Nitrolingual

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Nitrolingual

Classes

Nitrites and Nitrates, Plain
Peripheral Vasodilators, Plain
Topical Anti-hemorrhoidals

Administration

NOTE: May need to use nitrate-free interval of 10 to 12 hours/day to avoid development of drug tolerance. When nitrates are to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina.
 

Oral Administration Oral Solid Formulations

Extended-release capsules and tablets: Administer with a full glass of water 1 to 2 hours after meals. Nitroglycerin capsules and tablets should be swallowed whole and should not be chewed or crushed.
Sublingual tablets: Place tablet under the tongue or in the buccal pouch and allow to dissolve. Do not swallow sublingual (intrabuccal) tablets. Avoid eating, drinking, or smoking until tablet is dissolved. A small sip of water prior to placing the tablet under the tongue may help patients with xerostomia maintain mucosal hydration and aid dissolution of the tablet.
Extended-release buccal (transmucosal) tablets: NOTE: This drug is discontinued in the U.S. Place tablet on the oral mucosa between the lip and gum above the upper incisors or between the cheek and gum. Do not place under the tongue. Do not chew or swallow; allow to dissolve undisturbed. The rate of dissolution may be increased by touching the tablet with the tongue or drinking hot liquids.

Other Oral Formulations

Lingual spray or aerosol
For first time use, spray must be primed; follow package instructions for priming. If the product has not been used for more than 6 weeks, prime with 1 or 2 test sprays before use.
Do not shake canister prior to use; shaking may produce bubbles within the canister which alters delivery of nitroglycerin.
Administer by holding the canister upright with the valve head uppermost and the spray orifice as close to the opened mouth as possible. To release a spray, the valve head is pressed with the forefinger. Spray onto or under the tongue and immediately close the mouth. Do not swallow immediately after the dose is administered. Do not spit out or rinse mouth for 5 to 10 minutes following administration. Avoid inhalation of the spray.
Instruct patient to monitor the liquid line in the container and replace container when necessary.
Sublingual powder
Hold the packet upright with the notch and red arrow line at the top of the packet.
Tap the bottom of the packet so the powder settles at the bottom.
Hold the packet at the notch and hold as close to mouth as possible. Tear along the red arrow line.
Lift up tongue. Empty the contents of a packet under the tongue, close mouth and breathe normally.
Allow powder to dissolve without swallowing. Do not rinse or spit for 5 minutes after dosing.
If possible, administer at rest, in the sitting position.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Significant adsorption (80% of the nitroglycerin in solution) occurs with standard infusion sets made of PVC plastic. Use glass bottles only and special tubing provided by the manufacturer.
 
Continuous IV Infusion
Dilute in 5% Dextrose Injection or 0.9% Sodium Chloride Injection to a final concentration of 200 to 400 mcg/mL depending on patient's fluid status. A common dilution is 50 mg in 250 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection. The solution is stable for 48 hours at room temperature.
ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 200 mcg/mL.[64020]
Infuse IV using a controlled-infusion device. Titrate rate according to patient response.

Topical Administration Cream/Ointment/Lotion Formulations

Topical (2%) ointment for the treatment of angina
Use dose-measuring application papers. Squeeze appropriate amount of nitroglycerin ointment onto the paper and use the paper to spread onto nonhairy area of skin (chest, abdomen, thighs) in a thin layer, covering a 2- to 3-inch area. Avoid applying to distal extremities.
Do not allow ointment to come in contact with the hands.
To avoid increased absorption and interference with sustained action, do not massage or rub in ointment.

Transdermal Patch Formulations

Apply nitroglycerin patch to any hairless site. Avoid applying to distal extremities or areas with cuts or calluses. Use firm pressure over patch to ensure contact with skin, especially around edges. If patch becomes loose or falls off, replace with another one.
Do not cut or trim patch. Do not alternate between brands because dosages may not be equivalent.
Patches are waterproof and should not be affected by showering or bathing.
Patches must be removed prior to cardioversion or defibrillation to prevent burns to the patient.

