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  • CLASSES

    Arteriolar Smooth Muscle Drugs

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral vasodilator; used for HTN and CHF, although ACE inhibitors have largely replaced hydralazine for CHF; used for HTN during pregnancy; also used to treat pulmonary hypertension; its use in the general population for HTN has declined due to adverse effects and tachyphylaxis.

    COMMON BRAND NAMES

    Apresoline

    HOW SUPPLIED

    Apresoline/Hydralazine Hydrochloride Oral Tab: 10mg, 25mg, 50mg, 100mg
    Hydralazine Hydrochloride Intramuscular Inj Sol: 1mL, 20mg
    Hydralazine Hydrochloride Intravenous Inj Sol: 1mL, 20mg

    DOSAGE & INDICATIONS

    For the treatment of hypertension.
    Oral dosage
    Adults

    Initially, 10 mg PO 4 times daily for the first 2—4 days, increase to 25 mg PO 4 times daily for the balance of the first week. For the second and subsequent weeks, increase dosage to 50 mg PO 4 times daily; titrate to lowest effective dosage for blood pressure control. Although an initial dose of 10 mg is recommended, due to the significant first-pass effect of hydralazine, initial doses of 25 mg are usually safe. Maximum recommended dosage is 300 mg/day PO; however, the incidence of systemic lupus erythematosus is higher in patients receiving higher doses (e.g., > 200—400 mg/day PO).

    Infants†, Children†, and Adolescents†

    Initially, 0.75 mg/kg/day PO, given in 4 divided doses. Maximum initial dosage is 25 mg/dose. Titrate over 3—4 weeks up to a maximum of 7.5 mg/kg/day PO (not to exceed 200 mg/day PO).

    Neonates†

    Limited data in neonates. However, 0.25—1 mg/kg/dose PO administered 3—4 times daily has been suggested. Gradually increase as needed for blood pressure control to a maximum dosage of 7.5 mg/kg/day PO.

    Intravenous Route
    Adults

    10—20 mg IV bolus. Repeat as needed, usually every 4—6 hours. Switch to oral antihypertensive therapy as soon as possible, usually within 24—48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Infants†, Children†, and Adolescents†

    Initially, 0.2—0.6 mg/kg/dose IV (up to 20 mg) every 4 hours as needed for blood pressure control. Max: 1.7—3.5 mg/kg/day IV, given in divided doses every 4 hours as needed. Use IV route only if PO is not feasible. Switch to oral therapy as soon as possible, usually with 24—48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Neonates†

    Limited data in neonates. A dose of 0.15—0.6 mg/kg/dose IV administered every 4 hours has been suggested. Repeat as needed for blood pressure control. Only use IV route if PO is not feasible. Switch to oral antihypertensive therapy as soon as possible, usually within 24—48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Intramuscular dosage
    Adults

    10—50 mg IM. Repeat as needed, usually every 4—6 hours initially. Switch to oral antihypertensive therapy as soon as possible, usually within 24—48 hours.

    Infants†, Children†, and Adolescents†

    Initially, 0.2—0.6 mg/kg/dose IM (up to 20 mg) every 4 hours as needed for blood pressure control. Max: 1.7—3.5 mg/kg/day IM, given in divided doses every 4 hours as needed. Use IM route only if PO or IV is not feasible. Switch to oral therapy as soon as possible, usually with 24—48 hours.

    For the treatment of hypertensive emergency or hypertensive urgency.
    For the treatment of hypertension associated with severe preeclampsia or eclampsia.
    Intravenous dosage
    Adult females

    5 to 10 mg IV over 2 minutes for SBP of 160 or more or DBP of 110 or more mmHg. Check BP in 20 minutes and if either BP threshold is exceeded, give 10 mg IV over 2 minutes. Check BP in 20 minutes and if either threshold is exceeded, switch to labetalol 20 mg IV over 2 minutes and check BP in 10 minutes. If either BP threshold is still exceeded, give labetalol 40 mg IV over 2 minutes, obtain emergency consultation, and give additional antihypertensive medication per specific order. Once SBP is less than 160 and DBP is less than 110, check BP every 10 minutes for 1 hour, then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, and then once every hour for 4 hours.

