HYDROCODONE POLISTIREX AND CHLORPHENIRAMINE POLISTIREX
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is an opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Chlorpheniramine is an antihistamine that competitively antagonizes histamine at H1 receptors, reducing allergic symptoms.
| Metabolism | Hydrocodone is metabolized via CYP2D6 and CYP3A4 to hydromorphone and norhydrocodone; chlorpheniramine is metabolized via CYP2D6 and CYP3A4 to desmethylchlorpheniramine. |
| Excretion | Hydrocodone polistirex and chlorpheniramine polistirex are excreted primarily renally. Hydrocodone and its metabolites are eliminated via kidneys (about 60-70% as unchanged drug and conjugates), with a small amount in feces (<10%). Chlorpheniramine is also predominantly renally excreted (30-50% unchanged, with metabolites). Biliary/fecal excretion accounts for less than 20% of total clearance for both components. |
| Half-life | The terminal elimination half-life for hydrocodone from the polistirex formulation is approximately 3.8-4.5 hours in adults, with extended-release properties due to the polistirex complex. For chlorpheniramine polistirex, the half-life is about 20-24 hours, reflecting the prolonged release. These half-lives support twice-daily dosing in the extended-release formulation. |
| Protein binding | Hydrocodone is about 20% bound to plasma proteins. Chlorpheniramine is approximately 70% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Hydrocodone: Vd approximately 3.0-4.0 L/kg, indicating extensive tissue distribution. Chlorpheniramine: Vd about 5-7 L/kg, also widespread distribution. These high Vd values reflect deep tissue penetration. |
| Bioavailability | Oral bioavailability of hydrocodone from the polistirex formulation is around 30-50% due to first-pass metabolism; the polistirex complex provides sustained release. Chlorpheniramine polistirex oral bioavailability is about 25-50%, also with first-pass effect and extended release. Both components are well-absorbed in the gastrointestinal tract. |
| Onset of Action | For the oral extended-release suspension, onset of antitussive effect (hydrocodone) is typically 30-60 minutes; antihistaminic effect (chlorpheniramine) begins within 1-2 hours. Peak effects occur at 4-6 hours post-dose. |
| Duration of Action | Duration of action for hydrocodone as an antitussive is approximately 12 hours per dose, consistent with the extended-release polistirex design. Chlorpheniramine's antihistamine effects last about 12-24 hours, supporting twice-daily administration. Clinical duration may vary with renal/hepatic function. |
Adults: 10 mL (hydrocodone polistirex 10 mg/chlorpheniramine polistirex 8 mg) orally every 12 hours; not to exceed 20 mL per day.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | CrCl ≥30 mL/min: No adjustment. CrCl <30 mL/min: Avoid use due to accumulation of hydrocodone and chlorpheniramine. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B or C: Avoid use due to impaired clearance of hydrocodone and risk of toxicity. |
| Pediatric use | Children ≥6 years: 5 mL (hydrocodone polistirex 5 mg/chlorpheniramine polistirex 4 mg) orally every 12 hours; not to exceed 10 mL per day. Children <6 years: Not recommended. |
| Geriatric use | Initiate at lower doses due to increased bioavailability of hydrocodone and anticholinergic sensitivity; 5 mL orally every 12 hours, titrate cautiously to a maximum of 10 mL per day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | Hydrocodone: Excreted into breast milk; M/P ratio approximately 0.6; caution due to potential CNS depression in infants, especially in CYP2D6 ultra-rapid metabolizers. Chlorpheniramine: Excreted in milk in small amounts; may cause drowsiness or irritability. Consider benefit-risk; alternative preferred. |
| Teratogenic Risk |
■ FDA Black Box Warning
Hydrocodone is associated with risks of addiction, abuse, misuse, respiratory depression, neonatal opioid withdrawal syndrome, and cytochrome P450 3A4 interaction. Concomitant use with CNS depressants (e.g., alcohol, benzodiazepines) may cause profound sedation, respiratory depression, coma, and death.
| Common Effects | Cough |
| Serious Effects |
["Hypersensitivity to hydrocodone, chlorpheniramine, or any component.","Significant respiratory depression.","Acute or severe bronchial asthma in unmonitored setting or without resuscitative equipment.","Paralytic ileus known or suspected.","Concurrent use of MAO inhibitors or within 14 days of such therapy (hypertensive crisis).","Use in children <6 years (due to opioid and antihistamine risks).","Narrow-angle glaucoma (chlorpheniramine).","Urinary retention (chlorpheniramine).","Severe CNS depression (e.g., coma, head injury)."]
| Precautions | ["Respiratory depression risk especially in elderly, cachectic, or debilitated patients.","Addiction, abuse, and misuse potential.","Risk of accidental overdose; use lowest effective dose for shortest duration.","Interaction with other CNS depressants; avoid concurrent use.","Neonatal opioid withdrawal syndrome after prolonged use during pregnancy.","CYP450 interaction; avoid use with strong CYP3A4 inhibitors or inducers.","Risk of serotonin syndrome with serotonergic drugs.","Adrenal insufficiency with prolonged use.","Severe hypotension including orthostatic hypotension.","Risk of seizures in patients with seizure disorders.","Avoid in patients with severe hepatic or renal impairment.","May impair mental or physical abilities; caution with driving.","Anticholinergic effects (chlorpheniramine): hyperthermia, urinary retention, angle-closure glaucoma, cognitive impairment."] |
Loading safety data…
| First trimester: Inadequate human data for hydrocodone polistirex and chlorpheniramine polistirex combination; hydrocodone is an opioid and associated with neural tube defects and congenital heart defects in some studies; chlorpheniramine is generally considered low risk but data limited. Second and third trimesters: Chronic use may lead to opioid withdrawal in neonates; chlorpheniramine may cause anticholinergic effects. Near term: Prolonged use can cause respiratory depression, neonatal opioid withdrawal syndrome (NOWS). |
| Fetal Monitoring | Monitor maternal respiratory status, sedation level, and bowel function. Assess fetal growth and amniotic fluid index if chronic use. For prolonged use, monitor for neonatal withdrawal signs. Antepartum fetal surveillance (e.g., nonstress test or biophysical profile) may be appropriate for women on chronic high-dose opioids. |
| Fertility Effects | Hydrocodone may alter gonadotropin secretion, potentially causing menstrual irregularities or reduced fertility via hyperprolactinemia or hypothalamic-pituitary-adrenal axis suppression. Chlorpheniramine anticholinergic effects may affect cervical mucus but clinical significance uncertain. Limited human data. |