Apresoline Side Effects
Generic name: hydralazine
Note: This document contains side effect information about hydralazine. Some of the dosage forms listed on this page may not apply to the brand name Apresoline.
Some side effects of Apresoline may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
For the Consumer
Applies to hydralazine: oral tablet
Get emergency medical help if you have any of these signs of an allergic reaction while taking hydralazine (the active ingredient contained in Apresoline) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect such as:
fast or pounding heartbeats;
swelling in your face, stomach, hands, or feet;
numbness, burning, pain, or tingly feeling;
feeling like you might pass out;
confusion, unusual thoughts or behavior;
pale skin, easy bruising;
painful or difficult urination;
urinating less than usual or not at all; or
joint pain or swelling with fever, chest pain, weakness or tired feeling.
Less serious side effects of hydralazine may include:
nausea, vomiting, loss of appetite;
muscle or joint pain;
runny or stuffy nose; or
mild itching or skin rash.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.
For Healthcare Professionals
Applies to hydralazine: compounding powder, injectable solution, oral tablet
Immunologic side effects including the development of a lupus-like syndrome has been reported. It is more likely in patients who receive 400 mg or more of hydralazine (the active ingredient contained in Apresoline) per day, in female patients, or in patients who are slow acetylators. Of patients who receive less than 200 mg or 400 mg or more per day of hydralazine, 40% and 50%, respectively, develop a positive ANA titer, and up to 6% and 14%, respectively, develop a lupus-like syndrome.
The lupus syndrome may present as arthralgias (most common), myalgias, lethargy, malaise, a typical erythematous rash, weight loss, or dyspnea, but may be found incidentally in asymptomatic patients by urinalysis (proteinuria, hematuria), blood chemistry (elevated ESR, antinuclear antibody), or chest X-ray (interstitial lung disease, rare). Hypocomplementemia is an extremely rare finding in hydralazine-induced lupus.
Alternative therapy is recommended for patients who develop the clinical appearance of a lupus syndrome, sustained rises in the antinuclear antibody titer, or the presence of LE cells. The syndrome is reversible, but may take months to years to resolve.
Because up to 20% of patients who receive 400 mg per day or more develop a systemic lupus erythematosus syndrome, some experts recommend checking a patient's acetylator status before giving higher doses. Up to 70% of "resistant" patients are fast acetylators, in whom the dose can be relatively safely increased.
Data suggest that hydralazine lupus may represent a unique hypersensitivity reaction in which antibodies to native DNA occur. These antibodies are believed to account for the clinical similarities between hydralazine-induced lupus and systemic lupus erythematosus.
Provocation of ischemia in patients with compromised left ventricular systolic dysfunction may be due to the inability of hydralazine (the active ingredient contained in Apresoline) to decrease preload, or left ventricular filling pressures.
The mechanism of increased pulmonary hypertension in patients with PH or COPD is a decrease of systemic vascular resistance accompanied by an increase in cardiac output without a fall in the pulmonary vascular resistance. In case reports and small series of patients, the use of hydralazine in such patients resulted in palpitations, chest tightness, unchanged pulmonary vascular resistance, increased pulmonary artery pressure, decreased systemic vascular resistance, and increased heart rate and cardiac output. For this reason, if hydralazine must be used, many experts recommend hemodynamic monitoring during hydralazine therapy in such patients.
Cardiovascular side effects are related to the vasodilatory properties of hydralazine. Reflex tachycardia is commonly observed. Palpitations, flushing, edema, or chest pain have been reported in less than 5% of patients. The use of hydralazine in patients with severe chronic heart failure has been associated with ischemia, including episodes of myocardial infarction.
In patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD), hydralazine may increase pulmonary artery hypertension, especially during periods of hypoxia. The use of hydralazine in these patients may, on rare occasions, result in profound hypotension, tachycardia, and even death.
Rare cases of bradycardia or cardiac tamponade (associated with hydralazine-induced lupus) have been reported. Hydralazine does not have a deleterious effect on the lipid profile, and, in fact, has been shown to decrease total and LDL cholesterol.
Nervous system side effects including peripheral neuropathy is dose-related and is more common in slow acetylators. The neuropathy usually first presents as paresthesias, numbness, and tingling in the extremities. It is probably the result of pyridoxine deficiency, perhaps because formation of a pyridoxal-hydralazine (the active ingredient contained in Apresoline) complex inactivates the coenzyme, and can, therefore, be treated by administration of pyridoxine. Headache or dizziness have been reported in approximately 5% of patients.
A 61-year-old man with hypertension developed ataxia, numbness, and lower extremity weakness approximately six months after beginning hydralazine (up to 300 mg per day) and reserpine therapy. The neuropathy partially resolved after reduction of the hydralazine dosage to 60 mg daily. A complete evaluation revealed that this man was a slow acetylator of hydralazine.
A 48-year-old woman with hypertension developed dyspnea, hemoptysis, pleurisy, proteinuria, and hematuria one year after beginning hydralazine (the active ingredient contained in Apresoline) (150 mg per day), polythiazide, and atenolol therapy. Other associated findings included an elevated ESR, antinuclear factor, anti-DNA titer, a positive LE test, and radiographic findings of diffuse interstitial lung disease. Two weeks after stopping hydralazine, the signs and symptoms of lupus with pulmonary involvement disappeared.
At least one fatal case of hydralazine-induced lupus pneumonitis has been reported. The patient had been taking hydralazine for more than a year prior to developing symptoms.
A rare case of hydralazine-induced lupus presenting as laryngeal edema and right vocal fold paralysis has been reported. The patient had been taking hydralazine 50 mg three times daily and exhibited hoarseness of voice and inspiratory stridor. Discontinuation of hydralazine resulted in reversal of paralysis.
