PENNTUSS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENNTUSS (PENNTUSS).
PENNTUSS contains hydrocodone, a semisynthetic opioid agonist with antitussive activity, and pseudoephedrine, a sympathomimetic amine. Hydrocodone acts primarily on mu-opioid receptors in the cough center of the medulla oblongata to increase cough threshold. Pseudoephedrine stimulates alpha-adrenergic receptors in the respiratory tract mucosa, causing vasoconstriction and reducing nasal congestion.
| Metabolism | Hydrocodone is metabolized primarily by CYP3A4 and CYP2D6 to various metabolites, including hydromorphone (via CYP2D6). Pseudoephedrine is partially metabolized in the liver by N-demethylation to an inactive metabolite and undergoes renal excretion largely unchanged. |
| Excretion | Primarily renal as unchanged drug and metabolites. Approximately 60% of a dose is excreted renally within 24 hours (about 20% unchanged), with the remainder as glucuronide and oxidative metabolites. Minor biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is approximately 2–4 hours in adults. In renal impairment, half-life may be prolonged due to reduced clearance. |
| Protein binding | Approximately 35–50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is about 2–3 L/kg, suggesting extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 40–60% due to first-pass hepatic metabolism. |
| Onset of Action | Oral: Onset of antitussive effect within 15–30 minutes following oral administration. |
| Duration of Action | Oral: Duration of action is 4–6 hours per dose. No sustained-release formulation available; requires repeated dosing. |
5 mL (equivalent to hydrocodone 5 mg and homatropine 1.5 mg) orally every 4 to 6 hours as needed for cough; maximum 30 mL (hydrocodone 30 mg) per day.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | Not recommended in severe renal impairment (CrCl < 30 mL/min) due to risk of increased CNS effects and accumulation of hydrocodone metabolites. For moderate impairment (CrCl 30-60 mL/min): reduce dose frequency to every 8-12 hours. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). For moderate impairment (Child-Pugh Class B): reduce dose by 25-50% and extend dosing interval to every 8-12 hours. Use with caution in mild impairment. |
| Pediatric use | Not recommended for children under 18 years of age due to risk of respiratory depression and misuse. Safety and efficacy not established. |
| Geriatric use | Initiate at lower end of dosing range (2.5 mL every 6-8 hours) and monitor for respiratory depression, sedation, and constipation. Adjust dose based on renal function; avoid in patients with CrCl < 30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENNTUSS (PENNTUSS).
| Breastfeeding | Hydrocodone excreted into breast milk; relative infant dose estimated 2-4% of maternal weight-adjusted dose; M/P ratio ~2.0 at steady state. Chlorpheniramine excreted in small amounts. American Academy of Pediatrics considers hydrocodone compatible with breastfeeding, but monitor infant for sedation and respiratory depression. |
| Teratogenic Risk | PENNTUSS contains hydrocodone and chlorpheniramine. Hydrocodone: First trimester - limited data, possible association with congenital malformations; second and third trimesters - prolonged use may cause neonatal opioid withdrawal syndrome; risk of respiratory depression at delivery. Chlorpheniramine: Generally considered low risk, but high doses may be associated with minor malformations. |
■ FDA Black Box Warning
None listed.
| Serious Effects |
["Hypersensitivity to hydrocodone, pseudoephedrine, or any component","Patients with severe hypertension or coronary artery disease (due to pseudoephedrine)","Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI use","Patients with narrow-angle glaucoma","Urinary retention","Severe respiratory depression","Acute or severe bronchial asthma","Paralytic ileus","Children <18 years (due to risk of respiratory depression)"]
| Precautions | ["Risk of respiratory depression, particularly in elderly, debilitated, or patients with respiratory compromise","Potential for abuse, addiction, and diversion","Concomitant use with CNS depressants may increase CNS depression","Severe hypotension, especially in patients with compromised ability to maintain blood pressure","Adrenal insufficiency with prolonged use","Risk of misuse, abuse, and diversion","Serotonin syndrome with concomitant serotonergic drugs","Life-threatening respiratory depression in children","Exacerbation of cough hypersensitivity"] |
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| Fetal Monitoring | Monitor maternal respiratory status, sedation, constipation. In pregnancy, monitor for fetal growth and amniotic fluid volume; assess for neonatal withdrawal if used near term. During labor, monitor fetal heart rate variability. |
| Fertility Effects | No specific data for PENNTUSS; hydrocodone may cause hormonal alterations affecting ovulation or spermatogenesis with chronic use; chlorpheniramine may cause anticholinergic effects on reproductive function. |