Label: HYDRALAZINE HYDROCHLORIDE tablet

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.

Each tablet for oral administration contains 10 mg, 25 mg, 50 mg or 100 mg hydrALAZINE hydrochloride, USP. Tablets also contain magnesium stearate, microcrystalline cellulose, orange lake blend, silicon dioxide, and sodium starch glycolate. The orange lake blend consists of FD&C yellow #6.

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 Tests.)

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 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.

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.

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 hydrochloride tablets.

In a few resistant patients, up to 300 mg of hydrALAZINE hydrochloride tablets daily may be required for a significant antihypertensive effect. In such cases, a lower dosage of hydrALAZINE hydrochloride tablets 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.

HydrALAZINE Hydrochloride Tablets, USP are available as:

25 mg – Round, peach, core tablet, debossed EP over 102 on one side and plain on the reverse side.

Overbagged with 10 tablets per bag, NDC 55154-2141-0

50 mg – Round, peach, core tablet, debossed EP over 103 on one side and plain on the reverse side.

Overbagged with 10 tablets per bag, NDC 55154-2140-0

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

American Health Packaging unit dose blisters contain drug product from Avet Pharmaceuticals Inc.

Distributed by:
American Health Packaging
Columbus, OH 43217

Distributed By:

Cardinal Health

Dublin, OH 43017

L59249490225

L59249310624

8483301/0124

NDC 55154-2141-0

HydrALAZINE HYDROCHLORIDE

TABLETS, USP

25 mg

10 TABLETS

NDC 55154-2140-0

HydrALAZINE HYDROCHLORIDE

TABLETS, USP

50 mg

10 TABLETS