RAPLON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RAPLON (RAPLON).
RAPLON (levosimendan) is a calcium sensitizer that increases myocardial contractility by sensitizing troponin C to calcium, and it also opens ATP-sensitive potassium channels, causing vasodilation.
| Metabolism | Primarily metabolized by the liver via conjugation to a methyl ester, which is then further conjugated by glutathione-S-transferase. The active metabolite (OR-1896) has a long half-life. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 80-90% of administered dose within 24 hours); minor biliary/fecal elimination (less than 10%). |
| Half-life | Terminal elimination half-life is approximately 1.5-2.5 hours in patients with normal renal function; prolonged in renal impairment (up to 6-8 hours in end-stage renal disease). |
| Protein binding | Approximately 30-40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.2-0.3 L/kg, indicating distribution primarily into extracellular fluid. |
| Bioavailability | Intravenous: 100% (only route used clinically). Intramuscular: Not routinely used; bioavailability data limited. |
| Onset of Action | Intravenous: Rapid onset, within 1-2 minutes. Intramuscular: 5-10 minutes. |
| Duration of Action | Duration of neuromuscular blockade: Approximately 30-45 minutes after standard intubating dose; prolonged with repeated doses or in renal failure. |
0.2 mg/kg IV bolus over 30 seconds; may repeat once if necessary after 15 minutes.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required; RAPLON is not significantly renally eliminated. |
| Liver impairment | Child-Pugh A and B: no adjustment; Child-Pugh C: use with caution, consider reducing dose by 50% due to prolonged duration. |
| Pediatric use | 0.2 mg/kg IV bolus over 30 seconds; maximum single dose 10 mg; may repeat once after 15 minutes. |
| Geriatric use | Use 0.15 mg/kg IV bolus over 30 seconds due to increased sensitivity and risk of prolonged neuromuscular blockade. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RAPLON (RAPLON).
| Breastfeeding | Not recommended. No human data available on excretion into breast milk. M/P ratio unknown. |
| Teratogenic Risk | Pregnancy Category C. No adequate human studies. Trimester 1: Risk of fetal malformations cannot be ruled out; animal studies show decreased fetal weight at maternally toxic doses. Trimester 2-3: Potential for fetal respiratory depression or apnea when used near term; avoid during labor. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to levosimendan or any excipient; severe hypotension (systolic BP < 85 mmHg); severe tachyarrhythmia; significant mechanical obstruction affecting ventricular filling or outflow; history of torsades de pointes; severe renal impairment (CrCl < 30 mL/min); severe hepatic impairment.
| Precautions | Hypotension; tachyarrhythmias; renal impairment; electrolyte disturbances (hypokalemia, hypomagnesemia) may increase risk of arrhythmias; monitoring of blood pressure, heart rate, and ECG required; not recommended in severe hepatic impairment. |
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| Continuous fetal heart rate monitoring if used during pregnancy; observe neonate for respiratory depression if used near delivery. |
| Fertility Effects | No known effect on fertility in animal studies; human data unavailable. |