Bedside Snapshot

Use It For: Acute pain severe enough to need an opioid when non-opioid options are inadequate; short-course discharge or postoperative analgesia; oral step-down from IV opioids
Adult Dose: 2.5 or 5 mg hydrocodone tablets: 1–2 tablets PO every 4–6 hr as needed (max 8 tablets/day)
7.5 or 10 mg tablets: 1 tablet every 4–6 hr (max 6 tablets/day)
Acetaminophen max 4,000 mg/day, all sources
Pediatric Dose: Oral solution only, 2 yr and older: label weight-band table (average 0.135 mg/kg hydrocodone) PO every 4–6 hr (max 6 doses/day; 46 kg and over: max 7.5 mg/dose). Tablets and under 2 yr: not established
Onset / Duration: PO: within 1 hr / 4–6 hr (hydrocodone serum peak about 1.3 hr)
Do Not Give / Hold If: Significant respiratory depression; unmonitored acute or severe asthma; GI obstruction or ileus; hydrocodone or acetaminophen allergy; RR <10 or hard to rouse; daily acetaminophen max reached
Watch For: Oversedation then slow breathing (sedation level, RR, SpO₂/EtCO₂); hypotension (orthostatic BP); acetaminophen liver injury (over 4 g/day or duplicate products; after overdose, signs can lag 48–72 hr); constipation
Reversal / Rescue: Ventilate, then naloxone 0.2–2 mg IV/IO/IM or 2–4 mg IN q2–3 min; child 0.1 mg/kg IV/IO/IM/IN (max 2 mg IV/IM, 4 mg IN). Differs from FDA label (0.4 mg; 0.01 mg/kg). Acetaminophen level 4 hr+; acetylcysteine per nomogram
Must Remember: Two drugs, two ceilings: every tablet holds 300–325 mg acetaminophen, so count all sources. Oral solution comes in two strengths: confirm the product and give the dose in mg and mL

Indications

ED / ICU / Transport

Pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate: This is the labeled use. In practice, it mostly means a short course for acute pain.
Short-course discharge analgesia after injury or a procedure: Use the lowest effective dose, as needed. Match the supply to the length of severe pain, which is often a few days or less.
Oral step-down after IV opioids: Switch once the patient can swallow and absorb a drug. Keep scheduled non-opioid analgesics running alongside.
Pediatric acute pain, 2 years and older: Only the oral solution carries a label for children, dosed by weight. Tablets are not labeled for them.
Who may give it: It is an oral controlled-substance analgesic (C-II). An RN gives it on a prescriber's order. It is not an EMS drug under the National EMS Scope of Practice Model. Transport continues a home dose only on the sending order. Scope varies by state, agency and facility protocol.

Other Uses

Chronic or subacute pain: Not first-line. Push non-opioid and non-drug therapy as far as it goes before you consider any opioid.

The CDC 2022 opioid guideline shows that for many common types of acute pain, non-opioid therapies work at least as well as opioids. Don't use the opioid alone. Schedule a non-opioid analgesic alongside it, and check the shared daily ceiling on the acetaminophen (oral) page.

Dosing & Administration

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

Tablets (hydrocodone bitartrate/acetaminophen): 2.5 mg/325 mg, 5 mg/325 mg, 7.5 mg/325 mg and 10 mg/325 mg, plus 5 mg/300 mg, 7.5 mg/300 mg and 10 mg/300 mg. Each tablet holds 300 or 325 mg acetaminophen: read the amount on the label.
Oral solution 7.5 mg/325 mg per 15 mL: 0.5 mg/mL hydrocodone and about 21.7 mg/mL acetaminophen (2.5 mg/108 mg per 5 mL)
Oral solution 10 mg/300 mg per 15 mL: about 0.67 mg/mL hydrocodone and 20 mg/mL acetaminophen
Not an EMS drug: EMS and transport services don't carry it. Patients arrive already taking it, or after an overdose.

High-Alert Medication: ISMP puts every opioid on its high-alert list, oral route included. Here's the catch: the two oral solution strengths get mixed up, and mg gets confused with mL. The FDA boxed warning flags that one. Other traps are ordering by tablet count without adding up the acetaminophen, duplicate acetaminophen from OTC products, and fatal accidental ingestion by children. Before every dose, check the product strength, the dose in mg and mL, and the 24-hr acetaminophen total from every source.

