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  • CLASSES

    Nitrites and Nitrates, Plain
    Topical Anti-hemorrhoidals

    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.

    COMMON BRAND NAMES

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

    HOW SUPPLIED

    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
    Minitran/Nitro-Dur Percutaneous Film ER: 0.1mg, 0.2mg, 0.3mg, 0.4mg, 0.6mg, 0.8mg, 1h
    Nitro Bid Topical Ointment: 2%
    Nitroglycerin/Nitroglycerin, Dextrose/Nitronal/Tridil Intravenous Inj Sol: 1mL, 1mg, 5mg, 100-5%, 200-5%, 400-5%
    Nitroglycerin/Nitrolingual Sublingual Spray Met: 0.4mg, 1actuation
    Nitroglycerin/Nitrolingual/NitroMist Sublingual Aer 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%

    DOSAGE & INDICATIONS

    For the treatment of angina.
    For acute angina pectoris or for acute angina pectoris prophylaxis (i.e., situations likely to provoke an anginal attack).
    Sublingual dosage
    Adults

    1 tablet (300 mcg, 400 mcg, or 600 mcg) SL, dissolved under the tongue or in buccal pouch at the onset of an attack; may repeat with 1 tablet every 5 minutes as needed. No more than 3 tablets are recommended in a 15-minute period. During drug administration, the patient should rest, preferably in the sitting position. If chest pain persists after 3 tablets, prompt medical attention should be sought. Sublingual nitroglycerin tablets may be used prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack. Clinical practice guidelines for ST-elevation myocardial infarction (STEMI) management recommend advising a patient with suspected acute coronary syndromes (ACS) with a prior prescription for nitroglycerin to call 911 immediately if symptoms are persistent or worsened 5 minutes after 1 dose of nitroglycerin. Clinical practice guidelines for NSTEMI-ACS suggest use of up to 400 mcg nitroglycerin SL every 5 minutes for up to 3 doses for patients in early hospital care with continuing ischemic pain followed by an assessment for need for intravenous nitroglycerin.

    Lingual Spray or Aerosol (e.g., Nitrolingual, NitroMist)
    Adults

    400 or 800 mcg (1 or 2 metered spray doses) on or under the tongue at the onset of an attack; may repeat with 400 mcg (1 spray) every 5 minutes as needed. No more than 1200 mcg (3 sprays) is recommended during a 15-minute period. If chest pain persists after a total of 3 sprays, prompt medical attention should be sought. Lingual nitroglycerin spray may be used prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack. Clinical practice guidelines for ST-elevation myocardial infarction (STEMI) management recommend advising a patient with suspected acute coronary syndromes (ACS) with a prior prescription for nitroglycerin to call 911 immediately if symptoms are persistent or worsened 5 minutes after 1 dose of nitroglycerin. Clinical practice guidelines for NSTEMI-ACS suggest use of up to 400 mcg nitroglycerin SL every 5 minutes for up to 3 doses for patients in early hospital care with continuing ischemic pain followed by an assessment for need for intravenous nitroglycerin.

    Sublingual powder
    Adults

    400 or 800 mcg (1 or 2 packets) SL at the onset of an attack; may repeat 400 mcg (1 packet) every 5 minutes as needed. No more than 1200 mcg (3 packets) is recommended during a 15-minute period. If chest pain persists after a total of 3 packets, prompt medical attention should be sought. Sublingual nitroglycerin powder may be used prophylactically 5 to 10 minutes before participating in activities that may precipitate an acute attack. Clinical practice guidelines for ST-elevation myocardial infarction (STEMI) management recommend advising a patient with suspected acute coronary syndromes (ACS) with a prior prescription for nitroglycerin to call 911 immediately if symptoms are persistent or worsened 5 minutes after 1 dose of nitroglycerin. Clinical practice guidelines for NSTEMI-ACS suggest use of up to 400 mcg nitroglycerin SL every 5 minutes for up to 3 doses for patients in early hospital care with continuing ischemic pain followed by an assessment for need for intravenous nitroglycerin.

