nitroglycerin IV (glyceryl trinitrate IV, IV Nitroglycerin, NitroBid IV, NTG, Tridil)
Classes: Nitrates, Angina
Dosing and uses of Glyceryl trinitrate IV, IV Nitroglycerin (nitroglycerin IV)
Adult dosage forms and strengths
infusion solution
- 25mg/250mL
- 50mg/250mL
- 100mg/250mL
injectable solution
- 5mg/mL
Angina
If intolerant of or unresponsive to SL NTg
5 mcg/min
Increase by 5 mcg/min q3-5min up to 20 mcg/min, THEn
Increase by 10 mcg/min
May later increase by 20 mcg/min
Higher dosages required for PVC admin sets
Uninterrupted infusion >24 hours produces tolerance
Renal Failure
CrCl: 10-50 mL/min: Administer q24-72hr
CrCl: <10 mL/min: Administer q72-96hr
Other Indications & Uses
Angina pectoris, perioperative HTN, CHF in the setting of MI, induction of intra-operative hypotension
Off-label: hypertensive crisis, variceal bleeds (with vasopressin), sympathomimetic-induced cardiopulmonary toxicities
Pediatric dosage forms and strengths
infusion solution
- 25mg/250mL
- 50mg/250mL
- 100mg/250mL
injectable solution
- 5mg/mL
Congestive Heart Failure
Not FDA approved
Initial: 0.25-0.5 mcg/kg/min IV infusion, may increase by 0.5-1 mcg/kg/min q3-5min PRn
Usual range: 1-5 mcg/kg/min IV infusion
No more than 20 mcg/min
Glyceryl trinitrate IV, IV Nitroglycerin (nitroglycerin IV) adverse (side) effects
Common
Headache
Hypotension
Tachycardia
Dyspnea
Dizziness
Lightheadedness
Blurred vision
Flushing
N/V
Nervousness
Xerostomia
Serious
Methemoglobinemia (rare)
Syncope
Prolonged bleeding time
Exfoliative dermatitis
Unstable angina
Rebound hypertension
Thrombocytopenia
Warnings
Contraindications
Recent use (within several days) of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, or vardenafil) may cause dangerously low hypotension; the time course of the interaction appears to be related to the PDE-5 inhibitor half-life
Riociguat; coadministration may cause hypotension
Narrow angle glaucoma (controversial: may not be clinically significant)
Hypersensitivity
Symptomatic hypotension, uncorrected hypovolemia, increased intracranial pressure (head trauma, cerebral hemorrhage), severe anemia, constrictive pericarditis, pericardial tamponade, restrictive cardiomyopathy
Cautions
Use caution in alcohol use, hyperthyroidism, hypertrophic cardiomyopathy, postural hypotension, severe renal impairment, hepatic impairment
Gradually decrease dose to avoid withdrawal reaction
May need 10-12 hr/day nitrate-free interval to avoid tolerance development
Doses ~ 200 mcg/min
Some products contain alcohol and propylene glycoL
Remove topical forms when starting IV infusion
Use glass bottles and non-PVC (polyvinyl chloride) tubing to avoid adsorption of drug to delivery devices; use of PVC tubing in infusion sets may lead to loss of active ingredient due to adsorption of nitroglycerin to PVC tubing; dosage is affected; adsorption by PVC tubing is increased when tubing is long, flow rates are low, and nitroglycerin concentration of solution is high; delivered fraction of solution's original nitroglycerin content has been 20-60% in published studies; fraction varies with time during single infusion, and no simple correction factor can be used; if intravenous nitroglycerin is administered through non-adsorptive tubing, doses based upon published reports will generally be too high; some in-line intravenous filters also adsorb nitroglycerin and should be avoided
Solutions containing dextrose without electrolytes should not be administered through the same administration set as blood, as this may result in pseudoagglutination or hemolysis
Intravenous administration of solutions may cause fluid overloading resulting in dilution of serum electrolyte concentrations, overhydration and congested states of pulmonary edema; risk of dilutional states is inversely proportional to electrolyte concentrations of injections; risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to electrolyte concentration of injections