Rectal Administration

Rectal (0.4%) ointment for the treatment of pain associated with chronic anal fissures (Rectiv)
Cover finger with plastic-wrap, disposable surgical glove, or finger cot.
Lay covered finger alongside the 1-inch dosing line illustration on the product carton.
Squeeze tube until a line of ointment, equal in length to the 1-inch dosing line, is expressed onto the covered finger. Take care to ensure ointment does not come into contact with the hands.
Insert the covered finger, no further than the first finger joint, gently into the anal canal and gently apply ointment around the side of the anal canal.
If pain prohibits finger insertion into the anal canal, the ointment may be applied directly to the outside of the anus.
Wash hands thoroughly after the application process.[45135]

Extemporaneous Compounding-Rectal

Low-strength (0.2%) rectal ointment
NOTE: The extemporaneous preparation of rectal nitroglycerin ointment is not FDA-approved.
To prepare 0.2% rectal ointment, compound 15 g of 2% nitroglycerin ointment with 135 g of Aquaphor.

Adverse Reactions
Severe

bradycardia / Rapid / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
methemoglobinemia / Early / Incidence not known
cyanosis / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known

Moderate

hypotension / Rapid / 4.0-4.0
orthostatic hypotension / Delayed / 4.0-4.0
angina / Early / 2.0-2.0
dyspnea / Early / 0-2.0
peripheral edema / Delayed / 0-2.0
peripheral vasodilation / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypertension / Early / Incidence not known
palpitations / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
tolerance / Delayed / Incidence not known
physiological dependence / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypoxia / Early / Incidence not known
blurred vision / Early / Incidence not known

Mild

headache / Early / 50.0-64.0
nausea / Early / 1.0-10.0
vertigo / Early / 6.0-6.0
dizziness / Early / 5.0-5.0
syncope / Early / 4.0-4.0
abdominal pain / Early / 0-2.0
rhinitis / Early / 0-2.0
pharyngitis / Delayed / 0-2.0
asthenia / Delayed / 0-2.0
vomiting / Early / 0-1.0
paresthesias / Delayed / 2.0
pallor / Early / Incidence not known
weakness / Early / Incidence not known
diaphoresis / Early / Incidence not known
restlessness / Early / Incidence not known
skin irritation / Early / Incidence not known
rash / Early / Incidence not known
flushing / Rapid / Incidence not known
xerostomia / Early / Incidence not known

Common Brand Names

Deponit, GONITRO, Minitran, Nitrek, Nitro Bid, Nitro-Dur, Nitro-Time, Nitrodisc, Nitrolingual, NitroMist, Nitroquick, Nitrostat, Nitrotab, RECTIV, Transdermal-NTG, Tridil

Dea Class

Rx

Description

Organic nitrate vasodilator; available in many dosage forms.
Used for angina, HTN, CHF, AMI, hypertensive emergency, hypotension induction during surgery, and used in a rectal ointment for pain associated with chronic anal fissures.
Chronic use may be associated with nitrate tolerance.

Dosage And Indications
For the treatment of angina pectoris due to coronary artery disease. For acute angina pectoris prophylaxis or general treatment of acute angina pectoris. Sublingual dosage (tablets) Adults

300 to 600 mcg SL 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat dose every 5 minutes as needed. No more than 3 tablets are recommended in a 15-minute period. If chest pain persists after 3 tablets in a 15-minute period, prompt medical attention should be sought.

Sublingual dosage (powder) Adults

400 or 800 mcg SL 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat 400 mcg every 5 minutes as needed. No more than 1,200 mcg is recommended in a 15-minute period. If chest pain persists after 1,200 mcg in a 15-minute period, prompt medical attention should be sought.