    For 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; titrate to clinical response and adverse reactions as needed.

    Transmucosal dosage (extended-release buccal tablets)
    Adults

    NOTE: This drug is discontinued in the United States. 1 mg inserted transmucosally, (under the upper lip and dissolved in place) every 5 hours (during the waking hours). May increase dosage frequency and/or strength (1, 2, or 3 mg) if needed.

    Topical dosage (2% ointment)
    Adults

    15 to 30 mg (2.5 to 5 cm as squeezed from the tube, about 1 to 2 inches), applied topically to the skin every 8 hours while awake and at bedtime; frequency of application may be increased to every 6 hours if needed. Alternatively, a regimen providing a 12-hour nitrate-free interval may be used; apply dosage once each morning, then reapply 6 hours later. The maximum daily dosage is 75 mg (12.5 cm as squeezed from the tube). The ointment is applied in a thin layer covering approximately 2 to 3 inches of skin, but should not be massaged into the skin.

    Transdermal dosage
    Adults

    1 transdermal patch (0.1 to 0.8 mg/hour), applied topically to intact skin, every 24 hours. Initially, the smallest dosing amount should be used; increase the dosage as necessary. To prevent tolerance, leave the patch on 12 to 14 hours, then remove for 10 to 12 hours prior to applying the next patch. This allows for a drug-free interval, which may prevent nitrate tolerance and/or attenuation of anti-anginal effects.

    For the treatment of pain associated with anal fissures.
    For the treatment of pain associated with anal fissures† and hemorrhoids†.
    Topical rectal area dosage† (0.2% topical formulation†; investigational, requires compounding)
    Adults

    In one study, 0.2% nitroglycerin ointment administered topically to the anus and anal canal twice daily for 6 weeks resulted in anal fissure healing in 15 of 25 (60%) patients. This topical ointment requires extemporaneous compounding. The initial NDA for Cellegesic (previously known as Anogesic) was reviewed by the FDA for its use in the treatment of anal fissures and hemorrhoids; however, the FDA requested further data. Upon reevaluation of phase III data from a third trial, the FDA issued a "not approvable" letter in December 2004. Nitroglycerin relaxes the internal sphincter muscle and improves blood flow to anal tissues; these actions may promote healing and reduce pain associated with anal fissures.

    Rectal dosage (0.4% rectal ointment)
    Adults

    Apply 1 inch of 0.4% ointment (1.5 mg nitroglycerin) topically to the anal canal or directly to the outside of the anus every 12 hours. Treatment duration may extend for up to 3 weeks. During a 3-week clinical trial, patients with chronic anal fissures who received treatment with 0.4% nitroglycerin ointment every 12 hours experienced less pain (as assessed by change in the visual analog scale rating from baseline at treatment days 14—18) than those patients randomized to receive placebo (95% CI: -13.6 to -0.4 mm).

    For controlled hypotension induction during anesthesia; for IV 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

    Initially, 5 mcg/minute continuous IV infusion. Titrate by 5 mcg/minute IV every 3 to 5 minutes until clinical response, or to a dose of 20 mcg/minute IV. Dosage may then be further increased by increments of 10 mcg/minute, and, if the desired effect is still not achieved, dosage may be increased in increments of 20 mcg/minute. The maximum recommended titration is 20 mcg/minute every 3 to 5 minutes. The effective dosage range is 5 to 100 mcg/minute IV. Higher doses of 200 mcg/minute have been used.

    Adolescents

    5 to 10 mcg/minute continuous IV infusion. Titrate by 5 mcg/minute IV every 3 to 5 minutes until clinical response, or to a dose of 20 mcg/minute IV. Dosage may then be further increased by increments of 10 mcg/minute, and, if the desired effect is still not achieved, dosage may be increased in increments of 20 mcg/minute. The maximum recommended titration is 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. Titrate by 1 mcg/kg/minute IV every 15 to 20 minutes as tolerated. The usual dosage range is 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.

