Hydralazine
Hydrochloride Injection,
USP

Rx Only

Hydralazine Hydrochloride Injection, USP is an antihypertensive available in a 1 mL vial for intravenous and intramuscular administration. Each milliliter 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 q.s. The pH of the solution is 3.4 - 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, and has a molecular weight of 196.64.

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.

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.)

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, pruritus, fever, chills, arthralgia, eosinophilia, and, rarely, hepatitis.

Other: nasal congestion, flushing, lacrimation, conjunctivitis.

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. It 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.

Hydralazine Hydrochloride Injection, USP (20 mg/mL)

Store at controlled room temperature 15°-30°C (59°-86°F) (See USP).

IN0901
Rev. 1/03
MG #11928

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967