PROMETHAZINE PLAIN
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
Promethazine is a phenothiazine derivative that acts primarily as a histamine H1 receptor antagonist, blocking the effects of histamine at H1 receptors. It also has anticholinergic, antiemetic, sedative, and local anesthetic properties. Its antiemetic effect is mediated through blockade of dopamine D2 receptors in the chemoreceptor trigger zone.
| Metabolism | Extensively metabolized in the liver via oxidation (CYP2D6 and other cytochrome P450 enzymes) and conjugation. Metabolites are excreted in urine and feces. |
| Excretion | Primarily renal excretion of metabolites; less than 1% excreted unchanged. Biliary/fecal elimination accounts for approximately 25-30%. |
| Half-life | Terminal elimination half-life: 10-19 hours (average 12-15 hours). Clinical context: Requires repeated dosing for sustained effect; dosing interval typically every 6-12 hours. |
| Protein binding | Approximately 93% bound primarily to albumin and to a lesser extent to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 5-14 L/kg (mean ~10 L/kg). Large Vd indicates extensive tissue distribution, including brain and lungs. |
| Bioavailability | Oral: ~25% (first-pass metabolism); IM: ~70-80%; Rectal: ~70-90%; IV: 100%. |
| Onset of Action | Oral: 15-60 minutes; IM: 20 minutes; IV: 3-5 minutes; Rectal: 20-30 minutes. |
| Duration of Action | Oral/IM/IV: 4-12 hours (antihistaminic effects), 2-8 hours (sedative); note: duration shorter for antiemetic effects (4-6 hours). |
| Molecular Weight | 284.42 |
| Action Class | First-generation antihistamine (H1-receptor antagonist) with antiemetic and sedative properties |
25-50 mg orally, intramuscularly, or rectally every 4-6 hours as needed; maximum 100 mg per dose
| Dosage form | SYRUP |
| Renal impairment | No specific GFR-based dose adjustment recommended; use with caution in severe renal impairment (GFR <10 mL/min) due to risk of accumulation |
| Liver impairment | Child-Pugh Class A and B: no adjustment. Child-Pugh Class C: reduce dose by 50% or extend dosing interval (e.g., every 8-12 hours) due to decreased clearance |
| Pediatric use | Children >2 years: 0.25-0.5 mg/kg orally, intramuscularly, or rectally every 6 hours as needed; maximum 25 mg per dose. Not recommended for children <2 years due to risk of respiratory depression |
| Geriatric use | Initiate at lower dose (e.g., 12.5 mg orally every 6 hours) with cautious titration; increased sensitivity and risk of anticholinergic effects, sedation, and hypotension. Avoid in patients with cognitive impairment or delirium risk |
| 1st trimester | Avoid: Potential teratogenic effects; limited human data, animal studies show fetal harm. |
| 2nd trimester | Avoid: Not indicated for labor due to risk of maternal hypotension and fetal distress; use only if clearly needed. |
| 3rd trimester | Avoid: May cause respiratory depression in neonates if used near term; avoid during labor. |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Placental transfer | Crosses placenta; rapidly transferred to fetus with concentrations similar to maternal serum. |
| Breastfeeding |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years due to the risk of fatal respiratory depression. Use with caution in children aged 2 years and older; do not exceed recommended doses. Use of promethazine in children may cause severe respiratory depression and/or death.
| Common Effects | nausea/vomiting |
| Serious Effects | Respiratory depression (especially in children and with high doses), Severe tissue injury (including gangrene) with intravenous administration due to perivascular extravasation, Neuroleptic malignant syndrome (rare), Seizures, Cholestatic jaundice, Blood dyscrasias (leukopenia, agranulocytosis), QT prolongation and torsades de pointes (rare) |
Hypersensitivity to promethazine or any phenothiazineComatose statesConcomitant use with large amounts of CNS depressants (alcohol, barbiturates)Children <2 years (risk of fatal respiratory depression)Severe CNS depression
| Precautions | Respiratory depression: especially in children, elderly, or with respiratory compromise., CNS depression: additive effects with other CNS depressants (e.g., alcohol, opioids)., Neuroleptic malignant syndrome (NMS): rare but potentially fatal., Extrapyramidal symptoms: especially with high doses or in children., Akathisia, dystonia., Lowered seizure threshold., Anticholinergic effects: exacerbation of glaucoma, urinary retention, constipation., Use in hepatic impairment: may require dose adjustment., Use in renal impairment: caution., Photosensitivity: avoid prolonged sun exposure., Blood dyscrasias: agranulocytosis (rare)., Pregnancy: avoid during labor (may cause respiratory depression in neonate)., Lactation: may be excreted in breast milk; avoid. |
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| Excreted into breast milk in small amounts; may cause drowsiness or irritability in infants. Monitor for sedation and feeding difficulties. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data, no clear teratogenicity in humans at therapeutic doses; animal studies show no harm at low doses, but high doses cause skeletal anomalies. Second and third trimesters: Use associated with maternal respiratory depression and neonatal withdrawal if used near term; avoid in late pregnancy due to risk of hyperbilirubinemia in newborns. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to possible hypotension; fetal heart rate monitoring recommended with chronic use; assess for signs of neonatal sedation or withdrawal if used near term. |
| Fertility Effects | No direct evidence of impaired fertility in humans; animal studies show no adverse effects on fertility at therapeutic doses. |
| Food/Dietary | No significant food interactions. However, avoid alcohol and grapefruit juice as they may increase sedation and alter drug metabolism. Take with food if gastrointestinal upset occurs. |
| Clinical Pearls | Promethazine is a phenothiazine derivative with strong antiemetic, antihistaminic, and sedative properties. It is highly anticholinergic, which can cause confusion in elderly patients. Avoid intra-arterial or subcutaneous administration due to risk of necrosis. Use with caution in patients with asthma, COPD, or sleep apnea due to respiratory depression. May prolong QT interval, especially with other QT-prolonging drugs. Can cause extrapyramidal symptoms, particularly in children. Use lowest effective dose to minimize anticholinergic side effects. |
| Patient Advice | Avoid alcohol and other CNS depressants (e.g., sedatives, opioids) as they increase drowsiness and respiratory depression. · Do not drive or operate heavy machinery until you know how this medication affects you, as it causes significant drowsiness. · Take exactly as prescribed; do not exceed recommended dose. Overdose can cause severe side effects, including seizures and respiratory depression. · If you miss a dose, skip it and resume your regular schedule. Do not double the dose. · Stop taking and seek medical attention if you experience any of these: severe dizziness, slow heartbeat, trouble breathing, muscle stiffness, or uncontrolled movements. · Store at room temperature, away from light and moisture. Keep out of reach of children. |