    †Indicates off-label use

    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.

    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.

    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.
    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 nitroglycerin 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.
    Infuse IV using a controlled-infusion device. Titrate rate according to patient response.

    Topical Administration
    Cream/Ointment/Lotion Formulations

    Topical 2% ointment administered 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 non hairy 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 along side 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.

    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.

    STORAGE

    Generic:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Deponit:
    - Avoid excessive humidity
    - Protect from extreme heat
    - Store at room temperature (between 59 to 86 degrees F)
    GONITRO :
    - Store between 68 to 77 degrees F; brief excursions permitted to 104 degrees F
    Minitran:
    - Avoid excessive humidity
    - Avoid exposure to heat
    - Store at room temperature (between 59 to 86 degrees F)
    Nitrek:
    - Avoid excessive humidity
    - Protect from extreme heat
    - Store at room temperature (between 59 to 86 degrees F)
    Nitro Bid:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nitrodisc:
    - Avoid excessive humidity
    - Protect from extreme heat
    - Store at room temperature (between 59 to 86 degrees F)
    Nitro-Dur:
    - Avoid excessive humidity
    - Protect from extreme heat
    - Store at room temperature (between 59 to 86 degrees F)
    Nitrolingual:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    NitroMist :
    - Flammable, keep away from heat and flame
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store below 85 degrees F
    - Store upright
    Nitronal:
    - Protect from freezing
    - Protect from light
    - Store below 77 degrees F
    Nitroquick:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nitrostat:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nitrotab:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nitro-Time:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    RECTIV:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Use within 8 weeks of first opening
    Transdermal-NTG:
    - Avoid excessive humidity
    - Protect from extreme heat
    - Store at room temperature (between 59 to 86 degrees F)
    Tridil:
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Nitrates will amplify the vasodilatory effects of sildenafil or other phosphodiesterase inhibitors (e.g., vardenafil, tadalafil) if coadministered and result in severe hypotension. Coadministration of phosphodiesterase inhibitors with nitroglycerin is considered contraindicated (see Drug Interactions).

    Nitrate hypersensitivity

    Nitroglycerin is contraindicated in patients who have known nitrate hypersensitivity.

    Head trauma, increased intracranial pressure, intracranial bleeding

    Nitroglycerin injection, sublingual powder and tablet, lingual spray, and 0.4% ointment are contraindicated in patients with increased intracranial pressure (e.g., head trauma or intracranial bleeding) because the drug's vasodilatory effect on the meningeal blood vessels could increase cerebrospinal fluid pressure.

    Anemia

    Nitroglycerin sublingual powder and tablet, transmucosal spray, and 0.4% ointment are contraindicated in patients with severe anemia because the drug causes oxidation of hemoglobin to methemoglobin, which could exacerbate anemia.

    Aortic stenosis, cardiac tamponade, cardiomyopathy, constrictive pericarditis, mitral stenosis, shock

    Nitroglycerin sublingual powder and lingual spray are contraindicated in patients with acute circulatory failure or shock. Intravenous nitroglycerin is contraindicated in patients with constrictive pericarditis, restrictive cardiomyopathy, or cardiac tamponade because the drug reduces venous return, decreases preload, and decreases cardiac output, which can be worsened in patients with these conditions. Other nitroglycerin formulations should be administered with caution to patients with these pre-existing cardiovascular conditions. Severe hypotension, particularly with upright posture, may occur even with small doses of nitroglycerin particularly in patients with constrictive pericarditis, aortic stenosis or mitral stenosis, and in patients who may be volume-depleted, or are already hypotensive.