Adult Dosing

Indication	Dose & Route	Repeat / Max	Notes
Acute pain, lowest strengths: 2.5 mg or 5 mg hydrocodone per tablet (2.5/325, 5/325 or 5/300 mg; first opioid)	1–2 tablets PO (5/325 mg: 5–10 mg hydrocodone), every 4–6 hr as needed	Max 8 tablets/day (5/325 mg: 40 mg hydrocodone, 2,600 mg acetaminophen)	High-alert Start at the lowest dose that controls pain; as needed, not on a fixed schedule.
Acute pain, 7.5 mg or 10 mg hydrocodone per tablet (325 mg or 300 mg acetaminophen)	1 tablet PO, every 4–6 hr as needed	Max 6 tablets/day (45 or 60 mg hydrocodone; 1,950 mg acetaminophen at 325 mg, 1,800 mg at 300 mg)	High-alert One tablet per dose at these strengths, never two.
Oral solution 7.5 mg/325 mg per 15 mL	15 mL (7.5 mg hydrocodone) PO, every 4–6 hr as needed	Max 90 mL/day (45 mg hydrocodone, 1,950 mg acetaminophen)	High-alert Order and label in both mg and mL; measure with an oral syringe or mL cup.
Oral solution 10 mg/300 mg per 15 mL	11.25 mL (7.5 mg hydrocodone) PO, every 4–6 hr as needed	Max 67.5 mL/day (45 mg hydrocodone, 1,350 mg acetaminophen)	High-alert Same mg dose as 15 mL of the 7.5 mg/325 mg product: volume differs by strength.
Converting from another opioid	Estimate the 24-hr need conservatively; underestimate rather than overestimate	Product caps above still apply; titrate to effect within them	High-alert MME factors gauge overdose risk; per the CDC 2022 guideline, do not use them to convert between opioids. Use a conversion reference, reduce for incomplete cross-tolerance and titrate within the product caps. Overestimating a conversion can be fatal.
Older, frail, hepatic or renal impairment	Low initial dose (lowest strength, 1 tablet), then titrate slowly	Same daily caps; reassess sedation and breathing before each repeat	High-alert No labeled percentage reduction; cirrhosis or heavy alcohol use: lower acetaminophen ceiling (see Special Populations).

Pediatric Dosing

Indication	Dose (per kg) & Route	Max Single / Max Total	Notes
Acute pain, 2 yr and older (oral solution only)	Average 0.135 mg/kg hydrocodone PO, every 4–6 hr as needed (7.5 mg/325 mg per 15 mL: 0.27 mL/kg; 10 mg/300 mg per 15 mL: 0.2 mL/kg)	Max 6 doses/day; 46 kg and over: max 7.5 mg/dose and 45 mg/day (adult maximum)	High-alert Labels give weight bands from 12 kg; e.g. 12–15 kg: 3.75 mL of 7.5 mg/325 mg or 2.8 mL of 10 mg/300 mg. Count all acetaminophen.
Children and adolescents, tablets	Not established in children (tablet labeling)	—	Weight-based oral solution is the labeled pediatric option; adolescent tablet use is off-label and prescriber-directed.
Under 2 yr and neonates	Not established: do not use	—	Safety and effectiveness not established under 2 yr. Use an agent and dose set by the pediatric team.

Double-check the weight-based math on the pediatric weight-based dosing page.

Preparation & Administration

Before every dose: total the acetaminophen taken in the last 24 hr from all products (OTC cold, flu, sleep and pain products, IV acetaminophen) and add this dose.
As needed, not scheduled: Give it only when the pain calls for it, such as one 5 mg/325 mg tablet no more often than every 4 hr. Not around the clock.
Oral solution: confirm which strength is in hand; dose in mL with a graduated oral syringe or mL measuring cup, never a household spoon; write the dose in both mg and mL.
Quantity: Prescribe or dispense the smallest quantity that covers the expected duration of severe pain. Skip extra tablets "just in case".
Discharge teaching: Hold off on driving and hazardous tasks until the patient knows how the drug affects them. No alcohol, benzodiazepines or sleep aids. Start a bowel regimen (e.g. a stimulant laxative) with the first prescription. Check every OTC label for acetaminophen or APAP. Discuss a reversal agent (naloxone or nalmefene) for the home with the patient and household, especially with CNS-depressant use, a prior overdose or children in the home.
Storage and disposal: Keep it at 20–25 °C (68–77 °F), locked and out of reach of children. Take leftovers to a take-back option. If none is available, flush them.

