LORCET-HD
Clinical safety rating
cautionComprehensive clinical and safety monograph for LORCET-HD (LORCET-HD).
Hydrocodone is a mu-opioid receptor agonist, modulating pain perception and emotional response to pain. Acetaminophen inhibits cyclooxygenase (COX) and modulates descending serotonergic pathways, providing antipyretic and analgesic effects.
| Metabolism | Hydrocodone is metabolized primarily by CYP3A4 and CYP2D6 to hydromorphone and other metabolites. Acetaminophen is metabolized by CYP2E1, CYP1A2, CYP3A4, and glucuronidation/sulfation. |
| Excretion | Renal: 90% as morphine-3-glucuronide and morphine-6-glucuronide, 10% as unchanged morphine; biliary: minor (<5%); fecal: <5%. |
| Half-life | Morphine: 2-4 hours; hydrocodone: 3.8-6 hours. Clinical context: Immediate-release, dosing every 4-6 hours. |
| Protein binding | Morphine: 30-35% bound to albumin; hydrocodone: ~50% bound to albumin. |
| Volume of Distribution | Morphine: 3-5 L/kg; hydrocodone: 4-5 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: 20-40% (first-pass metabolism); rectal: similar. |
| Onset of Action | Oral: 10-30 minutes; peak effect at 30-60 minutes. |
| Duration of Action | 4-6 hours; extended with hepatic/renal impairment. |
| Molecular Weight | 299.37 |
1-2 tablets (hydrocodone 5-10 mg / acetaminophen 325-650 mg) orally every 4-6 hours as needed for pain; maximum acetaminophen 4 g/day (or 3 g/day in at-risk patients).
| Dosage form | CAPSULE |
| Renal impairment | eGFR < 30 mL/min: consider dose reduction or alternate therapy; hydrocodone accumulation risk. For severe renal impairment, avoid or use with extreme caution; initial dose reduction of 25-50% recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or extend interval; Child-Pugh C: contraindicated due to acetaminophen hepatotoxicity. |
| Pediatric use | Not FDA-approved for children <18 years. For weight-based dosing (if clinically justified): hydrocodone 0.1-0.2 mg/kg/dose orally every 4-6 hours; maximum single dose 10 mg; acetaminophen component not to exceed 75 mg/kg/day. |
| Geriatric use | Start with lowest effective dose (e.g., 1 tablet every 6 hours); monitor for respiratory depression, constipation, and cognitive impairment. Avoid in frail elderly; consider acetaminophen dose cap at 3 g/day. |
| 1st trimester | Not recommended due to risk of teratogenicity; avoid. |
| 2nd trimester | Use only if benefits outweigh risks; prolonged use may cause neonatal opioid withdrawal. |
| 3rd trimester | Avoid near term; may cause neonatal respiratory depression and withdrawal. |
Clinical note
Comprehensive clinical and safety monograph for LORCET-HD (LORCET-HD).
| Placental transfer | Readily crosses placenta; both hydrocodone and acetaminophen transfer. |
| Breastfeeding | Excreted into breast milk; use caution, monitor infant for drowsiness and respiratory depression. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Acetaminophen is generally considered safe at therapeutic doses; chronic high doses may be associated with adverse fetal outcomes. Hydrocodone is classified as FDA Pregnancy Category C; risk of neonatal opioid withdrawal syndrome (NOWS) with prolonged use during third trimester. Use in first trimester may be associated with neural tube defects, though data are limited. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status. Assess for signs of opioid withdrawal or toxicity. Fetal monitoring for growth and well-being if prolonged use; assess for NOWS in newborn. |
| Fertility Effects | Opioids may suppress gonadotropin-releasing hormone, leading to decreased libido, oligomenorrhea, or anovulation. Acetaminophen has no known significant effect on fertility. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion (especially in children) can be fatal; neonatal opioid withdrawal syndrome with prolonged use; risks from concomitant use with benzodiazepines or other CNS depressants (additive respiratory depression); Cytochrome P450 3A4 interaction with drugs affecting CYP3A4 may alter hydrocodone metabolism and increase risk of adverse effects.
| Serious Effects |
Hypersensitivity to hydrocodone or acetaminophenSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileusMAO inhibitor use within 14 days
| Precautions | Serotonin syndrome with serotonergic drugs; adrenal insufficiency; hypotension; head injury or increased intracranial pressure; seizure threshold; severe hepatic injury from acetaminophen (dose-dependent); use in patients with hepatic impairment; use in patients with pulmonary disease; use in elderly, cachectic, or debilitated patients; opioid-induced hyperalgesia; severe hypotension; use in patients with biliary tract disease; pancreatitis; use in patients with renal impairment; use in patients with suicidal ideation; drug abuse history; driving and operating machinery. |
| Food/Dietary | Avoid alcohol; increases hepatotoxicity of acetaminophen. Grapefruit juice may inhibit CYP3A4 and alter hydrocodone metabolism. High-fat meals may delay absorption. No specific dietary restrictions beyond avoiding excessive acetaminophen from other sources. |
| Clinical Pearls | Lorcet-HD contains hydrocodone and acetaminophen. Maximum acetaminophen dose should not exceed 4000 mg/day; check for hidden sources. Hydrocodone is a prodrug metabolized via CYP2D6 to hydromorphone; poor metabolizers may have reduced efficacy. Risk of respiratory depression; contraindicated in severe asthma or GI obstruction. Use with caution in patients with head injuries, hypothyroidism, or adrenal insufficiency. Taper to avoid withdrawal after prolonged use. Check state prescription drug monitoring program (PDMP). |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, other opioids) as they increase risk of severe drowsiness and respiratory depression. · Do not drive or operate heavy machinery until you know how this medication affects you. · This medication contains acetaminophen; do not take other acetaminophen-containing products to avoid liver damage. · Swallow tablets whole; do not crush, chew, or dissolve extended-release forms. · If you have a history of substance abuse, inform your doctor; misuse can lead to addiction, overdose, or death. · Store securely out of reach of children, and properly dispose of unused medication. · Do not stop abruptly without consulting your doctor; withdrawal symptoms may occur. |
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