HYCODAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYCODAN (HYCODAN).
Hydrocodone is a full mu-opioid receptor agonist; homatropine is an anticholinergic agent that reduces excessive respiratory tract secretions.
| Metabolism | Hydrocodone: CYP3A4 and CYP2D6 to hydromorphone; homatropine: not extensively metabolized. |
| Excretion | Renal elimination of unchanged drug (hydrocodone: ~26%; homatropine: negligible) and glucuronide conjugates (hydrocodone: ~40% as hydromorphone and norhydrocodone). Biliary/fecal excretion accounts for ~20-30%. |
| Half-life | Terminal elimination half-life of hydrocodone is 3.8-5.7 hours (mean 4.5 h) in adults; clinical duration of analgesia is 4-6 hours. Half-life may be prolonged in hepatic or renal impairment. |
| Protein binding | Hydrocodone: ~30-40% bound to plasma proteins (primarily albumin). Homatropine: minimal binding. |
| Volume of Distribution | Hydrocodone: Vd ~2.5-3.0 L/kg (range 2.0-3.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability of hydrocodone: ~50-70% (first-pass metabolism reduces bioavailability). |
| Onset of Action | Oral: 10-20 minutes for analgesia; peak effect at 30-60 minutes. |
| Duration of Action | Analgesic duration: 4-6 hours (immediate-release). Antitussive effect may persist up to 6 hours. |
| Molecular Weight | 299.37 |
1 tablet (5 mg hydrocodone/1.5 mg homatropine) orally every 4 to 6 hours as needed for cough; maximum 6 tablets per 24 hours.
| Dosage form | SYRUP |
| Renal impairment | eGFR 30-89 mL/min: No adjustment necessary. eGFR 15-29 mL/min: Initiate with 50% of usual dose and monitor for adverse effects. eGFR <15 mL/min or dialysis: Not recommended due to risk of toxicity. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% or extend dosing interval. Child-Pugh Class C: Avoid use. |
| Pediatric use | Children ≥6 years: 0.2 mL/kg (0.1 mg/kg hydrocodone) orally every 4-6 hours as needed; maximum 6 doses per 24 hours. Children <6 years: Not recommended. |
| Geriatric use | Initiate with 50% of adult dose (0.5 tablet) every 6 hours; titrate cautiously due to increased risk of respiratory depression, falls, and cognitive impairment. |
| 1st trimester | Use only if benefit outweighs risk. Avoid in first trimester due to potential teratogenicity; case reports of congenital malformations (e.g., neural tube defects) with codeine, a prodrug of hydrocodone. |
| 2nd trimester | Use with caution. Not associated with major malformations but may cause growth restriction if used chronically. |
| 3rd trimester | Avoid near term. Prolonged use may lead to neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. |
Clinical note
Comprehensive clinical and safety monograph for HYCODAN (HYCODAN).
| Placental transfer | Hydrocodone crosses the placenta readily, achieving fetal plasma concentrations similar to maternal levels. Evidence from cord blood sampling and case reports confirms placental transfer. |
| Breastfeeding | Hydrocodone and its active metabolite hydromorphone are excreted into breast milk in low concentrations (≤0.1% of maternal weight-adjusted dose). However, metabolism varies; codeine-containing prodrugs pose risk of CNS depression in breastfed infants, especially in mothers with CYP2D6 ultrarapid metabolizer phenotype. Use lowest effective dose for shortest duration. Monitor infant for drowsiness, difficulty breastfeeding, or respiratory depression. |
■ FDA Black Box Warning
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of even one dose may be fatal in children; neonatal opioid withdrawal syndrome; interaction with alcohol or CNS depressants; risks from concomitant use with benzodiazepines or other CNS depressants; additive effects when used with CNS depressants.
| Serious Effects |
Hypersensitivity to hydrocodone or any componentSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentParalytic ileusConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy
| Precautions | Respiratory depression, Drug dependence, Risk of abuse and addiction, Concomitant use with CYP3A4 inhibitors or inducers may alter effects, Risks in patients with head injury or increased intracranial pressure, Severe hypotension, Avoid in patients with known or suspected gastrointestinal obstruction |
| Food/Dietary | Avoid alcohol. Grapefruit juice may increase hydrocodone absorption; avoid concurrent ingestion. High-fat meals may delay onset of action but not significantly alter total exposure. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; opioid use associated with neural tube defects and congenital heart defects (odds ratio ~1.5-2.0). Second trimester: No specific malformation risk, but prolonged use may lead to fetal opioid dependence. Third trimester: Risk of neonatal opioid withdrawal syndrome (NOWS) in up to 60% of exposed neonates; also associated with preterm birth and low birth weight. |
| Fetal Monitoring | Maternal: Respiratory rate, sedation level, bowel function, signs of misuse. Fetal: Ultrasound for structural anomalies if first-trimester exposure; third-trimester: fetal heart rate monitoring and biophysical profile for signs of withdrawal or compromise. Neonatal: Observe for NOWS (e.g., irritability, poor feeding, tremors) for 48-72 hours after delivery; use Finnegan scoring if symptoms appear. |
| Fertility Effects | Opioids may cause menstrual irregularities and anovulation due to hypothalamic-pituitary-gonadal axis suppression. In males, reduced libido, erectile dysfunction, and decreased sperm motility. Effects are dose-dependent and generally reversible upon discontinuation. |
| Clinical Pearls | HYCODAN (hydrocodone bitartrate and homatropine methylbromide) is a fixed-dose combination antitussive. Hydrocodone is an opioid agonist; homatropine is an anticholinergic that reduces excessive respiratory secretions. Use with caution in patients with COPD, asthma, or respiratory depression. Avoid in patients with known opioid hypersensitivity, paralytic ileus, or acute asthma. Monitor for constipation and urinary retention. Dependence and tolerance develop with prolonged use. Administer with caution in patients with head injuries or increased intracranial pressure. Concomitant use with CNS depressants (e.g., alcohol, benzodiazepines) potentiates sedation and respiratory depression. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · This medication may cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you. · Do not consume alcohol or other CNS depressants (e.g., sedatives, tranquilizers) while taking HYCODAN. · Report any signs of respiratory depression (slow/shallow breathing), severe constipation, or difficulty urinating. · If you miss a dose, skip it and take the next dose at the regular time; do not double the dose. · Store at room temperature away from light and moisture; keep out of reach of children. |