HY-PHEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HY-PHEN (HY-PHEN).
HY-PHEN is a combination of hydrocodone (a mu-opioid receptor agonist) and acetaminophen (an analgesic and antipyretic). Hydrocodone binds to mu-opioid receptors in the CNS, altering pain perception and emotional response to pain. Acetaminophen inhibits cyclooxygenase (COX) enzymes, particularly in the CNS, reducing prostaglandin synthesis.
| Metabolism | Hydrocodone is metabolized via CYP3A4 to hydromorphone (active) and via CYP2D6 to norhydrocodone. Acetaminophen is primarily metabolized via glucuronidation and sulfation; a minor pathway via CYP2E1 produces a hepatotoxic metabolite (NAPQI) that is normally detoxified by glutathione. |
| Excretion | Renal (primarily as glucuronide conjugates and unchanged drug). Approximately 90-95% eliminated in urine within 24 hours; fecal excretion <5%. |
| Half-life | 2-3 hours (terminal elimination half-life). Clinical context: Short half-life requires frequent dosing (every 4-6 hours) for sustained analgesic effect. |
| Protein binding | 25-35% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | 0.9-1.5 L/kg. Clinical meaning: Moderate Vd indicates distribution into total body water; does not extensively accumulate in tissues. |
| Bioavailability | Oral: 60-90% (first-pass metabolism reduces systemic availability); Rectal: 70-80%; IV/IM: 100%. |
| Onset of Action | Oral: 30-60 minutes; Rectal: 30-90 minutes; IV: 5-10 minutes; IM: 10-20 minutes. |
| Duration of Action | Oral/Rectal: 4-6 hours; IV/IM: 3-4 hours. Clinical note: Duration is dose-dependent; higher doses may extend duration but increase risk of hepatotoxicity. |
| Molecular Weight | 289.37 |
1-2 tablets (acetaminophen 500 mg/hydrocodone 5-10 mg) orally every 4-6 hours as needed for pain; maximum 8 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: administer at 75% of usual dose every 6 hours; GFR <30 mL/min: administer at 50% of usual dose every 8 hours. Avoid in severe renal impairment. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and extend interval to every 8 hours; Class C: contraindicated. |
| Pediatric use | Not recommended for children under 18 years due to risk of opioid-related adverse effects; alternative analgesics preferred. |
| Geriatric use | Initiate with lowest effective dose (e.g., acetaminophen 500 mg/hydrocodone 5 mg) every 6 hours; monitor for respiratory depression, constipation, and falls; may require dose reduction by 25-50% compared to younger adults. |
| 1st trimester | Avoid. Hyoscyamine crosses placenta; risk of fetal anticholinergic effects, including tachycardia and possible teratogenicity. No adequate well-controlled studies. |
| 2nd trimester | Avoid. Use only if clearly needed and benefit outweighs risk. Anticholinergic effects may cause fetal/neonatal toxicity. |
| 3rd trimester | Avoid. May cause neonatal anticholinergic symptoms (e.g., tachycardia, constipation, hyperthermia). Use only if benefit clearly outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for HY-PHEN (HY-PHEN).
| Placental transfer | Hyoscyamine crosses the placenta. Human studies lack sufficient data to quantify degree, but anticholinergic effects have been reported in neonates after maternal use. |
| Breastfeeding | Hyoscyamine is excreted into breast milk in small amounts. Significant drowsiness, respiratory depression, or anticholinergic effects may occur in nursing infants, especially premature or young infants. Caution is advised; use only if necessary and monitor infant for effects. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of acetaminophen (especially in children) can cause hepatotoxicity; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risks from concomitant use with benzodiazepines or other CNS depressants (additive respiratory depression).
| Serious Effects |
Glaucoma (narrow-angle)Obstructive uropathy (e.g., bladder neck obstruction due to prostatic hypertrophy)Obstructive gastrointestinal tract disease (e.g., pyloroduodenal stenosis, achalasia)Myasthenia gravisUnstable cardiovascular status in acute hemorrhageToxic megacolon complicating ulcerative colitisParalytic ileusHypersensitivity to hyoscyamine or any component
| Precautions | Hepatotoxicity due to acetaminophen (dose-dependent); respiratory depression (especially in elderly, debilitated, or COPD); opioid-induced hyperalgesia; adrenal insufficiency; severe hypotension; seizures; serotonin syndrome with serotonergic drugs; urinary retention; bile duct spasm; use in patients with head injury or increased intracranial pressure (risk of masking neurological signs); neonatal withdrawal syndrome. |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) - Limited data; avoid if possible. |
| Teratogenic Risk | Pregnancy Category C. First trimester: No well-controlled studies; potential for fetal harm based on animal studies (cleft palate, skeletal anomalies). Second and third trimesters: Prolonged use may cause neonatal withdrawal syndrome (irritability, hypertonia, respiratory depression) if used near term. Avoid use in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | For pregnant patients: Monitor fetal heart rate and uterine contractions if used near term. For neonates: Observe for signs of respiratory depression and withdrawal if opioid used during third trimester. In breastfeeding infants: Monitor for sedation, poor feeding, and respiratory rate. |
| Fertility Effects | Hydrocodone may impair female fertility via hypothalamic-pituitary-gonadal axis suppression (decreased GnRH, LH, FSH) leading to ovulatory dysfunction. Acetaminophen has been associated with reduced fertility in animal studies at high doses. In males, chronic opioid use may cause hypogonadism and decreased sperm quality. |
| Avoid alcohol consumption due to increased risk of hepatotoxicity and CNS depression. Grapefruit juice may inhibit CYP2D6 metabolism of hydrocodone, potentially altering analgesic effect; avoid concurrent use. High-fat meals may increase absorption of hydrocodone; take consistently with or without food. |
| Clinical Pearls | HY-PHEN is a combination of hydrocodone and acetaminophen. Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen dose should not exceed 4 g from all sources. Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone; poor metabolizers may have reduced analgesia while ultra-rapid metabolizers risk toxicity. Avoid concurrent use with other CNS depressants including alcohol due to additive respiratory depression. Taper dose when discontinuing after prolonged use to prevent withdrawal. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not take other products containing acetaminophen (e.g., Tylenol, cold medicines) while using this medication to avoid liver damage. · Avoid alcohol completely while taking this drug; it increases the risk of liver damage and severe drowsiness. · Do not drive or operate heavy machinery until you know how this medication affects you; it may cause dizziness or drowsiness. · Store securely away from children and others; misuse can cause addiction, overdose, or death. · Do not stop taking suddenly after long-term use; your doctor will help you taper off to prevent withdrawal symptoms. |