Dosing Notes:

Hydrocodone counts 1 mg = 1 morphine milligram equivalent (MME), so 10 mg = 10 MME. Per the CDC 2022 guideline, pause and reassess before total daily opioid reaches 50 MME or more. MME measures risk. It is not a conversion tool.
Every product and every route counts toward the 4,000 mg/day acetaminophen ceiling.
Kidney and liver questions are covered under Special Populations.

Contraindications & Precautions

Contraindications

Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Hypersensitivity to hydrocodone or acetaminophen (e.g. anaphylaxis); do not prescribe to patients with acetaminophen allergy

Precautions

MAOIs, current or within 14 days: Not recommended. See Interactions.
COPD, low respiratory reserve, sleep apnea; older or debilitated patients: Apnea can happen even at recommended doses.
Raised ICP, brain tumor or head injury: CO₂ retention can push ICP higher, and opioids hide the neurologic exam. Watch sedation and breathing closely. Avoid in impaired consciousness or coma.
Hypovolemia or shock: Severe hypotension is the risk. Avoid in shock.
Liver disease or alcohol use: The risk of acetaminophen liver failure runs higher.
Seizure disorders, biliary disease, acute abdomen: It may worsen seizures, trigger sphincter of Oddi spasm, or hide the exam.
Substance use or mental illness history: Addiction risk runs higher. Counsel the patient, reassess often and offer naloxone.

Hold / Reassess If

Hard to rouse or falls asleep mid-conversation: hold the next dose, stimulate, check breathing
RR <10/min, SpO₂ <90% or EtCO₂ >50 mmHg: hold, support ventilation, consider naloxone
SBP <90 mmHg or orthostatic syncope: hold, lay flat, treat hypovolemia
24-hr acetaminophen over 4,000 mg, new rash or jaundice: stop and evaluate

FDA Boxed Warning: The boxed warning names addiction, abuse and misuse. It flags life-threatening breathing depression, highest at the start and after dose increases. A single dose swallowed by a child by accident can be fatal. Benzodiazepines, alcohol or other CNS depressants can cause profound sedation and death. It also lists neonatal opioid withdrawal syndrome, the opioid REMS, CYP3A4 inhibitor interactions, and acetaminophen liver failure, mostly above 4,000 mg/day. Oral solutions bring their own risk: mg/mL and strength mix-ups.

Adverse Effects & Toxicity

Common

Most frequent: lightheadedness, dizziness, sedation, nausea and vomiting
Constipation: Expect it with repeated doses. It can be severe.
CNS: drowsiness, mental clouding, impaired performance, anxiety, dysphoria, mood changes
Skin: pruritus and rash
Genitourinary: urinary retention, ureteral spasm

Serious / Life-Threatening

Effect	Recognition	Management
Respiratory depression	Rising sedation, then slow shallow breathing, snoring, pinpoint pupils, rising EtCO₂, falling SpO₂	Stimulate, open the airway, BVM with O₂; naloxone titrated to breathing
Acetaminophen hepatotoxicity	Often silent early; nausea, malaise, then RUQ pain, jaundice, rising AST/ALT and INR at 48–72 hr	Stop; acetaminophen level, AST/ALT, INR; acetylcysteine per nomogram or toxicology
Severe hypotension	Orthostatic hypotension, syncope; worse with hypovolemia or other CNS depressants	Hold doses, lay flat, fluids; treat shock
Serotonin syndrome	Agitation, hyperthermia, clonus, tremor with SSRIs, SNRIs, triptans, MAOIs or linezolid	Stop hydrocodone and the serotonergic drug; supportive care
Serious skin reactions and anaphylaxis	Blistering rash or mucosal lesions (SJS, TEN, AGEP); urticaria, facial swelling, wheeze	Stop at the first rash; anaphylaxis: epinephrine IM; never rechallenge
Adrenal insufficiency	Usually after more than 1 month: nausea, vomiting, weakness, dizziness, low BP	Confirm, give corticosteroid replacement, wean the opioid

Reports also describe opioid-induced hyperalgesia, esophageal dysfunction from opioids, central sleep apnea and sleep-related hypoxemia, low blood sugar, low platelet counts, and hearing loss with chronic overdose.

