NITROSTAT
Clinical safety rating
cautionComprehensive clinical and safety monograph for NITROSTAT (NITROSTAT).
Nitroglycerin is a prodrug that releases nitric oxide (NO), which activates guanylyl cyclase, increasing cGMP in vascular smooth muscle, leading to vasodilation. Preferentially dilates coronary arteries and veins, reducing preload and afterload.
| Metabolism | Rapidly metabolized in the liver by glutathione-organic nitrate reductase and by erythrocytes; CYP450 not primarily involved. |
| Excretion | Renal excretion of inactive metabolites accounts for approximately 60% of elimination; biliary/fecal excretion accounts for about 35%. Unchanged nitroglycerin is minimally excreted in urine (<1%). |
| Half-life | 2–3 minutes for initial distribution phase; terminal elimination half-life is approximately 1–4 minutes. Rapid clearance due to extensive metabolism in the liver and other tissues (via glutathione-organic nitrate reductase). |
| Protein binding | Approximately 60% bound to plasma proteins (albumin and possibly others). |
| Volume of Distribution | 3–4 L/kg, indicating extensive distribution into tissues, particularly vascular smooth muscle and other highly perfused organs. |
| Bioavailability | Sublingual: 30–60% (bypasses first-pass hepatic metabolism). Oral: <10% due to extensive first-pass metabolism. Transdermal: 10–20% depending on formulation and application site. Intravenous: 100%. |
| Onset of Action | Sublingual: 1–3 minutes. Transdermal: 30–60 minutes. Intravenous: immediate (within 1–2 minutes). |
| Duration of Action | Sublingual: 20–30 minutes. Transdermal: 8–12 hours (with patch removal, effects wane over 30–60 minutes). Sustained release oral: 4–8 hours. Clinical note: Tolerance develops with continuous exposure; a daily nitrate-free interval (8–12 hours) is recommended to maintain efficacy. |
| Molecular Weight | 227.09 |
0.3-0.6 mg sublingually or buccally every 5 minutes as needed for angina relief, up to a maximum of 3 doses in 15 minutes.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for renal impairment; use with caution in patients with severe renal impairment due to potential for hypotension. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Caution, consider dose reduction; Child-Pugh Class C: Avoid use due to increased risk of methemoglobinemia. |
| Pediatric use | Not recommended for use in children due to lack of safety and efficacy data. |
| Geriatric use | Initiate at lower end of dosing range (0.3 mg) due to increased sensitivity to vasodilation and higher risk of hypotension; monitor closely. |
| 1st trimester | Use only if clearly needed; no adequate studies in pregnant women. Animal studies show fetal risk. |
| 2nd trimester | Use only if clearly needed; risk of maternal hypotension and fetal hypoxia. |
| 3rd trimester | Use only if clearly needed; may cause uterine relaxation and hypotension. |
Clinical note
Comprehensive clinical and safety monograph for NITROSTAT (NITROSTAT).
| Placental transfer | Crosses placenta; fetal serum levels about 50% of maternal. |
| Breastfeeding | Excreted in breast milk in small amounts; unlikely to cause adverse effects in infant, but monitor for hypotension. |
| Lactation Rating | L2 |
| Teratogenic Risk | FDA Pregnancy Category C. Nitroglycerin crosses the placenta. Animal studies show no teratogenic effects. Use in first trimester only if clearly needed; second/third trimester: risk of fetal bradycardia and hypotension. Avoid near term due to potential for maternal hypotension and reduced uterine blood flow. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of hypotension. In late pregnancy, fetal heart rate monitoring recommended. Assess for headache, dizziness, and symptoms of hypotension. |
| Fertility Effects | No known adverse effects on fertility in human studies. Animal studies have not reported impaired fertility. |
■ FDA Black Box Warning
Do not use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) as this can cause severe hypotension, syncope, or myocardial ischemia.
| Serious Effects |
Hypersensitivity to nitroglycerinSevere anemiaIncreased intracranial pressureConcomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)Circulatory failure or shockConstrictive pericarditisPericardial tamponade
| Precautions | Hypotension and reflex tachycardia may occur, May exacerbate angina due to excessive hypotension, Tolerance may develop with prolonged use, Abrupt discontinuation may precipitate angina |
| Food/Dietary | Avoid alcohol, which can enhance hypotensive effects and cause severe dizziness or fainting. Grapefruit juice may increase nitroglycerin absorption and risk of adverse effects. No other significant food interactions. |
| Clinical Pearls | Nitroglycerin sublingual tablets (Nitrostat) are first-line for acute angina. Store in original glass bottle, tightly closed; potency degrades with exposure to light, heat, and moisture. Patients should feel a tingling or burning sensation under the tongue—if absent, tablet may be ineffective. Administer 0.3-0.6 mg at first sign of angina; may repeat every 5 minutes up to 3 doses. If pain persists after 3 doses, seek emergency care. Contraindicated with recent use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) due to severe hypotension. Hypotension and reflex tachycardia are common; monitor blood pressure. Tolerance develops with sustained use; use minimal effective dose and allow nitrate-free interval (10-12 hours daily) for long-acting forms. |
| Patient Advice | Take at the first sign of chest pain; do not wait for severe pain. · Place the tablet under the tongue or between the cheek and gum; do not swallow or chew. · Sit or lie down when taking to avoid dizziness or fainting from low blood pressure. · If no relief after 5 minutes, repeat one dose; if still no relief after 3 doses in 15 minutes, call 911 immediately. · Store in the original glass bottle, tightly closed, away from heat and light; do not store in bathroom or kitchen. · Replace the bottle 6 months after opening, as the medication loses potency. · Do not drink alcohol while taking this medication; it can cause severe hypotension. · Do not take with erectile dysfunction drugs (Viagra, Cialis, Levitra) as it can cause a fatal drop in blood pressure. · Avoid grapefruit juice as it may increase side effects. |
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