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    Arteriolar Smooth Muscle Drugs

    BOXED WARNING

    Aortic coarctation, arteriovenous shunt, hypotension

    Nitroprusside-induced hypotension can be severe, and this drug should be administered only in a setting where adequate equipment and personnel are available to monitor blood pressure closely. Nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or an arteriovenous shunt. The infusion should be titrated to maintain the desired blood pressure endpoints and clinical response (see Dosage and Administration). Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients coming to emergency surgery.

    Cyanide toxicity

    Cyanide ions, a byproduct of nitroprusside metabolism, can accumulate to toxic concentrations during nitroprusside therapy. Nitroprusside infusions more than 2 mcg/kg/minute generate cyanide ion faster than the body can buffer. Nitroprusside infusions of 10 mcg/kg/minute are considered maximal, and this rate should not be continued for more than 10 minutes to avoid cyanide toxicity. At this maximum infusion rate, the ability to buffer cyanide ion will be exceeded in less than 1 hour. Most of the cyanide produced during metabolism of nitroprusside is eliminated in the form of thiocyanate. Thiocyanate is life-threatening when concentrations reach 200 mg/L; therefore, routine monitoring of plasma thiocyanate concentrations is recommended in patients with normal renal function when cumulative nitroprusside doses exceed 7 mg/kg/day.

    DEA CLASS

    Rx

    DESCRIPTION

    Vasodilator; rapid onset and a short duration of action; useful when immediate reduction of preload or afterload is needed; prolonged infusions have a high potential for toxicity, especially in patients with renal failure.

    COMMON BRAND NAMES

    NIPRIDE RTU, Nitropress

    HOW SUPPLIED

    NIPRIDE RTU/Nitropress/Nitroprusside/Sodium Nitroprusside Intravenous Inj Sol: 0.5mg, 1mL, 25mg

    DOSAGE & INDICATIONS

    For the treatment of hypertensive emergency or hypertensive urgency; for controlled hypotension induction during anesthesia; or for adjunctive therapy in patients with acute congestive heart failure receiving appropriate cardiovascular monitoring.
    Intravenous dosage
    Adults

    Initially, 0.3 mcg/kg/minute; titrate every 5 minutes until desired effect or systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs. Average maintenance dose is about 3 mcg/kg/minute. Max: 10 mcg/kg/minute IV for 10 minutes.

    Infants, Children, and Adolescents

    Initially, 0.3 to 0.5 mcg/kg/minute IV; titrate every 5 minutes until desired effect or systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs. Usual dose range: 0.5 to 8 mcg/kg/minute. Average maintenance dose: 3 to 4 mcg/kg/minute. Max: 10 mcg/kg/minute for 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with increased risk of cyanide toxicity in pediatric patients.

    Neonates

    Initially, 0.2 to 0.3 mcg/kg/minute IV; titrate every 5 minutes until desired effect or systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs. Usual dose range: 0.5 to 8 mcg/kg/minute. Average maintenance dose: 3 to 4 mcg/kg/minute. Max: 10 mcg/kg/minute for no longer than 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with increased risk of cyanide toxicity in pediatric patients (including neonates).

    For the treatment of postoperative hypertension†.
    Intravenous dosage
    Adults

    In one study, the initial dose of nitroprusside was 0.5 mcg/kg/minute as an IV infusion, which was increased by 0.5 to 1.5 mcg/kg/minute at 5-minute intervals (Max: 10 mcg/kg/minute for 10 minutes) to therapeutic response. In this study, 139 patients with postoperative hypertension were randomized to receive nitroprusside (n = 68) or nicardipine (n = 71). The nitroprusside dose was adjusted, as needed, every 15 minutes to maintain blood pressure control. Therapeutic response (i.e., greater than 15% blood pressure reduction from pretreatment baseline) was achieved in 88% of the nitroprusside-treated group and 86% of the nicardipine-treated group.

