hydrocodone/acetaminophen (Vicodin, Lorcet, Hycet, Norco, Lortab Elixir, Anexsia, Vicodin ES, Vicodin HP, Xodol, Zamicet)

Dosing and uses of Vicodin, Lorcet (hydrocodone/acetaminophen)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet: Schedule II

• 2.5mg/325mg
• 5mg/300mg, 5mg/325mg
• 7.5mg/300mg, 7.5mg/325mg
• 10mg/300mg, 10mg/325mg

oral solution/elixir: Schedule II

• (7.5mg/325mg)/15mL
• (10mg/300mg)/15mL, (10mg/325mg)/15mL

 

Moderate to Severe Pain

1-2 tablets (2.5-10 mg hydrocodone; 300-325 mg acetaminophen) PO q4-6hr PRn

Acetaminophen: Not to exceed 1 g/dose or 4 g/24 hr

Hydrocodone: Maximum daily dose should not exceed 60 mg/24 hr

 

Dosing Modifications

Hepatic impairment: Avoid chronic use or high doses of acetaminophen (ie, >4 g/day) in hepatic impairment

 

Pediatric dosage forms and strengths

tablet: Schedule II

• 2.5mg/325mg,
• 5mg/300mg, 5mg/325mg
• 7.5mg/300mg, 7.5mg/325mg
• 10mg/300mg, 10mg/325mg

oral solution/elixir: Schedule II

• (7.5mg/325mg)/15mL, (7.5mg/500mg)/15mL
• (10mg/300mg)/15mL, (10mg/325mg)/15mL

 

Moderate to Severe Pain

<2 years: Safety and efficacy not established

2-12 years: 0.135 mg/kg hydrocodone PO q4-6hr PRn

>12 years: 1-2 tablets (2.5-10 mg hydrocodone; 300-325 mg acetaminophen) PO q4-6hr PRn

 

Vicodin, Lorcet (hydrocodone/acetaminophen) adverse (side) effects

Frequency not defined

Biliary tract spasm

Hallucinations

Circulatory collapse

Histamine release

Physical and psychological dependence with prolonged use

Urinary tract spasm

Bradycardia

Cardiac arrest

Confusion

Decreased urination

Dizziness

Drowsiness

Dyspnea

Fatigue

Hypotension

Coma

Dysphoria

Euphoria

Lethargy

Lightheadedness

Mood changes

Stupor

Mental clouding

Nausea

Sedation

Vomiting

Weakness

Peptic ulcer

Agranulocytosis

Hemolytic anemia

Hepatic necrosis

Respiratory depression

 

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 has been associated with cases of acute liver failure, at times resulting in liver transplantation or 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

CNS depression

Severe respiratory depression

 

Cautions

Use caution in debilitated patients, drug abuse history, elderly patients, G6PD deficiency, head injury, hepatic dysfunction, hypothyroidism, impaired pulmonary function, increased intracranial pressure, toxic psychosis, renal dysfunction

Hydrocodone may obscure diagnosis or clinical symptoms of acute abdominal conditions

May cause CNS depression and impair ability to operate heavy machinery

Use caution in patients with cardiovascular disease, hypovolemia, or drugs that may exacerbate hypotensive effects; may cause hypotension

Acetaminophen 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 associated with rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

Caution and awareness are necessary regarding misuse, abuse, or diversion

Constipation may occur; take measures to prevent constipation, such as, administering stool softener and increasing fiber

Chronic alcoholics should limit acetaminophen intake to <2 g/day

Use caution in patients with adrenocortical insufficiency, including Addison's disease; long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis

Use caution in patients with bliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi

Use caution in morbidly obese patients

Use hydrocodone with caution in patients with prostatic hyperplasia and/or urinary stricture

Use caution in patients with seizure disorders

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Excreted in breast milk; breastfeeding not recommended

 

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 Vicodin, Lorcet (hydrocodone/acetaminophen)

Mechanism of action

Acetaminophen: Acts on the hypothalamus to produce antipyresis; inhibits prostaglandin synthetase

Hydrocodone: Opioid analgesic agonist; blocks pain perception in the cerebral cortex; decreases synaptic chemical transmission throughout the CNS, which in turn inhibits pain sensation into higher centers

 

Metabolism

Acetaminophen: Primarily undergoes glucuronidation and sulfate conjugation; however, a small percentage is metabolized via CYP2E1 and CYP1A2 to a hepatotoxic metabolite

Hydrocodone: Metabolized in the liver to the active opioid hydromorphone via CYP2D6; also by O-demethylation, N-demethylation, and 6 ketosteroid reduction

CYP2D6 poor metabolizers may not achieve adequate analgesia

Ultrarapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

Metabolites (acetaminophen): N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI; further metabolized via conjugation with glutathione

 

Elimination

Half-life

• Hydrocodone: 3.3-4.4 hr
• Acetaminophen: 2-4 hr

Onset of action

• Hydrocodone: 10-20 min (analgesic effects)
• Acetaminophen: <1 hr (PO); 5-10 min (IV; analgesia)

Duration

• Hydrocodone: 4-8 hr
• Acetaminophen: 4-6 hr (analgesia); > 6hr (antipyretic)

Excretion

• Hydrocodone: Urine (26% of single dose)
• Acetaminophen: Urine (90-100%; principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)