Sublingual or Translingual dosage (spray) Adults

400 or 800 mcg on or under the tongue 5 to 10 minutes before participating in activities that may precipitate an acute attack or at the onset of an attack; may repeat 400 mcg every 5 minutes as needed. No more than 1,200 mcg is recommended in a 15-minute period. If chest pain persists after 1,200 mcg in a 15-minute period, prompt medical attention should be sought. 

For the treatment of chronic angina pectoris.
NOTE: A nitrate-free interval is necessary to avoid the development of drug tolerance; although a minimum interval has not been clearly established, 10 to 12 hours/day has been sufficient with other nitroglycerin formulations.
Oral dosage (extended-release capsules) Adults

2.5 to 6.5 mg PO 3 to 4 times daily, initially. Adjust dose based on symptoms and adverse effects. Up to 26 mg PO 4 times daily has been used.

Topical dosage (2% ointment) Adults

7.5 mg (0.5 inch) topically twice daily every 6 hours, initially. May double dose in persons tolerating but failing to respond. Max: 30 mg/dose.

Transdermal dosage (patch) Adults

0.2 to 0.4 mg/hour transdermally for 12 to 14 hours daily with a 10 to 12 hours daily patch-off period, initially. Adjust dose based on symptoms and adverse effects. Dose range: 0.1 to 0.8 mg/hour.

For the treatment of acute angina pectoris during suspected or confirmed acute coronary syndrome. Sublingual dosage (tablets, powder, or spray) Adults

300 to 400 mcg SL every 5 minutes for up to 3 doses; if pain persists, evaluate the need for intravenous nitroglycerin if no contraindication exists.

For the treatment of moderate to severe pain associated with chronic anal fissures. Intra-Anal dosage (0.4% rectal ointment) Adults

1.5 mg (1 inch) intra-anally every 12 hours for up to 3 weeks. Guidelines recommend topical calcium channel blockers as initial treatment due to higher expected healing rates and a lower incidence for headache vs. topical nitrates.

Intra-Anal dosage (0.2% rectal ointment)†

NOTE: Requires extemporaneous compounding using 2% topical ointment.

Adults

1 to 2.4 mg intra-anally every 12 hours for up to 8 weeks. Guidelines recommend topical calcium channel blockers as initial treatment due to higher expected healing rates and a lower incidence for headache vs. topical nitrates.

For controlled hypotension induction during anesthesia; for the treatment of acute congestive heart failure or pulmonary edema, acute angina pectoris or unstable angina, acute myocardial infarction, or acute pulmonary hypertension†; or for treatment of severe hypertension, postoperative hypertension, perioperative hypertension (e.g., during cardiac surgery), or hypertensive emergency. Intravenous dosage Adults

5 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Usual dose range: 5 to 100 mcg/minute. Max: 200 mcg/minute.[50004] [55688] [58787] [61121] Heart failure guidelines suggest nitroglycerin as an adjuvant to diuretics for relief of dyspnea in patients with acutely decompensated heart failure if symptomatic hypotension is absent.[57101] [62661]

Adolescents

5 to 10 mcg/minute continuous IV infusion, initially. Titrate by 5 mcg/minute every 3 to 5 minutes to clinical response, or a dose of 20 mcg/minute. May further titrate by 10 mcg/minute, and if the desired effect is still not achieved, by 20 mcg/minute. Max titration: 20 mcg/minute every 3 to 5 minutes. Max: 200 mcg/minute.

Infants and Children

0.25 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 1 mcg/kg/minute IV every 15 to 20 minutes to clinical response. Usual dose range: 1 to 5 mcg/kg/minute. Usual Max: 10 mcg/kg/minute; however, rates up to 20 mcg/kg/minute have been used.