    Infants, Children, and Adolescents

    Initially, 0.3 to 0.5 mcg/kg/minute IV; titrate every few minutes to effect to a usual dose range of 0.5 to 8 mcg/kg/minute. Average maintenance dose is 3 to 4 mcg/kg/minute. Maximum dosage is 10 mcg/kg/minute for no more than 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with an increased risk of cyanide toxicity in pediatric patients.

    Neonates

    Initially, 0.2 to 0.3 mcg/kg/minute IV; titrate every few minutes to effect to a usual dose range of 0.5 to 8 mcg/kg/minute. Average maintenance dose is 3 to 4 mcg/kg/minute. The maximum dosage is 10 mcg/kg/minute for no longer than 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with increased risk of cyanide toxicity in pediatric patients (including neonates).

    For management of patients with mitral regurgitation†, to decrease pulmonary congestion and increase forward cardiac index and stroke volume index.
    Intravenous dosage
    Adults

    Initially, 0.25 to 0.3 mcg/kg/minute IV, titrated to desired hemodynamic effect. The dosage range is 0.25 to 10 mcg/kg/minute. Maximum dosage is 10 mcg/kg/minute for 10 minutes.

    For acute vasodilator testing in pulmonary hypertension diagnosis†.
    Intravenous dosage
    Adults

    Dosage not established. Clinical practice guidelines recommend against the use of sodium nitroprusside for acute vasodilator testing.

    To increase cardiac output after cardiopulmonary resuscitation†, cardiac surgery†, or in patients with cardiogenic shock† and high SVR.
    Intravenous dosage
    Infants, Children, and Adolescents

    Initially, 0.3 to 0.5 mcg/kg/minute IV; titrate to effect to a usual dose range of 0.5 to 8 mcg/kg/minute IV. Average maintenance dose is 3 to 4 mcg/kg/minute. Max: 10 mcg/kg/minute for 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with an increased risk of cyanide toxicity in pediatric patients. Nitroprusside is recommended as a first line vasodilator in patients with epinephrine-resistant septic shock and normal blood pressure.

    Neonates

    Initially, 0.2 to 0.3 mcg/kg/minute IV; titrate every few minutes to effect to a usual dose range of 0.5 to 8 mcg/kg/minute. Average maintenance dose is 3 to 4 mcg/kg/minute. Max: 10 mcg/kg/minute for no longer than 10 minutes. Mean doses of approximately 2 mcg/kg/minute for greater than 24 hours have been associated with increased risk of cyanide toxicity in pediatric patients (including neonates).

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    10 mcg/kg/minute IV for 10 minutes.

    Geriatric

    10 mcg/kg/minute IV for 10 minutes.

    Adolescents

    10 mcg/kg/minute IV for 10 minutes.

    Children

    10 mcg/kg/minute IV for 10 minutes.

    Infants

    10 mcg/kg/minute IV for 10 minutes.

    Neonates

    10 mcg/kg/minute IV for 10 minutes.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available. Because nitroprusside is hepatically metabolized, use caution in patients with hepatic impairment; titrate dose carefully. Since cyanide is metabolized by hepatic enzymes, it may accumulate in patients with severe hepatic impairment.

    Renal Impairment

    eGFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
    eGFR less than 30 mL/minute/1.73 m2: Limit mean infusion rate to less than 3 mcg/kg/minute.
    Anuria: Limit the mean infusion rate to 1 mcg/kg/minute.

    ADMINISTRATION

     
    NOTE: Nitroprusside should be used only when appropriate monitoring equipment and personnel are available; blood pressure should be continuously monitored.
    NOTE: Prolonged use (i.e., more than several days) of nitroprusside infusions should be avoided in patients with renal insufficiency.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    NOTE: Nitroprusside should be used only when appropriate monitoring equipment and personnel are available; blood pressure should be continuously monitored.
    NOTE: Prolonged use (i.e., more than several days) of nitroprusside infusions should be avoided in patients with renal insufficiency.

