Dosing & Uses
Dosage Forms & 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
Dosing Consideration
Access to naloxone for opioid overdose
- Assess need for naloxone upon initiating and renewing treatment
-
Consider prescribing naloxone
- Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
- Household members (including children) or other close contacts at risk for accidental ingestion or overdose
-
Consult patients and caregivers on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)
Dosage Forms & 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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse 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
Addiction, abuse, and misuse
- Long-acting hydrocodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death
- Assess each patient’s risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
- Instruct patients to swallow capsules/tablets whole; crushing, chewing, or dissolving the extended-release dosage forms can cause rapid release and absorption of a potentially fatal dose of hydrocodone
Accidental exposure
- Accidental consumption of even 1 dose of hydrocodone, especially by children, can result in a fatal overdose of hydrocodone
Neonatal opioid withdrawal syndrome
- For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome
- Prolonged maternal use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening and requires management according to protocols developed by neonatology experts
Interaction with CNS depressants
- Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
- Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate Limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
- Coingestion with alcohol may increase hydrocodone plasma levels and result in a potentially fatal overdose (alters release of drug from capsule)
Interaction with CYP3A4 inhibitors
- Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of hydrocodone from hydrocodone ER
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
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to hydrocodone, ibuprofen, or any components of the drug product
Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity
Cautions
Do not prescribe for acute pain or as needed (prn) pain relief; only for severe chronic pain requiring continuous, around-the-clock opioid analgesia
Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone
Coadministration with other CNS depressants may cause profound sedation, respiratory depression, and death; if coadministration is required, consider dose reduction of 1 or both drugs
Monitor carefully in elderly, cachectic, debilitated patients, and those with chronic pulmonary disease because of increased risk for life-threatening respiratory depression
Monitor patients with head injury or increased ICP for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of CO2 retention
May cause severe hypotension, including orthostatic hypotension and syncope; added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone
Coadministration with CYP3A4 inhibitors may increase hydrocodone systemic exposure and result in toxicity; if co-administration with CYP3A4 necessary, monitor patients closely who are currently taking, or discontinuing, CYP3A4 inhibitors or inducers; evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved
Caution must be used with potentially hazardous activities
Avoid use of mixed agonist/antagonist analgesics (ie, pentazocine, nalbuphine, butorphanol) when taking full opioid agonist analgesics
Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency
May cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms
Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected
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
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 morbidly obese patients
Use hydrocodone with caution in patients with prostatic hyperplasia and/or urinary stricture
Use caution in patients with seizure disorders
Patient access to naloxone for emergency treatment of opioid overdose
- Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
- Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
- Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
Pregnancy & Lactation
Pregnancy
Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with opioids and major birth defects
Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly
Lactation
Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period
The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition
Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped
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
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)
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Formulary
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