nitroglycerin IV (glyceryl trinitrate IV, IV Nitroglycerin, NitroBid IV, NTG, Tridil)

Dosing and uses of Glyceryl trinitrate IV, IV Nitroglycerin (nitroglycerin IV)

• Adult
• Pediatric

 

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