Severe hypotension and shock may occur with even small doses of nitroglycerin; monitor patients who may be volume depleted or, for whatever reason, are already hypotensive; hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris
Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy
Tolerance development and occurrence of cross tolerance to other nitro compounds reported
Administer nitroglycerin in 5% dextrose Injection only via infusion pump that can maintain constant infusion rate
Monitor patients with known sub-clinical or overt diabetes mellitus when using solutions containing dextrose
Cases of methemoglobinemia reported with moderate doses of organic nitrates; when methemoglobinemia is diagnosed, discontinue treatment of nitroglycerin; if condition not reversed, treat with methylene blue, 1-2 mg/kg intravenously
Protect from freezing and light
Do not change brands unintentionally as not all are bioequivalent
Treat drug-induced headache with aspirin or acetaminophen
Provide nitrate-free interval (10-12 hr or overnight) to avoid development of tolerance
Use supportive treatment in overdose; there is no specific antidote for overdose; risk of overdose can be minimized by close monitoring during treatment
Drug interaction overview
- The vasodilating effects of nitroglycerin may be additive with those of other antihypertensives. (e.g., beta-blockers, calcium channel blockers and tricyclic antidepressants) and may cause increased hypotensive effects
- Concomitant use of nitroglycerin in 5% dextrose injection concomitant use with phosphodiesterase inhibitors (e.g. sildenafil, tadalafil, or vardenafil) in any form is contraindicated
- Concomitant use of nitroglycerin in 5% dextrose injection with riociguat, a soluble guanylate cyclase stimulator, can cause hypotension and is contraindicated
- Marked symptomatic orthostatic hypotension reported when calcium channel blockers and organic nitrates used in combination
- Nitroglycerin at higher dosages may interfere with anticoagulant effect of heparin; intravenous nitroglycerin can induce heparin resistance
Pregnancy and lactation
Pregnancy category: C
Lactation: Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nitroglycerin and any potential adverse effects on breastfed child from nitroglycerin or from underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Glyceryl trinitrate IV, IV Nitroglycerin (nitroglycerin IV)
Mechanism of action
Organic nitrate which causes systemic venodilation, decreasing preload
Cellular mechanism: enters vascular smooth muscle and is converted to nitric oxide (NO) which induces synthesis of cGMP and vasodilation
Relaxes smooth muscle via dose-dependent dilation of arterial and venous beds to reduce both preload and afterload, and myocardial O2 demand
Also improves coronary collateral circulation. Lower BP, increased HR, occasional paradoxical bradycardia
Pharmacokinetics
Half-life: 1-4 min
Onset: 1-3 min
Duration: 3-5 min
Protein bound: 60%
Vd: 3 L/kg
Metabolism: Mainly in liver, extrahepatic sites (vascular wall, RBC)
Metabolites: 1,3-glyceryl dinitrate, 1,2-glyceryl dinitrate, and glyceryl mononitrate (inactive)
Clearance: 5.5-11 L/min
Excretion: Urine
Dialyzable: No
Administration
IV Compatibilities
Additive: aminophylline, dobutamine, dopamine, furosemide, lidocaine, verapamiL
Syringe: heparin
Y-site: amiodarone, diltiazem, dobutamine, dopamine, famotidine, lidocaine, pancuronium, ranitidine, sodium nitroprusside, streptokinase, tacrolimus, vecuronium
IV Incompatibilities
Additive: hydralazine, phenytoin
Syringe: caffeine
Y-site: alteplase, hydralazine
IV Preparation
Solution: 50 mg in 250 mL (200 mcg/mL) D5W or Ns
IV Administration
3 mL/hr (10 mcg/min)
Only use glass IV bottles and administration sets