metabolism: Hydrocodone via hepatic CYP3A4/2D6; acetaminophen via hepatic glucuronidation and sulfation (toxic NAPQI metabolite in overdose)
Elimination: Primarily renal; dose adjustments needed in severe renal or hepatic impairment

Indications

Moderate to moderately severe acute pain not adequately controlled with non-opioid analgesics alone
ED discharge analgesia after procedures, trauma, or acute injury requiring short-term opioid therapy
ICU/hospital step-down therapy when transitioning from IV opioids to oral regimen
Post-operative pain management for outpatient procedures (limited duration)
Not recommended for chronic pain management or as first-line therapy when non-opioid alternatives are appropriate

Dosing & Administration

Available Forms:

Tablets: 5 mg/325 mg, 7.5 mg/325 mg, 10 mg/325 mg (hydrocodone/acetaminophen)
Oral Solution: Various concentrations available (verify strength before dosing)

Standard Adult Dosing:

Patient Population	Typical Dose	Frequency	Notes
Opioid-naïve adults (acute pain)	5 mg/325 mg (1 tablet)	Every 4-6 hours PRN	Start low; max 4 g APAP/day
Moderate pain (opioid-tolerant)	7.5-10 mg/325 mg (1 tablet)	Every 4-6 hours PRN	Titrate based on response; monitor APAP total
Maximum daily dose	Variable based on formulation	—	Never exceed 4 g acetaminophen/day (prefer ≤3 g/day)
Renal impairment (CrCl <30 mL/min)	Reduce dose by 25-50%	Extend interval to q6-8h	Monitor for accumulation and respiratory depression
Hepatic impairment (mild-moderate)	Reduce dose; limit APAP	Use with extreme caution	Consider non-APAP opioid in moderate-severe liver disease
Hepatic impairment (severe)	Avoid	—	Use alternative non-APAP analgesic
Geriatric patients (≥65 years)	Start 5 mg/325 mg	Every 6 hours PRN	Increased sensitivity; slower clearance; fall risk
Short-course discharge prescription	5-10 mg/325 mg	Q4-6h PRN	Limit to 3-7 day supply; counsel on risks

Contraindications

Absolute Contraindications:

Significant respiratory depression or acute/severe bronchial asthma in unmonitored settings
Known or suspected paralytic ileus or GI obstruction
Known hypersensitivity to hydrocodone, acetaminophen, or other opioids
Concurrent or recent (within 14 days) use of MAO inhibitors
Severe hepatic impairment (due to acetaminophen component)

Major Precautions:

Respiratory depression: Dose-related; increased risk with concurrent CNS depressants, elderly, debilitated patients
Acetaminophen hepatotoxicity: Cumulative doses >4 g/day can cause acute liver failure; lower threshold in chronic alcohol use, malnutrition, fasting
Opioid use disorder: Potential for abuse, misuse, and addiction; limit duration and quantity prescribed
Concurrent benzodiazepines/alcohol: Profound sedation, respiratory depression, coma, death; avoid combination when possible
Head injury/increased ICP: Opioids may obscure neurologic assessment and worsen respiratory depression
Adrenal insufficiency: Opioids may precipitate or worsen adrenal crisis

Black Box Warning: Risk of addiction, abuse, and misuse. Life-threatening respiratory depression. Accidental ingestion can result in fatal overdose, especially in children. Concomitant use with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death.

Acetaminophen Warning: Has been associated with acute liver failure, at times resulting in liver transplant and death. Most cases involve doses >4 g/day and often involve more than one acetaminophen-containing product.