    Acute myocardial infarction, dehydration, hypotension, hypovolemia, orthostatic hypotension

    Nitroglycerin should not be given to patients with uncorrected hypovolemia (or dehydration) due to the risk of inducing profound hypotension. Patients with normal or low pulmonary capillary wedge pressures may be unusually sensitive to the hypotensive effects of nitroglycerin. Nitroglycerin should be used with caution in patients with hypotension or orthostatic hypotension because the drug can worsen hypotension, cause a paradoxical bradycardia, and/or exacerbate angina. Nitrate-induced hypotension has resulted in fatalities. In a controlled setting, such as during surgery, IV nitroglycerin can be used to produce hypotension. Nitrate therapy can worsen angina due to hypertrophic cardiomyopathy. Sublingual nitroglycerin tablets are contraindicated for use in patients with acute myocardial infarction (MI). Use of any formulation of nitroglycerin during the early days of acute MI requires particular attention to hemodynamic monitoring and clinical status. Nitroglycerin should be used cautiously in patients who have had a recent MI because drug-induced hypotension and/or tachycardia can worsen ischemia. To minimize the risks of nitrates following acute MI, nitroglycerin should not be administered to patients with systolic blood pressure < 90 mmHg or >= 30 mmHg below baseline, severe bradycardia (< 50 beats per minute), tachycardia, or suspected right ventricular infarction.

    Geriatric, syncope

    Nitroglycerin should be used with caution in geriatric patients, especially those who are volume-depleted, hypotensive, and/or receiving multiple medications. Elderly patients may be more sensitive to the hypotensive effects of nitrates. Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly, even at therapeutic doses. The elderly are at higher risk for falling due to syncope at therapeutic doses of nitrates. Elderly patients may have reduced baroceptor function; severe orthostatic hypotension may occur when vasodilators such as nitrates are administered. Nitrate therapy can also worsen angina due to hypertrophic cardiomyopathy, particularly in the elderly. Clinical experience with sublingual nitroglycerin for acute anginal relief has not identified differences in responses between the elderly and younger adults. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. According to the Beers Criteria, vasodilators are considered potentially inappropriate medications (PIMs) in older adults and should be used cautiously in this population since vasodilators may exacerbate episodes of syncope in individuals with a history of syncope.

    Hepatic disease

    Nitroglycerin should be used cautiously in patients with hepatic disease because metabolism of the drug can be impaired, resulting in an increased risk of methemoglobinemia.

    Abrupt discontinuation

    When nitroglycerin is to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina.

    Defibrillation (cardioversion), magnetic resonance imaging (MRI)

    Remove nitroglycerin transdermal systems prior to defibrillation (cardioversion). Some nitroglycerin patches contain aluminum, which may result in damage to the paddles or burns to the patient. Additionally, skin burns have been reported at the patch site in several patients wearing an aluminized transdermal system during a magnetic resonance imaging (MRI) scan. It is recommended to remove the patch before undergoing an MRI.

    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 during organogenesis at doses greater than 64 times the human dose. Nitroglycerin should be given to a pregnant woman only if clearly needed.

    Breast-feeding

    It is not known if nitroglycerin is present in human 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 breast-fed child from nitroglycerin or from the underlying maternal condition.

    GI disease

    Extended-release nitroglycerin products should be avoided in patients with GI disease such as hypermotility or malabsorption syndromes. This dosage form may not dissolve and may be excreted intact in these conditions.

    Diabetes mellitus

    Monitor serum glucose in patients with sub-clinical or overt diabetes mellitus when administering intravenous nitroglycerin solutions containing dextrose.