    Intravenous Administration

    Must be diluted with dextrose 5% in water (D5W) before administration. Do not administer by direct injection.
    Administer diluted solution by IV infusion using a controlled infusion device.
     
    Reconstitution:
    Reconstitute 50 mg by adding 2—3 ml of D5W injection. Further dilute in 250, 500, or 1000 ml of D5W injection to provide concentrations of 200, 100, or 50 mcg/ml, respectively. In fluid-restricted patients, a final maximum concentration of 800 mcg/ml in D5W has been used. Other diluents are not recommended.
    After inspecting the solution, the container should be immediately wrapped in aluminum foil or other opaque material to protect from light. The solution should be discarded after 24 hours.
     
    Infusion:
    A controlled-infusion device, micro-drip regulator, or similar device should be used to administer nitroprusside infusions.
    Administer at a rate to maintain the desired effect (see Dosage below). Infusion rates which are too rapid may precipitate nausea/vomiting, diaphoresis, nasal stuffiness, headache, apprehension, palpitations, dizziness, muscle cramping or twitching, and abdominal pain. These symptoms can be alleviated by slowing the infusion rate or discontinuing the drug. Cyanide ions, a byproduct of nitroprusside metabolism, can build up to toxic levels during nitroprusside therapy. Nitroprusside infusions of 10 mcg/kg/min are considered maximal, and this rate should not be continued for more than 10 minutes. To maintain the steady-state thiocyanate concentration below 1 millimole/L, the rate of a prolonged infusion (i.e., > 72 hours) should not exceed 3 mcg/kg/minute (in normal patients), and 1 mcg/kg/minute in anuric patients.

    STORAGE

    NIPRIDE RTU :
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    Nitropress:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until contents are used
    - Use within 24 hours from time of preparation

    CONTRAINDICATIONS / PRECAUTIONS

    Aortic coarctation, arteriovenous shunt, hypotension

    Nitroprusside-induced hypotension can be severe, and this drug should be administered only in a setting where adequate equipment and personnel are available to monitor blood pressure closely. Nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or an arteriovenous shunt. The infusion should be titrated to maintain the desired blood pressure endpoints and clinical response (see Dosage and Administration). Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients coming to emergency surgery.

    High output acute heart failure, sepsis

    Sodium nitroprusside is contraindicated in the treatment of high output acute heart failure (such as that seen in patients with endotoxic sepsis) or other acute congestive heart failure associated with reduced peripheral vascular resistance.

    Cyanide toxicity

    Cyanide ions, a byproduct of nitroprusside metabolism, can accumulate to toxic concentrations during nitroprusside therapy. Nitroprusside infusions more than 2 mcg/kg/minute generate cyanide ion faster than the body can buffer. Nitroprusside infusions of 10 mcg/kg/minute are considered maximal, and this rate should not be continued for more than 10 minutes to avoid cyanide toxicity. At this maximum infusion rate, the ability to buffer cyanide ion will be exceeded in less than 1 hour. Most of the cyanide produced during metabolism of nitroprusside is eliminated in the form of thiocyanate. Thiocyanate is life-threatening when concentrations reach 200 mg/L; therefore, routine monitoring of plasma thiocyanate concentrations is recommended in patients with normal renal function when cumulative nitroprusside doses exceed 7 mg/kg/day.

    Anuria, renal disease, renal failure, renal impairment

    Nitroprusside should not be used in patients with severe renal disease, renal failure, anuria, or renal impairment because excretion of thiocyanate, a nitroprusside metabolite, might be decreased, leading to toxicity. Prolonged infusion (e.g., more than several days) of nitroprusside should be avoided in patients with renal impairment; thiocyanate serum concentrations may accumulate in patients with renal impairment (see Dosage). Use with caution in patients mild to moderate renal impairment, patients of advanced age, and those at risk of renal compromise including those with dehydration and/or other conditions resulting in insufficient renal circulation.

    Hepatic disease

    Nitroprusside should not be used in patients with hepatic disease. Thiocyanate is the metabolite of nitroprusside. Since cyanide is metabolized by hepatic enzymes, it may accumulate in patients with severe liver impairment.