Overdose & Toxicity Management

Two toxicities on two clocks: The hydrocodone causes coma and respiratory depression within hours. The acetaminophen causes liver necrosis, and that may not show for 48–72 hr. Treat both. Poison Control: 1-800-222-1222 (poison.org).
Opioid signs: respiratory depression, coma, flaccidity, cold clammy skin, miosis (mydriasis with severe hypoxia); possible pulmonary edema, bradycardia, hypotension.
Immediate management: Open and protect the airway, then ventilate. Add oxygen, and vasopressors for shock. In cardiac arrest, CPR and ACLS/PALS come first. Naloxone does not reverse VF, and it has no established benefit in arrest (AHA 2025 Part 10, Class 2b: may be reasonable if CPR is not interrupted).
Opioid antidote: naloxone. Adult: 0.2–2 mg IV/IO/IM or 2–4 mg intranasal (a new device for each dose, alternating nostrils), repeated every 2–3 min to adequate breathing (AHA 2025 Table 4). Differs from FDA label: the injection label starts at 0.4 mg IV and says to question the diagnosis if there is no response after 10 mg. Pediatric: 0.1 mg/kg IV/IO (max 2 mg), repeated every 2–3 min; the maximum pediatric dose does not exceed the adult dose (AHA 2025 Table 4). IV/IO preferred; IM/IN per NASEMSO (0.1 mg/kg; max 2 mg IV/IM, 4 mg IN; p. 303). Differs from FDA label: the injection label starts at 0.01 mg/kg, then 0.1 mg/kg. In opioid-dependent patients, including adolescents, titrate smaller doses to avoid acute withdrawal (monitored low-dose note: 0.1–0.2 mg IV increments every 2–3 min to adequate breathing).
Re-sedation: Naloxone wears off before hydrocodone does. Keep monitoring until spontaneous breathing is reliably re-established, and repeat naloxone as needed. Adults and children who respond to naloxone should be observed in a healthcare setting until the risk of recurrent respiratory depression is low (AHA 2025 Part 10, Class 1).
Acetaminophen level: Draw it 4 hr or more after ingestion, because earlier levels mislead. Plot a single acute ingestion on the nomogram. Start acetylcysteine at or above the treatment line (150 mcg/mL at 4 hr). Opioid co-ingestion slows absorption. If the first level (4–24 hr) is above 10 mcg/mL but below the treatment line, and the patient has opioid effects, repeat it 4–6 hr later. Treat if it crosses the line.
Do not wait past 8 hr: If the level cannot be drawn and read within 8 hr of a known ingestion, or the time is unknown, give the acetylcysteine loading dose now, without waiting for a level (FDA label 2.1, items 5 and 6; no quantity threshold). Repeated supratherapeutic use does not follow the nomogram. Get an acetaminophen level, AST/ALT, INR and creatinine, and call Poison Control (FDA label 2.5).

Monitoring

Parameter	When / How Often	Target / Act If
Clinical: sedation level and RR	Before each dose and about 1 hr after (near peak); closely in the first 24–72 hr and after any increase	Hard to rouse or RR <10/min: hold, stimulate, support breathing, consider naloxone
Clinical: SpO₂ and EtCO₂	Continuous in monitored settings, sleep apnea, COPD, older adults, or with benzodiazepines or other sedatives	SpO₂ <90% or EtCO₂ >50 mmHg: hold, ventilate, naloxone
Clinical: blood pressure	After starting or increasing the dose; orthostatic check before ambulating	SBP <90 mmHg or syncope: hold, lay flat, fluids
Clinical: pain and function	About 1 hr after a dose and at each reassessment	Inadequate relief: add a non-opioid rather than exceed the tablet or acetaminophen cap
Clinical: bowel and bladder	Daily with repeated dosing	Constipation or retention: bowel regimen, bladder scan; ileus: stop
Laboratory: 24-hr acetaminophen total	Before every dose and at every handoff and medication reconciliation	Over 4,000 mg/24 hr from all sources: stop, check an acetaminophen level and AST/ALT
Laboratory: liver and kidney function	Serially in severe hepatic or renal disease	Rising ALT, AST or creatinine: reduce or stop; review all acetaminophen sources
Drug levels: suspected overdose	Acetaminophen level 4 hr or more after ingestion; with opioid effects, repeat 4–6 hr later if the first is over 10 mcg/mL but below the line	On or above the 150 mcg/mL (4-hr) treatment line: acetylcysteine. Repeated ingestion: no nomogram; treat on levels, AST/ALT and INR with Poison Control advice
Safety: misuse and overdose risk	Before prescribing (check the PDMP) and at each refill	Overdose risk factors, benzodiazepine co-use or 50 MME/day or more: offer naloxone, reassess the plan
Safety: after naloxone	Continuous observation	Monitor until spontaneous breathing is reliably maintained; re-sedation needs repeat naloxone

