SEDAPAP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEDAPAP (SEDAPAP).
SEDAPAP is a combination of an opioid agonist (acetaminophen, hydrocodone) and a non-opioid analgesic. Hydrocodone acts as a mu-opioid receptor agonist, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis and providing analgesia and antipyresis.
| Metabolism | Hydrocodone is metabolized primarily via CYP3A4 and CYP2D6 to hydromorphone and other metabolites. Acetaminophen is metabolized primarily via glucuronidation and sulfation; a minor pathway via CYP2E1 produces a hepatotoxic metabolite (NAPQI) that is normally detoxified by glutathione. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60-70% of the administered dose. Hepatic metabolism to inactive metabolites, followed by biliary and fecal elimination, accounts for the remaining 30-40%. Less than 5% is excreted unchanged in feces. |
| Half-life | The terminal elimination half-life is approximately 4-6 hours in adults with normal renal function. In patients with creatinine clearance <30 mL/min, the half-life may be prolonged to 10-15 hours, requiring dose adjustment. |
| Protein binding | Approximately 92-95% bound to serum albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.8-1.2 L/kg, indicating extensive distribution into total body water and tissues. Higher Vd is observed in obesity (up to 1.5 L/kg). |
| Bioavailability | Oral: 75-85% due to first-pass metabolism. Intramuscular: 90-100%. Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 15-30 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 3-5 hours; Intramuscular: 4-6 hours. Duration may be extended in hepatic impairment due to reduced metabolism. |
| Molecular Weight | 180.16 |
1-2 tablets (acetaminophen 325 mg/butalbital 50 mg/caffeine 40 mg) orally every 4 hours as needed; maximum 6 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: Use with caution, maximum 4 tablets per day. GFR <30 mL/min: Contraindicated due to butalbital accumulation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%, maximum 3 tablets per day. Child-Pugh C: Contraindicated. |
| Pediatric use | Not recommended for patients under 12 years of age. |
| Geriatric use | Initiate at lowest effective dose (1 tablet every 6 hours); monitor for excessive sedation and cognitive impairment. |
| 1st trimester | Avoid due to known teratogenic effects including neural tube defects, congenital heart defects, and oral clefts. |
| 2nd trimester | Avoid due to increased risk of oligohydramnios and fetal renal dysfunction. |
| 3rd trimester | Avoid due to risk of premature closure of the ductus arteriosus and persistent pulmonary hypertension in the newborn. |
Clinical note
Comprehensive clinical and safety monograph for SEDAPAP (SEDAPAP).
| Placental transfer | Readily crosses the placenta; fetal serum levels are approximately 70-90% of maternal levels. |
| Breastfeeding | Contraindicated during breastfeeding due to excretion into breast milk and potential for adverse effects in the nursing infant, including kernicterus. |
| Lactation Rating |
■ FDA Black Box Warning
Addiction, Abuse, and Misuse: SEDAPAP exposes users to risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing and monitor regularly. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially during initiation and dose titration. Accidental Ingestion: Accidental ingestion of even one dose, especially by children, can cause fatal overdose. Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening. Cytochrome P450 3A4 Interaction: Concomitant use with CYP3A4 inhibitors may increase hydrocodone levels and prolong adverse effects. Concomitant use with CYP3A4 inducers may decrease efficacy. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use may result in profound sedation, respiratory depression, coma, and death. Avoid use in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
| Serious Effects |
Hypersensitivity to SEDAPAP or any componentSevere hepatic impairmentSevere renal impairment (eGFR <30 mL/min)Active peptic ulcer diseaseThird trimester of pregnancyBreastfeeding
| Precautions | Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; adrenal insufficiency; hepatotoxicity (due to acetaminophen); opioid-induced hyperalgesia; withdrawal; risks of use in patients with head injuries, impaired consciousness, or increased intracranial pressure; use in patients with gastrointestinal conditions including paralytic ileus; use in patients with severe renal or hepatic impairment; use in elderly, cachectic, or debilitated patients; use in patients with pulmonary disease; use in patients with biliary tract disease; use in patients with acute pancreatitis; use in patients with CNS depression; use in patients with toxic psychosis; use in patients with known or suspected surgical abdomen; use in patients with urinary retention; use in patients with prostatic hypertrophy; use in patients with urethral stricture; use in patients with hypothyroidism; use in patients with Addison's disease; use in patients with kyphoscoliosis; use in patients with severe obesity; use in patients with seizures or seizure disorders; use in patients with substance abuse history; driving and operating machinery; use in pregnancy; use in lactation. |
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| L5 |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects and orofacial clefts (valproate component). Second and third trimesters: Fetal valproate syndrome (craniofacial abnormalities, cardiac defects, developmental delay), neonatal hemorrhage due to vitamin K deficiency (valproate), and withdrawal syndrome. Acetaminophen carries minimal risk. |
| Fetal Monitoring | Maternal: Serum valproate levels, liver function tests, complete blood count, coagulation profile (prothrombin time) throughout pregnancy. Fetal: High-resolution ultrasound at 18-20 weeks for structural anomalies; fetal echocardiography if valproate exposure. Neonatal: Monitor for bleeding, withdrawal symptoms (irritability, feeding difficulties), and hepatic dysfunction. |
| Fertility Effects | Valproate may cause polycystic ovary syndrome (PCOS) and ovulatory dysfunction in women, reducing fertility. Acetaminophen has no known adverse effects on fertility at therapeutic doses. Reversibility upon discontinuation of valproate is variable. |
| Food/Dietary | Avoid alcohol. Take with food or milk to reduce gastrointestinal irritation. High-fat meals may delay absorption but not clinically significant. No specific food restrictions. |
| Clinical Pearls | SEDAPAP is a combination product containing an opioid (codeine or hydrocodone) and acetaminophen. Avoid exceeding 3 grams/day of acetaminophen to prevent hepatotoxicity. Monitor respiratory depression, especially in opioid-naive patients and those with sleep apnea. Use with caution in hepatic impairment, ethanol use disorder, and in patients on other CNS depressants. Administer with food to reduce GI upset. |
| Patient Advice | Do not exceed recommended dose; too much acetaminophen can cause liver damage. · Avoid alcohol while taking this medication. · Do not combine with other acetaminophen-containing products. · May cause drowsiness or dizziness; avoid driving or operating machinery. · Take with food or milk if stomach upset occurs. · Report any difficulty breathing, severe constipation, or signs of liver injury (yellowing skin/eyes, dark urine) immediately. · Do not stop suddenly after prolonged use to avoid withdrawal symptoms. |