Norco - Drug Monograph

Introduction

Norco is a widely prescribed combination analgesic medication containing hydrocodone bitartrate, a semi-synthetic opioid agonist, and acetaminophen, a non-opioid analgesic and antipyretic. This Schedule II controlled substance is commonly used for the management of moderate to moderately severe pain when non-opioid analgesics alone are insufficient.

Mechanism of Action

Indications

• Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate
• Approved for short-term treatment of acute pain (typically not exceeding 3-5 days for acute pain)
• Not indicated for chronic pain management due to risks of addiction, abuse, and misuse

Dosage and Administration

• Adults: 1-2 tablets every 4-6 hours as needed for pain
• Maximum daily dose: Limited by acetaminophen component (≤ 4,000 mg acetaminophen daily; ≤ 3,000 mg daily in certain populations)

• Hydrocodone 5 mg/acetaminophen 325 mg
• Hydrocodone 7.5 mg/acetaminophen 325 mg
• Hydrocodone 10 mg/acetaminophen 325 mg

• Renal impairment: Use with caution; consider reduced dosing
• Hepatic impairment: Contraindicated in severe hepatic impairment
• Elderly: Start with lower doses due to increased sensitivity
• Pediatrics: Safety and effectiveness not established in children

Pharmacokinetics

• Hydrocodone: Well absorbed from GI tract; bioavailability ~50% due to first-pass metabolism
• Acetaminophen: Rapidly absorbed from GI tract; peak concentrations in 30-60 minutes

• Hydrocodone: Volume of distribution ~4 L/kg; protein binding ~20%
• Acetaminophen: Volume of distribution ~1 L/kg; protein binding ~20%

• Hydrocodone: Extensive hepatic metabolism via CYP3A4 and CYP2D6 to active (hydromorphone) and inactive metabolites
• Acetaminophen: Primarily metabolized in liver via glucuronidation and sulfation; minor pathway via CYP2E1 produces hepatotoxic metabolite (NAPQI)

• Hydrocodone: Half-life ~4 hours; renal excretion
• Acetaminophen: Half-life ~2-3 hours; renal excretion of metabolites

Contraindications

• Significant respiratory depression
• Acute or severe bronchial asthma
• Known or suspected gastrointestinal obstruction
• Hypersensitivity to hydrocodone or acetaminophen
• Concurrent monoamine oxidase inhibitor use or within 14 days

Warnings and Precautions

• Addiction, abuse, and misuse: Risk of opioid addiction, abuse, and misuse
• Life-threatening respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur
• Accidental ingestion: Accidental ingestion by others, especially children, can result in fatal overdose
• Neonatal opioid withdrawal syndrome: Prolonged use during pregnancy can result in neonatal withdrawal syndrome
• Cytochrome P450 3A4 interaction: Concomitant use with CYP3A4 inhibitors may increase hydrocodone levels
• Hepatotoxicity: Acetaminophen associated with acute liver failure

• Risk of medication errors due to confusion with other combination products
• Risks from concomitant use with benzodiazepines or other CNS depressants
• Adrenal insufficiency, severe hypotension, and gastrointestinal effects

Drug Interactions

• CNS depressants (benzodiazepines, alcohol, sedatives): Additive CNS depression
• CYP3A4 inhibitors (ketoconazole, ritonavir): Increased hydrocodone levels
• CYP3A4 inducers (rifampin, carbamazepine): Decreased hydrocodone efficacy
• Anticholinergics: Increased risk of urinary retention and constipation
• Mixed agonist/antagonist opioids (pentazocine, butorphanol): May reduce analgesic effect

Adverse Effects

• Nausea and vomiting
• Constipation
• Dizziness
• Somnolence
• Headache

• Pruritus
• Dry mouth
• Sweating
• Fatigue
• Anxiety

• Respiratory depression
• Hypotension
• Adrenal insufficiency
• Severe hypersensitivity reactions
• Serotonin syndrome (with serotonergic drugs)
• Hepatotoxicity (acetaminophen-related)

Monitoring Parameters

• Pain assessment and relief using standardized scales
• Respiratory rate and oxygen saturation
• Mental status and sedation level
• Bowel function and need for bowel regimen
• Signs of misuse, abuse, or addiction
• Liver function tests with prolonged use
• Renal function in patients with renal impairment
• Blood pressure, especially during initiation

Patient Education

• Take only as prescribed; do not increase dose without consulting provider
• Do not crush, chew, or break tablets
• Avoid alcohol and other CNS depressants
• Recognize signs of overdose: extreme sleepiness, confusion, difficulty breathing
• Report severe constipation, nausea, or dizziness
• Store securely to prevent theft or accidental ingestion
• Dispose of unused medication properly
• Understand risks of dependence and addiction
• Be aware of acetaminophen content in other medications
• Do not drive or operate machinery until effects are known

References

1. U.S. Food and Drug Administration. (2019). Norco prescribing information. 2. Trescot AM, Datta S, Lee M, et al. Opioid pharmacology. Pain Physician. 2008;11(2 Suppl):S133-S153. 3. Dart RC, Bailey E. Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy. 2007;27(9):1219-1230. 4. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315(15):1624-1645. 5. Webster LR. Hydrocodone: changing for the better? J Pain Res. 2013;6:629-639. 6. National Institute on Drug Abuse. (2021). Opioid overdose crisis. 7. American Pain Society. (2016). Guidelines on the management of postoperative pain. 8. Micromedex Solutions. (2023). Hydrocodone/Acetaminophen monograph.