    Hypothyroidism

    Thiocyanate, the metabolite of nitroprusside, inhibits the uptake and binding of iodine by the thyroid. Thus, nitroprusside should not be used in patients with hypothyroidism.

    Cerebrovascular disease, coronary artery disease

    Use nitroprusside with caution in patients with cerebrovascular disease or insufficiency, or coronary artery disease as they may be less tolerant of drug-induced hypotension.

    Hereditary optic nerve atrophy (Leber's disease), toxic amblyopia

    Nitroprusside use is contraindicated in patients with hereditary optic nerve atrophy (Leber's disease) or toxic amblyopia as such patients are deficient in rhodanase, an enzyme that is crucial for the metabolism of nitroprusside. These patients may be at an increased risk of developing cyanide toxicity while receiving nitroprusside therapy.

    Increased intracranial pressure

    Nitroprusside can cause increases in intracranial pressure and therefore should not be used in patients with preexisting increased intracranial pressure including encephalopathy.

    Pulmonary disease

    Nitroprusside should be used with caution in patients with pulmonary disease. Nitroprusside may aggravate pre-existing hypoxemia.

    Anemia, hypovolemia

    Nitroprusside should be used with caution in when used in patients for controlled hypotension during anesthesia have anemia or hypovolemia. The patient's ability to compensate may be diminished. These conditions should be corrected prior to use of nitroprusside.

    Pregnancy

    Prolonged use of large doses of nitroprusside during pregnancy may lead to cyanide toxicity that may be fatal to the fetus. In the unusual case that there is no appropriate alternative to nitroprusside, advise any pregnant woman of the potential risk to the fetus. Post-marketing reports of nitroprusside use in pregnant women with pregnancy-induced hypertension are insufficient to inform a drug-associated risk of adverse pregnancy outcomes. A small number of cases have reported adverse events, including stillbirths, in pregnant woman treated with nitroprusside. Studies in pregnant sheep indicate nitroprusside crosses the placenta and that fetal cyanide concentrations were dose-related to maternal concentrations of nitroprusside. The metabolic transformation of nitroprusside administered to pregnant sheep led to fatal concentrations of cyanide in the fetuses.

    Breast-feeding

    There is no information about the presence of nitroprusside in breast milk, the effects on the breast-fed infant, or the effects on milk production. Thiocyanate, a metabolite of nitroprusside, is present in human milk. It is unknown how long, if ever, concentrations of thiocyanate in milk are clinically relevant. Because of the potential for adverse reactions in breast-feeding infants, discontinue breast-feeding or to discontinue nitroprusside, taking into account the importance of the drug to the mother.

    Geriatric

    Because sodium nitroprusside can induce essentially unlimited blood-pressure reduction, the blood pressure of a patient receiving this drug must be continuously monitored. Special caution should be used in geriatric patients, since they may be more sensitive to the hypotensive effects of the drug. Those geriatric patients with impaired renal function are more likely than those with normal renal function to develop thiocyanate toxicity after prolonged, rapid infusions. According to the Beers Criteria, vasodilators are considered potentially inappropriate medications (PIMs) in older adults and should be used cautiously in geriatric patients since vasodilators may exacerbate episodes of syncope in individuals with a history of syncope.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    coma / Early / Incidence not known
    cyanide toxicity / Delayed / Incidence not known
    thiocyanate toxicity / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    methemoglobinemia / Early / Incidence not known

    Moderate

    hypotension / Rapid / 10.0
    metabolic acidosis / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    hyperreflexia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    confusion / Early / Incidence not known
    ataxia / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    hypothyroidism / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known