    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 (unspecified) / Early / Incidence not known
    flushing / Rapid / Incidence not known
    xerostomia / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: 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; Butalbital; Caffeine; Codeine: 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; Caffeine; Dihydrocodeine: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Codeine: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Dextromethorphan; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Dichloralphenazone; Isometheptene: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Guaifenesin; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetaminophen; Hydrocodone: 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: 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; Propoxyphene: 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; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Acetazolamide: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Acetylcysteine: Sulfhydryl groups are believed to be important in the response to vasodilator nitrates used in the treatment of ischemic heart disease. The concurrent use of acetylcysteine, a sulfhydryl donor and antioxidant, augments the pharmacologic response to nitrates.
    Acrivastine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Alfentanil: 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: 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: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Alprazolam: 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, tPA: 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.
    Amide local anesthetics: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Amitriptyline: 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.
    Amitriptyline; Chlordiazepoxide: 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. 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.
    Amoxapine: 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.
    Amphetamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Amphetamine; Dextroamphetamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Angiotensin II receptor antagonists: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Angiotensin-converting enzyme inhibitors: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Apomorphine: Parkinson's patients receiving apomorphine may experience orthostatic hypotension, hypotension, and/or syncope. Extreme caution should be exercised if apomorphine is used concurrently with antihypertensive agents, or vasodilators such as nitrates.
    Articaine; Epinephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Aspirin, ASA: 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: 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; Codeine: 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. 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; Caffeine; Dihydrocodeine: 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. 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; Carisoprodol: 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: 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. 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; Dipyridamole: 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: 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: 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. 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; Pravastatin: 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.
    Atomoxetine: 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 Alkaloids; Ergotamine; Phenobarbital: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Belladonna; Opium: 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: 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: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Beta-adrenergic blockers: 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.
    Bosentan: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Bromocriptine: Nitroglycerin can cause hypotension, and bromocriptine can cause hypotension or hypertension. Bromocriptine also is contraindicated in patients with uncontrolled hypertension and should not be used in patients with a history of coronary artery disease or other severe cardiovascular conditions, which are the primary patient populations for which nitroglycerin is utilized. If concomitant use is necessary, blood pressure should be monitored closely.
    Brompheniramine; Carbetapentane; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Brompheniramine; Guaifenesin; Hydrocodone: 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.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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.
    Brompheniramine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Bupivacaine Liposomal: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Bupivacaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Bupivacaine; Lidocaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Bupropion: 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: 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.
    Cabergoline: Avoid the concomitant use of cabergoline and nitroglycerin. Cabergoline may produce hypotension, but is contraindicated in patients with uncontrolled hypertension and in patients with a history of pericardial or cardiac valvular disease, which are patient populations for which nitroglycerin is utilized.
    Caffeine; Ergotamine: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Calcium-channel blockers: 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.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbetapentane; Diphenhydramine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbetapentane; Guaifenesin; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbetapentane; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbetapentane; Phenylephrine; Pyrilamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbetapentane; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbinoxamine; Hydrocodone; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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.
    Carbinoxamine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbinoxamine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Carbonic anhydrase inhibitors: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Central-acting adrenergic agents: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Cetirizine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlophedianol; Guaifenesin; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlordiazepoxide: 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: 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: Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorpheniramine; Codeine: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Dihydrocodeine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Guaifenesin; Hydrocodone; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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: 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; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlorpheniramine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Chlorpromazine: 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: 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: 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: 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: 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.
    Codeine: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Promethazine: 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.
    Desipramine: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dexmethylphenidate: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dextroamphetamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dextromethorphan; Guaifenesin; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dextromethorphan; Quinidine: 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: 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: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Diethylpropion: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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.
    Dihydroergotamine: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Diphenhydramine; Hydrocodone; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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.
    Diphenhydramine; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dobutamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Dopamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Doxepin: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Epinephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Eplerenone: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Epoprostenol: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Ergoloid Mesylates: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Ergonovine: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Ergot alkaloids: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Ergotamine: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Escitalopram: 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: 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: The combination of ethanol and nitroglycerin could theoretically produce additive vasodilation, possibly leading to cardiovascular collapse. Patients receiving nitroglycerin should be advised to use ethanol with caution.
