LEVOPROME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVOPROME (LEVOPROME).
Phenothiazine antipsychotic that blocks postsynaptic dopamine receptors (D2) in the central nervous system, particularly in the mesolimbic and mesocortical pathways; also has anticholinergic, antihistaminic, and alpha-adrenergic blocking effects.
| Metabolism | Hepatic via CYP2D6, CYP3A4; active metabolites include methotrimeprazine sulfoxide, N-desmethylmethotrimeprazine. |
| Excretion | Primarily renal (approx. 70% as conjugated metabolites, <1% unchanged), with biliary/fecal excretion (approx. 20%). |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 12–36 hours). Accumulation occurs with repeated dosing, requiring dose adjustment in hepatic impairment. |
| Protein binding | >99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 7 L/kg (range 5–10 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: 40–50% (first-pass effect); Intramuscular: 70–80%. |
| Onset of Action | Intravenous: 5–15 minutes; Intramuscular: 10–20 minutes; Oral: 30–60 minutes. |
| Duration of Action | Intravenous: 2–4 hours; Intramuscular: 3–6 hours; Oral: 4–6 hours. Longer duration with hepatic impairment. |
| Molecular Weight | 326.5 |
25 to 50 mg intramuscularly every 6 to 8 hours; initial dose may be 25 to 75 mg. Maximum dose 150 mg per day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: Administer 75% of usual dose; CrCl <10 mL/min: Administer 50% of usual dose. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 25-50%; Child-Pugh Class C: Avoid use. |
| Pediatric use | Children >12 years: 0.5-1 mg/kg intramuscularly every 6-8 hours; maximum 2 mg/kg/day. Not recommended for children under 12 years. |
| Geriatric use | Initial dose: 12.5 to 25 mg intramuscularly; titrate cautiously due to increased sensitivity and risk of orthostatic hypotension. |
| 1st trimester | Insufficient human data; animal studies show potential risk. Use only if benefit outweighs risk. |
| 2nd trimester | Insufficient human data; may cause maternal hypotension and uteroplacental insufficiency. Use with caution. |
| 3rd trimester | Avoid near term due to risk of maternal hypotension, neonatal respiratory depression, and adverse effects on uterine tone. |
Clinical note
Comprehensive clinical and safety monograph for LEVOPROME (LEVOPROME).
| Placental transfer | Crosses placenta; detected in fetal circulation. |
| Breastfeeding | Excreted into breast milk in small amounts; monitor infant for sedation and feeding difficulties. Consider benefit of therapy versus risk. |
| Lactation Rating |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis; risk of tardive dyskinesia; neuroleptic malignant syndrome (NMS).
| Serious Effects |
Hypersensitivity to levoprome or related compoundsConcomitant use with MAOIs or within 14 daysSevere CNS depressionComatose states
| Precautions | Neuroleptic malignant syndrome, tardive dyskinesia, hypotension, seizures, anticholinergic effects, QT prolongation, agranulocytosis, photosensitivity, elevation of prolactin levels. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase serum levels of methotrimeprazine. Limit caffeine intake as it may exacerbate side effects like restlessness. No specific food restrictions otherwise. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data; animal studies show increased fetal resorption and skeletal anomalies at high doses. Second and third trimesters: No evidence of major malformations; risk of neonatal extrapyramidal symptoms and jaundice with third-trimester use. |
| Fetal Monitoring | Monitor maternal liver function, renal function, and complete blood count; fetal ultrasound for growth and anatomy; neonatal assessment for extrapyramidal symptoms if used near term. |
| Fertility Effects | No specific human data; animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | Levoprome (methotrimeprazine) is a phenothiazine neuroleptic with potent analgesic properties. It may cause significant hypotension, especially in elderly or hypovolemic patients; use with caution and monitor blood pressure. Extrapyramidal symptoms are less common than with typical antipsychotics but may occur. Avoid subcutaneous extravasation due to tissue irritation. |
| Patient Advice | This medication may cause drowsiness or dizziness; do not drive or operate machinery until you know how it affects you. · Avoid alcohol and other central nervous system depressants. · Rise slowly from sitting or lying positions to prevent fainting. · Report any unusual muscle movements or stiffness to your healthcare provider. · Use sunscreen and protective clothing as this drug may increase sensitivity to sunlight. |