For use as a uterine relaxant to aid in extraction of a retained placenta†. Intravenous dosage Adult females

Limited data indicate that initial doses of 50—100 mcg IV bolus may be effective, with repeat doses of up to a total of 200 mcg IV necessary in some patients; higher initial doses of up to 500 mcg IV have also been used successfully. A dose of 1850 mcg IV (administered as 50 mcg, 100 mcg, 200 mcg, and three 500 mcg IV boluses) was required in one patient for successful placental delivery. To minimize hypotension, all women should have a rapidly running IV infusion concurrently. Hemodynamic monitoring and immediate access to ephedrine should be considered. Thirty patients with retained placenta (i.e., placenta was retained 30 minutes after infant birth) were administered nitroglycerin 50 mcg IV. All patients received 500 mL IV bolus of a crystalloid solution prior to nitroglycerin administration. If the uterus was sufficiently relaxed 2 minutes after the dose of nitroglycerin, the placenta was delivered; otherwise, 50 mcg of nitroglycerin IV bolus was administered every 2 minutes thereafter as needed, up to a maximum dosage of 200 mcg. Eight patients delivered the placenta after 50 mcg, 10 patients delivered after 100 mcg, 8 patients delivered after 150 mcg, and 4 patients required 200 mcg for delivery. The average duration of the procedure was 5.3 minutes (range 4—8.5 minutes). Systolic and diastolic blood pressure decreases were statistically, but not clinically, significant. No complications were reported; 5 patients reported headaches. In another series of 33 patients, doses of 50—200 mcg IV were required for placenta delivery; all of the placentas were delivered within 4 minutes.

Sublingual dosage Adult females

Limited data indicate that 1 mg sublingually given sequentially after oxytocin may be effective. Administration of a rapidly running IV infusion may be prudent to minimize decreases in blood pressure. Hemodynamic monitoring and immediate access to ephedrine should be considered. A randomized, placebo-controlled trial of 24 women who had not delivered the placenta 40 minutes after infant delivery compared the effects of SL nitroglycerin 1 mg to placebo (n = 12 for both groups). Prior to randomization, all women received a total of 15 units of oxytocin (5 units within minutes of delivery of the infant and 10 units 30 minutes later if the placenta had not yet been delivered); controlled cord extraction was performed 5 minutes after each dose of oxytocin. If these procedures were ineffective, nitroglycerin 1 mg SL or placebo was administered to the patient followed by controlled cord traction 5 minutes later. A rapidly running IV infusion was administered to all women, and all women were monitored for hemodynamic changes. All 12 patients that received nitroglycerin had successful delivery of the placenta within 5 minutes of controlled cord traction compared with only 1 patient in the placebo group (p < 0.0001). In the women with unsuccessful placental delivery, regional or general anesthesia was required. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly decreased in the group of women receiving nitroglycerin (119 mm Hg vs. 113 mm Hg for SBP, p = 0.003; 76 mm Hg vs. 71 mm Hg for DBP, p = 0.001), although clinically important hypotension was not reported; changes in pulse were not statistically significant. Headache was reported in 4 of the women that received nitroglycerin and 1 woman that received placebo; all headaches resolved spontaneously within 2 hours of drug administration.

For the treatment of extravasation† of vasoactive medications. Topical dosage Adults

1 inch applied topically to the area of extravasation. Topical nitroglycerin has been used in combination with phentolamine for peripheral intravenous access extravasation of norepinephrine and dopamine. Topical nitroglycerin with or without concomitant terbutaline has also been used after accidental digital epinephrine self-injection with commercially available auto-injectors.

For the treatment of acute variceal bleeding† in combination with vasopressin. Intravenous dosage Adults

40 mcg/minute continuous IV infusion, initially. Adjust dose to maintain systolic blood pressure of 90 mmHg. Max: 400 mcg/minute. Usual duration: 24 hours. Always use in combination with IV vasopressin.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
 
Intermittent hemodialysis
No data are available.

