LARGON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LARGON (LARGON).
Propionazine is a phenothiazine derivative that acts as a central dopamine receptor antagonist, particularly at D2 receptors. It also exhibits antihistaminergic, anticholinergic, and sedative effects by blocking histamine H1 and muscarinic receptors.
| Metabolism | Propionazine is extensively metabolized in the liver via cytochrome P450 enzymes, including CYP2D6 and CYP3A4. Metabolites are primarily excreted in urine. |
| Excretion | Primarily renal (approximately 50-80% as unchanged drug and metabolites) via glomerular filtration and tubular secretion; minor biliary/fecal elimination (~10-15%). |
| Half-life | Terminal elimination half-life is 20-30 hours in healthy adults, extending up to 40-60 hours in patients with hepatic impairment or elderly. |
| Protein binding | 90-95% bound primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 10-20 L/kg, indicating extensive tissue distribution and accumulation in peripheral compartments. |
| Bioavailability | Oral bioavailability is 30-50% due to extensive first-pass metabolism in the liver. |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 15-30 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral/IM: 4-6 hours; IV: 3-4 hours. Clinical effects (e.g., sedation) may persist longer due to active metabolites. |
50 mg intramuscularly every 4-6 hours as needed for nausea and vomiting. Maximum: 300 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. In severe renal impairment (GFR <30 mL/min), consider reducing dose by 50% due to potential accumulation. |
| Liver impairment | For Child-Pugh class A: no adjustment. Child-Pugh class B: reduce dose by 50%. Child-Pugh class C: avoid use or use with caution at 25% of normal dose. |
| Pediatric use | Not recommended for pediatric use due to risk of extrapyramidal symptoms. No established dosing guidelines. |
| Geriatric use | Initial dose should be reduced to 25 mg intramuscularly due to increased sensitivity and risk of adverse effects. Titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LARGON (LARGON).
| Breastfeeding | Cyclizine is excreted into breast milk in small amounts. The M/P ratio is not established. However, due to low oral bioavailability in infants, adverse effects are unlikely. Caution is advised in preterm or low-birth-weight infants due to potential anticholinergic effects. A safety score of L2 (safer) is assigned by LactMed. |
| Teratogenic Risk | Largon (cyclizine) is an antihistamine with anticholinergic properties. In the first trimester, there is no evidence of increased risk of major congenital malformations from human data; however, animal studies are insufficient. Second and third trimester exposure: no documented fetal harm, but anticholinergic effects may cause neonatal respiratory depression or withdrawal if used near term. FDA Pregnancy Category B. |
■ FDA Black Box Warning
LARGON (propionazine) injection carries a black box warning for increased mortality in elderly patients with dementia-related psychosis. Phenothiazines are not approved for this condition and may increase the risk of death.
| Serious Effects |
["Hypersensitivity to propionazine or other phenothiazines.","Comatose states or severe CNS depression (e.g., from alcohol, barbiturates, or opioids).","Concurrent use of large doses of other CNS depressants.","Pediatric patients (safety and efficacy not established).","Pregnancy (may cause neonatal withdrawal syndrome, especially if used in third trimester).","Lactation (excreted in breast milk; potential for adverse effects in nursing infants)."]
| Precautions | ["Increased risk of cerebrovascular events in elderly with dementia-related psychosis.","Potential for neuroleptic malignant syndrome (NMS), which is a life-threatening condition requiring immediate discontinuation.","QT prolongation and risk of torsade de pointes; caution in patients with cardiac disease or electrolyte imbalances.","Severe hypotension, including orthostatic hypotension, especially with parenteral use.","Extrapyramidal symptoms (EPS) and tardive dyskinesia with prolonged use.","Central nervous system depressant effects; additive when combined with alcohol or other CNS depressants.","Cholestatic jaundice and hepatic injury; monitor liver function.","Agranulocytosis and leukopenia; monitor blood counts with prolonged therapy."] |
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| Fetal Monitoring | Maternal: Monitor for excessive sedation, anticholinergic effects (dry mouth, urinary retention, blurred vision). Fetal: No specific monitoring required, but assess neonatal heart rate and respiratory status if used near delivery. Ultrasound for fetal growth is not indicated based on cyclizine use. |
| Fertility Effects | No significant effects on human fertility have been reported. Animal studies show no impairment of fertility at therapeutic doses. |