TRIPROLIDINE HYDROCHLORIDE, PSEUDOEPHEDRINE HYDROCHLORIDE AND CODEINE PHOSPHATE
Clinical safety rating: safe
CNS depressants may enhance sedative effects May cause marked drowsiness and impair mental and physical abilities.
Triprolidine is a first-generation antihistamine that competes with histamine for H1-receptor sites, reducing allergic symptoms. Pseudoephedrine is a sympathomimetic amine that acts as a nasal decongestant via alpha-adrenergic receptor activation, causing vasoconstriction. Codeine is an opioid agonist at mu-opioid receptors, producing antitussive effects by suppressing the cough center in the medulla.
| Metabolism | Triprolidine undergoes hepatic metabolism via CYP450 enzymes, primarily CYP3A4. Pseudoephedrine is partially metabolized in the liver by N-demethylation via CYP2D6. Codeine is metabolized by CYP2D6 to morphine (active) and by CYP3A4 to norcodeine. UGT2B7 also participates in metabolism. |
| Excretion | Triprolidine: predominantly renal (85% as metabolites, <5% unchanged). Pseudoephedrine: renal (70-90% unchanged, dependent on urine pH). Codeine: renal (86% total, 5-15% unchanged, rest as conjugates and metabolites including morphine). |
| Half-life | Triprolidine: 3-6 hours (increased in elderly). Pseudoephedrine: 5-8 hours (prolonged with alkaline urine; up to 16 hours at pH 8). Codeine: 2.5-3.5 hours (terminal half-life; morphine metabolite ~2-3 hours). |
| Protein binding | Triprolidine: ~60-70% (serum proteins). Pseudoephedrine: negligible (<10%). Codeine: ~25-30% (primarily albumin). |
| Volume of Distribution | Triprolidine: ~2-3 L/kg. Pseudoephedrine: ~2.6-3.5 L/kg. Codeine: ~3-4 L/kg. |
| Bioavailability | Oral: Triprolidine ~80-90%; Pseudoephedrine ~90-100% (first-pass minimal); Codeine ~50% (extensive first-pass metabolism to morphine and other metabolites). |
| Onset of Action | Oral: Triprolidine 30-60 min; Pseudoephedrine 15-30 min; Codeine 30-60 min. Peak effect: 1-2 hours for all components. |
| Duration of Action | Triprolidine: 4-6 hours (antihistamine effect). Pseudoephedrine: 4-6 hours (decongestant). Codeine: 4-6 hours (antitussive effect at therapeutic doses). |
Each 5 mL oral solution contains triprolidine HCl 1.25 mg, pseudoephedrine HCl 30 mg, and codeine phosphate 10 mg. Adult dose: 10 mL (2 teaspoonfuls) every 4 to 6 hours, not to exceed 40 mL in 24 hours.
| Dosage form | SYRUP |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-50 mL/min), administer every 8-12 hours and reduce dose by 25-50%. Monitor for excessive sedation and respiratory depression. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% and extend dosing interval to every 8 hours. Child-Pugh Class C: Avoid use due to risk of encephalopathy and accumulation of codeine. |
| Pediatric use | Children 6-12 years: 5 mL (1 teaspoonful) every 4-6 hours, not to exceed 20 mL in 24 hours. Children 12-18 years: same as adult dosing (10 mL every 4-6 hours, max 40 mL daily). Contraindicated in children <6 years due to risk of respiratory depression. |
| Geriatric use | Initiate at 5 mL every 6-8 hours due to increased sensitivity to anticholinergic effects, sedation, and respiratory depression. Monitor for confusion, urinary retention, and hypotension. Avoid in patients with cognitive impairment or falls risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and impair mental and physical abilities.
| FDA category | Animal |
| Breastfeeding | Codeine is excreted into breast milk; M/P ratio approximately 2.5; risk of neonatal CNS depression, especially in CYP2D6 ultra-rapid metabolizers (can produce toxic morphine levels). Pseudoephedrine passes into milk, may cause irritability or decreased milk supply. Triprolidine is excreted in small amounts but may cause drowsiness. Contraindicated during breastfeeding due to codeine. |
| Teratogenic Risk |
■ FDA Black Box Warning
Codeine is contraindicated for post-operative pain management in children undergoing tonsillectomy and/or adenoidectomy due to risk of respiratory depression and death. Codeine is contraindicated in children under 12 years of age for treatment of pain or cough. The combination product should not be used in children under 18 years of age due to risks of respiratory depression, addiction, and accidental overdose.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to any component; children under 18 years of age; severe hypertension; severe coronary artery disease; MAOI use within 14 days; acute or severe bronchial asthma; gastrointestinal obstruction; urinary retention; narrow-angle glaucoma; breastfeeding (due to codeine); concomitant use with other CNS depressants including alcohol; history of substance abuse; respiratory depression; suspected prior opioid tolerance.
| Precautions | Respiratory depression, especially in children and elderly; risk of opioid abuse, addiction, and diversion; severe hypotension; serotonin syndrome with concurrent serotonergic drugs; CNS depression; exacerbation of glaucoma, prostatic hypertrophy, or urinary retention; hypertension; increased intraocular pressure; hyperthyroidism; diabetes mellitus; ischemic heart disease; driving impairment; avoid alcohol; use with caution in patients with asthma, COPD, or other chronic respiratory conditions. |
Loading safety data…
| First trimester: Codeine phosphate is associated with increased risk of congenital malformations, particularly cardiovascular defects, in some studies; pseudoephedrine may be linked to gastroschisis; triprolidine hydrochloride has limited data but low risk. Second/third trimester: Codeine can cause neonatal respiratory depression and withdrawal if used near term; pseudoephedrine may reduce placental blood flow. All trimesters: Avoid due to potential fetal harm; use only if benefit clearly outweighs risk. |
| Fetal Monitoring | Monitor maternal respiratory rate, heart rate, blood pressure. Fetal surveillance: ultrasound for growth and anatomy if first-trimester exposure; non-stress test or biophysical profile in third trimester. Neonatal monitoring for signs of opioid withdrawal (e.g., irritability, poor feeding) and respiratory depression. |
| Fertility Effects | Codeine may suppress gonadotropin-releasing hormone, leading to menstrual irregularities and reduced fertility. Pseudoephedrine has no known direct effect on fertility. Triprolidine may cause anticholinergic effects but impact on fertility is not established. Limited data on combined product. |