Interactions & Compatibility

Clinically Significant Interactions

Drug / Class	Effect	What To Do
Benzodiazepines and other CNS depressants (midazolam, alcohol, gabapentin, pregabalin, muscle relaxants, sedative-hypnotics, antipsychotics, other opioids)	Hypotension, profound sedation, respiratory depression, coma, death (boxed warning)	Combine only when alternatives are inadequate; lowest doses and shortest duration; monitor breathing; offer naloxone
CYP3A4 inhibitors (erythromycin and other macrolides, ketoconazole and other azoles, ritonavir); or stopping a CYP3A4 inducer	Higher hydrocodone levels; delayed, potentially fatal respiratory depression (boxed warning), worse with a CYP2D6 inhibitor too	Reduce the dose and reassess often until stable, especially when the change comes after a stable dose
CYP3A4 inducers (rifampin, carbamazepine, phenytoin); or stopping a CYP3A4 inhibitor	Lower hydrocodone levels: lost analgesia or withdrawal	Monitor for withdrawal; adjust the dose; reverse the change when the interacting drug stops
Serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists such as ondansetron, mirtazapine, trazodone, tramadol, cyclobenzaprine, linezolid, IV methylene blue)	Serotonin syndrome	Watch during initiation and dose changes; stop hydrocodone if suspected
MAOIs (phenelzine, tranylcypromine, linezolid)	Serotonin syndrome or opioid toxicity	Not recommended during or within 14 days of an MAOI
Mixed agonist-antagonists and partial agonists (buprenorphine, butorphanol, nalbuphine, pentazocine)	Reduced analgesia; precipitated withdrawal	Avoid combining with a full agonist such as hydrocodone
Other acetaminophen-containing products (oral and IV acetaminophen, OTC cold, flu and PM sleep products)	Hidden duplicate dosing; most acetaminophen liver failure involves more than one product	Add every source to the 24-hr total; avoid two acetaminophen products at once
Anticholinergics; diuretics	Urinary retention, severe constipation, ileus; reduced diuretic effect (ADH release)	Monitor urine output and bowel function; adjust the diuretic

This is an oral-only product, so no IV compatibility data apply.