    Fenoldopam: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Fentanyl: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Fluoxetine: 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.
    Fluoxetine; Olanzapine: 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: 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: 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: 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.
    Gallium Ga 68 Dotatate: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Glimepiride; Rosiglitazone: 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.
    Guaifenesin; Hydrocodone: 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; Hydrocodone; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Guaifenesin; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Halothane: General anesthetics can potentiate the hypotensive effects of other antihypertensive agents and nitrates.
    Hawthorn, Crataegus laevigata: Hawthorn, Crataegus laevigata (also known as C. oxycantha) may potentially interact with nitrates. Following hawthorn administration, the cardiac action potential duration is increased and the refractory period is prolonged. Hawthorn may also lower peripheral vascular resistance. Patients with known cardiovascular conditions should be advised to only use hawthorn with their prescribed medications after discussion with their prescriber. Patients who choose to take hawthorn should receive periodic blood pressure and heart rate monitoring.
    Heparin: 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.
    Heterocyclic antidepressants: 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.
    Homatropine; Hydrocodone: 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: Concomitant use of nitrates with antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Hydralazine; Hydrochlorothiazide, HCTZ: Concomitant use of nitrates with antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Hydralazine; Isosorbide Dinitrate, ISDN: Concomitant use of nitrates with antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Hydrocodone: 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: 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; Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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; Potassium Guaiacolsulfonate: 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; Potassium Guaiacolsulfonate; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. 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: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Iloprost: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Imipramine: 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: 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.
    Isoproterenol: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Levobupivacaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Levorphanol: 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: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Lisdexamfetamine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Loop diuretics: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Loratadine; Pseudoephedrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Lorazepam: 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: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Maprotiline: 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.
    Mepenzolate: Additive anticholinergic effects may be seen when mepenzolate is used concomitantly with nitrates. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Meperidine: 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.
    Meperidine; Promethazine: 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: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Mepivacaine; Levonordefrin: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Mesoridazine: 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.
    Metformin; Rosiglitazone: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Methazolamide: Nitrates can cause hypotension. This action may be additive with other agents that can cause hypotension such as diuretics.
    Methylergonovine: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Methylphenidate: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Methysergide: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Midazolam: 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.
    Midodrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Minoxidil: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Mirtazapine: 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.
    Monoamine oxidase inhibitors: 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.
    Morphine: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Nefazodone: 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: The potential for hypotension may be increased when coadministering nesiritide with other vasodilators or hypotensive drugs, such as nitrates.
    Nitroprusside: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Norepinephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Nortriptyline: 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.
    Opiate Agonists: 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: 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: 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: 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.
    Paroxetine: 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.
    Pemoline: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Pergolide: Ergot alkaloids are contraindicated in patients with hypertension, angina, or coronary artery disease; which are the primary patient populations for which nitroglycerin is utilized. Because of the potential to cause coronary vasospasm, ergot alkaloids can oppose the vasodilatory actions of nitroglycerin and, in doing so, may precipitate angina. In addition, oral administration of nitroglycerin decreases the first-pass metabolism of dihydroergotamine, thereby increasing its oral bioavailability.
    Perphenazine: 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: 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. 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Phenelzine: 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.
    Phenothiazines: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Phentermine; Topiramate: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Phenylephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Phenylephrine; Promethazine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Phosphodiesterase inhibitors: 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: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Prilocaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Prilocaine; Epinephrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Procainamide: Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as procainamide.
    Procaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Prochlorperazine: 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.
    Propoxyphene: 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.
    Protriptyline: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Quazepam: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Remifentanil: 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.
    Reserpine: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Riociguat: 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.
    Ritodrine: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Ropivacaine: Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects.
    Rosiglitazone: 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: 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.
    Selegiline, Transdermal: 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.
    Selegiline: 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.
    Sertraline: 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: 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: 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: Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension.
    Temazepam: 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: 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: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Thiethylperazine: 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.
    Thioridazine: 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.
    Tranylcypromine: 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.
    Trazodone: 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.
    Treprostinil: Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Triazolam: 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: 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: 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: 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.

    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 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 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 breast-fed child from nitroglycerin or from the underlying maternal condition.

    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.