TRIDIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIDIL (TRIDIL).
Nitroglycerin is a vasodilator that acts directly on vascular smooth muscle, causing relaxation. It primarily dilates venous capacitance vessels, reducing preload, and at higher doses dilates arterioles, reducing afterload. The mechanism involves nitric oxide-mediated activation of guanylyl cyclase, increasing cGMP levels.
| Metabolism | Primarily hepatic metabolism via nitrate reductase, forming dinitrates and mononitrates. |
| Excretion | Renal (87% as inorganic nitrite/nitrate and metabolites), biliary/fecal (minimal, <1%) |
| Half-life | Terminal elimination half-life of nitroglycerin is 1-4 minutes; clinical effects are limited by rapid metabolism |
| Protein binding | 60% bound to plasma proteins (mainly albumin) |
| Volume of Distribution | 3.3 L/kg (large Vd indicating extensive tissue distribution) |
| Bioavailability | Intravenous: 100%; Sublingual: approximately 40% (first-pass metabolism); Transdermal: variable (70-80% systemic absorption with controlled delivery); Oral: <1% due to extensive hepatic first-pass effect |
| Onset of Action | Intravenous: 1-2 minutes; Sublingual: 1-3 minutes; Transdermal: 30-60 minutes; Topical ointment: 15-30 minutes |
| Duration of Action | Intravenous: 3-5 min after infusion cessation; Sublingual: 30-60 min; Transdermal: 8-12 hours (tolerance develops with continuous use); Topical: 3-6 hours |
Initial adult dose: 5 mcg/min IV via continuous infusion, titrated by 5 mcg/min every 3-5 minutes to achieve desired effect; usual therapeutic range 10-200 mcg/min.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for renal impairment; however, monitor for accumulation of thiocyanate (toxic metabolite) in patients with severe renal failure (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B and C: reduce initial dose by 50% and titrate cautiously due to reduced clearance. |
| Pediatric use | Initial: 0.25-0.5 mcg/kg/min IV; titrate by 0.5-1 mcg/kg/min every 3-5 minutes; usual range 1-5 mcg/kg/min; maximum 10 mcg/kg/min. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 5 mcg/min) and titrate slowly; increased sensitivity and risk of hypotension; consider reduced initial dose (2.5-5 mcg/min). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIDIL (TRIDIL).
| Breastfeeding | Nitroglycerin is excreted in breast milk in small amounts; M/P ratio is unknown. No reported adverse effects in nursing infants. Caution advised, especially with high doses or prolonged use. Monitor infant for hypotension or methemoglobinemia. |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. Nitroglycerin crosses the placenta. In animal studies, it caused fetal toxicity at high doses. Use only if clearly needed, weighing benefit against risk. Specific trimester risks: First trimester: limited data; potential for adverse effects based on animal studies. Second and third trimesters: may cause maternal hypotension and fetal bradycardia; avoid in cases of preeclampsia or volume depletion. |
■ FDA Black Box Warning
Do not use in patients with erectile dysfunction using phosphodiesterase inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
| Serious Effects |
["Hypersensitivity to nitrates","Severe anemia","Increased intracranial pressure","Concurrent use with phosphodiesterase inhibitors","Constrictive pericarditis","Cardiac tamponade"]
| Precautions | ["Risk of severe hypotension","Can cause paradoxical bradycardia","May increase intracranial pressure","Tolerance may develop with prolonged use","Avoid in patients with hypovolemia"] |
Loading safety data…
| Fetal Monitoring | Continuous ECG and blood pressure monitoring during infusion. Assess for fetal heart rate abnormalities if used in pregnancy. Monitor for signs of methemoglobinemia (pulse oximetry, arterial blood gas with co-oximetry) with prolonged high doses. Monitor maternal heart rate, blood pressure, and symptoms of hypotension. Assess for headache, dizziness, or syncope. |
| Fertility Effects | No known effects on fertility in humans. Animal studies have not shown impaired fertility. No specific data on ovulatory or spermatogenic effects. |