    Intravenous dosage
    Adults

    Initially, 10 to 20 mg IV bolus. Repeat as needed, usually every 4 to 6 hours. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Infants†, Children†, and Adolescents†

    0.1 to 0.2 mg/kg/dose IV every 4 hours as needed for blood pressure control. Max: 0.4 mg/kg/dose, up to 20 mg/dose. Switch to oral therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Neonates†

    Limited data in neonates. A dose of 0.15 to 0.6 mg/kg/dose IV administered every 4 hours has been suggested. Repeat as needed for blood pressure control. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours. When switching from IV to oral therapy, the IV dose should generally be doubled and administered orally; titrate the oral dose to response.

    Intramuscular dosage
    Adults

    Initially, 10 to 50 mg IM. Repeat as needed, usually every 4 to 6 hours initially. Switch to oral antihypertensive therapy as soon as possible, usually within 24 to 48 hours.

    Infants†, Children†, and Adolescents†

    0.1 to 0.2 mg/kg/dose IM every 4 hours as needed for blood pressure control. Max: 0.4 mg/kg/dose, up to 20 mg/dose. Switch to oral therapy as soon as possible, usually within 24 to 48 hours.

    Oral dosage
    Children† and Adolescents†

    0.25 mg/kg/dose (Max: 25 mg/dose) PO every 6 to 8 hours as needed is recommended for severely hypertensive patients with non-life-threatening symptoms.

    For the treatment of heart failure†.
    Oral dosage
    Adults

    Initially, 25 to 50 mg PO 3 to 4 times daily. Dosage may be increased weekly (e.g., by 25 mg/dose) to a target dose of 100 mg PO 3 times daily. Guidelines recommend hydralazine plus isosorbide dinitrate in combination with angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI) for black patients with reduced ejection fraction heart failure (HFrEF) NYHA class III or IV to reduce morbidity and mortality. The combination of isosorbide dinitrate and hydralazine with an ARNI has not been robustly tested; blood pressure response should be carefully monitored.

    Infants, Children, and Adolescents

    0.25 to 1 mg/kg/dose PO every 6 to 8 hours. Increase dose as needed. Maximum dose is 7 mg/kg/day PO. The incidence of systemic lupus erythematosus is higher in patients receiving doses more than 200 mg/day.

    Intravenous dosage
    Infants, Children, and Adolescents

    0.1 to 0.5 mg/kg/dose IV every 6 to 8 hours. Switch to oral therapy as soon as possible.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    300 mg/day PO for hypertension. Higher doses have been used to treat patients with heart failure; however, doses greater than 200—300 mg/day PO are associated with a higher risk of drug-induced systemic lupus erythematosus. Titrate IV and IM dosage as needed for blood pressure control.

    Geriatric

    300 mg/day PO for hypertension. Higher doses have been used to treat patients with heart failure; however, doses greater than 200—300 mg/day PO are associated with a higher risk of drug-induced systemic lupus erythematosus. Titrate IV and IM dosage as needed for blood pressure control.

    Adolescents

    Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 200 mg/day PO, whichever is less, or 3.5 mg/kg/day IV or IM have been used.

    Children

    Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 200 mg/day PO, whichever is less, or 3.5 mg/kg/day IV or IM have been used.

    Infants

    Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 3.5 mg/kg/day IV or IM have been used.

    Neonates

    Safety and efficacy not established; however, doses up to 7.5 mg/kg/day PO or 0.6 mg/kg/dose IV have been used.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available. Hydralazine is extensively metabolized in the liver and is subject to polymorphic acetylation; patients with slow acetylation status have higher plasma levels of hydralazine and these patients require lower doses to maintain control of blood pressure.

    Renal Impairment

    CrCl > 50 mL/min: no dosage adjustment needed.
    CrCl 10—50 mL/min: administer every 8 hours.
    CrCl < 10 mL/min: administer every 8—16 hours. Interval may be extended to 12—24 hours based on patient response.
     
    Intermittent Hemodialysis:
    Administer every 12 to 24 hours depending on patient blood pressure.
     
    Peritoneal Dialysis:
    Administer every 12 to 24 hours depending on patient blood pressure.

    ADMINISTRATION

    Oral Administration

    Administer consistently with regards to timing around meals/food to ensure consistent oral absorption of hydralazine.

    Injectable Administration

    Hydralazine can be administered intramuscularly or as a rapid IV injection. Do not add hydralazine to any IV solutions.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Administer dose immediately after opening the vial.
    Hydralazine changes color after contact with metal, discard any discolored hydralazine solution.
    Blood pressure should be checked frequently following administration of injectable hydralazine.

    Intravenous Administration

    Inject undiluted injection IV via Y-site or a 3-way stopcock at a rate of 10 mg over at least 1 minute.

    Intramuscular Administration

    No dilution necessary.
    Inject deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Apresoline:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Slow acetylation, systemic lupus erythematosus (SLE)

    Hydralazine may produce a clinical picture simulating systemic lupus erythematosus (SLE) including glomerulonephritis. Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine. Hydralazine is subject to polymorphic acetylation; slow acetylation status results in higher plasma levels of hydralazine and these patients require lower doses to maintain control of blood pressure. Thus, the patient's acetylation phenotype will affect the plasma concentration of hydralazine. Patients who are slow acetylators as well as patients with decreased renal function are more likely than fast acetylators to develop lupus-like symptoms or potentially other hydralazine toxicity. Patients with decreased renal function, patients receiving more than 200 mg/day, and patients with a family history of autoimmune disease are also more likely to develop this condition. It is difficult to provide guidelines regarding administration of hydralazine to patients with preexisting systemic lupus erythematosus (SLE). Although hydralazine has been administered safely to these patients, with no exacerbation of underlying disease, and the mechanism of hydralazine-induced lupus syndrome appears to be distinct from idiopathic lupus, hydralazine should nevertheless be used cautiously in this population. Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy, even if the patient does not have any symptoms; these tests are also indicated if a patients develops arthralgia, fever, chest pain, continued malaise, or other unexplained symptoms. If hydralazine-induced SLE occurs, the drug should be discontinued, unless the benefit of continued antihypertensive therapy with this drug outweighs the risk. Signs and symptoms of lupus usually regress when the drug is discontinued; however, residual signs and symptoms have been detected many years later. Long-term treatment with systemic steroids may be necessary.

    Renal failure, renal impairment

    Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine. In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate (GFR). In some instances where control values were below normal, improved renal function has been noted after administration of the drug. However, as with any antihypertensive agent, hydralazine should be used with caution in patients with advanced renal damage. Some references state to consider extended dose intervals in patients with renal impairment (CrCl 10 to 50 mL/min). Patients with renal impairment should receive the drug every 8 hours. Patients with renal failure (CrCl less than 10 mL/min) should receive the drug every 8 to 16 hours; based on patient response, intervals of 12 to 24 hours may be needed.

    Acute myocardial infarction, angina, coronary artery disease, heart failure, myocardial infarction, rheumatic heart disease

    Hydralazine is contraindicated in patients with mitral valve rheumatic heart disease because it can increase pulmonary artery pressure. Additionally, it has been implicated in causing angina and myocardial infarction secondary to reflex sympathetic nervous system stimulation (i.e., reflex tachycardia); therefore, hydralazine is contraindicated in patients with coronary artery disease as reflex tachycardia increases myocardial oxygen demand and can aggravate angina and ischemia and precipitate acute myocardial infarction. Use hydralazine cautiously in patients with an aortic aneurysm. Because hydralazine can cause sodium and fluid retention, its use is generally not recommended in patients with congestive heart failure, although it has been used in patients with intractable left ventricular dysfunction. However, when used with isosorbide dinitrate, this 2-drug combination is considered to be an appropriate alternative to patients who cannot tolerate standard heart failure therapy, mainly angiotensin converting enzyme (ACE) inhibitors. Furthermore, combination therapy of isosorbide dinitrate and hydralazine, in conjunction with standard therapy, has been shown to improve mortality, rate of first hospitalizations, and quality of life in black patients; a fixed-dose combination of isosorbide dinitrate and hydralazine (BiDIl) is FDA-approved for the treatment of heart failure in black patients.

    Increased intracranial pressure, stroke

    Use hydralazine cautiously in patients with acute stroke or cerebral vascular accident as hydralazine in this setting can further worsen brain function. When hydralazine is used in the presence of increased intracranial pressure, lowering of the blood pressure may result in increased cerebral ischemia.

    Pregnancy

    Hydralazine is classified as FDA pregnancy risk category C. Although no adequate human studies have examined the effects of this drug on the fetus, animal reproduction studies have shown hydralazine to have adverse fetal effects. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother. Historically, hydralazine has been regarded as the antihypertensive of choice during preeclampsia ; however, most recent evidence indicates that other drugs such as labetalol and/or calcium channel blockers are associated with improved maternal and fetal outcomes and should be considered before hydralazine. In a meta-analysis on the use of hydralazine for preeclampsia, hydralazine was associated with more maternal hypotension, placental abruption, cesarean section, maternal oliguria, adverse fetal heart rates, and lower Apgar scores at one minute when compared with labetalol or nifedipine. It should be noted that adverse effects associated with hydralazine, such as headache, nausea, and vomiting, can mimic deteriorating pre-eclampsia.

