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. |
| Molecular Weight | Hydrocodone polistirex: 299.36 Da (free base); Chlorpheniramine polistirex: 274.79 Da (free base) |
| Action Class | Opioid agonist and antihistamine combination |
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 | Avoid due to risk of congenital malformations (e.g., neural tube defects, heart defects) associated with opioid exposure in early pregnancy. Chlorpheniramine is generally considered low risk but data are limited. |
| 2nd trimester | Use only if clearly needed; opioid use may lead to fetal dependence and withdrawal. Chlorpheniramine appears safe but lacks robust data. |
| 3rd trimester | Avoid prolonged use; risk of neonatal opioid withdrawal syndrome (NOWS) and respiratory depression. Chlorpheniramine is not known to cause significant neonatal effects. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Hydrocodone crosses the placenta (maternal-fetal transfer ratio ~0.6-1.0). Chlorpheniramine also crosses but to a lesser extent. |
■ 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 | Respiratory depression, Addiction, abuse, and misuse, Neonatal opioid withdrawal syndrome, Adrenal insufficiency, Severe hypotension, Seizures, Serotonin syndrome (with concomitant serotonergic drugs), Life-threatening respiratory depression in children |
Hypersensitivity to hydrocodone or chlorpheniramineSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileusUse of MAOIs within 14 days
| 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. |
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| Breastfeeding | Hydrocodone is excreted into breast milk in low amounts but can cause infant sedation and respiratory depression. Chlorpheniramine may reduce milk supply and cause sedation in infants. Use lowest effective dose for shortest duration; monitor infant for drowsiness, poor feeding, and breathing difficulties. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | 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. |
| Food/Dietary | Avoid alcohol. Grapefruit juice may increase hydrocodone levels; limit or avoid consumption. No specific food restrictions. |
| Clinical Pearls | Hydrocodone polistirex is an extended-release formulation; avoid crushing or chewing. Chlorpheniramine polistirex provides sustained antihistamine effect. Monitor for respiratory depression, especially in opioid-naive patients. Use with caution in patients with asthma or COPD. May cause anticholinergic effects (dry mouth, urinary retention). |
| Patient Advice | Take exactly as prescribed; do not crush, chew, or dissolve the capsules. · Avoid alcohol and other CNS depressants (sedatives, tranquilizers). · Do not drive or operate machinery until you know how this medicine affects you. · Notify your doctor if you have trouble breathing, severe drowsiness, or difficulty urinating. · Store at room temperature away from moisture and heat. |