NITROL
Clinical safety rating
cautionComprehensive clinical and safety monograph for NITROL (NITROL).
NITROL (nitroglycerin) is a vasodilator that relaxes vascular smooth muscle via the release of nitric oxide (NO), which activates guanylate cyclase and increases cyclic guanosine monophosphate (cGMP) levels, leading to vasodilation.
| Metabolism | Primarily metabolized by nitrate reductase in the liver; also undergoes denitration by glutathione-dependent organic nitrate reductase and by hemoglobin in red blood cells. |
| Excretion | Renal: minimal, <1% unchanged; extensive metabolism by liver, metabolites excreted renally. Biliary/fecal: negligible. |
| Half-life | 1-4 minutes for nitroglycerin; clinical effect disappears within 30-60 minutes due to rapid metabolism and redistribution. |
| Protein binding | Approximately 60% bound to albumin. |
| Volume of Distribution | 3.3 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Sublingual: ~40-60% (first-pass metabolism); Oral: <10% due to high first-pass; Transdermal: ~20-30% with continuous delivery; Intravenous: 100%. |
| Onset of Action | Sublingual tablet: 1-3 minutes; Transdermal: 30-60 minutes; Intravenous: immediate; Topical ointment: 15-30 minutes. |
| Duration of Action | Sublingual: 30-60 minutes; Transdermal: 8-12 hours with patch removal, tolerance develops rapidly; Intravenous: duration dependent on infusion rate; Topical: 3-4 hours. |
| Molecular Weight | 227.09 |
| Action Class | Alkaloids-cytotoxic agents |
| Brand Substitutes | Netalem 2mg Injection |
Sublingual: 0.3-0.6 mg every 5 minutes as needed for angina, up to 3 doses in 15 minutes. Translingual spray: 1-2 sprays (0.4 mg/spray) under tongue every 5 minutes as needed, max 3 doses in 15 minutes. Transdermal: 0.2-0.8 mg/hour patch applied daily for 12-14 hours. Intravenous: Initial 5 mcg/min, titrate by 5 mcg/min every 3-5 minutes until response, usual range 10-200 mcg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific adjustment for GFR; monitor for hypotension and methemoglobinemia in severe impairment. Use with caution in dialysis patients. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% and titrate carefully. Child-Pugh C: Avoid use or use with extreme caution, consider alternative therapy. |
| Pediatric use | Sublingual/translingual: 5 mcg/kg/dose every 5-10 minutes as needed for acute angina, max 4 doses. IV: Start 0.25-0.5 mcg/kg/min, titrate by 0.5-1 mcg/kg/min, max 5 mcg/kg/min. Not recommended for neonates due to risk of methemoglobinemia. |
| Geriatric use | Start at low end of adult dose (sublingual 0.3 mg, transdermal 0.2 mg/hr, IV 5 mcg/min). Titrate slowly due to increased sensitivity and risk of hypotension. Monitor for orthostatic hypotension. |
| 1st trimester | Avoid; associated with fetal bradycardia and hypotension; case reports of birth defects. |
| 2nd trimester | Use with caution; monitor fetal heart rate; risk of maternal hypotension and reduced placental perfusion. |
| 3rd trimester | Avoid near term; may inhibit uterine contractions and cause fetal bradycardia. |
Clinical note
Comprehensive clinical and safety monograph for NITROL (NITROL).
| Placental transfer | Crosses placenta readily; detected in fetal circulation. |
| Breastfeeding | Excreted in breast milk in small amounts; unlikely to cause adverse effects in infant; use with caution. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, nitroglycerin has been shown to be embryotoxic in rats and rabbits at doses 20 times the human dose. Use in first trimester only if clearly needed. During second and third trimesters, may be used for management of preterm labor or pregnancy-induced hypertension, but monitor for maternal hypotension and fetal bradycardia. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate monitoring during infusion in pregnancy. Assess for signs of hypotension, headache, and reflex tachycardia. In obstetrics, monitor uterine contractions and fetal heart rate pattern continuously. For intravenous use, monitor ECG and invasive blood pressure in acute settings. |
| Fertility Effects | No data on effect of nitroglycerin on human fertility. Animal studies have not shown impaired fertility at therapeutic doses. Potential transient effects due to vasodilation and hormonal changes not established. |
■ FDA Black Box Warning
Contraindicated in patients with erectile dysfunction who are using phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Serious Effects |
Hypersensitivity to nitroglycerinSevere anemiaIncreased intracranial pressureConstrictive pericarditisCardiac tamponadeConcomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil)
| Precautions | Risk of severe hypotension and syncope, especially in volume-depleted patients or those with low systolic blood pressure; tolerance and cross-tolerance with other nitrates may develop; abrupt cessation may precipitate angina; caution in patients with hypertrophic obstructive cardiomyopathy. |
| Food/Dietary | Alcohol can exacerbate hypotensive effects and should be avoided. No specific food restrictions; however, high-fat meals may delay sublingual absorption but not clinically significant. |
| Clinical Pearls | Nitrol (nitroglycerin) is a potent vasodilator used primarily for angina pectoris. Sublingual tablets should be administered at first sign of attack; patient should be sitting to prevent syncope from hypotension. If pain persists after 3 doses 5 minutes apart, seek emergency care. Tolerance develops with sustained use; avoid long-acting formulations for acute episodes. Monitor for orthostatic hypotension and headache, common side effects. Contraindicated with concurrent use of PDE-5 inhibitors (e.g., sildenafil) due to risk of severe hypotension. |
| Patient Advice | Take sublingual nitroglycerin at the first sign of chest pain; do not swallow. Place tablet under tongue and allow to dissolve. · Sit down before taking to avoid fainting due to drop in blood pressure. · If pain is not relieved after 1 dose, take a second dose after 5 minutes. If not relieved after 3 doses, call 911 immediately. · Store tablets in original glass container, tightly closed, away from light and heat. Replace every 6 months as potency decreases. · Avoid alcohol and erectile dysfunction drugs (e.g., Viagra, Cialis) as they can cause severe hypotension. · Common side effects include headache, dizziness, and flushing. Headache may indicate effectiveness. |
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