SODIUM NITROPRUSSIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SODIUM NITROPRUSSIDE (SODIUM NITROPRUSSIDE).
Sodium nitroprusside is a prodrug that releases nitric oxide (NO) in vascular smooth muscle cells, activating guanylate cyclase and increasing cGMP, leading to vasodilation of both arterial and venous vessels.
| Metabolism | Sodium nitroprusside undergoes non-enzymatic degradation in erythrocytes and tissues, releasing cyanide. Cyanide is metabolized by rhodanese (thiosulfate sulfurtransferase) to thiocyanate, primarily in the liver and kidneys. |
| Excretion | Renal: approximately 75% as thiocyanate (metabolite) with 25% unchanged; biliary/fecal: minimal (<5%) |
| Half-life | Sodium nitroprusside itself has a half-life of approximately 2 minutes (converted to cyanide in erythrocytes); the metabolite thiocyanate has a terminal half-life of 2.7-7 days (prolonged in renal impairment, requiring monitoring) |
| Protein binding | Sodium nitroprusside: negligible protein binding (<5%); thiocyanate: weakly bound to plasma proteins (approximately 5%) |
| Volume of Distribution | Sodium nitroprusside: approximately 0.2 L/kg (distributes primarily in extracellular fluid); thiocyanate: approximately 0.2-0.3 L/kg (distributes similarly to extracellular water) |
| Bioavailability | Intravenous: 100% (only route of administration); oral: not applicable (no oral bioavailability due to instability and extensive first-pass metabolism) |
| Onset of Action | IV infusion: 30-60 seconds (direct vasodilation); immediate on administration |
| Duration of Action | IV infusion: effects persist only for the duration of infusion, dissipate rapidly (within 1-10 minutes) upon discontinuation due to rapid metabolism; prolonged effects may occur with high doses due to cyanide accumulation |
Intravenous infusion: Initial 0.3-0.5 mcg/kg/min; titrate up to 10 mcg/kg/min, maximum 10 mcg/kg/min for up to 10 minutes. Usual therapeutic dose: 3 mcg/kg/min. Max cumulative dose: 3.5 mg/kg.
| Dosage form | INJECTABLE |
| Renal impairment | GFR <60 mL/min: Use with caution; reduce initial dose by 50% and monitor for cyanide toxicity. GFR <30 mL/min: Avoid due to risk of thiocyanate accumulation. |
| Liver impairment | Child-Pugh Class B: Reduce initial dose by 50% and monitor for cyanide toxicity; maximum infusion rate 2 mcg/kg/min. Child-Pugh Class C: Contraindicated due to risk of severe cyanide toxicity. |
| Pediatric use | Children: Intravenous infusion 0.3-1 mcg/kg/min initially; titrate to effect, not to exceed 10 mcg/kg/min. Neonates: 0.5-1 mcg/kg/min; maximum 5 mcg/kg/min. |
| Geriatric use | Elderly: Lower initial doses (0.3-0.5 mcg/kg/min) with slower titration; increased sensitivity to hypotension. Monitor for thiocyanate accumulation (normal renal function may decline with age). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SODIUM NITROPRUSSIDE (SODIUM NITROPRUSSIDE).
| Breastfeeding | It is unknown if sodium nitroprusside is excreted in human breast milk. The M/P ratio is not available. Due to the short half-life and rapid metabolism, exposure to the nursing infant is likely minimal, but caution is advised. |
| Teratogenic Risk | Pregnancy Category C. Risk cannot be ruled out. Animal reproduction studies have not been conducted with sodium nitroprusside. It should only be used in pregnant women if the potential benefit justifies the potential risk to the fetus. Due to its vasodilatory effects and potential for maternal hypotension, fetal hypoxia may occur. Use during labor may cause uterine relaxation and prolonged labor. |
■ FDA Black Box Warning
Sodium nitroprusside can cause excessive hypotension and cyanide toxicity. Continuous monitoring of blood pressure and cyanide/thiocyanate levels is required. Prolonged infusion or high doses increase risk of cyanide poisoning.
| Serious Effects |
["Pre-existing hypotension","Compensatory hypertension (e.g., coarctation of aorta)","Leber's optic atrophy (cytochrome oxidase deficiency)","Severe renal impairment","Congenital optic atrophy","Poorly compensated heart failure"]
| Precautions | ["Risk of cyanide toxicity, especially with prolonged infusion or renal impairment","Thiocyanate toxicity with renal failure","Hypotension requiring continuous blood pressure monitoring","Methemoglobinemia (rare)"] |
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| Fetal Monitoring | Continuous blood pressure monitoring via intra-arterial line is recommended. Monitor heart rate, cardiac output, and systemic vascular resistance. Monitor for signs of cyanide toxicity (metabolic acidosis, altered mental status), especially with prolonged use or in renal impairment. Fetal heart rate monitoring should be considered during labor. |
| Fertility Effects | No human data on fertility effects. Animal studies have not been conducted. No known direct impact on fertility, but severe hypotension or toxicity could potentially affect reproductive function. |