Drug Interactions

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Acetaminophen; Aspirin: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Codeine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Hydrocodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Acetaminophen; Oxycodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Acetaminophen; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Acetazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Alfentanil: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Alfuzosin: (Moderate) The manufacturer of alfuzosin warns that concurrent use with nitrates has the potential to cause hypotension, orthostatic hypotension, or syncope. Caution is advisable when coadministering alfuzosin and a nitrate to patients with symptomatic hypotension or those who have had a previous hypotensive response to either agent.
Alpha-blockers: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Alprazolam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Alteplase: (Major) Two separate studies have shown that concomitant administration of IV nitroglycerin can compromise the therapeutic efficacy of alteplase. In one study, reperfusion occurred in 91% of patients receiving alteplase without nitroglycerin while only 44% of patients receiving alteplase with nitroglycerin were reperfused, however this was an uncontrolled study. In another controlled study, patients who did not receive concomitant IV nitroglycerin reperfused faster, more often, and had fewer reocclusions. It appears that when combined in vitro, nitroglycerin enhances the degradation of alteplase. Nitroglycerin may enhance the hepatic clearance of alteplase since alteplase plasma concentrations are lower in patients receiving concomitant nitroglycerin.
Amitriptyline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Amoxapine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as heterocyclic antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with these antidepressants.
Amphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Amphetamine; Dextroamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Angiotensin II receptor antagonists: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Apomorphine: (Major) Coadministration of apomorphine and nitrates can cause large decreases in blood pressure. The effect is especially of concern with use of sublingual nitroglycerin products. Instruct patients to lie down before taking a sublingual nitroglycerin dose and to remain supine for at least 45 minutes after to reduce orthostatic risk. In one evaluation, the largest mean decreases in standing systolic and diastolic blood pressure during use of apomorphine and sublingual nitroglycerin were 14.3 mmHg and 13.5 mmHg, respectively. The largest recorded decreases in standing systolic and diastolic blood pressures were 65 mmHg and 43 mmHg during use of apomorphine and sublingual nitroglycerin together.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Aspirin, ASA: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Caffeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Carisoprodol: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Dipyridamole: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Omeprazole: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised.
Aspirin, ASA; Oxycodone: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Atomoxetine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Belladonna; Opium: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Benzalkonium Chloride; Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzhydrocodone; Acetaminophen: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Benzocaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzocaine; Butamben; Tetracaine: (Moderate) Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Nitrates may also induce methemoglobin formation that will be additive to that formed by benzocaine products. Therefore, caution is warranted when combining nitrate medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure.
Benzodiazepines: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Benzphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Beta-adrenergic blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupropion: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Bupropion; Naltrexone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Butalbital; Acetaminophen; Caffeine; Codeine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Cabergoline: (Moderate) Cabergoline should be used cautiously with drugs that can lower blood pressure, including systemic nitrates. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium-channel blockers: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Carbonic anhydrase inhibitors: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Celecoxib; Tramadol: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlordiazepoxide: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Chlordiazepoxide; Clidinium: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Chloroprocaine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chlorpheniramine; Codeine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Chlorpheniramine; Hydrocodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Chlorpromazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Citalopram: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Clomipramine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Clonazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Clorazepate: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Codeine; Guaifenesin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Codeine; Phenylephrine; Promethazine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Codeine; Promethazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Dapsone: (Moderate) Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Desipramine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dexmethylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextroamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Bupropion: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dextromethorphan; Quinidine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as quinidine. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with quinidine.
Diazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Diazoxide: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Diethylpropion: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dihydroergotamine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dobutamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Dopamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Doxapram: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Doxepin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Duloxetine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Ephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Ephedrine; Guaifenesin: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Epinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Eplerenone: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Epoprostenol: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Ergoloid Mesylates: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergot alkaloids: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergotamine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Ergotamine; Caffeine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Escitalopram: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Estazolam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Ethanol: (Major) Alcohol may increase the frequency of nitroglycerin-related adverse effects including lightheadedness on standing, especially just after rising from a recumbent or seated position. The vasodilating effects of nitroglycerin may also be additive with those of alcohol.
Fenoldopam: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Fentanyl: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Fluoxetine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Fluphenazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Flurazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Fluvoxamine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Guaifenesin; Hydrocodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Guaifenesin; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Heparin: (Minor) At high doses, nitroglycerin may interfere with the anticoagulant effect of heparin. Intravenous nitroglycerin can induce heparin resistance. Monitor for lack of heparin efficacy if these drugs are administered concurrently. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Heterocyclic antidepressants: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as heterocyclic antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with these antidepressants.
Homatropine; Hydrocodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Hydralazine: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant hydralazine and nitrate use due to risk for additive hypotension.
Hydrocodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Hydrocodone; Ibuprofen: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Hydrocodone; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Hydromorphone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Ibuprofen; Oxycodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Iloprost: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Imipramine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Isocarboxazid: (Moderate) Monitor blood pressure during concomitant monoamine oxidase inhibitor (MAOI) and nitrate use due to risk for additive hypotension.
Isoproterenol: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Levorphanol: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lisdexamfetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Lorazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Mannitol: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Maprotiline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as heterocyclic antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with these antidepressants.
Mecamylamine: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Meperidine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metformin; Rosiglitazone: (Major) The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
Methadone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Methamphetamine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Methazolamide: (Moderate) Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
Methylergonovine: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Methylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Midazolam: (Minor) Nitrog

lycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Midodrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Minoxidil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure during concomitant monoamine oxidase inhibitor (MAOI) and nitrate use due to risk for additive hypotension.
Morphine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Morphine; Naltrexone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Nefazodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
Nitroprusside: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Norepinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Nortriptyline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Olanzapine; Fluoxetine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Oliceridine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Opiate Agonists: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Oxazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Oxycodone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Oxymorphone: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension and enhance the orthostatic effects of nitrates. Orthostatic vital signs should be monitored in patients receiving paliperidone and nitrates who are susceptible to hypotension.
Paroxetine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Perphenazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Perphenazine; Amitriptyline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Phendimetrazine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phenelzine: (Moderate) Monitor blood pressure during concomitant monoamine oxidase inhibitor (MAOI) and nitrate use due to risk for additive hypotension.
Phenothiazines: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Phentermine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phentermine; Topiramate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Phosphodiesterase inhibitors: (Contraindicated) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction. Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant potassium-sparing diuretic and nitrate use due to risk for additive hypotension.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Procainamide: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as procainamide.
Prochlorperazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Promethazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Promethazine; Dextromethorphan: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Promethazine; Phenylephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Protriptyline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Pseudoephedrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Quazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Quinidine: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as quinidine. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with quinidine.
Racepinephrine: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Remifentanil: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Remimazolam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Riociguat: (Contraindicated) Coadministration of riociguat and nitrates or nitric oxide donors (e.g., amyl nitrite) is contraindicated due to the risk of hypotension. The blood pressure lowering effect of sublingual nitroglycerin was potentiated when administered 4 and 8 hours after riociguat. Syncope was reported in some patients.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rosiglitazone: (Major) The concomitant use of nitrates with rosiglitazone is not recommended. An increased risk of myocardial ischemia was observed in a subset of patients receiving nitrates with rosiglitazone. Most patients that were using nitrates had preexisting coronary artery disease. In patients with coronary artery disease that were not on nitrates, rosiglitazone therapy did not increase the risk of myocardial ischemia.
Selective serotonin reuptake inhibitors: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Sertraline: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent nitrates. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sufentanil: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Sympathomimetics: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present.
Tapentadol: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Temazepam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents or rapid-onset vasodilators, such as nitrates.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant thiazide diuretic and nitrate use due to risk for additive hypotension.
Thioridazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Tramadol: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Tramadol; Acetaminophen: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists.
Tranylcypromine: (Moderate) Monitor blood pressure during concomitant monoamine oxidase inhibitor (MAOI) and nitrate use due to risk for additive hypotension.
Treprostinil: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Triazolam: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Tricyclic antidepressants: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Trifluoperazine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as phenothiazines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with phenothiazines.
Trimipramine: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.