    Mild

    mydriasis / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    headache / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    flushing / Rapid / Incidence not known
    dizziness / Early / Incidence not known
    restlessness / Early / Incidence not known
    diaphoresis / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acetaminophen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Acrivastine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Aldesleukin, IL-2: (Moderate) Vasodilators may potentiate the hypotension seen with aldesleukin, IL 2.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Aliskiren: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Amlodipine: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Aliskiren; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure. (Moderate) Aliskiren can enhance the effects of vasodilators on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Blood pressure and electrolytes should be routinely monitored in patients receiving aliskiren.
    Alpha-blockers: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as the vasodilators, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
    Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Amlodipine; Olmesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Amlodipine; Telmisartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Amlodipine; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Amphetamine; Dextroamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Amyl Nitrite: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Angiotensin II receptor antagonists: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Angiotensin-converting enzyme inhibitors: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Apomorphine: (Moderate) 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.
    Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
    Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Articaine; Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Avanafil: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine. (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
    Azilsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Azilsartan; Chlorthalidone: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Benzphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Beta-blockers: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
    Bromocriptine: (Moderate) Nitroprusside can cause hypotension, and bromocriptine can cause hypotension or hypertension. In addition, bromocriptine 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 nitroprusside is utilized. If concomitant use is necessary, blood pressure should be monitored closely.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Brompheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Cabergoline: (Moderate) Cabergoline has minimal affinity for adrenergic receptors; however, it has been associated with hypotension in some instances. Cabergoline should be used cautiously in those receiving antihypertensive agents or other medications known to cause hypotension.
    Caffeine; Ergotamine: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Calcium-channel blockers: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Candesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbetapentane; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Carbinoxamine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Central-acting adrenergic agents: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Cetirizine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Chlorthalidone; Clonidine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Clonidine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
    Cod Liver Oil: (Moderate) Fish oil supplements may cause mild, dose-dependent reductions in systolic or diastolic blood pressure in untreated hypertensive patients. Relatively high doses of fish oil are required to produce any blood pressure lowering effect. Additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Codeine; Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Conjugated Estrogens: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Conjugated Estrogens; Bazedoxifene: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Desloratadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and vasodilators could lead to additive hypotension and bradycardia; use together with caution. In clinical trials where vasodilators were co-administered with dexmedetomidine an additive pharmacodynamic effect was not observed. However, both vasodilators and dexmeditomidine may cause symptomatic hypotension. If hypotension occurs, dose reduction of one or both drugs may be needed and supportive measures instituted.
    Dexmethylphenidate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextroamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Dienogest; Estradiol valerate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Diethylpropion: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Diethylstilbestrol, DES: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dihydroergotamine: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dobutamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Dopamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Doxazosin: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Drospirenone; Estradiol: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Drospirenone; Ethinyl Estradiol: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
    Enflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Eplerenone: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Epoprostenol: (Major) Further reductions in blood pressure may occur when vasodilators are combined with epoprostenol.
    Eprosartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Ergoloid Mesylates: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Ergonovine: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Ergot alkaloids: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Ergotamine: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Esterified Estrogens: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Esterified Estrogens; Methyltestosterone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estradiol: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estradiol; Levonorgestrel: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estradiol; Norethindrone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estradiol; Norgestimate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estrogens: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Estropipate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Desogestrel: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Etonogestrel: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Levonorgestrel: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norelgestromin: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norethindrone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norgestimate: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Ethinyl Estradiol; Norgestrel: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Fexofenadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10. (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fluoxetine; Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Fospropofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Guanabenz: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Guanfacine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Halothane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Hawthorn, Crataegus laevigata: (Moderate) Hawthorn, Crataegus laevigata may lower peripheral vascular resistance. Hawthorn use in combination with vasodilators may lead to additional reductions in blood pressure in some individuals. Patients receiving hawthorn concurrently with antihypertensive medications should receive periodic blood pressure monitoring.