United States - English - NLM (National Library of Medicine)
HYDRALAZINE HYDROCHLORIDE - hydralazine hydrochloride injection
A-S Medication Solutions
Hydralazine Hydrochloride Injection, USP
Hydralazine Hydrochloride Injection, USP is an antihypertensive available in a 2 mL vial for intravenous
and intramuscular administration. Each mL of the sterile, nonpyrogenic colorless solution contains
hydralazine hydrochloride USP, 20 mg; methylparaben NF, 0.65 mg; propylparaben NF, 0.35 mg;
propylene glycol USP, 103.6 mg, and Water for Injection USP q.s. The pH of the solution is 3.4 to 4.4.
pH may be adjusted with hydrochloric acid and/or sodium hydroxide. Hydralazine hydrochloride is 1-
hydrazinophthalazine monohydrochloride, and its structural formula is:
Hydralazine hydrochloride USP is a white to off-white, odorless crystalline powder. It is soluble in
water, slightly soluble in alcohol, and very slightly soluble in ether. It melts at about 275°C, with
Although the precise mechanism of action of hydralazine is not fully understood, the major effects are
on the cardiovascular system. Hydralazine apparently lowers blood pressure by exerting a peripheral
vasodilating effect through a direct relaxation of vascular smooth muscle. Hydralazine, by altering
cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle
that are responsible for initiating or maintaining the contractile state.
The peripheral vasodilating effect of hydralazine results in decreased arterial blood pressure (diastolic
more than systolic); decreased peripheral vascular resistance; and an increased heart rate, stroke volume
and cardiac output. The preferential dilatation of arterioles, as compared to veins, minimizes postural
hypotension and promotes the increase in cardiac output. Hydralazine usually increases renin activity in
plasma presumably as a result of increased secretion of renin by the renal juxtaglomerular cells in
response to reflex sympathetic discharge. This increase in renin activity leads to the production of
angiotensin II, which then causes stimulation of aldosterone and consequent sodium reabsorption.
Hydralazine also maintains or increases renal and cerebral blood flow.
The average maximal decrease in blood pressure usually occurs 10-80 minutes after administration of
hydralazine hydrochloride injection. No other pharmacokinetic data on hydralazine hydrochloride
injection are available.
INDICATIONS AND USAGE:
Severe essential hypertension when the drug cannot be given orally or when there is an urgent need to
lower blood pressure.
Hypersensitivity to hydralazine, coronary artery disease, mitral valvular rheumatic heart disease.
In a few patients, hydralazine may produce a clinical picture simulating systemic lupus erythematosus
including glomerulonephritis. In such patients, hydralazine should be discontinued unless the benefit-
to-risk determination requires continued antihypertensive therapy with this drug. Symptoms and signs
usually regress when the drug is discontinued but residua have been detected many years later. Long-
term treatment with steroids may be necessary (see PRECAUTIONS, Laboratory Tests).
Myocardial stimulation produced by hydralazine can cause anginal attacks and ECG changes of
myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must,
therefore, be used with caution in patients with suspected coronary artery disease.
The “hyperdynamic” circulation caused by hydralazine may accentuate specific cardiovascular
inadequacies. For example, hydralazine may increase pulmonary artery pressure in patients with mitral
valvular disease. The drug may reduce the pressor responses to epinephrine. Postural hypotension
may result from hydralazine but is less common than with ganglionic blocking agents. It should be used
with caution in patients with cerebral vascular accidents.
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. In some instances where
control values were below normal, improved renal function has been noted after administration of
hydralazine. However, as with any antihypertensive agent, hydralazine should be used with caution in
patients with advanced renal damage.
Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. Publishing
evidence suggests an antipyridoxine effect and that pyridoxine should be added to the regimen if
Complete blood counts and antinuclear antibody titer determinations are indicated before and
periodically during prolonged therapy with hydralazine even though the patient is asymptomatic. These
studies are also indicated if the patient develops arthralgia, fever, chest pain, continued malaise or other
unexplained signs or symptoms.
A positive antinuclear antibody titer requires that the physician carefully weigh the implications of the
test results against the benefits to be derived from antihypertensive therapy with hydralazine
Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia,
agranulocytosis, and purpura, have been reported. If such abnormalities develop, therapy should be
MAO inhibitors should be used with caution in patients receiving hydralazine.
When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with
hydralazine, patients should be continuously observed for several hours for any excessive fall in blood
pressure. Profound hypotensive episodes may occur when diazoxide injection and hydralazine
hydrochloride injection are used concomitantly.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a lifetime study in Swiss albino mice, there was a statistically significant increase in the incidence of
lung tumors (adenomas and adenocarcinomas) of both male and female mice given hydralazine
continuously in their drinking water at a dosage of about 250 mg/kg per day (about 80 times the
maximum recommended human dose). In a 2-year carcinogenicity study of rats given hydralazine by
gavage at dose levels of 15, 30 and 60 mg/kg/day (approximately 5 to 20 times the recommended human
daily dosage), microscopic examination of the liver revealed a small, but statistically significant
increase in benign neoplastic nodules in male and female rats from the high-dose group and in female
rats from the intermediate-dose group. Benign interstitial cell tumors of the testes were also
significantly increased in male rats from the high-dose group. The tumors observed are common in
aged rats and a significantly increased incidence was not observed until 18 months of treatment.