    Breast-feeding

    According to the manufacturer, caution should be exercised when hydralazine is administered to a nursing woman ; however, some experts consider hydralazine to be compatible with breast-feeding. The American Academy of Pediatrics considers hydralazine to be generally compatible with breast-feeding. Hydralazine is distributed into human milk. In one case report of a mother taking hydralazine 50 mg PO three times daily, the milk levels of hydralazine were 130 mcg/L at 0.5 and 2 hours after a dose. Based on these levels, the authors estimated that a nursing infant would receive 13 mcg of hydralazine per 75 ml of breast-milk.  Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Driving or operating machinery

    Hydralazine can induce disorientation or confusion. Patients should use caution when driving or operating machinery until they are aware of the effects of the medication.

    Geriatric

    Clinical experience has not identified differences in responses to hydralazine between geriatric and younger adult patients. Hydralazine may be eliminated more slowly in geriatric patients. When dosing hydralazine in the elderly, it may be prudent to start the dose at the low end of the dosing range and monitor the patients closely for hypotensive effects. Subsequent dosage adjustments should be made based on clinical response. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that nitrates may cause headaches, dizziness, lightheadedness, faintness, or symptomatic orthostatic hypotension, particularly when initially started or when taken with antihypertensives.[60742] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. There are many drug interactions that can potentiate the effects of antihypertensives. Some agents require a gradual taper to avoid adverse consequences caused by abrupt discontinuation.

    ADVERSE REACTIONS

    Severe

    myocardial infarction / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    glomerulonephritis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known

    Moderate

    angina / Early / 1.0-10.0
    sinus tachycardia / Rapid / 10.0
    palpitations / Early / 10.0
    edema / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    peripheral edema / Delayed / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    fluid retention / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    erythema / Early / Incidence not known
    hepatitis / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    splenomegaly / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known

