United States - English - NLM (National Library of Medicine)
HYDRALAZINE HYDROCHLORIDE- hydralazine hydrochloride tablet, film coated
HydrALAZINE hydrochloride, USP, is an antihypertensive, for oral administration. Its chemical name 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
decomposition, and has a molecular weight of 196.64.
Each tablet for oral administration contains 10 mg, 25 mg, 50 mg, or 100 mg hydrALAZINE
hydrochloride, USP. Tablets also contain FD&C Red #40/Allura Red AC Aluminum Lake,
hypromellose, lactose anhydrous, light mineral oil, microcrystalline cellulose, magnesium stearate,
pregelatinized starch, sodium lauryl sulfate, and titanium dioxide.
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.
HydrALAZINE is rapidly absorbed after oral administration, and peak plasma levels are reached at 1 to
2 hours. Plasma levels of apparent hydrALAZINE decline with a half-life of 3 to 7 hours. Binding to
human plasma protein is 87%. Plasma levels of hydrALAZINE vary widely among individuals.
HydrALAZINE is subject to polymorphic acetylation; slow acetylators generally have higher plasma
levels of hydrALAZINE and require lower doses to maintain control of blood pressure.
HydrALAZINE undergoes extensive hepatic metabolism; it is excreted mainly in the form of
metabolites in the urine.
Essential hypertension, alone or as an adjunct.
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
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. Published
evidence suggests an antipyridoxine effect, and that pyridoxine should be added to the regimen if
Information for Patients
Patients should be informed of possible side effects and advised to take the medication regularly and
continuously as directed.
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
Drug /Drug Interactions
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
are used concomitantly.
Administration of hydrALAZINE with food results in higher plasma levels.
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 to 30 times the maximum daily
human dose of 200 to 300 mg and possibly in rabbits at 10 to15 times the maximum daily human dose,
but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of
facial and cranial bones.
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 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 in pediatric patients. The usual
recommended oral starting dosage is 0.75 mg/kg of body weight daily in four divided doses. Dosage
may be increased gradually over the next 3 to 4 weeks to a maximum of 7.5 mg/kg or 200 mg daily.
Adverse reactions with hydrALAZINE 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
Common: Headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris.
Less Frequent:Digestive: constipation, paralytic ileus.
Cardiovascular: hypotension, paradoxical pressor response, edema.
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, pruritus, fever, chills, arthralgia, eosinophilia, and rarely,
Other: nasal congestion, flushing, lacrimation, conjunctivitis.
Acute Toxicity: No deaths due to acute poisoning have been reported. Highest known dose survived:
adults, 10 g orally.
Oral LD50 in rats: 173 and 187 mg/kg.
Signs and Symptoms: Signs and symptoms of overdosage include hypotension, tachycardia, headache,
and generalized skin flushing.
Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac
arrhythmia, and profound shock.
Treatment: There is no specific antidote.
The gastric contents should be evacuated, taking adequate precautions against aspiration and for
protection of the airway. An activated charcoal slurry may be instilled if conditions permit. These
manipulations may have to be omitted or carried out after cardiovascular status has been stabilized,
since they might precipitate cardiac arrhythmias or increase the depth of shock.
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.
Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10
mg four times daily for the first 2 to 4 days, increase to 25 mg four times daily for the balance of the
first week. For the second and subsequent weeks, increase dosage to 50 mg four times daily. For
maintenance, adjust dosage to the lowest effective levels.
The incidence of toxic reactions, particularly the L.E. cell syndrome, is high in the group of patients
receiving large doses of hydrALAZINE.
In a few resistant patients, up to 300 mg of hydrALAZINE daily may be required for a significant
antihypertensive effect. In such cases, a lower dosage of hydrALAZINE combined with a thiazide
and/or reserpine or a beta blocker may be considered. However, when combining therapy, individual
titration is essential to ensure the lowest possible therapeutic dose of each drug.[/S]
HydrALAZINE Hydrochloride Tablets, USP
10 mg - round, convex, pink film coated tablet engraved with HP above 1 on one side and plain on the
Bottles of 100 w/ CRCBottles of 1000
25 mg - round, convex, pink film coated tablet engraved with HP above 2 on one side and plain on the
Bottles of 100 w/ CRC Bottles of 1000
50 mg - round, convex, pink film coated tablet engraved with HP above 3 on one side and plain on the
Bottles of 100 w/ CRCBottles of 1000
100 mg - round, convex, pink film coated tablet engraved with HP above 4 on one side and plain on the
Bottles of 100 w/ Bottles of 1000
Dispense in a tight, light-resistant container as defined in the USP.
Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-
MANUFACTURED FOR: Heritage Pharmaceuticals Inc East Brunswick, NJ 08816 1-866-901-DRUG
hydralazine hydrochloride tablet, film coated
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:6 19 19 -312(NDC:23155-0 0 2)
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
HYDRALAZINE HYDRO CHLO RIDE (UNII: FD171B778 Y) (HYDRALAZINE -
UNII:26 NAK24LS8 )
Stre ng th
STARCH, CO RN (UNII: O8 232NY3SJ)
TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)
ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)
MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )
FD&C RED NO . 4 0 (UNII: WZB9 127XOA)
HYPRO MELLO SES (UNII: 3NXW29 V3WO)
CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)
MINERAL O IL (UNII: T5L8 T28 FGP)
SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)
no sco re
S hap e
S iz e
Marketing Start Date
Marketing End Date
NDC:6 19 19 -312-9 0
9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct
0 8 /13/20 19
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 8 6 242
0 8 /13/20 19
Ad d re s s
Busine ss Ope rations
Dire c t_Rx
0 79 254320
re pa c k(6 19 19 -312)