Hydralazine was shown to be mutagenic in bacterial systems (Gene Mutation and DNA Repair) and in
one of two rats and one rabbit hepatocyte in vitro DNA repair studies. Additional in vivo and in vitro
studies using lymphoma cells, germinal cells and fibroblasts from mice, bone marrow cells from
Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for
The extent to which these findings indicate a risk to man is uncertain. While long-term clinical
observation has not suggested that human cancer is associated with hydralazine use, epidemiologic
studies have so far been insufficient to arrive at any conclusions.
Pregnancy Category C
Animal studies indicate that hydralazine is teratogenic in mice at 20-30 times the maximum daily human
dose of 200-300 mg and possibly in rabbits at 10-15 times the maximum daily human dose, but that it is
nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and
There are no adequate and well-controlled studies in pregnant women. Although clinical experience
does not include any positive evidence of adverse effects on the human fetus, hydralazine should be
used during pregnancy only if the expected benefit justifies the potential risk to the fetus.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when hydralazine injection is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established in controlled clinical trials,
although there is experience with the use of hydralazine hydrochloride in pediatric patients. The usual
recommended parenteral dosage, administered intramuscularly or intravenously, is 1.7-3.5 mg/kg of
body weight daily, divided into four to six doses.
Adverse reactions with hydralazine hydrochloride are usually reversible when dosage is reduced.
However, in some cases it may be necessary to discontinue the drug.
The following adverse reactions have been observed, but there has not been enough systematic
collection of data to support an estimate of their frequency.
Common: Headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris.
Less Frequent: Digestive-constipation, paralytic ileus.
Cardiovascular - hypotension, paradoxical pressor response, edema.
Respiratory - dyspnea.
Neurologic - peripheral neuritis, evidenced by paresthesia, numbness, and tingling; dizziness; tremors;
muscle cramps, psychotic reactions characterized by depression, disorientation, or anxiety.
Genitourinary - difficulty in urination.
Hematologic - blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia,
agranulocytosis, purpura; lymphadenopathy; splenomegaly.
Hypersensitive Reactions - rash, urticaria, pruritis, fever, chills, arthralgia, eosinophilia, and, rarely,
Other - nasal congestion, flushing, lacrimation, conjunctivitis.
No deaths due to acute poisoning have been reported.
Highest known dose survived: adults, 10 g orally.
Oral LD in rats: 173 and 187 mg/kg.
Signs and Symptoms
Signs and symptoms of overdosage include hypotension, tachycardia, headache, and generalized skin
Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac
arrhythmia, and profound shock.
There is no specific antidote.
Support of the cardiovascular system is of primary importance. Shock should be treated with plasma
expanders. If possible, vasopressors should not be given, but if a vasopressor is required, care should
be taken not to precipitate or aggravate cardiac arrhythmia. Tachycardia responds to beta blockers.
Digitalization may be necessary, and renal function should be monitored and supported as required.
No experience has been reported with extracorporeal or peritoneal dialysis.
DOSAGE AND ADMINISTRATION:
When there is urgent need, therapy in the hospitalized patient may be initiated intramuscularly or as a
rapid intravenous bolus injection directly into the vein. Hydralazine Hydrochloride Injection should be
used only when the drug cannot be given orally. The usual dose is 20-40 mg, repeated as necessary.
Certain patients (especially those with marked renal damage) may require a lower dose. Blood
pressure should be checked frequently. It may begin to fall within a few minutes after injection, with the
average maximal decrease occurring in 10-80 minutes. In cases where there has been increased
intracranial pressure, lowering the blood pressure may increase cerebral ischemia. Most patients can
be transferred to oral hydralazine hydrochloride within 24-48 hours.
The product should be used immediately after the vial is opened. The product should not be added to
infusion solutions. Hydralazine Hydrochloride Injection may discolor upon contact with metal;
discolored solutions should be discarded.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration, whenever solution and container permit.
NDC: 50090-4518-0 1 mL in a VIAL, SINGLE-DOSE
Revised: September 2017
Store at 68 to 77 degrees f
hydralazine hydrochloride injection
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code
(S ource )
NDC:50 0 9 0 -4518 (NDC:6 3323-
A-S Medication Solutions
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
HYDRALAZINE HYDRO CHLO RIDE (UNII: FD171B778 Y) (HYDRALAZINE -
UNII:26 NAK24LS8 )
in 1 mL
Stre ng th
PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)
10 3.6 mg in 1 mL
METHYLPARABEN (UNII: A2I8 C7HI9 T)
0 .6 5 mg in 1 mL
PRO PYLPARABEN (UNII: Z8 IX2SC1OH)
0 .35 mg in 1 mL
HYDRO CHLO RIC ACID (UNII: QTT1758 2CB)
SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)
NDC:50 0 9 0 -4518 -
1 mL in 1 VIAL, SINGLE-DOSE; Type 0 : No t a Co mbinatio n
Pro duc t
0 9 /11/20 19
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 40 38 8
0 9 /0 5/20 0 1
A-S Medication Solutions (830016429)
Ad d re s s
Busine ss Ope rations
A-S Medicatio n So lutio ns
8 30 0 16 429
RELABEL(50 0 9 0 -4518 ) , REPACK(50 0 9 0 -4518 )