HYDROCODONE POLISTIREX AND CHLORPHENIRAMNE POLISTIREX
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is a mu-opioid receptor agonist; chlorpheniramine is a histamine H1 receptor antagonist.
| Metabolism | Hydrocodone: CYP3A4 and CYP2D6 (to hydromorphone); chlorpheniramine: CYP2D6 and CYP3A4. |
| Excretion | Renal excretion: hydrocodone primarily as conjugates and unchanged drug (~60%), chlorpheniramine primarily as metabolites (~80% renal). Fecal excretion: minimal (<10%). |
| Half-life | Hydrocodone: 3.8-6 hours (extended-release formulation may have biphasic elimination). Chlorpheniramine: 21-27 hours. Clinical context: Steady-state reached in 2-5 days for chlorpheniramine. |
| Protein binding | Hydrocodone: 20-30% bound to albumin. Chlorpheniramine: 72-74% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Hydrocodone: 3.3-4.7 L/kg (extensive tissue distribution). Chlorpheniramine: 5-7 L/kg (large Vd due to high lipophilicity). |
| Bioavailability | Hydrocodone: 50-70% (oral, with first-pass metabolism). Chlorpheniramine: 25-50% (oral, extensive first-pass metabolism). |
| Onset of Action | Hydrocodone: 30-60 min (oral extended-release). Chlorpheniramine: 1-2 hours (oral). |
| Duration of Action | Hydrocodone: 12 hours (extended-release). Chlorpheniramine: 12-24 hours (polistirex formulation). |
5 mL (hydrocodone 10 mg/chlorpheniramine 8 mg) orally every 12 hours; maximum 10 mL (20 mg hydrocodone/16 mg chlorpheniramine) per 24 hours.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: same dose but monitor for adverse effects. CrCl 10-29 mL/min: reduce dose by 50% or extend interval to every 18-24 hours. CrCl <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% or extend interval to every 18-24 hours. Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for children under 18 years due to risk of respiratory depression and death. |
| Geriatric use | Start at lower end of dosing range (e.g., 2.5 mL every 12 hours). Monitor for respiratory depression, sedation, and constipation. Avoid in patients with significant respiratory compromise. |
| 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: M/P ratio ~2.0; small amounts excreted. Chlorpheniramine: M/P ratio unknown; low levels expected. Use with caution; monitor infant for sedation, respiratory depression, and poor feeding. American Academy of Pediatrics recommends avoiding codeine/hydrocodone due to CYP2D6 variability. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; risks from concomitant use with benzodiazepines or other CNS depressants; neonatal opioid withdrawal syndrome; and risks of medication errors involving hydrocodone.
| Common Effects | Cough |
| Serious Effects |
["Hypersensitivity to hydrocodone or chlorpheniramine","Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting","Paralytic ileus","Concurrent use of MAOIs or within 14 days","Postoperative pain management in children after tonsillectomy/adenoidectomy"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion","Neonatal opioid withdrawal syndrome","Risks from concomitant use with CNS depressants","Risks of medication errors","Interaction with MAOIs","Adrenal insufficiency","Hypotension and bradycardia","Seizures","Opioid-induced hyperalgesia","Severe hypotension","Gastrointestinal effects","Anticholinergic effects (chlorpheniramine)"] |
Loading safety data…
| First trimester: Limited data; potential for neural tube defects (OR 1.3 for opioids). Second/third trimester: Risk of neonatal opioid withdrawal syndrome (NOWS); use only if benefit outweighs risk. Avoid near term due to respiratory depression in neonate. |
| Fetal Monitoring | Maternal: Respiratory rate, sedation level, bowel function, signs of abuse/dependence. Fetal: Ultrasound for growth restriction if chronic use; non-stress test or biophysical profile if opioid dependence. Neonatal: Observe for NOWS (irritability, poor feeding, tremors) for 3-5 days post-delivery. |
| Fertility Effects | Opioids may disrupt menstrual cycle via hypothalamic-pituitary-gonadal axis suppression (decreased LH/FSH), potentially impairing ovulation. Reversible upon discontinuation. No direct evidence of impaired fertility in males or females. |