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Hydrocodone; Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Ibuprofen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Iloprost: (Moderate) Vasodilators may have additive hypotensive effects when given with other antihypertensive agents.
    Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. This may be desirable, but occasionally orthostatic hypotension may occur. Dosages should be adjusted based on clinical response.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Irbesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levomilnacipran: (Moderate) Levomilnacipran has been associated with an increase in blood pressure. The effectiveness of sodium nitroprusside may be diminished during concurrent use of levomilnacipran. It is advisable to monitor blood pressure if the combination is necessary.
    Lisdexamfetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Loop diuretics: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Loratadine; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Losartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Mepivacaine; Levonordefrin: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Mestranol; Norethindrone: (Minor) The administration of estrogens may increase blood pressure, and thereby antagonizing the antihypertensive effects of nitroprusside.
    Methamphetamine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
    Methyldopa: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Methylergonovine: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Methylphenidate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Methysergide: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Milnacipran: (Moderate) Milnacipran has been associated with an increase in blood pressure. The effectiveness of antihypertensive agents may be diminished during concurrent use of milnacipran. It is advisable to monitor blood pressure if the combination is necessary.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Naproxen; Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Nebivolol; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Nesiritide, BNP: (Moderate) The potential for hypotension may be increased when coadministering nesiritide with vasodilators. Reduce the dose of or discontinue nesiritide in patients who develop hypotension. In clinical trials, no drug interactions were detected except for an increase in symptomatic hypotension in patients receiving afterload reducers, such as vasodilators.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially peripheral vasodilators. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
    Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Norepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olmesartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by vasodilators. Also vasodilators can antagonize the effectiveness of oxymetazoline. If these drugs are used together, closely monitor for changes in blood pressure.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses of paliperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Pemoline: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
    Pergolide: (Major) The combined use of vasodilators and the ergot alkaloids will likely result in antagonism of the vasoconstrictive effects of the ergot derivative. Clinically, for example, vasodilators may be used for supportive care of ergot alkaloid toxicity; with precautions to avoid hypotension.
    Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Phenoxybenzamine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Phentermine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phentermine; Topiramate: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phentolamine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Phenylephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Phosphodiesterase inhibitors: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside.
    Potassium-sparing diuretics: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Prazosin: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Prilocaine; Epinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pseudoephedrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Racepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Reserpine: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ritodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Sacubitril; Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Selegiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Sildenafil: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside.
    Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Sympathomimetics: (Major) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Also, vasodilators can antagonize pressor responses to epinephrine. Patients should be monitored to confirm that the desired antihypertensive effect is achieved.
    Tadalafil: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside.
    Telmisartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Terazosin: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
    Thiazide diuretics: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Thiopental: (Moderate) Additive hypotensive effects may occur when vasodilators are used concomitantly with thiopental. Dosages should be adjusted carefully, according to blood pressure.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
    Tranylcypromine: (Severe) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Treprostinil: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Valsartan: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Vardenafil: (Moderate) The hypotensive effects of nitroprusside may be augmented by phosphodiesterase inhibitors. Monitor blood pressure when co-administering phosphodiesterase inhibitors and blood pressure lowering medications, like nitroprusside. Phosphodiesterase inhibitors have vasodilatory properties, and nitroprusside is a potent vasodilator. In addition, phosphodiesterase type-5 (PDE5) is found in platelets, and PDE5 inhibitors may potentiate the nitric oxide-mediated platelet anti-aggregatory activity of nitroprusside.
    Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled BP.
    Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