Adverse Effects

Common:

Nausea, vomiting (dose-related; often improves with continued use)
Constipation (persistent; prophylactic stool softeners recommended)
Drowsiness, sedation, dizziness, lightheadedness
Pruritus (itching)
Dry mouth

Serious:

Respiratory depression (potentially fatal; monitor closely)
Hepatotoxicity from acetaminophen overdose (acute liver failure)
Hypotension, orthostatic hypotension, syncope
Opioid use disorder, physical dependence, withdrawal syndrome
Severe allergic reactions including anaphylaxis
Serotonin syndrome (rare, with concurrent serotonergic drugs)
Adrenal insufficiency

Special Populations

Renal Impairment:

Mild-moderate (CrCl 30-60 mL/min): Use with caution; may need dose reduction
Severe (CrCl <30 mL/min): Reduce dose by 25-50% and extend dosing interval; monitor closely

Hepatic Impairment:

Mild-moderate: Use with extreme caution; limit acetaminophen exposure; consider non-APAP opioid
Severe: Avoid; use alternative analgesic without acetaminophen

Pregnancy:

Category C; use only if benefits outweigh risks
Prolonged use during pregnancy can cause neonatal opioid withdrawal syndrome
Inform patients of risk and ensure appropriate management is available

Lactation:

Hydrocodone and acetaminophen are excreted in breast milk
Monitor infant for sedation, respiratory depression, and withdrawal upon discontinuation

Pediatric Use:

Generally restricted and discouraged in children due to respiratory risks
Avoid in children with obstructive sleep apnea, obesity, or respiratory compromise
If used, dosing is weight-based; consult pediatric references

Geriatric Patients:

Start with lowest dose (5 mg/325 mg)
Increased sensitivity to opioid effects; slower clearance
Higher risk of falls, confusion, constipation, respiratory depression
Use extended dosing intervals (every 6 hours rather than every 4 hours)

Monitoring

Clinical Monitoring:

Pain relief vs. adverse effects (use validated pain scales)
Respiratory rate, oxygen saturation, level of sedation (especially first 24-72 hours)
Total daily acetaminophen intake from all sources (prescription and OTC)
Bowel function (constipation is nearly universal; initiate prophylaxis)
Mental status, fall risk in elderly patients
Aberrant drug-related behaviors or signs of misuse

Laboratory Monitoring:

Baseline and periodic liver function tests (AST, ALT, bilirubin) if prolonged use or risk factors
Signs of hepatic injury: jaundice, dark urine, right upper quadrant pain, unexplained fatigue

Clinical Pearls

Short-Course Step-Down Agent Only: Norco is best used as a bridge medication for 3-7 days when transitioning from IV opioids or for acute self-limited pain. Avoid chronic prescribing due to addiction risk.

Always Track the APAP Ceiling: Many patients take OTC acetaminophen, cold medications, or other combination products containing APAP. Verify total daily intake to prevent exceeding 4 g/day (or 3 g/day in high-risk patients).

Liver Disease Considerations: In patients with moderate-to-severe hepatic impairment or chronic alcohol use, avoid Norco entirely. Use a non-acetaminophen opioid (e.g., oxycodone alone, hydromorphone) to eliminate hepatotoxicity risk.

Patient Education is Critical: Counsel patients on proper storage (locked, away from children), avoiding alcohol and benzodiazepines, recognizing signs of overdose, and proper disposal of unused medication.

Constipation Prophylaxis: Nearly all patients on opioids develop constipation. Start a bowel regimen (stool softener + stimulant laxative) at the same time you prescribe the opioid, especially in elderly or immobile patients.

Discharge Prescribing: Limit initial prescriptions to smallest effective quantity (e.g., 10-15 tablets for 3-5 days). Reassess need for refills rather than automatically prescribing larger quantities.

References

1. Lexicomp. (2024). Hydrocodone and acetaminophen: Drug information. Wolters Kluwer.
2. U.S. Food and Drug Administration. (2023). Norco (hydrocodone bitartrate and acetaminophen) tablets [Package insert].
3. Dowell, D., Ragan, K. R., Jones, C. M., Baldwin, G. T., & Chou, R. (2022). CDC clinical practice guideline for prescribing opioids for pain—United States, 2022. MMWR Recommendations and Reports, 71(3), 1-95. https://doi.org/10.15585/mmwr.rr7103a1
4. Substance Abuse and Mental Health Services Administration. (2023). Opioid overdose prevention toolkit. SAMHSA Publication No. PEP22-06-02-001.
5. Benyamin, R., Trescot, A. M., Datta, S., Buenaventura, R., Adlaka, R., Sehgal, N., Glaser, S. E., & Vallejo, R. (2008). Opioid complications and side effects. Pain Physician, 11(2 Suppl), S105-S120.