HOMATROPINE METHYLBROMIDE AND HYDROCODONE BITARTRATE
Clinical safety rating: avoid
Animal studies have demonstrated safety
Hydrocodone is a mu-opioid receptor agonist; homatropine methylbromide is an anticholinergic that reduces gastrointestinal motility and secretions.
| Metabolism | Hydrocodone is metabolized by CYP3A4 and CYP2D6; homatropine methylbromide is minimally metabolized. |
| Excretion | Hydrocodone: Renal excretion of metabolites (hydromorphone, norhydrocodone) as glucuronide conjugates (~60%) and unchanged drug (<10%). Biliary/fecal elimination accounts for ~20-30%. Homatropine methylbromide: Predominantly fecal elimination via biliary excretion as unchanged quaternary ammonium compound (~70-80%); renal excretion of unchanged drug (~10-20%). |
| Half-life | Hydrocodone: Terminal elimination half-life 3.8-6.4 hours (mean ~4.5 h) in adults; prolonged in hepatic/renal impairment (up to 12-15 h). Homatropine methylbromide: Terminal half-life ~4-6 hours via quaternary structure limiting CNS penetration. |
| Protein binding | Hydrocodone: ~20-30% bound to albumin and alpha-1-acid glycoprotein. Homatropine methylbromide: Minimal protein binding (<10%) due to quaternary amine. |
| Volume of Distribution | Hydrocodone: Vd 4-5 L/kg (total body water); distributes extensively into tissues. Homatropine methylbromide: Vd 0.5-1 L/kg (limited to extracellular fluid due to poor lipid solubility). |
| Bioavailability | Hydrocodone: Oral bioavailability ~70-80% (first-pass metabolism). Homatropine methylbromide: Oral bioavailability ~5-10% due to poor absorption and presystemic metabolism. |
| Onset of Action | Hydrocodone: Oral immediate-release: 10-20 min; peak effect 30-60 min. Homatropine methylbromide: Oral: 30-60 min (antimuscarinic effects). |
| Duration of Action | Hydrocodone: Analgesia 4-6 hours (immediate-release); extended-release formulations 8-12 hours. Homatropine methylbromide: Antispasmodic effect 4-6 hours. |
| Molecular Weight | Homatropine methylbromide: 370.28 Da; Hydrocodone bitartrate: 494.49 Da (as salt; hydrocodone free base: 299.37 Da) |
1 tablet (containing homatropine methylbromide 5 mg and hydrocodone bitartrate 5 mg) orally every 4 to 6 hours as needed for cough. Maximum 6 tablets per 24 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: administer 75% of usual dose every 6 hours; CrCl 10-29 mL/min: administer 50% of usual dose every 8 hours; CrCl <10 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50% and monitor; Child-Pugh Class C: not recommended. |
| Pediatric use | Children ≥6 years: 0.25 to 0.5 mL of oral solution (1.25 mg hydrocodone/1 mg homatropine per 5 mL) every 4 to 6 hours, max 4 doses/24h; children <6 years: not recommended. |
| Geriatric use | Initiate at lowest effective dose, e.g., 0.5 tablet every 4-6 hours, with caution due to increased sensitivity, anticholinergic effects, and risk of respiratory depression. Monitor renal function and consider extended intervals. |
| 1st trimester | Hydrocodone: Animal studies show fetal harm; human data limited. Use only if benefit outweighs risk. Homatropine: No malformation data; avoid due to anticholinergic effects. |
| 2nd trimester | Hydrocodone: Risk of fetal dependence and withdrawal with prolonged use. Homatropine: Avoid due to potential fetal anticholinergic effects. |
| 3rd trimester | Hydrocodone: Risk of neonatal respiratory depression, withdrawal, and poor adaptation syndrome. Homatropine: Avoid due to risk of neonatal anticholinergic effects. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| Placental transfer | Hydrocodone is known to cross the placenta. Homatropine methylbromide is a quaternary ammonium compound with limited placental transfer due to low lipid solubility. |
| Breastfeeding | Hydrocodone is excreted in breast milk; risk of infant sedation, respiratory depression, and withdrawal. Homatropine methylbromide is poorly absorbed orally; minimal excretion expected but caution advised. Benefit-risk assessment required. |
■ FDA Black Box Warning
Hydrocodone is an opioid with risks of addiction, abuse, and misuse; concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death; use in children <18 years is not recommended due to risk of fatal respiratory depression.
| Common Effects | Cough |
| Serious Effects |
Severe respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusHypersensitivity to hydrocodone, homatropine, or any component of the formulation
| Precautions | Risk of respiratory depression, Risk of opioid-induced hyperalgesia, Anticholinergic effects (dry mouth, urinary retention, blurred vision), Interactions with CNS depressants, Use in children and adolescents |
| Food/Dietary |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Homatropine methylbromide is a quaternary ammonium anticholinergic with negligible systemic absorption; however, hydrocodone bitartrate (FDA Pregnancy Category C) crosses the placenta. First trimester: limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: chronic maternal use may cause neonatal opioid withdrawal syndrome (NOWS); high doses near term may cause neonatal respiratory depression. Risk of congenital malformations not established. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, and bowel function. Fetal monitoring (non-stress test or biophysical profile) in third trimester with prolonged use. Assess neonate for signs of opioid withdrawal (e.g., irritability, poor feeding, tremors) and respiratory depression. Consider umbilical cord drug testing if maternal opioid use is suspected. |
| Fertility Effects | No published data on homatropine methylbromide effects on fertility. Hydrocodone may cause menstrual irregularities and ovulatory dysfunction via suppression of gonadotropin-releasing hormone. In males, chronic opioid use can reduce libido, erectile function, and sperm quality. Effects are generally reversible upon discontinuation. |
| Avoid grapefruit and grapefruit juice as they may enhance hydrocodone CNS depression. High-fat meals can delay absorption but clinical significance minimal. Avoid alcohol entirely due to additive CNS depression. No specific food restrictions for homatropine methylbromide. |
| Clinical Pearls | Homatropine methylbromide is a quaternary ammonium anticholinergic with limited CNS penetration, reducing central anticholinergic effects. Hydrocodone is a potent opioid antitussive; monitor for respiratory depression, especially in COPD or elderly. Use with caution in patients with glaucoma, urinary retention, or GI obstruction. Combination product primarily for cough; avoid in patients with known opioid tolerance or addiction history. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency due to addiction potential. · May cause drowsiness or dizziness; avoid driving or operating heavy machinery until effects known. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines) to prevent excessive sedation. · Report severe constipation, difficulty urinating, blurred vision, or worsening cough. · Use sugar-free lozenges or gum to manage dry mouth caused by homatropine. · Keep medication in a secure place; improper use can lead to overdose or death. |