HYDRALAZINE HYDROCHLORIDE injection

United States - English - NLM (National Library of Medicine)

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Active ingredient:
HYDRALAZINE HYDROCHLORIDE (UNII: FD171B778Y) (HYDRALAZINE - UNII:26NAK24LS8)
Available from:
A-S Medication Solutions
Administration route:
INTRAVENOUS
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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.
Product summary:
Product: 50090-4518 NDC: 50090-4518-0 1 mL in a VIAL, SINGLE-DOSE
Authorization status:
Abbreviated New Drug Application
Authorization number:
50090-4518-0

HYDRALAZINE HYDROCHLORIDE - hydralazine hydrochloride injection

A-S Medication Solutions

----------

Hydralazine Hydrochloride Injection, USP

DESCRIPTION:

Rx only

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

decomposition.

CLINICAL PHARMACOLOGY:

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.

CONTRAINDICATIONS:

Hypersensitivity to hydralazine, coronary artery disease, mitral valvular rheumatic heart disease.

WARNINGS:

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).

PRECAUTIONS:

General

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

symptoms develop.

Laboratory Tests

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

hydrochloride.

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

discontinued.

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

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

hydralazine.

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

Teratogenic Effects

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

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.

Nursing Mothers

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.

Pediatric Use

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:

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,

hepatitis.

Other - nasal congestion, flushing, lacrimation, conjunctivitis.

OVERDOSAGE:

Acute Toxicity

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

flushing.

Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac

arrhythmia, and profound shock.

Treatment

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.

HOW SUPPLIED:

Product: 50090-4518

NDC: 50090-4518-0 1 mL in a VIAL, SINGLE-DOSE

www.fresenius-kabi.us

45854F

Revised: September 2017

Storage

Store at 68 to 77 degrees f

HYDRALAZINE HYDROCHLORIDE

HYDRALAZINE HYDROCHLORIDE

hydralazine hydrochloride injection

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code

(S ource )

NDC:50 0 9 0 -4518 (NDC:6 3323-

6 14)

A-S Medication Solutions

Route of Administration

INTRAVENOUS,

INTRAMUSCULAR

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

HYDRALAZINE HYDRO CHLO RIDE (UNII: FD171B778 Y) (HYDRALAZINE -

UNII:26 NAK24LS8 )

HYDRALAZINE

HYDROCHLORIDE

20 mg

in 1 mL

Inactive Ingredients

Ingredient Name

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)

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

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

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 38 8

0 9 /0 5/20 0 1

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

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 )

Revised: 9/2019

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