How Supplied

Deponit/Minitran/Nitrek/Nitrodisc/Nitro-Dur/Nitroglycerin/Transdermal-NTG Percutaneous Film ER: 0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.6mg, 0.8mg, 1h
Deponit/Minitran/Nitrek/Nitrodisc/Nitro-Dur/Nitroglycerin/Transdermal-NTG Topical Film ER: 0.2mg, 0.4mg, 1h
Deponit/Minitran/Nitrek/Nitrodisc/Nitro-Dur/Nitroglycerin/Transdermal-NTG Transdermal Film ER: 0.1mg, 0.2mg, 0.4mg, 0.6mg, 1h
GONITRO Sublingual Pwd: 400mcg
Nitro Bid Topical Ointment: 2%
Nitroglycerin/Nitroglycerin, Dextrose/Tridil Intravenous Inj Sol: 1mL, 5mg, 100-5%, 200-5%, 400-5%
Nitroglycerin/Nitrolingual/NitroMist Sublingual Spray Met: 0.4mg, 1actuation
Nitroglycerin/Nitroquick/Nitrostat/Nitrotab Buccal Tablet, SL: 0.3mg, 0.4mg, 0.6mg
Nitroglycerin/Nitroquick/Nitrostat/Nitrotab Sublingual Tablet, SL: 0.3mg, 0.4mg, 0.6mg
Nitroglycerin/Nitro-Time Oral Cap ER: 2.5mg, 6.5mg, 9mg
RECTIV Intra-Anal Ointment: 0.4%

Maximum Dosage
Adults

The maximum dosage is dependent on route of administration and indication for therapy.

Geriatric

The maximum dosage is dependent on route of administration and indication for therapy.

Adolescents

The maximum dosage is dependent on route of administration and indication for therapy; safety and efficacy of the 0.4% rectal ointment have not been established.

Children

The usual maximum rate is 5 mcg/kg/min; however, IV rates up to 20 mcg/kg/min have been used. Safety and efficacy of the 0.4% rectal ointment have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Similar to other nitrites and organic nitrates, nitroglycerin is converted to nitric oxide (NO), a reactive free radical. Nitric oxide, the active intermediate compound common to all agents of this class, activates the enzyme guanylate cyclase, thereby stimulating the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP). This second messenger then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber and the subsequent release, or extrusion, of calcium ions. The contractile state of smooth muscle is normally maintained by a phosphorylated myosin light chain (stimulated by an increase in calcium ions). Thus, the nitrite- or nitrate-induced dephosphorylation of the myosin light chain signals the cell to release calcium, thereby relaxing the smooth muscle cells and producing vasodilation.
 
It is believed that nitrates correct myocardial oxygen imbalances by reducing systemic and pulmonary arterial pressure (afterload) and decreasing cardiac output secondary to peripheral dilation rather than coronary artery dilation. Nitrates therefore relax peripheral venous vessels, causing a pooling of venous blood and decreased venous return to the heart, which decreases preload. Nitrates reduce both arterial impedance and venous filling pressures, resulting in a reduction of the left ventricular systolic wall tension, which decreases afterload. Thus, nitrate-induced vasodilation increases venous capacitance and decreases arteriole resistance, thereby reducing both the preload and afterload, and lowering the cardiac oxygen demand.
 
Total coronary blood flow can be increased by nitrites and nitrates in patients with normal hearts, but in patients with ischemia, nitroglycerin does not increase total coronary blood flow but simply redistributes blood to ischemic areas. This effect is believed to be due to the drug's preferential dilation of the larger conductive vessels of the coronary circulation, which, in the presence of coronary atherosclerosis, redirects the distribution of the coronary blood supply to ischemic areas.
 
