WYGESIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WYGESIC (WYGESIC).
WYGESIC (ibuprofen and hydrocodone) combines a nonsteroidal anti-inflammatory drug (ibuprofen) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, and a narcotic analgesic (hydrocodone) that acts as a mu-opioid receptor agonist.
| Metabolism | Hydrocodone is metabolized primarily via CYP2D6 and CYP3A4 mediated O-demethylation and N-demethylation to hydromorphone and norhydrocodone, respectively. Ibuprofen is metabolized via CYP2C9 and CYP2C8. |
| Excretion | Primarily renal: 90% as unchanged drug and glucuronide conjugate; <5% fecal. |
| Half-life | 3–4 hours in healthy adults; prolonged to 5–6 hours in moderate renal impairment (CrCl 30–50 mL/min) and >11 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 20–25% bound to albumin. |
| Volume of Distribution | 3.0–4.7 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 50–70% (first-pass effect); rectal: 50–60%; intravenous: 100%. |
| Onset of Action | Oral: 30–60 minutes; rectal: 60–90 minutes; intravenous: 5–10 minutes. |
| Duration of Action | Oral/rectal: 4–6 hours; intravenous: 3–5 hours; prolonged in hepatic or renal impairment. |
| Molecular Weight | 306.3 |
1-2 tablets (paracetamol 325 mg / tramadol 37.5 mg) orally every 4-6 hours as needed for pain, not to exceed 8 tablets per day.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥30 mL/min: no adjustment; CrCl <30 mL/min: extend dosing interval to every 12 hours, maximum 4 tablets per day. Not recommended for CrCl <10 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: extend interval to every 12 hours; Child-Pugh Class C: avoid use. |
| Pediatric use | Weight ≥50 kg: same as adult; weight 36-49 kg: 1 tablet (paracetamol 325 mg / tramadol 37.5 mg) every 4-6 hours, max 4 tablets daily. Not recommended for weight <36 kg. |
| Geriatric use | Patients >75 years: initial dose 1 tablet every 6 hours; maximum 4 tablets per day. Use with caution due to increased risk of respiratory depression and falls. |
| 1st trimester | Avoid use due to risk of neural tube defects and other congenital anomalies; limited data suggest potential teratogenicity. |
| 2nd trimester | Use only if clearly needed; may cause fetal nephrotoxicity and oligohydramnios. |
| 3rd trimester | Avoid due to risk of premature closure of ductus arteriosus and persistent pulmonary hypertension in the newborn; may also inhibit labor. |
Clinical note
Comprehensive clinical and safety monograph for WYGESIC (WYGESIC).
| Placental transfer | Crosses the placenta; detected in fetal tissues and amniotic fluid. Extent of transfer is moderate to high. |
| Breastfeeding | Excreted in breast milk in low concentrations; however, due to potential adverse effects in infants (e.g., renal impairment, gastrointestinal bleeding), caution is advised. Weigh benefits against risks. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of even one dose of hydrocodone, especially by children, can result in fatal overdose; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction; risks from concomitant use with benzodiazepines or other CNS depressants; risk of cardiovascular thrombotic events (ibuprofen); serious gastrointestinal adverse events including bleeding, ulceration, and perforation.
| Serious Effects |
Hypersensitivity to active substance or excipientsHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA Class IV)Severe renal impairment (eGFR <30 mL/min/1.73 m2)Treatment of perioperative pain in coronary artery bypass graft (CABG) surgery
| Precautions | Addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion, Neonatal opioid withdrawal syndrome, Cytochrome P450 3A4 interaction, Risks from concomitant use with benzodiazepines or other CNS depressants, Risk of cardiovascular thrombotic events (NSAIDs), Gastrointestinal bleeding, ulceration, and perforation, Hypertension and heart failure, Renal toxicity, Anaphylactoid reactions, Serious skin reactions, Drug abuse and dependence, Driving and operating machinery |
Loading safety data…
| Lactation Rating |
| L3 - Moderately Safe |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Prolonged use may cause neonatal withdrawal; high doses near term associated with respiratory depression in neonate. FDA Pregnancy Category C. |
| Fetal Monitoring | Monitor maternal vital signs, pain scores, and sedation level. Monitor fetal heart rate and uterine activity if used during labor. Neonatal monitoring for respiratory depression and withdrawal symptoms if used chronically near term. |
| Fertility Effects | No specific human studies; animal studies suggest no significant impairment of fertility at therapeutic doses. Opioid use may affect hormone levels (e.g., prolactin) but clinical significance unclear. |
| Food/Dietary | Avoid grapefruit and grapefruit juice; they may increase hydrocodone levels and side effects. Avoid alcohol completely; enhances CNS depression and acetaminophen hepatotoxicity. High-fat meals may delay absorption but do not require dose adjustment. Maintain adequate hydration to prevent constipation. |
| Clinical Pearls | WYGESIC (hydrocodone/acetaminophen) is a schedule II controlled substance with high abuse potential; use the lowest effective dose for the shortest duration. Caution in patients with hepatic impairment due to acetaminophen content; maximum acetaminophen dose is 4 g/day from all sources. Monitor for respiratory depression, especially in opioid-naive patients or those with COPD. Avoid concurrent use with other CNS depressants, including alcohol, benzodiazepines, and other opioids. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush, chew, or break extended-release tablets; swallow whole. · Avoid alcohol while taking this medication; it increases risk of liver damage and severe drowsiness. · Do not drive or operate machinery until you know how this medication affects you. · Store securely out of reach of children; properly dispose of unused medication via take-back programs. · Contact your doctor immediately if you experience signs of liver injury (yellow skin/eyes, dark urine, abdominal pain) or respiratory difficulty. · Do not stop abruptly; withdrawal symptoms may occur. Taper under medical supervision. · Inform all healthcare providers you are taking this medication, especially before surgery or starting new medications. |