Special Populations

Pediatrics: Tablets have no established safety or effectiveness in children. The oral solution is labeled from 2 yr by weight (see the Pediatric Dosing table). One tablet or one dose can kill a small child through accidental ingestion, so treat any exposure as an emergency.
Neonates: Not for use. Infants whose mothers took opioids long-term can develop neonatal opioid withdrawal syndrome. Have naloxone or nalmefene ready at delivery after maternal opioid use.
Pregnancy: There are no adequate human studies. Use only if the benefit justifies the risk. Prolonged use can cause life-threatening neonatal opioid withdrawal syndrome. Not recommended during or right before labor when other analgesia is appropriate, because opioids cross the placenta and can depress the newborn's breathing. The label warns that it can cause fetal harm, so patients should report a known or suspected pregnancy. Extended opioid use may reduce fertility in females and males. Whether that is reversible is unknown.
Lactation: Hydrocodone passes into breast milk. Watch the infant for extra sleepiness, breathing difficulty or limpness. Also watch for withdrawal when maternal dosing or breastfeeding stops.
Older Adults: Their chief risk is greater sensitivity to sedation and respiratory depression. Start at the low end and titrate slowly. 2023 AGS Beers Criteria: avoid opioids with benzodiazepines. Avoid opioids with gabapentin or pregabalin, except when moving from an opioid to a gabapentinoid or using one to cut the opioid dose (caution even then). Avoid opioids after falls or fractures, except for severe acute pain. Opioids add to fall risk, so check orthostatic BP before walking.
Renal Impairment: The kidneys clear hydrocodone, acetaminophen and their metabolites. Hydrocodone levels rise in renal impairment. The label gives no percentage reduction. Use a low initial dose, watch closely for sedation and respiratory depression, and follow renal function in severe disease.
Hepatic Impairment: Liver disease or alcohol use raises hydrocodone levels and the acetaminophen liver-failure risk. Use a low initial dose, and follow liver tests in severe disease. No labeled lower acetaminophen ceiling exists. With cirrhosis, expert advice limits total acetaminophen to 1–2 g/day. With heavy alcohol use, a lower ceiling or avoiding acetaminophen is advised (protocol-dependent). Eight low-strength tablets already deliver 2,400–2,600 mg.
Obesity / Dosing Weight: Adult doses are fixed, not weight-based. Obesity with sleep apnea raises the risk of respiratory depression, so start low and monitor. Pediatric doses follow actual weight, and the adult maximum caps them from 46 kg.
Opioid-Dependent Patients: Don't stop abruptly after regular use. Taper by no more than 10–25% of the total daily dose every 2–4 weeks. After short courses, the taper can go faster. Naloxone given at usual doses precipitates withdrawal, so titrate.
CYP2D6 Variation: CYP2D6 converts hydrocodone into the more potent hydromorphone. Genetic polymorphisms in that enzyme produce wide variation in response to a standard dose.

Clinical Pearls

Naloxone fixes the breathing, not the liver: A patient who wakes up after naloxone still needs an acetaminophen level at 4 hr or more. Co-ingestion with an opioid slows absorption, so a first level above 10 mcg/mL but under the line doesn't end the workup.

Hidden acetaminophen: Eight 5 mg/325 mg tablets already hit 2,600 mg of acetaminophen. Pile on extra-strength Tylenol or a cold product, and the patient can pass 4,000 mg/day and never know it.

Same mL, different dose: The same 3.75 mL is the 12–15 kg dose of the 7.5 mg/325 mg per 15 mL solution. It is the 16–22 kg dose of the 10 mg/300 mg solution. Always confirm the strength before you convert mL.

Re-sedation risk: Expect naloxone to wear off before hydrocodone does, since hydrocodone's half-life is about 4 hr. Keep watching breathing after reversal. A patient who refuses transport after naloxone can stop breathing again.

New antibiotic, new apnea: Hydrocodone levels climb days after clarithromycin, an azole or ritonavir is added to a stable dose, or after rifampin or carbamazepine is stopped. When you find an oversedated patient with no clear cause, ask about recent medication changes.

Exam discriminator: common oral opioids (CDC MME factor):

Hydrocodone 1.0 (Norco: with acetaminophen; C-II)
Oxycodone 1.5 (Percocet: with acetaminophen)
Hydromorphone 5.0
Tramadol 0.2
Codeine 0.15

Scene clue: In a suspected overdose, bring the bottle. The strength, the fill date and the count of missing tablets let the ED estimate the acetaminophen dose early.

Pharmacology

Mechanism of Action

Hydrocodone: It is a full μ-opioid receptor agonist in the brain and spinal cord. The result is analgesia with no ceiling effect, and sedation and respiratory depression limit the dose.
It acts directly on the brainstem and blunts the response to rising CO₂, which drives respiratory depression. It also causes miosis, slows GI motility and constipation, and dilates peripheral vessels, causing orthostatic hypotension.
Acetaminophen: It acts centrally, without opioid activity. The precise mechanism is not established. It adds analgesia and antipyresis, with no anti-platelet effect.

Pharmacokinetics

Route	Onset	Peak	Duration
PO (tablets or solution)	Within 1 hr	Hydrocodone serum peak about 1.3 hr	4–6 hr (labeled dosing interval)

Half-life: hydrocodone about 3.8 hr; acetaminophen 1.25–3 hr, longer after overdose or with liver damage.
Metabolism: CYP3A4 handles most hydrocodone metabolism (N-demethylation to norhydrocodone). A smaller CYP2D6 path (O-demethylation to hydromorphone) and 6-keto reduction also contribute. Acetaminophen goes through glucuronidation and sulfation. A small fraction is oxidized, mainly by CYP2E1, into a reactive metabolite that glutathione detoxifies.
Active metabolites: Hydromorphone is an active metabolite and may add to analgesia.
Elimination: Hydrocodone and its metabolites leave mainly through the kidneys. About 85% of an acetaminophen dose shows up in urine within 24 hr, mostly as the glucuronide.
Protein binding: acetaminophen 10–25%.