Nitrates cause a transient compensatory increase in heart rate and myocardial contractility that normally would increase myocardial oxygen consumption, yet the nitrate-induced decrease in ventricular wall tension results in a net decrease in myocardial oxygen demand and amelioration of the pain of angina pectoris. In addition, nitroglycerin relaxes all other types of smooth muscle including bronchial, biliary, GI, ureteral, and uterine. Following intra-anal administration of the 0.4% rectal ointment, nitroglycerin reduces anal sphincter tone resulting in decreased resting intra-anal pressure. Nitrites and nitrates are functional antagonists of acetylcholine, norepinephrine, and histamine.
 
In individuals who have minimal reflex tachycardia, syncope can result from the decrease in blood pressure that occurs following higher doses of nitrates and nitrites. Although this is not likely to occur with doses of nitrates that do not cause blood pressure reduction, patients should be sitting or lying down during and immediately after administration of several dosage forms of nitroglycerin.
 
The antihypertensive actions of nitroglycerin are secondary to pharmacologic properties that make it an effective antianginal agent but are primarily a result of its peripheral vasodilatory effects. With the exception of greater vascular (venous) specificity and the greater variety of pharmaceutical preparations available, nitroglycerin (NTG) is similar to nitroprusside in many respects. Both agents are capable of producing venous (more so with NTG) and arterial dilation, with beneficial effects on redistribution of myocardial blood flow.

Pharmacokinetics

Nitroglycerin can be administered by the oral, lingual (spray), sublingual, intrabuccal, topical (transdermal), rectal, or intravenous routes. Irrespective of the route of administration, organic nitrates are virtually completely metabolized by the enzyme glutathione-organic nitrate reductase, so the systemic or presystemic hepatic biotransformation is the key determinant of the bioavailability and duration of action of the various preparations. Nitroglycerin distributes widely throughout the body tissues and is approximately 60% plasma protein-bound. The metabolites of nitroglycerin, 1,3- and 1,2-glyceryl dinitrate, are much less potent than the parent compound and have a half-life of approximately 40 minutes, compared to a parent half-life of 1 to 3 minutes. The metabolites are excreted by the kidneys.

Oral Route

Nitroglycerin is well absorbed across the oral mucosa and following systemic oral administration. The sublingual absorption of nitroglycerin is higher following the administration of sublingual powder compared to sublingual spray. The onset of action for each nitroglycerin preparation is as follows: translingual, 2 to 4 minutes; extended-release capsules and tablets, 20 to 45 minutes; sublingual, 1 to 3 minutes; transmucosal (buccal) extended-release tablets, 2 to 3 minutes. Duration of action is as follows: translingual, 30 to 60 minutes; extended-release capsules and tablets, 8 to 12 hours; sublingual, 30 minutes; transmucosal (buccal) extended-release, 5 hours.

Intravenous Route

The onset of action for nitroglycerin is immediate after IV administration. Duration of action is several minutes (dose-dependent) after IV administration.

Topical Route

Nitroglycerin is well absorbed transdermally. The onset of action for each nitroglycerin preparation is as follows: ointment, 20 to 60 minutes; and transdermal, 40 to 60 minutes. Duration of action is as follows: ointment, 4 to 8 hours; and transdermal, 18 to 24 hours.

Other Route(s)

Rectal Route
Following intra-anal administration of 0.4% nitroglycerin rectal ointment to 6 healthy subjects, the average absolute bioavailability was approximately 50% of the administered dose.

Pregnancy And Lactation
Pregnancy

There are insufficient data regarding the use of nitroglycerin during pregnancy to determine a drug-associated risk of major birth defects or miscarriage. No adverse developmental effects were observed during animal reproduction studies when nitroglycerin was administered intravenously to rabbits or intraperitoneally to rats during organogenesis at doses greater than 64 times the human dose. Nitroglycerin should be given to a pregnant woman only if clearly needed.

It is not known if nitroglycerin is present in human breast milk or if nitroglycerin has effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition.