NITROPRESS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NITROPRESS (NITROPRESS).
Nitroprusside is a direct-acting vasodilator that releases nitric oxide (NO), which activates guanylyl cyclase in vascular smooth muscle, increasing cGMP levels and causing relaxation of both arterioles and venules.
| Metabolism | Nitroprusside is rapidly broken down in red blood cells and tissues, releasing nitric oxide and cyanide. Cyanide is further metabolized in the liver to thiocyanate via the enzyme rhodanese, which requires thiosulfate. |
| Excretion | Renal: approximately 60% as unchanged drug; hepatic metabolism to inactive metabolites excreted in bile and feces: approximately 40%. |
| Half-life | Terminal elimination half-life: 1–4 minutes (mean 2 minutes) due to rapid metabolism by RBC and tissue esterases; clinical effect dissipates within 10 minutes of infusion cessation. |
| Protein binding | Approximately 60% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.596 L/kg (range 0.5–0.7 L/kg); indicates moderate distribution into total body water and some tissue binding. |
| Bioavailability | Intravenous: 100%; oral: negligible (<1%) due to extensive first-pass metabolism; sublingual/buccal: variable and not clinically reliable. |
| Onset of Action | Intravenous infusion: 30–60 seconds; sublingual: 2–5 minutes (not approved route). |
| Duration of Action | Intravenous infusion: 1–10 minutes after stopping infusion; duration is dose-dependent and titratable for acute hypertensive crises or controlled hypotension. |
Initial dose: 0.3 mcg/kg/min IV continuous infusion; titrate to desired effect. Usual dose: 0.5-10 mcg/kg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for GFR; use with caution in renal impairment due to potential thiocyanate accumulation. Monitor thiocyanate levels if infusion >3 mcg/kg/min for >24 hours. |
| Liver impairment | No specific Child-Pugh based adjustment; use with caution in severe hepatic impairment due to reduced clearance. |
| Pediatric use | Initial: 0.5-1 mcg/kg/min IV; titrate as needed. Maximum: 10 mcg/kg/min. |
| Geriatric use | Start at low end of dosing range (0.3 mcg/kg/min) due to increased sensitivity and risk of hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NITROPRESS (NITROPRESS).
| Breastfeeding | No human data on excretion in breast milk. Sodium nitroprusside and its metabolite thiocyanate are likely excreted. M/P ratio unknown. Potential for thiocyanate accumulation in infant, leading to hypothyroidism or neurotoxicity. Breastfeeding is contraindicated during therapy and for 72 hours post-infusion. |
| Teratogenic Risk | Pregnancy Category C. Animal studies have shown fetal harm (skeletal abnormalities, reduced ossification) at doses below human exposure. No adequate human studies. First trimester: Potential risk of teratogenicity; use only if benefit outweighs risk. Second and third trimesters: May cause fetal cyanide toxicity due to metabolism to thiocyanate; prolonged exposure (≥24 hours) associated with increased fetal mortality and goiter. Avoid use during pregnancy unless no alternative. |
■ FDA Black Box Warning
Cyanide toxicity: Prolonged infusion or high doses can cause cyanide poisoning, especially in patients with hepatic impairment. Sodium thiosulfate should be co-administered to reduce risk.
| Serious Effects |
Hypersensitivity to nitroprusside, severe anemia, hypovolemia, uncorrected hypoxia, and known inadequate cerebral circulation (risk of stroke). Also contraindicated in patients with compensatory hypertension (e.g., coarctation of aorta, arteriovenous shunt).
| Precautions | Monitor for cyanide toxicity (metabolic acidosis, confusion, seizures) and thiocyanate toxicity (weakness, tinnitus, hypothyroidism). Use caution in renal impairment (thiocyanate accumulation) and hepatic impairment (cyanide accumulation). Avoid in patients with Leber's optic atrophy or tobacco amblyopia due to increased cyanide susceptibility. |
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| Fetal Monitoring | Continuous maternal blood pressure monitoring; invasive arterial BP recommended. Monitor fetal heart rate by electronic fetal monitoring during infusion. Monitor maternal thiocyanate levels if infusion >24 hours or in renal impairment (target <10 mg/dL). Assess maternal acid-base status, methemoglobin levels, and oxygen saturation. In prolonged use, monitor fetal growth and thyroid function postpartum. |
| Fertility Effects | No human data on fertility effects. In animal studies, sodium nitroprusside did not impair fertility in rats at doses up to 4 mg/kg/day. Theoretical concern due to cyanide release; however, no specific fertility effects documented. Use with caution in patients attempting conception. |