    PREGNANCY AND LACTATION

    Pregnancy

    Prolonged use of large doses of nitroprusside during pregnancy may lead to cyanide toxicity that may be fatal to the fetus. In the unusual case that there is no appropriate alternative to nitroprusside, advise any pregnant woman of the potential risk to the fetus. Post-marketing reports of nitroprusside use in pregnant women with pregnancy-induced hypertension are insufficient to inform a drug-associated risk of adverse pregnancy outcomes. A small number of cases have reported adverse events, including stillbirths, in pregnant woman treated with nitroprusside. Studies in pregnant sheep indicate nitroprusside crosses the placenta and that fetal cyanide concentrations were dose-related to maternal concentrations of nitroprusside. The metabolic transformation of nitroprusside administered to pregnant sheep led to fatal concentrations of cyanide in the fetuses.

    There is no information about the presence of nitroprusside in breast milk, the effects on the breast-fed infant, or the effects on milk production. Thiocyanate, a metabolite of nitroprusside, is present in human milk. It is unknown how long, if ever, concentrations of thiocyanate in milk are clinically relevant. Because of the potential for adverse reactions in breast-feeding infants, discontinue breast-feeding or to discontinue nitroprusside, taking into account the importance of the drug to the mother.

    MECHANISM OF ACTION

    Mechanism of Action: The peripheral vasodilatory effects of nitroprusside are due to a direct action of the drug on arterial and venous smooth muscle. Other smooth muscle tissue in the body is not affected, and myocardial contractility is unaffected. Nitroprusside's hypotensive effects are enhanced by other hypotensive agents and are not inhibited by adrenergic blocking agents. Pressor agents that exert a direct stimulatory effect on the myocardial tissue (i.e., epinephrine) are the only class of drugs that can cause an increase in blood pressure during nitroprusside therapy. Almost any desired blood pressure can be maintained with various infusion rates of the drug.Nitroprusside-induced peripheral vasodilation results in a reduced left ventricular afterload, and this, along with a reduced venous return to the heart (due to venous pooling of the blood and decreased arteriolar resistance), results in a slight increase in heart rate and decrease in cardiac output in hypertensive patients. In patients with congestive heart failure, nitroprusside improves left ventricular heart performance, with increases in cardiac index, cardiac output, and stroke volume. Heart rate also slows in these patients, and arrhythmias can be reduced or abolished. Nitroprusside also can decrease myocardial oxygen demand, which is beneficial to patients with ischemia. Diuresis also occurs during nitroprusside therapy, producing increased urine volumes and increased sodium excretion.

    PHARMACOKINETICS

    Nitroprusside is administered intravenously. The distribution kinetics of the drug are unknown, but it is believed to penetrate cell membranes slowly and to be distributed predominantly into the extracellular space. It is not known whether the drug crosses the placenta or the blood-brain barrier, or if it is secreted into breast milk. Nitroprusside is rapidly metabolized to cyanide radicals, which are then converted to thiocyanate in the liver via the enzyme rhodanase (see below). These metabolites are excreted almost entirely in the urine. The circulatory half-life of nitroprusside is 2 minutes.
     
    Nitroprusside is metabolized to cyanide and thiocyanate, which, although they do not contribute to the antihypertensive action, have the potential to cause severe toxic reactions. Nitroprusside molecules begin to break down immediately after contact with sulfhydryl groups located in the cell wall. An intraerythrocytic reaction occurs, in which a molecule of nitroprusside reacts with an equivalent amount of hemoglobin, forming methemoglobin and liberating five cyanide ions. One of these cyanide ions then reacts with the methemoglobin molecule to form cyanmethemoglobin, a biologically inert compound. A patient with a normal red cell count and normal methemoglobin concentration is able to buffer approximately 175 mcg of cyanide ion per kg body weight. In other words, an otherwise healthy patient can buffer a little less than 500 mcg/kg of infused nitroprusside.
     
    Once the intraerythrocytic methemoglobin supply is saturated, the remaining cyanide radicals are converted to thiocyanate in the liver via the hepatic enzyme rhodanase. This reaction requires a sulfur donor, typically thiosulfate, cysteine, or cystine. Physiological concentrations of thiosulfate (11 mg/L) can convert cyanide ions to thiocyanate at about 1 mcg/kg/minute (roughly equivalent to a nitroprusside infusion of about 2 mcg/kg/minute). Cyanide accumulates at infusion rates that exceed this rate, and excess cyanide binds to mitochondrial cytochromes, inhibiting cellular respiration and possibly causing cell death. Thiocyanate toxicity occurs at plasma levels of 50—100 mcg/mL.

    Intravenous Route

    Nitroprusside is short-acting, with hypotensive effects lasting only 1—10 minutes following infusion.