PROMETH FORTIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).
Promethazine is a phenothiazine derivative that acts as a histamine H1 receptor antagonist, with additional anticholinergic, antiemetic, and sedative properties. It blocks histamine at H1 receptors, reducing allergic symptoms and motion sickness, and exerts antiemetic effects by blocking dopamine D2 receptors in the chemoreceptor trigger zone.
| Metabolism | Primarily metabolized in the liver via oxidation and conjugation, with involvement of CYP2D6 isoenzyme. |
| Excretion | Primarily renal as inactive metabolites; <1% excreted unchanged. Total elimination: renal ~70%, fecal ~30%. |
| Half-life | Terminal elimination half-life: 9–16 hours (mean ~12 hours). In children and elderly, half-life may be prolonged (up to 20 hours). |
| Protein binding | Protein binding: 93–98%, primarily to albumin. |
| Volume of Distribution | Volume of distribution: 10–15 L/kg (range 6–20 L/kg). Large Vd indicates extensive tissue distribution and penetration into CNS. |
| Bioavailability | Oral: ~25% (due to extensive first-pass metabolism); Intramuscular: ~75–80%; Rectal: ~25–30%. |
| Onset of Action | Oral: 15–60 minutes; Intramuscular: 20–30 minutes; Intravenous: 3–5 minutes; Rectal: 30–60 minutes. |
| Duration of Action | Oral: 4–6 hours; Intramuscular: 6–12 hours; Intravenous: 4–8 hours; Rectal: 4–6 hours. Clinical note: Duration varies with dose and indication; antiemetic effect may persist longer than sedative effect. |
| Molecular Weight | 284.42 |
Adults: 12.5-25 mg intramuscular or intravenous every 4-6 hours as needed for nausea. For severe nausea up to 50 mg IM/IV. Maximum single dose 50 mg, maximum daily dose 200 mg.
| Dosage form | SYRUP |
| Renal impairment | No specific guidelines; use caution in severe renal impairment (eGFR <30 mL/min) due to potential for accumulation and increased sedative effects; consider dose reduction or interval prolongation. |
| Liver impairment | Child-Pugh A: No adjustment necessary. Child-Pugh B: Consider 50% dose reduction and monitor. Child-Pugh C: Contraindicated or use with caution; avoid use if possible. |
| Pediatric use | Children >2 years: 0.25-0.5 mg/kg intramuscular or intravenous every 4-6 hours as needed, maximum 25 mg per dose. Alternatively: age 2-5 years: 5 mg IM/IV every 4-6 hours; 6-12 years: 10 mg IM/IV every 4-6 hours; >12 years: 12.5-25 mg IM/IV every 4-6 hours. |
| Geriatric use | Use lowest effective dose (e.g., 12.5 mg IM/IV every 6-8 hours) due to increased sensitivity to anticholinergic effects, sedation, and risk of falls; avoid in patients with dementia or cognitive impairment. |
| 1st trimester | Avoid use in first trimester due to risk of congenital malformations, especially cardiovascular defects; limited data. |
| 2nd trimester | Use only if clearly needed; may cause temporary extrapyramidal signs in neonates if used near term. |
| 3rd trimester | Avoid during late pregnancy and labor; may cause respiratory depression in neonates, prolonged labor due to anti-cholinergic effects. |
Clinical note
Comprehensive clinical and safety monograph for PROMETH FORTIS (PROMETH FORTIS).
| Placental transfer | Promethazine crosses the placenta extensively; fetal concentrations approximate maternal levels. |
| Breastfeeding | Promethazine is excreted into breast milk in small amounts. May cause drowsiness, irritability, or apneic episodes in infants, especially in neonates or premature infants. Avoid use in breastfeeding mothers if possible; if used, monitor infant for sedation and feeding difficulties. |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years of age due to the risk of potentially fatal respiratory depression. Use in children aged 2 to 18 is also cautioned, with lowest effective dose recommended.
| Serious Effects |
Coma or severe central nervous system depressionConcurrent use of large doses of other CNS depressants (e.g., barbiturates, alcohol)Hypersensitivity to promethazine or any phenothiazineChildren <2 years of age due to risk of respiratory depression and sudden infant death syndromeConcurrent use of MAOIsAcute asthmatic attackSevere hypertension or hypotensionBone marrow depressionClosed-angle glaucomaProstatic hypertrophy with urinary retentionPyloroduodenal obstructionSeizure disorders (may lower seizure threshold)Jaundice or hepatic impairment
| Precautions | May cause severe respiratory depression, especially in children and in combination with other CNS depressants. Avoid use in patients with respiratory compromise. Use cautiously in patients with asthma, COPD, sleep apnea, or other respiratory conditions. May cause extrapyramidal reactions, neuroleptic malignant syndrome, and anticholinergic effects. May lower seizure threshold. Use caution in elderly patients. Avoid subcutaneous or intra-arterial administration due to tissue necrosis risk. |
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| Lactation Rating | L3 - Limited Data |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: May cause transient neonatal withdrawal symptoms (irritability, tremors) with prolonged use near term. No documented structural anomalies. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, sedation level. Fetal: Nonstress test and biophysical profile in third trimester if used chronically; neonatal observation for withdrawal symptoms after delivery. |
| Fertility Effects | No known direct effects on fertility. Anticholinergic and sedative properties may indirectly affect reproductive function (e.g., decreased libido). No specific ovulation or spermatogenesis data. |
| Food/Dietary | Avoid alcohol and grapefruit juice (may increase sedation and risk of QT prolongation). No significant food restrictions. |
| Clinical Pearls | Prometh Fortis (promethazine 25 mg) is an antiemetic, antihistamine, and sedative. Use with caution in elderly due to anticholinergic effects (confusion, urinary retention). Avoid in children <2 years due to risk of respiratory depression. Can cause extrapyramidal symptoms; use lowest effective dose. Monitor for QTc prolongation if combined with other QT-prolonging drugs. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · May cause drowsiness; avoid driving or operating machinery until you know how you react. · Avoid alcohol and other CNS depressants (sedatives, tranquilizers). · Report any muscle stiffness, tremors, or involuntary movements. · Do not use in children under 2 years of age. · Notify your doctor if you have glaucoma, enlarged prostate, or breathing problems like asthma or COPD. · Store at room temperature away from light and moisture. |