    Mild

    diarrhea / Early / 1.0-10.0
    vomiting / Early / 1.0-10.0
    anorexia / Delayed / 1.0-10.0
    nausea / Early / 10.0
    headache / Early / 10.0
    syncope / Early / Incidence not known
    dizziness / Early / Incidence not known
    weight gain / Delayed / Incidence not known
    chills / Rapid / Incidence not known
    weakness / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    myalgia / Early / Incidence not known
    rash / Early / Incidence not known
    fever / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    tremor / Early / Incidence not known
    lacrimation / Early / Incidence not known
    nasal congestion / Early / Incidence not known
    flushing / Rapid / Incidence not known
    muscle cramps / Delayed / Incidence not known
    anxiety / Delayed / 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) 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.
    Alosetron: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as hydralazine, however, this interaction has not been studied.
    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.
    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.
    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 antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Apomorphine: (Moderate) Concurrent use of apomorphine and vasodilators can cause greater decreases in blood pressure than use of apomorphine alone. Patients receiving a combination of apomorphine and vasodilators should be closely monitored for hypotension and orthostasis.
    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.
    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: (Minor) Use of vasodilators and ergot alkaloids may result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside used for supportive care of ergot alkaloid toxicity.
    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.
    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 (including orthostatic hypotension) was reported in roughly 12 percent of patients; most events were mild to moderate in severity, with more dramatic hypotension reported in 4 percent of drug recipients. Additionally, bortezomib and hydralazine can both cause peripheral neuropathy; coadminister these drugs cautiously, as the risk of peripheral neuropathy may be additive.
    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.
    Caffeine; Ergotamine: (Minor) Use of vasodilators and ergot alkaloids may result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside used for supportive care of ergot alkaloid toxicity.
    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.
    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.
    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.
    Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
    Codeine; 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 can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Conjugated Estrogens; Bazedoxifene: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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.
    Diazoxide: (Moderate) Hypotension and bradycardia have been reported when diazoxide and hydralazine were administered together. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving hydralazine.
    Dienogest; Estradiol valerate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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 can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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: (Minor) 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.
    Drospirenone; Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Drospirenone; Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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.
    Epoprostenol: (Major) Further reductions in blood pressure may occur when vasodilators are combined with epoprostenol.
    Ergonovine: (Minor) The combined use of vasodilators and ergot alkaloids may result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside used for supportive care of ergot alkaloid toxicity.
    Ergotamine: (Minor) Use of vasodilators and ergot alkaloids may result in antagonism of the vasoconstrictive effects of the ergot derivative. This interaction is used to clinical benefit, i.e., nitroprusside used for supportive care of ergot alkaloid toxicity.
    Esterified Estrogens: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Esterified Estrogens; Methyltestosterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol; Levonorgestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol; Norethindrone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol; Norgestimate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estradiol; Progesterone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estrogens: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Estropipate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Desogestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Etonogestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Levonorgestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norelgestromin: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norethindrone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norgestimate: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    Ethinyl Estradiol; Norgestrel: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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) 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.
    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 antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Hydrocodone; 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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    Ibritumomab Tiuxetan: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    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.
    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.
    Isocarboxazid: (Moderate) Monoamine oxidase inhibitors (MAOIs) potentiate the concentration of catecholamines in the CNS. These effects can be additive with those of hydralazine, so caution should be used when administering these drugs together. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, a serious interaction with hydralazine is expected to be less likely to occur with rasagiline.
    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 antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    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 hydralazine 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.
    Lofexidine: (Major) Because the central alpha-2 agonist effects of lofexidine can cause hypotension and orthostasis, the drug should be avoided, if possible, in combination with other medications that can decrease blood pressure such as systemic vasodilators. If coadministration is required, blood pressure should be monitored, particularly after dose changes of either agent. Adjustments should be made as clinically indicated.
    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.
    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.
    Mesoridazine: (Moderate) Antihypertensives that can exacerbate the hypotensive effects of mesoridazine include hydralazine. Patients should be monitored for maintenance of appropriate clinical response to antihypertensive therapy if a phenothiazine is added; these combinations should be avoided whenever possible.
    Mestranol; Norethindrone: (Minor) The administration of estrogens can increase fluid retention, which increases blood pressure, thereby antagonizing the antihypertensive effects of hydralazine.
    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.
    Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing 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.
    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.
    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 antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with antihypertensives can cause additive hypotensive effects. Dosage adjustments may be necessary. A study of 28 patients with heart failure indicated that concomitant administration of oral hydralazine prevented the development of tolerance to continuous nitroglycerin infusions.
    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.
    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, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and hydralazine who are susceptible to hypotension.
    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.
    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: (Major) Additive hypotensive effects may be seen when phenelzine, a MAOI, is combined with hydralazine, a potent vasodilator. In addition, hydralazine may cause pronounced tachycardia when combined with MAOIs. 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 during concurrent use of phenelzine and an antihypertensive agent.
    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.
    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.
    Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
    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) Monoamine oxidase inhibitors (MAOIs) potentiate the concentration of catecholamines in the CNS. These effects can be additive with those of hydralazine, so caution should be used when administering these drugs together. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, a serious interaction with hydralazine is expected to be less likely to occur with rasagiline.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and hydralazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
    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.
    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.
    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.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    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.
    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.
    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.
    Vincristine Liposomal: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
    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.
    Zalcitabine, ddC: (Major) Coadministration of zalcitabine, ddC with drugs associated with peripheral neuropathy, such as hydralazine, should be avoided when possible.
    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

    Hydralazine is classified as FDA pregnancy risk category C. Although no adequate human studies have examined the effects of this drug on the fetus, animal reproduction studies have shown hydralazine to have adverse fetal effects. Therefore, in making the decision to administer this drug during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother. Historically, hydralazine has been regarded as the antihypertensive of choice during preeclampsia ; however, most recent evidence indicates that other drugs such as labetalol and/or calcium channel blockers are associated with improved maternal and fetal outcomes and should be considered before hydralazine. In a meta-analysis on the use of hydralazine for preeclampsia, hydralazine was associated with more maternal hypotension, placental abruption, cesarean section, maternal oliguria, adverse fetal heart rates, and lower Apgar scores at one minute when compared with labetalol or nifedipine. It should be noted that adverse effects associated with hydralazine, such as headache, nausea, and vomiting, can mimic deteriorating pre-eclampsia.