Respiratory side effects include nasal stuffiness, seen in approximately 3% of patients. A case of "hydralazine lung", associated with hydralazine-induced lupus has been reported.
Hematologic abnormalities have been associated with the hydralazine-induced lupus-like syndrome. Anemia may be caused by one of at least four hydralazine-associated problems; hemolysis, the formation of a circulating anticoagulant, thrombocytopenia, and vasculitis. Rare cases of leukopenia and agranulocytosis have been reported.
A 71-year-old man with hypertension developed anorexia, weight loss, petechiae, and a microcytic anemia during therapy with hydralazine and oxprenolol. Evaluation for iron deficiency, hemolysis, or marrow depression was negative. The patient was found to have fecal blood loss, anti-DNA antibodies, decreased complement levels, a normal upper GI series, and biopsy-proven vasculitis. The syndrome resolved within two weeks after discontinuation of hydralazine.
Renal side effects are common in idiopathic systemic lupus erythematosus; however, immune complex glomerulonephritis is rare in drug-induced lupus. Rare cases of rapidly progressive and focal glomerulonephritis associated with the hydralazine-induced lupus syndrome are often accompanied by anemia, a positive anti-DNA antibody titer, and a positive ANA titer.
In one study, rapidly progressive glomerulonephritis (RPGN) is described in 4 of 444 patients, all of whom were men who were treated for 5 to 11 years with daily doses of 100 to 250 mg. In three of the four cases, biopsy revealed a focal and segmental glomerular necrosis with crescents and positive immunofluorescence. The antinuclear antibody titer became positive in three. Renal function improved in all but one after the withdrawal of hydralazine and institution of corticosteroid therapy. A number of other cases of RPGN are reported. It appears to be far more common in patients who are slow acetylators.
A 65-year-old man with ischemic cardiomyopathy developed a pruritic, erythematous, generalized rash within two months after beginning hydralazine (the active ingredient contained in Apresoline) (200 mg per day) therapy. There were no clinical or laboratory signs of lupus. The rash persisted upon gradual withdrawal of the patient's other medications, but cleared only after discontinuation of hydralazine. Rechallenge resulted in a recurrent pruritic rash.
Dermatologic manifestations of the hydralazine-induced lupus-like syndrome include cutaneous vasculitis. A generalized, pruritic rash without evidence of lupus has been associated with hydralazine. Rare cases of Sweet's syndrome (neutrophilic dermatosis) have been associated with hydralazine.
A 59-year-old woman with hypertension and cholecystic gallbladder disease developed abdominal pain, nausea, vomiting, painful hepatomegaly, elevated serum transaminases, direct hyperbilirubinemia, and liver biopsy findings of subacute hepatitis (with bridging necrosis) within two days after hydralazine (the active ingredient contained in Apresoline) was added to her medical regimen. The signs and symptoms of hepatitis resolved after all medications were withheld, but returned upon rechallenge with hydralazine.
Hepatic reactions are rare. Less than ten cases of hepatitis have been reported, many of which were believed to be due to hypersensitivity. Histological findings include hepatocellular, cholestatic, mixed hepatocellular-cholestatic, and granulomatous patterns.
A 44-year-old woman with hypertension and acute sinusitis developed acute renal failure, edema, and a generalized maculopapular erythematous rash during therapy with ampicillin (for sinusitis), hydrochlorothiazide, and hydralazine (the active ingredient contained in Apresoline) A complete evaluation revealed bilateral hydronephrosis and hydroureters secondary to ureteral obstruction due to retroperitoneal fibrosis. Renal function returned to baseline after oral prednisone therapy. It is unclear whether this problem was due to one or more of her medications.
Hypersensitivity reactions are rare. Many of the rare cases of hepatitis are believed to be due to hypersensitivity. A case of retroperitoneal fibrosis and of occupational asthma are believed to be due to hypersensitivity.
Genitourinary side effects including impotence in male patients have been reported rarely.
At least two cases of male impotence associated with hydralazine are reported. The mechanism is unclear. There was no evidence of a neuropathy in either case.
Musculoskeletal manifestations of hydralazine-induced lupus include joint pain, arthralgias, and myalgias. Arthritis in the hands and wrists is a particularly common clinical manifestation.
The incidence of hydralazine-induced systemic lupus erythematosus (SLE) is estimated at 5.4% for patients receiving 100 mg daily, 10.4% for those receiving 200 mg daily, and 10% to 20% for those receiving 400 mg or more daily. It should be noted that hydralazine-induced SLE has occurred at doses as low as 50 mg daily. Risk factors associated with development of hydralazine-induced SLE include slow acetylator status, HLA-DRw4 phenotype, female gender, high daily dose, therapy longer than 3 months, and a family history of autoimmune disease. Black patients appear to develop hydralazine-induced SLE less frequently than other populations. Musculoskeletal symptoms appear to be the most common clinical manifestation of hydralazine-induced SLE; however, it appears that any organ system can be involved. Laboratory findings that may aid in the diagnosis of hydralazine-induced SLE include antinuclear antibody (ANA), lupus erythematosus cells, rheumatoid factor, and antihistone antibodies.
More Apresoline resources
- Apresoline Concise Consumer Information (Cerner Multum)
- Apresoline Advanced Consumer (Micromedex) - Includes Dosage Information
- Apresoline Prescribing Information (FDA)
- Hydralazine Prescribing Information (FDA)
- Hydralazine Hydrochloride Monograph (AHFS DI)
- hydralazine MedFacts Consumer Leaflet (Wolters Kluwer)
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