HYDRALAZINE HYDROCHLORIDE

INDICATIONS AND USAGE: Severe essential hypertension when the drug cannot be given orally or when there is an urgent need to lower blood pressure.

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 mg to 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 minutes to 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 hours to 48 hours. The product should be used immediately after the vial is opened. It should not be added to infusion solution. 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. Discard unused portion.

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

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, pruritus, fever, chills, arthralgia, eosinophilia, and, rarely, hepatitis. Other : nasal congestion, flushing, lacrimation, conjunctivitis. To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc. at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . OVERDOSAGE Acute Toxicity: No deaths due to acute poisoning have been reported. Highest known dose survived: adults, 10 g orally. Oral LD 50 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.

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.

DESCRIPTION Hydralazine Hydrochloride Injection, USP is an antihypertensive available in a 1 mL vial for intravenous and intramuscular administration. Hydralazine Hydrochloride Injection, USP is a sterile, nonpyrogenic colorless solution. Each mL contains : Active : Hydralazine Hydrochloride, USP, 20 mg Preservatives : Methylparaben, NF, 0.65 mg; Propylparaben, NF, 0.35 mg Inactives : Propylene Glycol, USP, 103.6 mg; Sodium Hydroxide and/or Hydrochloric Acid to adjust pH (3.4 to 4.4) and Water for Injection. Hydralazine Hydrochloride, USP is 1-hydrazinophthalazine monohydrochloride, and its structural formula is: Molecular Formula C 8 H 8 N 4 •HCl 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. Structural Formula

OVERDOSAGE: Acute Toxicity No deaths due to acute poisoning have been reported. Highest known dose survived: adults, 10 g orally. Oral LD 50 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.

Acute Toxicity No deaths due to acute poisoning have been reported. Highest known dose survived: adults, 10 g orally. Oral LD 50 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.

HOW SUPPLIED HYDRALAZINE HYDROCHLORIDE INJECTION, USP is supplied in the following dosage forms. NDC 51662-1376-1 HYDRALAZINE HYDROCHLORIDE INJECTION, USP 20mg per mL 1mL VIAL NDC 51662-1376-2 HYDRALAZINE HYDROCHLORIDE INJECTION, USP 20mg per mL 1mL VIAL (Pouch) NDC 51662-1376-3 HYDRALAZINE HYDROCHLORIDE INJECTION, USP 20mg per mL 1mL VIAL (BOX OF 25) HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms The container closure is not made with natural rubber latex. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. How supplied