    According to the manufacturer, caution should be exercised when hydralazine is administered to a nursing woman ; however, some experts consider hydralazine to be compatible with breast-feeding. The American Academy of Pediatrics considers hydralazine to be generally compatible with breast-feeding. Hydralazine is distributed into human milk. In one case report of a mother taking hydralazine 50 mg PO three times daily, the milk levels of hydralazine were 130 mcg/L at 0.5 and 2 hours after a dose. Based on these levels, the authors estimated that a nursing infant would receive 13 mcg of hydralazine per 75 ml of breast-milk.  Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Hydralazine is a peripheral vasodilator; it causes relaxation of arteriolar smooth muscle via a direct effect. Although stimulation of the sympathetic nervous system is associated with hydralazine administration, this is a compensatory response and not a component of its mechanism. The molecular explanation of hydralazine's mechanism is not fully understood; however, similar to organic nitrates and nitroprusside, it is thought that hydralazine interferes with the calcium movements within vascular smooth muscle that are responsible for initiating and maintaining the contractile state. In contrast to organic nitrates and sodium nitroprusside, however, hydralazine is selective for arterioles. The peripheral vasodilating effects of hydralazine result in decreased arterial blood pressure (diastolic more than systolic) and peripheral vascular resistance. In addition, the hydralazine-induced reflex autonomic response increases heart rate, stroke volume, cardiac output, and left ventricular ejection fraction. The preferential dilation of arterioles, as compared to veins, minimizes postural hypotension and promotes the increase in cardiac output even though the hypotensive effects of hydralazine are diminished somewhat by this increase in cardiac output. There is also evidence suggesting hydralazine exerts a positive inotropic effect on the failing human ventricle.
     
    Animal and limited human data indicate that nitric oxide (NO) may be generated from hydralazine that also has an antioxidant quality to enhance the effects of nitrates and to mitigate the tolerance associated with chronic nitrate therapy. The antioxidant effect of hydralazine can be attributed to its ability in inhibiting oxidase formation. The accumulation of oxidative free radicals creates an environment where chronic reductions in NO bioavailability contribute to a loss of skeletal muscle microvessels. This effect, in turn, leads to impaired muscle perfusion with elevated metabolic demand. Studies show that treatment with hydralazine markedly inhibits oxidase which plays a role in regulating the bioactivity of NO, produced either endogenously or when administered exogenously.
     
    Cerebral, coronary, splanchnic, and renal blood flow usually increase following administration of hydralazine, while urinary parameters are generally unaffected. Hydralazine increases renin activity in plasma, presumably by the renal juxtaglomerular cells in response to sympathetic nervous system stimulation; the increase in renin activity leads to the production of angiotensin II, which stimulates aldosterone and thus, sodium reabsorption. Due to fluid retention, plasma volume increases. As a result, tolerance can develop, which may account for the absence of improvement in some patients receiving the drug for prolonged periods of time.
     
    As an antihypertensive, hydralazine does not lead to improvements in LVH. Hydralazine may actually worsen LVH, potentially due to reflex tachycardia and sympathetic stimulation, which may counteract the benefits of afterload reduction.

    PHARMACOKINETICS

    Hydralazine is administered orally and parenterally. Hydralazine distributes throughout the body tissues and has a particularly high affinity for arterial walls. The drug crosses the placenta and distributes in breast milk, but not to a clinically significant degree. Plasma protein binding is about 87%. Hydralazine is extensively hepatically metabolized and plasma levels can vary due to polymorphic acetylation. Both the unchanged drug (25%) and its metabolites are excreted in the urine and feces. The half-life of the drug in a normal patient is 3—7 hours.

    Oral Route

    Although hydralazine is approximately 90% absorbed following oral administration, systemic bioavailability is considerably lower after oral versus intramuscular or intravenous administration due to extensive first-pass metabolism. Oral bioavailability is also dependent on the acetylation phenotype of the patient, and it is approximately 50% in 'slow' acetylators and 30% in 'fast' acetylators. Although food in the gut enhances absorption of hydralazine, food-related reductions in hydralazine blood levels have been associated with reduced antihypertensive effects, possibly due to an increase in intravascular conversion of the drug to hydralazine pyruvic acid hydrazone. For this reason, it has been suggested that patients take this medication at a fixed time in relationship to meals. Peak hydralazine plasma concentration is reached in 1—2 hours. Hypotensive effects occur 20—30 minutes following an oral dose. The antihypertensive effects of an oral hydralazine dose last about 2—4 hours.

    Intravenous Route

    Hypotensive effects occur 5—30 minutes after an IV dose. The antihypertensive effects of an IV dose last 2—6 hours on average, although the effects of a parenteral dose can last up to 12 hours; the affinity of hydralazine for arterial walls may partially explain the prolonged effect.

    Intramuscular Route

    Hypotensive effects occur 10—30 minutes after an IM dose. The antihypertensive effects of an IM dose last 2—6 hours on average, although the effects of a parenteral dose can last up to 12 hours possibly due to the affinity of hydralazine for arterial walls.