HYDRALAZINE HYDROCHLORIDE- hydralazine hydrochloride tablet
DESCRIPTION
HydrALAZINE hydrochloride, USP, is an antihypertensive, for oral administration. Its chemical name is -hydrazinophthalazine monohydrochloride.
C8 H8 N4 .HCl
HydrALAZINE hydrochloride, USP is 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 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 anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, stearic acid and FD&C Yellow 6.
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 peripheral vasodilating effect through 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 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.
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 combinahon 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.
Pregnancy Category C
DOSAGE AND ADMINISTRATION
Initiate therapy in gradually increasing dosages; adjust according to individual response. Start with 10 mg four times daily for the first to 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 few resistant patients, up to 300 mg of hydrALAZINE daily may be required for significant antihypertensive effect. In such cases, lower dosage of hydrALAZINE combined with thiazide and/or reserpine or beta blocker may be considered. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug.
