HYDROCODONE BITARTRATE AND PSEUDOEPHEDRINE HYDROCHLORIDE
Clinical safety rating: safe
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
Hydrocodone is a semi-synthetic opioid agonist that binds to mu-opioid receptors in the CNS, altering pain perception and emotional response to pain. Pseudoephedrine is a sympathomimetic amine that acts as a decongestant by stimulating alpha-adrenergic receptors in the respiratory tract mucosa, causing vasoconstriction.
| Metabolism | Hydrocodone is metabolized primarily by CYP3A4 and CYP2D6 to hydromorphone and other metabolites. Pseudoephedrine is partially metabolized by hepatic N-demethylation and excreted unchanged in urine. |
| Excretion | Hydrocodone is primarily excreted renally as unchanged drug and metabolites (norhydrocodone, hydromorphone, conjugated metabolites); about 26% of a dose is excreted in urine as unchanged hydrocodone and about 25% as norhydrocodone. Pseudoephedrine is predominantly excreted unchanged in urine (55–75%) with the remainder as N-demethylated metabolites; renal excretion is pH-dependent, with acidic urine enhancing elimination. Biliary/fecal excretion is minimal for both components. |
| Half-life | Hydrocodone terminal elimination half-life is approximately 3.8–4.5 hours in adults. Pseudoephedrine half-life is about 4–6 hours, but may be prolonged to 10–20 hours in patients with acidic urine or renal impairment. The combination product's half-life reflects individual components. |
| Protein binding | Hydrocodone: about 36% bound to plasma proteins (primarily albumin). Pseudoephedrine: negligible protein binding (<5%). |
| Volume of Distribution | Hydrocodone: approximately 3.3–4.7 L/kg, indicating extensive tissue distribution. Pseudoephedrine: Vd ~2.5–3.5 L/kg, also widely distributed. |
| Bioavailability | Oral hydrocodone bioavailability is about 70–80% (with high first-pass metabolism). Oral pseudoephedrine bioavailability is approximately 100% after oral administration. |
| Onset of Action | Oral: Hydrocodone antitussive effect begins within 10–30 minutes; pseudoephedrine decongestant effect onset is within 15–30 minutes. |
| Duration of Action | Hydrocodone antitussive effect lasts approximately 4–6 hours; pseudoephedrine decongestant effect lasts 4–6 hours (immediate-release). Dosing interval is every 4–6 hours as needed. |
| Molecular Weight | Hydrocodone bitartrate: 494.49 Da; pseudoephedrine HCl: 201.69 Da; combination: not applicable as separate compounds. |
One tablet (hydrocodone bitartrate 5 mg/pseudoephedrine HCl 60 mg) orally every 4 to 6 hours as needed for pain and nasal congestion; maximum: 4 tablets per day.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-60 mL/min: Use with caution; consider dose reduction or extended interval. GFR <30 mL/min: Not recommended due to accumulation of hydrocodone and pseudoephedrine. |
| Liver impairment | Child-Pugh Class A: No adjustment needed. Class B: Reduce dose or extend interval (e.g., start with half the usual dose). Class C: Use is contraindicated due to risk of respiratory depression and toxicity. |
| Pediatric use | Not recommended for children under 12 years of age. For children ≥12 years: Same adult dosing (one tablet every 4-6 hours, max 4 tablets/day) with caution. |
| Geriatric use | Initiate at half the usual adult dose (e.g., one tablet every 6 hours) due to increased sensitivity to opioids and anticholinergic effects; monitor renal and hepatic function closely. |
| 1st trimester | Avoid due to potential teratogenic effects; hydrocodone associated with congenital malformations (e.g., neural tube defects) in epidemiological studies; pseudoephedrine may increase risk of gastroschisis. |
| 2nd trimester | Use only if clearly needed; hydrocodone may cause fetal dependence and pseudoephedrine can reduce uteroplacental blood flow. |
| 3rd trimester | Avoid; hydrocodone can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression; pseudoephedrine may induce uterine contractions and affect fetal heart rate. |
Clinical note
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
| FDA category | Animal |
| Placental transfer | Hydrocodone crosses placenta readily; pseudoephedrine also crosses placenta. Both detected in fetal circulation. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; and risk of death from accidental overdose due to hydrocodone.
| Common Effects | Insomnia |
| Serious Effects |
Hypersensitivity to hydrocodone or pseudoephedrineSevere hypertensionCoronary artery diseaseConcurrent use of MAOIs or within 14 daysGlaucomaUrinary retentionSevere respiratory depression without resuscitative equipmentAcute or severe bronchial asthmaParalytic ileusHypovolemia (with pseudoephedrine)
| Precautions | Addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; interactions with CNS depressants; risk of serotonin syndrome; severe hypotension; adrenal insufficiency; and risk of overdose in patients with compromised respiratory function. |
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| Breastfeeding |
| Hydrocodone excreted into breast milk; levels vary but can cause infant sedation and respiratory depression; pseudoephedrine reduces milk production and may cause irritability in infant. Consider safer alternatives. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Limited data; opioid use associated with neural tube defects, gastroschisis, and congenital heart defects (small increased risk). Second trimester: Risk of spontaneous abortion with opioid use. Third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Pseudoephedrine: First trimester use associated with gastroschisis (odds ratio 1.8-3.0); second/third trimester may reduce uterine blood flow. |
| Fetal Monitoring | Maternal: Monitor for respiratory depression (O2 sat, RR), sedation, constipation, and blood pressure (pseudoephedrine may elevate BP). Fetal: Ultrasound for growth restriction (pseudoephedrine vasoconstriction risk); fetal heart rate monitoring during labor if used. Neonatal: Observe for NOWS (e.g., tremors, irritability, poor feeding) for 48-72 hours postpartum. |
| Fertility Effects | Opioids may disrupt hypothalamic-pituitary-gonadal axis, causing amenorrhea, anovulation, or reduced sperm motility in males (dose- and duration-dependent). Pseudoephedrine has no known direct effect on fertility. |
| Food/Dietary |
| Avoid alcohol; increases CNS depression. Avoid high-tyramine foods (e.g., aged cheeses, cured meats) if taking MAOIs. No specific food interactions noted for pseudoephedrine, but caffeine may enhance stimulant effects. |
| Clinical Pearls | Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone; ultra-rapid metabolizers risk toxicity. Coadministration with serotonergic drugs (e.g., SSRIs, MAOIs) may precipitate serotonin syndrome. Pseudoephedrine is a sympathomimetic; avoid in severe hypertension, coronary artery disease, or concurrent MAOI use. Monitor for CNS depression and respiratory depression, especially with alcohol or benzodiazepines. Abuse potential is high; limit quantity and duration. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · Avoid alcohol and other sedatives (e.g., benzodiazepines). · May cause drowsiness or dizziness; avoid driving until tolerance is known. · Pseudoephedrine may raise blood pressure; avoid if you have heart disease or hypertension. · Do not use with other products containing pseudoephedrine or other decongestants. · Discontinue and seek medical attention if you experience symptoms of serotonin syndrome (agitation, hallucinations, rapid heart rate, fever, muscle stiffness) or severe allergic reaction. · Store securely, out of reach of children; dispose of unused medication properly. |