PHENYLEPHRINE HYDROCHLORIDE AND PROMETHAZINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
Phenylephrine is a selective alpha-1 adrenergic receptor agonist causing vasoconstriction; promethazine is a phenothiazine derivative that blocks histamine H1 receptors and has anticholinergic, antiemetic, and sedative effects.
| Metabolism | Phenylephrine undergoes hepatic metabolism by monoamine oxidase (MAO); promethazine is extensively metabolized in the liver via CYP2D6 and other pathways. |
| Excretion | Phenylephrine: renal (80% as unchanged drug and sulfate conjugates). Promethazine: renal (70-80% as metabolites and unchanged drug), fecal (20-30%). |
| Half-life | Phenylephrine: 2-3 hours (terminal). Promethazine: 10-14 hours (terminal in adults; prolonged in elderly and hepatic impairment). |
| Protein binding | Phenylephrine: 95% primarily to albumin. Promethazine: 93% primarily to albumin. |
| Volume of Distribution | Phenylephrine: 0.3-0.5 L/kg (distributes into extracellular fluid; does not cross blood-brain barrier significantly). Promethazine: 5-15 L/kg (large distribution due to high lipophilicity; extensive tissue binding including CNS). |
| Bioavailability | Phenylephrine: oral ~38% (due to first-pass metabolism), IM ~100%, IV 100%. Promethazine: oral ~25% (extensive first-pass), IM ~70-80%, IV 100%, rectal ~15-25%. |
| Onset of Action | Phenylephrine: IV (immediate), IM (10-15 min), oral (15-20 min), topical (vasoconstriction within 5 min). Promethazine: IM (20 min), IV (3-5 min), oral (20 min), rectal (20-30 min). |
| Duration of Action | Phenylephrine: IV (15-20 min), IM (30-60 min), oral (1-2 hours), topical nasal decongestion (4 hours). Promethazine: IM/IV (2-8 hours depending on effect; antiemetic 4-6 hours, sedation up to 8 hours), oral (6-12 hours). |
IV: 0.1-0.5 mg phenylephrine and 12.5-25 mg promethazine as a single dose.
| Dosage form | SYRUP |
| Renal impairment | Not specifically defined. Use with caution in severe renal impairment; no dose adjustment recommended. |
| Liver impairment | Child-Pugh A and B: Use with caution. Child-Pugh C: Avoid use due to promethazine metabolism. |
| Pediatric use | Not established for combination; individual components: Phenylephrine IV 5-20 mcg/kg/dose; Promethazine: not recommended in children <2 years, 0.25-1 mg/kg/dose IM/IV. |
| Geriatric use | Elderly patients may be more sensitive to anticholinergic and hypotensive effects. Use lower initial doses and monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Breastfeeding | Phenylephrine: M/P ratio unknown; excreted in breast milk in small amounts; likely safe. Promethazine: M/P ratio unknown; small amounts excreted; may cause drowsiness in infant. Use caution. |
| Teratogenic Risk | First trimester: Phenylephrine may reduce uterine blood flow; promethazine is not associated with major malformations but caution due to anticholinergic effects. Second/third trimester: Phenylephrine may cause fetal hypoxia; promethazine risk of neonatal respiratory depression if used near term. |
■ FDA Black Box Warning
Respiratory depression risk in children under 2 years; contraindicated in this age group. Not recommended for use in children under 6 years.
| Common Effects | nausea/vomiting |
| Serious Effects |
Hypersensitivity to phenylephrine, promethazine, or any component; children under 2 years (black box); concurrent MAOI use; severe hypertension or coronary artery disease; narrow-angle glaucoma; urinary retention; severe prostatic hypertrophy; breastfeeding; concomitant use of CNS depressants (relative).
| Precautions | May cause respiratory depression, especially in children; avoid use in children under 6. Use with caution in patients with asthma, COPD, sleep apnea, or other respiratory conditions. May cause sedation and impair mental/physical abilities. Risk of CNS stimulation, including seizures. May cause hypotension or hypertension. Monitor for extrapyramidal symptoms with prolonged use. Use in elderly may increase risk of confusion, dizziness, and falls. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and fetal heart rate. Assess for uterine contractions and signs of fetal distress. |
| Fertility Effects | Phenylephrine: No known significant impact on fertility. Promethazine: May cause menstrual irregularities or transient infertility due to hyperprolactinemia. |