GONITRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GONITRO (GONITRO).
Nitric oxide (NO) donor; activates guanylyl cyclase, increasing cGMP in vascular smooth muscle, leading to vasodilation.
| Metabolism | Extensively metabolized by mitochondrial aldehyde dehydrogenase (ALDH2) in vascular smooth muscle; also metabolized by glutathione S-transferases and cytochrome P450 (CYP3A4). |
| Excretion | Primarily renal: 80-90% as inactive metabolites (dinitrates, mononitrates); minor biliary/fecal (<10%) |
| Half-life | Terminal elimination half-life approximately 2-3 minutes for nitroglycerin; clinical effects cease within 30-60 minutes due to rapid redistribution and metabolism |
| Protein binding | 60% bound, primarily to plasma albumin |
| Volume of Distribution | Approximately 3.3 L/kg; extensive tissue distribution with high affinity for vascular smooth muscle |
| Bioavailability | Sublingual: 40-60%; Oral (immediate-release): <10% due to first-pass hepatic metabolism; Transdermal: 70-90% (drug-in-adhesive); Intravenous: 100% |
| Onset of Action | Sublingual: 1-3 minutes; Transdermal: 30-60 minutes; Intravenous: immediate (1-2 minutes); Oral (sustained-release): 20-45 minutes |
| Duration of Action | Sublingual: 30-60 minutes; Transdermal: patch-dependent (8-14 hours with patch removal); Intravenous: 3-5 minutes after infusion stop; Oral (sustained-release): 8-12 hours |
Sublingual: 0.3-0.6 mg at onset of angina, may repeat every 5 minutes up to 3 doses within 15 minutes. Prophylactic: 0.3-0.6 mg 5-10 minutes before activity. Transdermal: Apply 0.2-0.8 mg/hour patch once daily, remove at bedtime to prevent tolerance. Intravenous: Start at 5 mcg/min, titrate by 5-20 mcg/min every 3-5 minutes based on hemodynamic response; usual range 10-200 mcg/min.
| Dosage form | POWDER |
| Renal impairment | No specific dose adjustment required for renal impairment. However, use with caution in severe renal dysfunction (CrCl <30 mL/min) due to increased risk of hypotension and methemoglobinemia. |
| Liver impairment | Child-Pugh A: No adjustment needed. Child-Pugh B: Reduce dose by 50% due to decreased clearance. Child-Pugh C: Avoid use or use with extreme caution; consider alternative therapy. |
| Pediatric use | Sublingual: 5-10 mcg/kg/dose, maximum 0.3 mg per dose, may repeat every 5 minutes up to 3 doses. Intravenous: Start at 0.25-0.5 mcg/kg/min, titrate up to 1-5 mcg/kg/min based on response. Not recommended for children <1 year due to limited data. |
| Geriatric use | Initiate at lower doses due to increased sensitivity: Sublingual: 0.15-0.3 mg; Transdermal: 0.2 mg/day patch; Intravenous: Start at 5 mcg/min, titrate slowly. Monitor for hypotension and syncope. Avoid sustained-release formulations due to prolonged half-life. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GONITRO (GONITRO).
| Breastfeeding | Not recommended during breastfeeding. No data on M/P ratio; minimal excretion into breast milk expected but safety not established. Potential for infant hypotension and bradycardia. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: no increased risk of major malformations in human studies; animal studies show fetal toxicity at high doses. Second/third trimesters: risk of fetal bradycardia, hypotension, and reduced uteroplacental perfusion; avoid near term due to risk of maternal hypotension and neonatal bradycardia. |
■ FDA Black Box Warning
Do not use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Serious Effects |
Concomitant use with PDE-5 inhibitors (sildenafil, tadalafil, vardenafil), severe anemia, increased intracranial pressure, hypersensitivity to nitrates, acute myocardial infarction with low filling pressure.
| Precautions | Hypotension (especially with volume depletion or diuretic therapy), reflex tachycardia, tolerance (intermittent dosing with nitrate-free interval recommended), abrupt discontinuation may cause angina rebound. |
Loading safety data…
| Fetal Monitoring |
| Continuous fetal heart rate monitoring during use for preterm labor or acute maternal indications. Maternal blood pressure and heart rate monitoring; avoid profound hypotension. Uterine activity monitoring if used for tocolysis. |
| Fertility Effects | No adverse effects on fertility reported in animal studies; human data insufficient. |