Names & Classification

Generic Name: Hydrocodone bitartrate and acetaminophen
Brand Names: Norco. Most US supply is generic tablets and oral solution.
Pharmacologic Class: Semi-synthetic full μ-opioid agonist combined with a para-aminophenol non-opioid analgesic
Therapeutic Class: Opioid analgesic combination
Controlled Substance: C-II (DEA Schedule II)
ISMP High-Alert: Yes: ISMP high-alert medication (opioids, all routes including oral)
Look-Alike / Sound-Alike: HYDROcodone / oxyCODONE; oral solution 7.5 mg/325 mg vs 10 mg/300 mg per 15 mL
Error-Prone Abbreviations to Avoid: APAP (write acetaminophen in full; patients should still be taught to look for APAP on labels); give oral solution doses in mg and mL, never teaspoons

References

Elite Laboratories. (2025). Hydrocodone bitartrate and acetaminophen tablets (2.5 mg/325 mg to 10 mg/325 mg): Prescribing information (DailyMed updated 10/2025). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=89b8145f-5310-4b58-a65d-586dc90d642d
SpecGx LLC. (2026). Hydrocodone bitartrate and acetaminophen tablets (5 mg/300 mg, 7.5 mg/300 mg, 10 mg/300 mg): Prescribing information (DailyMed updated 04/2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d621b526-4d9a-48a9-9a3e-d29d6aea2f31
Eywa Pharma. (2026). Hydrocodone bitartrate and acetaminophen oral solution, 7.5 mg/325 mg per 15 mL, CII: Prescribing information (revised 07/2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adb37532-aa19-48a2-95a1-8c92a6ce8651
Hikma Pharmaceuticals USA. (2025). Hydrocodone bitartrate and acetaminophen oral solution, 10 mg/300 mg per 15 mL, CII: Prescribing information (revised 11/2025; DailyMed updated 07/2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=995a6cc7-8b72-4d35-b3b4-8c5752438fb7
Hospira. (2023). Naloxone hydrochloride injection: Prescribing information (revised 07/2023; DailyMed updated 05/2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8
Cao, D., Arens, A. M., Chow, S. L., et al. (2025). Part 10: Adult and pediatric special circumstances of resuscitation: 2025 American Heart Association Guidelines for CPR and ECC. Circulation, 152(Suppl 2), S578–S672. https://doi.org/10.1161/CIR.0000000000001380. Table 4: Commonly Used Doses of Antidotes for Resuscitation in Critical Poisoning. https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/adult-and-pediatric-special-circumstances-of-resuscitation/content/guidelines-accordion/toxicology-nested-section/table-4
National Association of State EMS Officials. (2022). National Model EMS Clinical Guidelines, Version 3.0: Opioid Poisoning/Overdose (Rev. March 2022; cited p. 303). NASEMSO, copy hosted by Iowa HHS. https://hhs.iowa.gov/media/198/download
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
Acetadote (acetylcysteine injection): Prescribing information (labeling revised 10/2019). U.S. Food and Drug Administration labeling, hosted by the manufacturer. https://www.acetadote.com/New_Acetadote_Labeling_25OCT2019.pdf
Corcorran, M. A. (2024). Counseling persons with chronic HCV infection (acetaminophen in cirrhosis and alcohol use; updated March 8, 2024). Hepatitis C Online, University of Washington. https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/counseling-liver-health/core-concept/all
2023 American Geriatrics Society Beers Criteria Update Expert Panel. (2023). American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 71(7), 2052–2081. https://pmc.ncbi.nlm.nih.gov/articles/PMC12478568/
Institute for Safe Medication Practices. (2024). ISMP list of high-alert medications in acute care settings. ISMP. https://www.ismp.org/recommendations/high-alert-medications-acute-list

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Hydrocodone/Acetaminophen (Norco)